Background: Over the past two decades, the Copenhagen Psychosocial Questionnaire (COPSOQ) has been established as a valid instrument to measure psychosocial stress at work. Currently, the COPSOQ international network is responsible for monitoring and improving COPSOQ. In 2019, a new questionnaire was published, and the Greek version is now being validated. Methods: The measurement qualities of the Greek COPSOQ III have been explored in accordance with the usual requirements of a validation study as defined by DIN EN ISO 10075-3. A sample of observations from 2,189 participants surveyed with the COPSOQ in Greece was used to validate the current version with appropriate statistical analyses. Exploratory factor analysis was used to assess the statistical relationships for many scales. Results: With its 108 items and 40 scales, the Greek COPSOQ III includes all psychosocial work factors that have been internationally validated and remain compatible with approximately 72% of the COPSOQ III German version content. In addition to the primary results, congruence with widely used theoretical approaches such as the demand-control (−support) model (DCM) or the job demands-resources model (JDR) is generally satisfactory. In summary, our validation study for the Greek COPSOQ III version showed adequate reliability and validity, which is in line with the findings of the COPSOQ III questionnaire from other European countries, and it is also compatible with the validation of the German COPSOQ III (Lincke, 2021). Our regression analysis revealed that 34 psychosocial work factors (34 “context” scales) could adequately predict the scores of the satisfactory and health scales (6 “outcome” scales). The analysis also revealed the top five (5) predictors (context variables) for each of the six (6) “effect” scales (outcome variables). Conclusions: With the launch of COPSOQ III in Greece, current and new workplace psychosocial aspects could be explored. COPSOQ III (GR) is a beneficial instrument for enterprise research and risk assessment.

Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg/mL, 0.5 mg/mL or 2.5 mg/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in Aβ plaque burden in the hippocampus and cortex and an attenuation of neuroinflammatory markers. Antioxidant response genes were upregulated in the cortex of WSAq treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy.

Several technologies have been introduced into neurorehabilitation programs to en-hance traditional treatment of individuals with Spinal Cord Injury (SCI). Their effec-tiveness has been widely investigated but their adoption has not been properly quanti-fied. The aim of this study is to assess the distribution of conventional (Treatment As Usual – TAU) and technology-aided (Treatment With Technologies – TWT) treatments, conveniently grouped based on different therapeutic goals, in a selected SCI unit. Data from 104 individuals collected in 29 months were collected in a custom database and categorized according to both the conventional American Impairment Scale classifica-tion and a newly developed multifactor (MF) clustering approach, that considers addi-tional sources of information (the lesion level, the level of independence in the activi-ties of daily living and the hospitalization duration). Results indicated an average technology adoption of about 30%. Moreover, the MF clusters were less overlapped and the differences in TWT adoption were more pronounced than in AIS-based clus-tering. MF clustering was capable of grouping individuals based both on neurological features and functional abilities. In particular, individuals with motor complete inju-ries were grouped together, whereas individuals with sensorimotor incomplete SCI were collected separately based on the lesion level. Analyzing TWT adoption, we found that in case of motor complete SCI, TWT for muscle tone control and modulation were mainly selected while the other types of TWT were seldom adopted. Even for in-dividuals with incomplete SCI the most frequent rehabilitation goal was muscle tone modulation, regardless of the AIS level, and technologies to improve walking ability and balance control were mainly used for individuals with thoracic or lumbar lesions. Analyzing TAU distribution, we found that the highest adoption of muscle tone mod-ulation strategies was reported in case of individuals with motor complete SCI, i.e. in cases when almost no gait training was pursued. In case of cervical motor incomplete SCI, compared to thoracic and lumbar incomplete SCI, there was a greater focus on muscle tone control and force recruitment in addition to walking, than on balance training.

Procedural and reporting guidelines frame the process of scientific practices and communications among researchers and the community at large. In the pursuit of fostering reproducibility, several methodological frameworks have been proposed by several initiatives. Nevertheless, recent studies indicate that data leakage and reproducibility are still prominent challenges. Recent studies have shown the transforming potential of incorporating the FAIR (Findable, Accessible, Interoperable and Reusable) principles in the work-flow of different context such as software and machine learning model development stages to cultivate open science. In this work, we introduce a framework to calibrate reporting guidelines against the FAIR principles in order to foster reproducibility and open science. We adapted the “Best fit” framework synthesis approach to develop the calibration framework. We propose a series of defined workflows to calibrate reporting guidelines with FAIR principles and a use case to demonstrate the process. By integrating FAIR principles with established reporting guidelines, the proposed framework bridges the gap in accommodating both FAIR metrics and reporting guidelines and benefits from advantages of these major integrated components.

Background: Positive person-centered attributes of inpatient rehabilitation need to be identified from the patient perspective to be further developed and sustained. Purpose: To identify which attributes patients openly evoke as being great care experiences, using an open appreciative inquiry during the inpatient rehabilitation stay. Methods: Qualitative secondary analysis of appreciative patient comments during a bedside patient experience rounding, facilitated by a neutral party. Two independent analysts employed an inductive, summative form of content analysis. Results: Among 150 patients rounded, 122 provided categorizable appreciative accounts. Over two thirds of the patients (67.2%) focused on “staff attributes” in their great-experience accounts. Those attributes were mostly interpersonal such as being “attentive & caring - beyond clinical duty” and being “encouraging (but not too hard) & reassuring”. These interpersonal staff attributes were reported with words showing deep levels of personal significance or patient appreciation. Beyond staff attributes, the perceived quality of the “patient care” (31.1%) and opportunities for “leisure and social activities” (9.0%) were also frequently evoked. Amenities like food or costumer service were the least evoked, rarely so as an exclusive attribute (0.8% for each). Conclusions: The human(e) factor, especially the interpersonal qualities of staff, emerged as greatly appreciated from the patient experience perspective during inpatient rehabilitation. These experiences help identify which person-centered attributes of care might be further developed and sustained.

Although mask-wearing is now widespread, knowledge of how to quantify or improve its performance remains surprisingly limited and largely based on empirical evidence. The objective of this study was to visualize the expiratory airflows from facemasks and evaluate aerosol transmission between two persons. Different visualization methods were explored, including the Schlieren optical system, laser/LED-particle imaging system, thermal camera, and vapor-SarGel system. The leakage flows and escaped aerosols were quantified using a hotwire anemometer and a particle counter, respectively. The results show that mask-wearing reduces the exhaled flow velocity from 2~4 m/s (with no facemask) to around 0.1 m/s, thus decreasing droplet transmission speeds. Cloth, surgical, and KN95 masks showed varying leakage flows at the nose top, sides, and chin. The leakage rate also differed between inhalation and exhalation. The neck gaiter has low filtration efficiency and high leakage fractions, providing low protection efficiency. There was considerable deposition in the mouth-nose area, as well as the neck, chin, and jaw, which heightened the risk of self-inoculation through spontaneous face-touching. A face shield plus surgical mask greatly reduced droplets on the head, neck, and face, indicating that double face coverings can be highly effective when a single mask is insufficient. The vapor-SarGel system provided a practical approach to study interpersonal transmission under varying close contact scenarios or with different face coverings.

Antimicrobial resistance has been stated to be a global health problem. In Chile, the use of antibiotics should be declared by medical prescription, however, it is unknown what happens to the drugs once the treatment ends. One possibility is that these end up being disposed of in the trash or down the drain. In both scenarios, antibiotics could accumulate in the environment, stimulating the emergence of antimicrobial resistance mechanisms and their transfer between microorganisms. Unfortunately, sometimes wastewater ends up in bodies of water, due to the dragging of elements by rain, or by the presence of illegal water discharges. In this work, we use shotgun metagenomics to elucidate the functional and microbial composition of biohazard elements in the bay of Puerto Varas City, Chile. As expected, we found a high diversity in microbial communities, with bacterial elements described as human or animal pathogens. Also, we detect a diverse repertory of virulence and antibiotic-resistant genes (ARGs), related with macrolides, beta-lactams, and tetracyclines resistance, which are consistent with the families of antibiotics most used in Chile. Similar ARGs were identified in DNA mobile elements. In addition, we tested the AMR ability in 20 bacterial strains recovered from the Llanquihue lake. This is the first report of the presence of genomic elements that could constitute a health problem for the people who live around the Llanquihue Lake of Chile, considering the importance of the interconnection between environmental, animal, and human health, a concept known as One Health.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards, and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit set and yield in tree fruit production systems. Here we describe the metagenomics-based detection of plant viruses through bee and pollen samples collected during the spring bloom period from a mixed Prunus and Malus orchard. Twenty-one unique viruses were detected in samples collected during apricot (Prunus armeniaca), sweet cherry (Prunus avium), peach (Prunus persica), and apple blooms. Ilarviruses prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV), Secoviridae family members tomato necrotic ringspot virus, tobacco necrotic ringspot virus, and prunus virus F, and Capillovirus cherry virus A (CVA) were detected in all time points, while other viruses were detected with restricted ranges. These results demonstrate the benefits of area-wide monitoring through bee pollination activities, and provide new insights into the diversity of viruses in tree fruit pollination ecosystems.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between stiff AA and reduced longitudinal strain and subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). A proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in-silico utilizing Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with A) Elastic AA; B) Stiff AA; and C) Stiff AA with free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that can abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of LV longitudinal strain are common in patients HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

: Pearl millet (Pennisetum glaucum L) R. Br) is a subtropical grain and forage crop. It is privileged with several desirable forage attributes. Nevertheless, research on pearl millet is limited especially as a forage crop in the developing countries. Therefore, the objectives of this study were to investigate the field performance and stability of pearl millet genotypes for forage yield across seven environments. The study was conducted in seven environments (combination of locations and seasons) during 2016/2017-2018/2019 seasons. Twenty-five pearl millet genotypes, selected based on forage yield from a core collection of 200 accessions, were arranged in alpha lattice design with three replications. The parameters measured were fresh forage yield, days to flowering, plant height, number of culms m-2, leaf to stem ratio, and stem girth. The combined analysis revealed that environments, genotypes and their interaction had significant effects on all traits studied except the genotypic effect on stem girth. Across the seven environments, four genotypes (G14, G01, G12, and G22) out-yielded the check genotype in fresh matter yield by 20.7, 16.5, 11.0 and 9.8%, respectively. The additive main effects and multiplicative interaction (AMMI) analysis showed that the genotype, environment and their interaction were highly significant (P≤0.001) for fresh matter yield. The results of AMMI Stability Values (ASV) and the genotype selection index (GSI) combined with the AMMI estimate-based selection showed that genotypes G14, G22 and G01 were the most stable and adapted genotypes and were superior to the check genotype. These results indicate that forage pearl millet varieties could be developed directly through evaluation of the wealth available collections or indirectly through hybridization in crop breeding programs.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.

Introduction: Bovine tuberculosis is a zoonotic disease of considerable impact, especially in livestock countries, which can cause human disease. Despite its importance, Colombia is a country in which few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. Objective: To describe the temporal-spatial distribution of bovine tuberculosis in Colombia between 2001 and 2019. Methods: Retrospective cross-sectional descriptive study, based on reports by the Colombian Agricultural Institute, of tuberculosis surveillance in cattle on farms in Colombia from 2001 to 2019. The data were converted into databases in Microsoft Access 365®, and multiple epidemiological maps were generated with the Kosmo RC1®3.0 software coupled to shape files of all the country's departments. Results: During the study period, 5,273 tuberculosis cases in bovines were identified in the different departments of Colombia (mean 278 cases/year). Regarding its temporal distribution, the number of cases varied from a maximum of 903 cases (17.12% of the total) in 2015 to a minimum of 0 between 2001 and 2004 and between 2017 and 2019 (between 2005 and 2016, the minimum was 46 cases, 0.87%). Conclusions: GIS is an essential tool for understanding the temporospatial behaviour of zoonotic diseases in Colombia, as is the case of bovine tuberculosis, with its potential implications for Human and One Health.

Tumor infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, and total TILs (CD4+, CD8+, Treg, B cells) within chemotherapy-treated tumors compared to chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic response with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherpy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

This work assesses the dietary use of two insect meals of Tenebrio molitor (TM) larvae reared in conventional (TM-10) or MAPs-enriched substrates (MAP-TM-10) as fish meal replacements (10%) in the diets of gilthead seabream (Sparus aurata). Fish (n=4,500; 207.19 ± 1.47 g) were divided into three groups with triplicates: Control (fed conventional diet), TM-10 and MAP-TM-10 groups.The fish were reared in floating cages for 12 weeks and The dietary effects on white blood cell ac-tivation, heat shock proteins, MAPKs, and apoptosis of the fish were evaluated. The MAP-TM-10 group exhibited the highest eosinophilic induction and plasma cells. Phosphorylated levels of p38 MAPK; p44/42 MAPK; HSP70 and HSP90 increased in the TM-10 and MAP-TM-10. In terms of apoptosis, Bax levels were lower in the TM groups compared to the Control, and the MAP-TM-10 group showed even lower levels than the TM-10 group. Bcl-2 levels increased in the TM-10 compared to the Control, and further increased in the MAP-TM-10 group. The Bax/Bcl-2 ratio, an apoptosis indicator, decreased in the TM groups, with the MAP-TM-10 group showing a further decrease compared to TM-10. These findings suggest that insects breeding substrate enriched with MAPs modulated the effect of TM on cellular stress and apoptosis.

The snATAC + snRNA platform allows epigenomic profiling of open chromatin and gene expression with single-cell resolution. The most critical assay step is to isolate high-quality nuclei to proceed with droplet-base single nuclei isolation and barcoding. With the increasing popularity of multiomic profiling in various fields, there is a need for optimized and reliable nuclei isolation methods, mainly for human tissue samples. Herein we compared different nuclei isolation methods for cell suspensions, such as peripheral blood mononuclear cells (PBMC, n=18) and a solid tumor type, ovarian cancer (OC) (n=18), derived from debulking surgery. Nuclei morphology and sequencing output parameters were used to evaluate the quality of preparation. Our results show that NP-40 detergent-based nuclei isolation yields better sequencing results than collagenase tissue dissociation for OC, significantly impacting cell identification and analysis. Given the utility of applying such techniques to frozen samples, we also tested frozen preparation and digestion (n=6). A paired comparison between frozen and fresh samples validated the quality of both specimens. Finally, we demonstrate the reproducibility of scRNA and snATAC + snRNA platform, by comparing the gene expression profiling of PBMC. Our results highlight how the choice of nuclei isolation methods is critical for obtaining quality data in multiomic assays. It also shows that the measurement of expression between scRNA and snRNA is comparable and effective for cell type identification.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [18F]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [18F]FET PET data, i.e. early and late tu-mor-to-background (TBR5-15, TBR20-40) images and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume-of-interest mirrored to the con-tralateral hemisphere. Differences between tumor and healthy tissue features were compared us-ing Wilcoxon test. Additionally, the ability to distinguish tumor from healthy tissue was assessed using logistic regression. 5 % of features derived from TBR20-40 images were significantly differ-ent; 16 % of features derived from TBR5-15 images and 69 % of features derived from TTP images. The high number of significantly different features derived from TTP images was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [18F]FET up-take in static images. However, the differences did not reach satisfactory predictability for ma-chine learning based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [18F]FET PET data may extract additional information even in [18F]FET-negative glio-mas, which should be investigated in larger cohorts and correlated with histological and out-come features in future studies.

Biomarker directed selection of targeted anti-neoplastic agents such as immune check-point inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Review of the existing bibliography shows that the direction and magnitude of the long-term trends of UV irradiance, and their main drivers, vary significantly throughout Europe. Analysis of total ozone and spectral UV data recorded at four European stations during 1996 – 2017 reveals that long-term changes in UV are mainly driven by changes in aerosols, cloudiness, and surface albedo, while changes in total ozone play a less significant role. The variability of UV irradiance is large throughout Italy due to the complex topography and large latitudinal extension of the country. Analysis of the spectral UV records of the urban site of Rome, and the alpine site of Aosta reveals that differences between the two sites follow the annual cycle of the differences in cloudiness and surface albedo. Comparisons between the noon UV index measured at the ground at the same stations and the corresponding estimates from the DWD forecast model and OMI/Aura observations reveal differences of up to 6 units between individual measurements, which are likely due to the different spatial resolution of the different datasets, and average differences of 0.5 – 1 unit, possibly related to the use of climatological surface albedo and aerosol optical properties in the retrieval algorithms.

Chan and colleagues in their paper titled “Human origins in a southern African palaeo-wetland and first migrations” (https://www.nature.com/articles/s41586-019-1714-1) report 198 novel whole mitochondrial DNA (mtDNA) sequences and infer that ‘anatomically modern humans’ originated in the Makgadikgadi–Okavango palaeo-wetland of southern Africa around 200 thousand years ago. This claim relies on weakly informative data. In addition to flawed logic and questionable assumptions, the authors surprisingly disregard recent evidence and debate on human origins in Africa. As a result, the emphatic and high profile conclusions of the paper are unjustified.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Microplastics (plastic particles < 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

All types of sports are potential application scenarios for automatic and real-time visual object and event detection. In rink hockey, the popular roller quad skate variant of hockey team sports, it is of great interest to automatically track player’s movements and positions, player’s sticks and, also, making other judgments, such as being able to locate the ball. In this work, we introduce a real-time pipeline composed by an object detection model, created specifically for rink hockey games, followed by a knowledge-based event detection module. Even in the presence of occlusions and quick motions, our deep learning object detection model effectively identifies and tracks, in real-time, important visual elements such as: ball; players; sticks; referees; crowd; goalkeeper; and goal. Using a curated dataset composed by a collection of videos of rink hockey, comprising 2525 annotated frames, we trained and evaluated the algorithm performance and compare it to state of the art object detection techniques. Our object detection model, based on YOLOv7, presents a global accuracy of 80%, and presents a good performance in terms of accuracy and speed, according to our results, making it a good choice for rink hockey applications. In our initial tests, the event detection module successfully detected one important event type in rink hockey games, the occurrence of penalties.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

Current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. The emerging use of theranostic technologies to improve surgical outcomes can further augment the efficacy of adjuvant radiosurgery/radiotherapy and systemic therapies. Stanford Neurosurgery is a leader in the field of translational neuro-oncology. In this review, we provide an expert view of how theranostics can be integrated into future therapeutic treatment algorithms to help improve survival for patients with brain tumors.

The enterprise software sector is experiencing a significant transformation driven by rapid technological progress and evolving business needs. An effective release management process is crucial for the solution providers and customers, as they incorporate the principles of Industry 4.0 and 5.0. With the growing dependence on software solutions and services, ensuring their quality, reliability, and security is highly necessary. The release management process incorporates strategic planning, regression testing, accurate deployment, and continuous monitoring of software updates. However, the rapid advancements in artificial intelligence (AI) and machine learning (ML) create a unique challenge to the release management process. The existing research needs to address the necessary adaptations for Industry 5.0, mainly in product-based software organizations, to the release management process without a change management system. After working with several software solution stakeholders, based on the responses from SaaS project stakeholders, we have presented a revised software release readiness workflow by incorporating a change management module. The preliminary result based on data over a limited period of time indicates that the revised workflow has the potential to improve the management of slippage, particularly by more effectively addressing NFR-related issues, thereby resulting in more predictable and reliable release cycles.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Legal consideration hold significant importance in the cloud migration process, encompassing contractual arrangements, data sovereignty concerns, and liability matters. Organizations need to make sure that their contracts with cloud service providers (CSPS) cover important aspects such as data ownership, usage rights, and indemnification clauses. In the ever-changing world of smart cities, the importance of ensuring secure, compliant, and efficient data migration across international borders has become more crucial than ever. This paper introduces a new framework that combines natural language processing (NLP), and blockchain smart contracts to tackle the intricate legal issues involved in moving data across borders in cloud settings. The framework starts by utilizing an NLP model to ensure compliance with data protection regulations, such as GDPR, CCPA, and DPDPA, which are specific to the destination jurisdiction of the data. After confirming the verification, the smart contract initiates the data transfer process, securely recording metadata such as file hash, timestamp, and transfer details on the blockchain, guaranteeing transparency and immutability. After the transfer, an international vendor at the destination verifies the data against the relevant legal requirements, guaranteeing compliance before storing it in the destination cloud. By adopting this approach, we can ensure the legal validity of cross-border data transfers, while also promoting trust and accountability among all parties involved in smart city ecosystems. The findings indicate that this framework has the potential to greatly reduce the risks associated with data sovereignty, liability, and contractual obligations when moving data to the cloud.

In the era of cloud computing, guaranteeing the safety and effectiveness of data management is of utmost importance. This investigation presents a novel approach that amalgamates sharding concept, encryption, zero-knowledge proofs (zkp), and blockchain technology for secure data retrieval and data access control to improve data security, efficiency in cloud storage and migration. Further we utilize user-specific digital wallets for secure encryption keys in order to encrypt the file before storing into the cloud. As Large files ( greater than 50 MB) or Big data file ( grater than 1 TB) computational complexity is more we leverage on sharding concept to enhance both space and time complexity in cloud storage, hence the large files are divided into shards and stored in different database servers. We also employed blockchain smart contract to enhance secure retrieval of the file and also a secure access method which ensures the privacy of the user. The zk-snark protocol is utilized to ensure the safe transfer of data between different cloud services. By utilizing this approach, data privacy is preserved, as only the proof of the data’s authenticity is shared with the verifier at the destination cloud, rather than the actual data itself. The suggested method tackles important concerns related to data protection, privacy, and efficient resource utilization in cloud computing settings by ensuring it meets all the cloud policies require to store data. As the environment maintains privacy of the user data and by not storing the raw data of the user anywhere, the entire environment is setup as a Zero trust model.

A comprehensive design framework is proposed for optimizing sparse MIMO (multiple-input, multiple-output) arrays to enhance multi-target detection. The framework emphasizes efficient utilization of antenna resources, including strategies for minimizing inter-element mutual coupling and exploring alternative grid-based sparse array (GSA) configurations by efficiently separating interacting elements. Alternative strategies are explored to enhance angular beamforming metrics, including beamwidth (BW), peak-to-sidelobe ratio (PSLR), and grating lobe limited field of view. Additionally, a set of performance metrics is introduced to evaluate virtual aperture effectiveness and beamwidth loss factors. The study employs the desirability function and explores optimization strategies for the partial sharing of antenna elements in multi-mode radar applications. A novel machine learning initialization approach is introduced for rapid convergence. Observations include the potential for peak-to-sidelobe ratio (PSLR) reduction in dense arrays and insights into GSA feasibility and performance compared to uniform arrays. The study validates the efficacy of the proposed framework through simulated and measured results. The study underscores the importance of effective sparse array processing in multi-target scenarios and highlights the advantages of the proposed design framework, offering clarity on sparse array efficiency and applicability in processing hardware providing clarity on its advantages over uniform and nonuniform arrays.

In the fast-changing world of software development, the protection of software products has emerged as an imperative requirement. This paper presents a new way to increase the maturity of development teams to reach the highest level of software security. Based on these, the framework uses the Fuzzy Analytic Hierarchy Process (Fuzzy-AHP) to systematically evaluate and enhance the people maturity of software development projects. The essence of the fuzzy logic and AHP technique interaction is to handle the uncertainty and complexity of human factors and team dynamics in the evaluation framework. Using the decision-making model allows the project managers and stakeholders to determine the appropriate areas for improvement and develop the right strategies and actions to nurture a secure and mature development culture. The paper identifies 24 human success factors (HSFs) and human security vulnerabilities (HSVs) and 38 practices for addressing these HSFs and HSVs. Furthermore, we discuss the local and global ranks of each HSF and HSV practice and categorize the identified practices into 9 categories to determine the ranks and weight of each category. Based on collected data, FAHP prioritized these practices; the category “C4: Skill Development and Stakeholder Engagement” is ranked highest at rank-1 and possesses the most significant weight of 0.12435. Similarly, the highest global weight is 0.051506, and the global ranked (rank-1) HSF and HSV practice is “P15: Hands-On Practice and Stakeholder Communication”. Research evidence and case discussions show how the described framework assists in building secure software development (SSD) practices, which can be considered evidence of the application of team maturity to improve cybersecurity in organizations. Additional research directions include improving the framework, especially using highly developed learning techniques and applying the framework to other forms of development.

This study aims to characterize the molecular profile of hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and the broader society.

We previously found that chronic adenosine A1 receptor stimulation with N6-Cyclopentyladenosine increased α-synuclein misfolding and neurodegeneration in a novel α-synucleinopathy model, a hallmark of Parkinson’s disease. Here, we aimed to synthesize a dimer caffeine-indan linked by a 6-carbon chain to cross the blood-brain barrier and tested its ability to bind α-synuclein, reducing misfolding, behavioural abnormalities, and neurodegeneration in our rodent model. Behavioural tests and histological stains assessed neuroprotective effects of the dimer compound. A rapid synthesis of the 18F-labelled analogue enabled Positron Emission Tomography and Computed Tomography imaging for biodistribution measurement. Molecular docking analysis showed that the dimer binds to α-synuclein N- and C-termini and the non-amyloid-β-component (NAC) domain, similar to 1-aminoindan, and this binding promotes a neuroprotective α-synuclein “loop” conformation. The dimer also binds to the orthosteric binding site for adenosine within the adenosine A1 receptor. Immunohistochemistry and confocal imaging showed the dimer abolished α-synuclein upregulation and aggregation in the substantia nigra and hippocampus, and the dimer mitigated cognitive deficits, anxiety, despair, and motor abnormalities. The 18F-labelled dimer remained stable post-injection and distributed in various organs, notably in the brain, suggesting its potential as a Positron Emission Tomography tracer for α-synuclein and adenosine A1 receptor in Parkinson’s disease therapy.

Microplastic pollution (MP) in marine environments around the globe is severe and enough precautions have not been taken so far for its prevention. The focus of this study is to quantify MPs from beach sediment and seawater samples and to identify their distribution and types along the western coast of Sri Lanka from the Kelani River estuary to the Mahaoya estuary. Nine sites along this 42 km stretch were selected and random sampling was employed to collect a minimum of 8 sediment samples from each site between October and December 2021. Water samples were also collected, parallel to the sediments, from the ocean surface. FTIR analysis revealed that most of the MPs found were polyethylene(PE), polypropylene(PP), polystyrene(PS), polyethylene terephthalate(PET), and phenol formaldehyde resin. The mean abundance of MPs varied from 2.0 ± 0.6 items/L to 161.0 ± 15.7 items/L in water samples and, from 3.0 ± 0.3 items/m2 to 656.0 ± 34.5 items/m2 in sediment samples. The MPs found were identified in different shapes as fragments (80.2%), pellets (14.9%), fibers (2.7%) and foams (2.5%). Analysis revealed that the beach sediments were contaminated with PS, phenol formaldehyde resin, PET, PP and PE, while surface seawater is dominated by phenol formaldehyde resin, PS, PP and PE.

To enable net zero sustainable thermal building energy this study develops an open-source thermal house model to couple solar photovoltaic (PV) and heat pumps (HP) for grid-connected residential housing. The calculation of both space heating and cooling thermal loads and the selection of HP is accomplished with a validated Python model for air-source heat pumps. The capacity of PV required to supply the HPs is calculated using an System Advisor Model integrated Python model. Self-sufficiency and self-consumption of PV and the energy imported/exported to the grid for a case study are provided, which shows that simulations based on the monthly load profile have a significant reduction of 43% for energy sent to/from the grid compared to the detailed hourly simulation and an increase from 30% to 60% for self-consumption and self-sufficiency. These results show the importance of more granular modeling and also indicate mismatches of PV generation and HP load based on hourly simulation datasets. The back-calculation PV sizing algorithm combined with HP and thermal loads presented in this study exhibited robust performance. The results indicate this approach can be used to accelerate the solar electrification of heating and cooling to offset the use of fossil fuels in northern climates.

Total ankle replacement (TAR) implants are an effective option to restore the range of motion of the ankle joint for arthritic patients. An effective tool for analyzing these implants’ mechanical performance and longevity in-silico is finite element analysis (FEA). ABAQUS FEA was used to statically analyze the von Mises stress and contact pressure on the articulating surface of the bearing component in two newly installed fixed-bearing total ankle replacement implants (the Wright Medical INBONE II and the Exactech Vantage). This ultra-high molecular weight polyethylene (UHMWPE) bearing commonly fails and is the cause for surgeon revisions. Six different FEA models for various gait percentages during stance (10%-60%) were created. They varied in magnitude of the compressive load and the ankle dorsiflexion/plantarflexion angle. The results indicated that the von Mises stress and contact pressure distributions increased as compressive load increased, and the largest magnitudes occurred at high dorsiflexion angles (15-30°). High magnitudes occurred in regions where the thickness of the bearing was the least. Additionally, high contact pressures were examined in areas near the talar component's edge or at the bearing's edges. To the author’s knowledge, this is the first study available to the research community that analyzes the Vantage implant with FEA. This study lays an essential foundation for future researchers in presenting a thorough literature review of TAR and methods for a simple FEA model setup. This study provides valuable information that can be beneficial to medical company designers and orthopedic surgeons in understanding the stress response and contact pressure of TAR implants during use.

In current transportation hubs, it is a common phenomenon that passengers travel with necessary wheeled-luggage or suitcases. Due to the fact that most luggage occupies certain space within dense passenger crowds with giant mass inertia, its abnormal motions, such as drifting, frequently trig unavoidable local disturbances and turbulence in surrounding pedestrian flows, further increasing security risk. While, current researches primarily concentrate on examining the impact of luggage on crowd evacuation efficiency through scenario-based experiments and analyzing the spatial characteristics of crowd distribution in surveillance videos. There still lacks of the dynamic disturbance mechanisms and crowd stability associated with the combined motion of passengers and luggage. Therefore, this study considers the luggage-laden passenger as a deformable particle, the resulting disturbance on surrounding non-luggage passengers is analyzed and quantified into a nonlinear pressure term. Subsequently, the disturbance propagation model of passenger-luggage is developed by adapting the classical Aw-Rascle traffic flow model with incorporation of the pressure term. Simulation experiments of disturbances caused by luggage drifting and retrograding validate that the proposed propagation model aligns with real-world situations in transportation hubs. Quantitively, when luggage-laden passenger drifted left, the disturbing force of left side crowd can reach a peak of 238N in the passenger density of 3.0 p/m2, and the maximum difference between the left and right sides disturbing force can reach 153N. Furthermore, it is recommended that the proposed model can be applied to crowd flow analysis and risk assessment.

Photovoltaic (PV) technologies are developing rapidly as a result of their ability to reduce energy consumption from conventional sources as well as the growth of global energy expenditures. Nevertheless, several impact categories during the PV panel life cycle occur and some principal sectors are affected. These impact categories are assessed by applying life cycle analysis (LCA) techniques through various software programs, databases and methods. Such analyses of energy technologies are crucial, as they can reveal the occurrence of hazardous emissions at distinct life cycle stages. In the present paper, a PV panel impact assessment through life cycle analysis is carried out. More precisely, a combination of PV technologies—monocrystalline, multicrystalline, copper indium gallium selenide (CIGS), amorphous, and ribbon—is studied. The impact categories of ozone depletion, human toxicity, particulate matter, ionising radiation, photochemical ozone formation, acidification, eutrophication, and ecotoxicity, as well as the sectors of human health, ecosystem quality, and environment, are assessed using the openLCA software, the ecoinvent database, the eco-indicator 99, IMPACT 2002+, ReCiPe, and TRACI methods.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in associate with other head and neck cancers. Archived tumour tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, P = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, P = 0.006), but no significant difference between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of critical limb ischaemia (CLI) patients undergoing lower limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018-02/2020), 106 CLI-patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020-07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%) and hospitalised patients decreased. Patients treated in <=14/5 days after referral significantly increased to 64/63%. Kaplan-Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target lesion revascularisation decreased during COVID-19. 1-year mortality was significantly worse in hospitalised as compared to day cases (14% vs 43%) at similar wound healing rates (83% vs 84%). The most frequent known-causes-of-death were infectious disease (64%) and cardiovascular (21%) was less frequent. Despite COVID-19 restriction a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLI should be treated more aggressively and earlier.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

STUDY QUESTION: Which are the main research interests among patients of assisted reproductive technologies (ART)? SUMMARY ANSWER: Patients identified as research priorities that deserve further investigation: success rates and risks of ART, side-effects of treatments, resources to cope with infertility, effectiveness of alternative therapies, lifestyle habits to protect fertility, oocyte quality and ovarian reserve, and causes of genetic or hereditary infertility. WHAT IS KNOWN ALREADY: The involvement of patients and caregivers in setting research agendas in medicine has gathered significant momentum in the last decade. Patients’ involvement in setting research priorities offers several benefits: improved patient knowledge and awareness of their condition; greater understanding of the medical professionals of the impact of the condition on patients’ quality of life; reduced costs associated with redundant research activities. This is may be also applicable to research in infertility and ART, where patients’ interests have never been explored before. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study that consists of an anonymous online survey, which was sent up to three times to 2112 patients from 11 fertility centers in 5 countries between January-December 2018. The study design was based on the James Lind Alliance priority setting partnership model, which comprises the identification of patients groups, the exploration of the research agenda, the analysis of collected data and identification of priorities. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 2112 patients were contacted, and 945 surveys were answered (RR: 44.7%). Patients were asked to identify research questions relevant to them in the areas of infertility causes and prevention, fertility treatments (medication and ART), and the emotional aspects of infertility. Answers were categorized in topics and ranked by frequency. A long list of the top-30 research topics was extracted from the aggregate results, from which, a short list of the top-10 research topics was created. At the end, 10 research questions related to each of the 10 research topics were constructed, based on the answers given by patients. MAIN RESULTS AND THE ROLE OF CHANCE: Female (845, 89.4%) and male (100, 10.6%) patients were included. The mean age of patients was 37.8 (SD 1.74). Most of the patients did not have children at the time of the survey (523, 59%), while 51 (5.7%) were pregnant. Sixty (6.3%) patients did not start treatment, 579 (61.3%) were performing a treatment with their own gametes and 304 (32.2%) were treated through gamete donation. Patients were mainly interested in the effectiveness of ART -especially per clinical profile-, side effects of drugs, protection of fertility and prevention of infertility –especially through diet and exercise-, and psychological aspects of the infertility journey. The top-10 research questions (and weight) obtained were: 1) What are the side-effects of ART treatments? (41.6%); 2) What are the most effective methods to cope with infertility from the psychological point of view? (37.2%); 3) What effects could diet have on fertility? (25.9%); 4) What are ART success rates per clinical profile? (25.9%); 5) Are there habits and lifestyle factors that could prevent infertility? (20.0%); 6) What are the long-term risks associated to ART? (18.5%); 7) Are alternative therapies such as acupuncture, yoga, and meditation effective to treat/prevent infertility? (18.5%); 8) What is the impact of exercise on fertility? (15.4%); 9) How does oocytes quantity and quality affect fertility? (9.5%); 10) What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). LIMITATIONS, REASONS FOR CAUTION: Although all respondents had attended a fertility center, not all of them were diagnosed as infertile (i.e. single women) and had started treatment at the time of response, while a few were pregnant; their priorities for research might have been influenced by their infertility journey. Also, all participants attended private fertility centers: areas of interest may be different in public settings. WIDER IMPLICATIONS FOR THE FINDINGS: Researchers and clinicians should keep in mind that, in addition to improvement of treatments’ success rates and side-effects, patients greatly value research on causes, prevention and emotional aspects of infertility. As their views might differ from those of medical professionals, patients’ voices should be incorporated in setting infertility research priorities.

The research field of two dimensional (2D) materials strongly relies on optical microscopy characterization tools to identify atomically thin materials and to determine their number of layers. Moreover, optical microscopy-based techniques also opened the door to study the optical properties of these nanomaterials. We present a comprehensive study of the differential reflectance spectra of 2D semiconducting transition metal dichalcogenides (TMDCs), MoS₂, MoSe₂, WS₂ and WSe₂, with thickness ranging from one layer up to six layers. We analyze the thickness-dependent energy of the different excitonic features, indicating the change in the band structure of the different TMDC materials with the number of layers. Our work provides a route to employ differential reflectance spectroscopy for determining the number of layers of MoS₂, MoSe₂, WS₂ and WSe₂.

There is evidence that optimal nutrition is fundamental to human health and in the prevention of non-communicable diseases (NCDs) later in adult life. The identification, production and consumption of functional foods worldwide can increase health benefits for all who can access and afford such foods subject to advice from nutritionists. Recent meetings organized by the health agencies, give a crucial opportunity to make nutrition, a central part of the post-2015 sustainable human and agricultural development agenda. The aim of discussions in these meetings was to provide functional crops and foods to achieve optimal health by prevention of NCDs. It is possible that these efforts might ensure that the goals and targets set in the agenda are adequate to address the many challenges of global undernutrition as well as obesity which are major risk factors of NCDs. In many developing and middle income countries, food security provided by the governments, in one sense understandably, gave least consideration to functional foods supply and the prevention of obesity and metabolic syndrome, resulting in to emergence of NCDs. The Thailand Declaration reiterates that commitments to eradicate hunger and undernutrition as well as over-nutrition, and to increase investments in effective interventions; designers foods and designers crops. However, in planning coherent policies, our past experience on rapidly absorbed, energy-rich processed foods should be taken in to account while developing sustainable food systems. The food industry should be educated to exploit the expertise of food scientists and health professionals in designing functional foods taking cognizance of manufacturing and processing. Similarly, agriculture scientists may be actively involved in educating farmers so as to grow cash crops providing functional foods. The aim should be to achieve an increase in the availability of functional foods to an extent, or by a policy, by which such foods are available to poors, at affordable cost to prevent hunger and undernutrition and related diseases as well as NCDs. In addition our efforts might help in developing an international consensus on how to approach the development of new designer foods by farmers and food industry to produce low glycemic index foods. Such efforts may establish an international framework for the prevention of NCDs, so that human susceptibility to these diseases is substantially diminished.

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

A standard method assessing postural control is the measurement in standing position. However, the implementation is usually only possible to a limited extent. Recording of postural control directly on the trunk, in seated position, could provide an alternative diagnostic method for quantifying neuromuscular control. Comparison of the measurements of Center of Pressure (CoP) in standing and seated position was performed on 66 healthy adult subjects. Reliability of measurements in seated position was tested on 23 subjects. In addition, the extension force of all test subjects was recorded. The assessments of CoP fluctuations in standing and seated position showed adequate agreement (deviation 9.1%). Furthermore, good internal consistencies with a sufficient test re test reliability could be demonstrated for the measurements in seated position. Both CoP measurement methods showed a comparable Spearman correlation to obtained extension force measurements (standing: 0.24, seated: 0.23). Our results show that recording CoP flucutations in the seated position is a reliable and valid additional method to measurements in the single legged stance. It could serve as an additional alternative to quantify neuromuscular control in impaired patients in whom single-leg stance cannot be performed adequately. In addition, the measurement in sitting position enables the direct recording of neuromuscular control on the trunk.

Objective: With just ten questions, the Berlin questionnaire (BQ) stands out as one of the simplest and most widely implemented non-invasive screening tools for detecting subjects at high risk for Obstructive Sleep Apnea (OSA), a still underdiagnosed syndrome characterized by partial or complete obstruction of the upper airways during sleep. The main aim of this study was to enhance the diagnostic accuracy of the BQ through Machine Learning (ML) techniques. Methods: A ML classifier (hereafter, ML-10) was trained using the ten questions of the standard BQ. A simplified variant of the BQ, BQ-2, which comprises only two questions out of the total of ten, was also assessed in a ML context. A 10-fold cross validation scheme was used. Ground truth was provided by the Apnea-Hypopnea Index (AHI) measured by Home Sleep Apnea Testing. Model performance was determined comparing ML-10 and BQ-2 with the standard BQ by the Receiver Operating Characteristic Curve (ROC), Area Under the Curve (AUC), sensitivity, specificity, and accuracy. Results: ML-10 demonstrated superior performance in predicting the risk for OSA compared to the standard BQ and was also capable in classifying OSA with two different AHI thresholds (AHI>=15, AHI>=30), typically used in clinical practice. Remarkably, BQ-2 was also better in sensibility to assess moderate to severe OSA (AHI≥ 15) compared to the ML-10. Conclusions: The study underscores the importance of integrating ML techniques for early OSA detection, suggesting a direction for future research to improve diagnostic processes and patient outcomes in sleep medicine.

A diet with low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) are established treatment for irritable bowel syndrome (IBS), with well-documented efficiency. A starch- and sucrose-reduced diet (SSRD) has shown similar promising effects. This randomized, non-inferiority study aimed to test SSRD against low FODMAP and compare the responder rates to a 4-week dietary intervention of either diet. 155 IBS patients were randomized to SSRD (n=77) or low FODMAP (n=78) for 4 weeks, with a follow-up 5 months later without food restrictions. The questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS) were completed at baseline and after 2 and 4 weeks and 6 months. Weight, height, waist circumference, and blood pressures were measured. Comparisons were made within the groups and between changes in the two groups. There were no differences between groups at baseline. The responding rate (RR=∆Total IBS-SSS ≥−50) of SSRD was non-inferior compared with low FODMAPs at week 2 (79.2% vs. 73.1%;p=0.661;95% confidence interval (CI)=-20-7.2) and week 4 (79.2% vs. 78.2%;p=1.000;95%CI=-14-12), with borderline-significance at follow-up (36.4% vs. 42.3%;p=0.252;95%CI=-9.4-21). All gastrointestinal and extraintestinal symptoms were equally improved (p<0.001 in most variables). SSRD rendered greater reductions in weight (p=0.006), body mass index (BMI) (p=0.005), and sugar craving (p=0.05), whereas waist circumference and blood pressure were equally decreased. Weight and BMI were regained at follow-up. In the SSRD group, responders at 6 months still had lowered weight (-0.7 (-2.5-0.1) vs. 0.2 (-0.7-2.2) kg; p=0.005) and BMI (-0.25 (-0.85-0.03) vs. 0.07 (-0.35-0.77) kg/m²; p=0.009) compared with baseline in contrast to non-responders. Those who had tested both diets preferred SSRD (p=0.032). A 4-week SSRD intervention was non-inferior to low FODMAP regarding effects on gastrointestinal and extraintestinal IBS symptoms. Reductions of weight, BMI, and sugar craving were most pronounced following SSRD.

Organosilicate glass (OSG) films are a vital component in modern electronic devices, with their electrical properties playing a crucial role in device performance. This comprehensive review systematically examines the influence of chemical composition, vacuum ultraviolet (VUV) irradiation, and plasma treatment on the electrical properties of OSG films. Through an extensive survey of literature and experimental findings, we elucidate the intricate interplay between these factors and the resultant alterations in electrical conductivity, dielectric constant, and breakdown strength of OSG films. Key focus areas include the impact of diverse organic moieties incorporated into the silica matrix, the effects of VUV irradiation on film properties, and the modifications induced by various plasma treatment techniques. Furthermore, we discuss the underlying mechanisms governing these phenomena, shedding light on the intricate molecular interactions and structural rearrangements occurring within OSG films under different environmental conditions. This review not only consolidates existing knowledge but also identifies gaps in understanding and suggests avenues for future research, thereby advancing our comprehension of OSG film behavior and paving the way for enhanced performance in next-generation electronic and photonic devices.

Analytical instruments used for scientific research and education are often expensive. This limitation poses a challenge for schools and educators in low-income countries to provide practical science training to students. To address this problem, the improvisation of analytical instruments and instructional materials has emerged as a viable solution. By incorporating practical experiments into science education, students have the opportunity to engage directly with scientific instruments, conduct investigations, and collect data. This hands-on approach fosters a deeper understanding of scientific principles, enhances critical thinking skills, and cultivates scientific mindsets among students. Herein, we review and discuss, step-by-step, the approach of using a smartphone for quantitative analysis, referred to as smartphone digital image colorimetry (SDIC). SDIC, with its practicality and accessibility, utilizes smartphone digital cameras for image acquisition and the freely available image processing programs, such as ImageJ and smartphone Apps, for image quantification. Using SDIC can enable students in low-income countries to develop essential scientific skills, including critical thinking, data interpretation, and an evidence-based approach to scientific research. By leveraging the ubiquity and affordability of smartphone technology, SDIC offers an accessible and cost-effective approach to practical science education, bridging the gap between theory and practice in resource-constrained settings.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Trematode infections cause long-term suffering and debilitation, posing a significant threat to global animal health and production and leading to considerable economic losses. Studies on the epidemiology and control of these infections in Tanzania are limited, and most have been conducted in abattoir settings. The study aims to fill the knowledge gap by determining the prevalence, distribution, and risk factors for trematode infections in domesticated ruminants in two ecological zones of Tanzania. A cross-sectional study was conducted in Lake Victoria and the southern highlands of Tanzania. Rectal fecal samples were collected and examined for Fasciola spp., paramphistomes, and schistosome infections using the sedimentation technique. A total of 1367 domesticated ruminants were sampled and examined for trematode infections. Prevalence of trematode infections was found to be 65.7%. The individual frequency of F. gigantica, paramphistomes, and S. bovis (based on egg morphology only,) was 35.1%, 60.2% and 3.1%, respectively. Adult cattle were more likely to be infected with paramphistomes (AOR: 1.98; 95% CI: 1.40-2.78) and S. bovis (AOR: 8.5; 95% CI: 1.12–64.19) than weaners. It was found that trematode infections in domesticated ruminants are prevalent across Tanzania, therefore effective and community-acceptable prevention and control strategies are highly needed.

Cassava brown streak disease (CBSD) threatens cassava production in sub-Saharan Africa despite the availability of resistant varieties since extreme environmental factors weakens plant defenses hence reduce CBSD resistance. This study examined the inheritance of CBSD in cassava populations, assessed genetic variability and identified superior sources of resistance through F1, S1 and half-sib offspring of populations derived from resistant sources. The offsprings underwent field evaluation at two distinct sites from 2019 to 2021, and the symptoms free genotypes were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Resistance to CBSD was categorized as most resistant, resistant, most tolerant and tolerant based on symptoms and virus titer. The findings of the study indicate that the resistance to Cassava Brown Streak Disease (CBSD) is highly influenced by genotypes, F1/S1 types, and environmental conditions. The analysis of combining abilities revealed significant general combining abilities (GCA) for CBSD, cassava mosaic disease (CMD), and traits associated with yield. The heritability estimates for resistance to CBSD varied between 43.4% to 63.2% for foliar symptoms and 14.6% to 57.9% for root necrosis across locations. The inheritance pattern involved a combination of additive and recessive genes and selfed (S1) populations displayed stronger and effective resistance to the disease. There was a high prevalence of cassava brown streak virus (CBSV) and a low prevalence of Ugandan cassava brown streak virus (UCBSV). Four genotypes were identified to be highly resistant to Cassava Brown Streak Disease (CBSD) that could be used as key sources of resistance to CBSD.

Triazole derivatives of fluorescein containing N,N-dimethylaminopropyl fragments and their ammonium salts were synthesized with yields of 74 - 85%. The resulting compounds exhibit fluorescent properties in the green region of the visible spectrum. The critical aggregation concentration (CAC) was estimated using a py-rene fluorescent probe corresponding to a range of 0.28 - 1.43 mM, and at concentrations above the CAC the compounds form stable aggregates ranging from 165 to 202 nm. A relative quantum yield of 5-24% has been calculated based on fluorescence and UV spectra. The best value is shown by a derivative containing a tetradecyl substituent. When studying the photocatalytic properties of synthesized compounds through the reaction between N-substituted 1,2,3,4-tetrahydroisoquinoline and malonic ester, the mono-tetradecyl deriva-tive demonstrated the best results. According to gas chromatography-mass spectrometry (GC-MS) data, the conversion of the initial heterocycle reached 95%. Therefore, these resulting compounds have the potential to act as an effective photocatalysts.

This study delves into the dynamics of 'Variations' and 'Claims' within construction projects, specifically under the FIDIC-Red Book 1999 framework. The study aims to identify, categorize, and devise mitigation strategies for key types of variations and claims aligning with the FIDIC conditions of contract. The research is drawing on inputs from construction industry professionals including contract administrators and project managers, focusing on the MENA region. This choice is driven by the region's extensive adoption of FIDIC standards and its rapidly growing construction sector. Data collection encompassed a questionnaire distributed to 80 industry experts predominantly through interviews that focused on countries like Saudi Arabia, UAE, Kuwait, and Egypt. These locations were chosen to reflect diverse construction practices and the involvement of international firms. Utilizing SPSS-V.25 for statistical analysis, the study uncovers the most prevalent and impactful causes of variations and claims, highlighting the critical need for managerial intervention. A key feature is the integration of scientometric analysis for a quantitative finding. A significant addition to the methodology is the implementation of a k-means clustering analysis. The survey had high internal consistency with a Cronbach's alpha of 0.97, and respondents reported frequent and significant claims like delayed drawings, ambiguous documents, and client changes. The results showed that effective claims management requires clear communication and balanced contracts, while poor design and contract documentation cause variations and claims. Spearman's correlation showed strong positive relationships between certain claim types and causes, emphasizing the importance of dealing with these factors to reduce claims. Most respondents said the survey could predict and reduce claims.

Acute myeloid leukemias (AMLs) are heterogeneous hematologic cancers that occur prevalently in older patients as the result of a complex pathobiology. The clinical outcomes of older patients with AML, often unsuitable for intensive chemotherapy and allogeneic stem cell transplantation, are generally disappointing. However, recent advances in understanding molecular pathogenesis and other biological mechanisms recognized in AML development and progression have changed the treatment approach, especially for this particularly vulnerable category of patients. Indeed, non-intensive biologically tailored approaches, such as combining venetoclax with hypomethylating agents, have changed the therapeutic paradigm in this field. Moreover, other promising compounds and treatment strategies are currently under advanced clinical development. This article delves into the latest biological understanding and therapeutic advances in the clinical management of older AML patients into new conceptual frameworks that progressively transform the clinical practice in this challenging setting.

A comparative analysis between Bidirectional Evolutionary Structural Optimization (BESO) and Smoothing-ESO (SESO), simultaneously considering Reliability-Based Topology Optimization (RBTO) and the structure's self-weight in the case of three-dimensional elasticity, is presented in this study. Due to the important role of the existence of uncertainties in making the structural design more realistic, geometry, volumetric fraction, modulus of elasticity, compliance, and loading are considered random variables with normal probability distribution. When adopting the First Order Reliability Method (FORM), the failure probability is calculated based on the reliability index. Furthermore, considering the influence of self-weight in problems involving large structures in civil engineering, especially in the case of bridges, makes the optimal configuration more reliable for design. A series of examples are covered to validate the methods presented, showing their efficiency and robustness.

κ Draconis is a binary system with a classical Be star as the primary component. Its emission-line spectrum consists of hydrogen lines, notably the Hα line with a peak intensity ratio (V/R) variations phase-locked with the orbital period P = 61.55 days. Among binaries demonstrating the Be phenomenon, κ Dra stands out as one of a few systems with a discernible mass of its secondary component. Based on more than 200 spectra obtained in 2014 − 2023, we verified the physical parameters and constructed the mass function. We used part of these data obtained in 2014 − 2021 to investigate regions in the circumstellar disk of the primary component that emit the Hα line using the Doppler tomography method. The results show that the disk has a non-uniform density distribution with a prominent enhancement at Vy≈ 99 km s−1 and Vx≈−6 km s−1 that corresponds to a cloud-like source of the double-peaked Hα line profile. We argue that this enhancement’s motion is responsible for the periodic variations of the Hα V/R ratio, which is synchronised in orbital phase with the radial velocity (RV) of absorption lines from the atmosphere of the primary component.

Cellulose nanofibrils (CNFs) are materials with high aspect ratio. Typically, TEMPO-oxidised, or cationic CNFs consist of long fibrils (up to 2 μm) with very low thickness (less than 10 nm). Derived from their high aspect ratio, CNFs form strong hydrogels with high elasticity at low concentrations. Thus, CNF suspensions appear as an interesting rheology modifier to be applied in cosmetics, paints, foods, as a mineral suspending agent, among other applications. The high viscosity results from the strong 3D fibril network, which is related to good fibrillation of the material, allowing the nanofibrils to overlap. The overlap concentration (c*) was found to vary from ca. 0.13 to ca. 0.60 wt.% depending on the type and intensity of the pre-treatment ap-plied during the preparation of the CNFs. The results confirm the higher tendency for the fibres treated with CHPTAC (cationic) and TEMPO to form a 3D network, resulting in the lowest c*. For the TEMPO-oxidised CNF suspensions, it was also found that aggregation is improved at acidic pH conditions due to lower charge repulsion among fibrils, leading to an increase in the suspension viscosity, as well as higher apparent yield stresses. TEMPO CNF suspensions with low content of carboxylic groups tend to precipitate at moderate acidic pH values.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

Background: Although endoscopic submucosal dissection (ESD) can provide a high rate of curative resection, remaining gastric mucosa after ESD is at risk of metachronous recurrence. We investigated risk factors for metachronous superficial gastric epithelial neoplasms (MSGENs) following ESD. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. The primary endpoint was to identify clinicopathological risk factors for the occurrence of MSGENs. The secondary endpoint was to evaluate the association of Helicobacter pylori (Hp) eradication with the MSGENs. Results: Twenty-seven MSGENs were occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in upper or middle part (INUM) in the MSGEN group. The HIM group and INUM group had significantly higher cumulative incidence of MSGENs. We compared the 27 patients of MSGEN group and 27 patients of matched not-MSGEN (Mnot-MSGEN) group that was matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of Hp spontaneous eradication in the MSGEN group. Conclusion: HIM, INUM and Hp spontaneous eradication may be clinicopathological risk factors for developing MSGENs after ESD.

Initial evaluations of the System of Rice Intensification in India and elsewhere have mainly fo-cused on its impact on yield and income and have usually covered just one or two seasons. Re-searchers at the ICAR-Indian Institute of Rice Research conducted a more comprehensive evalua-tion of SRI methods over six years (six wet and six dry seasons), comparing these methods with three other rice crop management systems: modified, partially mechanized SRI (MSRI); direct-seeded rice (DSR); and normal transplanting with inundated fields (NTP). SRI grain yield was found to be about 50% higher than with NTP (6.35 t ha-1 vs 4.27 t ha-1), while the MSRI yield was essentially the same (6.34 t ha-1) and 16% higher than with DSR (5.45 t ha-1). Compared to NTP, SRI methods significantly enhanced soil microbial populations over time, bacteria by 12%, fungi by 8%, and actinomycetes by 20%. Indicators of biological activity in the rhizosphere were also higher, dehydrogenase by 8.5% and FDA enzymes by 16%. Glucosidase activity, an indicator of soil organic matter, was 78% higher. Relative to normal transplanting methods, SRI reduced GHG emissions by 21%, while DSR reduced them by 23% and MSRI by 13%, which indicated pos-itive effects of the alternate and improved methods over normal transplanting. Economic analy-sis showed that both gross and net economic returns to be higher with SRI than with MSRI and the other management systems evaluated. While the six-year study documented many ad-vantages of SRI crop management, the MSRI version evaluated is a promising adaptation that provide similar benefits but with lower labor requirements.

The Golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in challenge dose. The tissue burden of virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). Follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals [CI] for the outcome in PhyS C and PhyS D were 1.84 (95% CI 0.73 to 4.61) and 7.88 (95% CI 1.54 to 40.41) respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.10 (95% CI 0.39 to 3.06) and 0.99 (95% CI 0.24 to 4.10) respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA receiving apixaban.

Physical processes play important roles in controlling eutrophication and oligotrophication. In stratified lakes, internal waves can cause vertical transport of heat and nutrients without breaking the stratification, through boundary mixing events. Such is the case in tropical Valle de Bravo (VB) lake, where strong diurnal winds drive internal waves, boundary mixing and hypolimnetic warming during stratification periods. We monitored VB during 18 years (2001-2018) when important water-level fluctuations (WLF) occurred, affecting mixing and nutrient flux. Mean hypolimnetic temperature increase (0.06–1.04°C month-1) occurred in all the stratifications monitored. We analyzed temperature distributions and modeled the hypolimnion heat budget to assess vertical mixing between layers (26,618–140,526 m-3h-1), vertical diffusivity coefficient KZ (6.2x10-7–3.3x10-6 m2s-1) and vertical nutrient entrainment to epilimnion on monthly scale. Stability also varied as a function of WLF. Nutrient flux to the epilimnion ranged 0.36–5.99 mg m-2d-1 for soluble reactive phosphorus (SRP) and 5.8–97.1 mg m-2d-1 for dissolved inorganic nitrogen (DIN). During low water-level years, vertical nutrient fluxes increase and can account for up to &gt;40% of the total external nutrients load to the lake. Vertical mixing changes related to WLF affect nutrient recycling, their flux to sediments, ecosystemic metabolic balance and planktonic composition of VB.

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

Research on the coral-eating crown-of-thorns starfish (CoTS) has waxed and waned over the last few decades, mostly in accordance with the occurrence of population outbreaks at key locations, such as Australia’s Great Barrier Reef. This review considers advances in our understanding of the biology and ecology of CoTS based on the latest resurgence of research interest, which culminated in this current special issue on the Biology, Ecology and Management of Crown-of-Thorns Starfish. More specifically, this review considers progress against 41 specific research questions posed in the seminal review by P. Moran 30 years ago, as well as exploring new directions for CoTS research. Despite the plethora of research on CoTS (>1,200 research articles), there are persistent knowledge gaps that constrain effective management of outbreaks. Although directly addressing some of these questions will be extremely difficult, there have been considerable advances in understanding the biology of CoTS, if not the proximal and ultimate cause(s) of outbreaks. Moving forward, researchers need to embrace new technologies and opportunities to advance understanding of CoTS biology and behaviour, with focus given to key questions that will improve effectiveness of management to reduce the frequency and likelihood of future outbreaks, if not preventing them altogether.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and an UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogels pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC-spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies.

Many farms are replacing the lighting with light emitting diode (LED) bulbs because of the technological modernization. We aimed to investigate the effects of incandescent light (IL) and LED lighting on Cobb500 broiler chickens for six weeks. Production parameters (body weight, feed consumption, feed conversion ratio), calculated slaughter values (yield%, relative breast%, thigh%) and breast meat quality parameters (pH at 45 min and 24 h postmortem, color, drip loss, kitchen equipment losses, shear force, meat composition) were recorded. Non-stop recordings were used to analyze the behavior of the birds in several periods of the rearing. LED group was significantly better in body weigh parameter between week 1-5 and feed conversion ratio between week 2-3. The most significant difference in behavior was observed in the middle of the rearing period. The chickens in the LED group spent more eating time, drinking time, interacting, and resting less. There was no difference in the meat quality parameters, only shear force was significantly lower in the LED group (1781.95±0.33 g/s vs. 2098.82±0.42 g/s). Based on our results, LED lighting can bring positive changes in animal production efficiency, behavior, and important characteristics for meat consumers.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Lassa fever, commonly known as Lassa hemorrhagic fever (LHF), is one of the progressive illnesses invading a large population of two to three million individuals in West Africa. The infection transmitted through the rodents severely impacts the local population and the medical professionals in surrounding areas, which were also the primary target of LHF. In epidemic areas, Lassa fever causes a public health threat since it poses a significant morbidity and fatality Case rate (CFR) ≥ 50%). The disease is widespread in West Africa and has developed into one of the most common and life-threatening viral hemorrhagic fevers. Monitoring and preventing persistent disease outbreaks has been challenging in affected regions due to insufficient healthcare facilities, diagnostics labs, care centers, and low socioeconomic conditions. An absence of public awareness and the emergence of an ecological niche is advantageous for the survival and multiplication of the mouse (Mastomys natalensis) inhabiting the Lassa virus serving as the disease's natural host and reservoir. The current review focuses on early diagnosis and appropriate treatment, highlighting the immediate requirement of clinically approved vaccines for LHF, causing preventative and control actions more difficult in the present era.

'Xinomavro' (V. vinifera L.) is an important native red wine grape variety in Northern Greece, particularly in PDO regions. Despite its significance, there is limited research on the effects of pruning type and severity on 'Xinomavro' vine physiology, yield, and berry quality across diverse environmental conditions. This study aims to address this knowledge gap and provide growers with crucial information for optimizing vineyard management practices. The study was conducted over two consecutive years (2016 and 2017) in a vineyard in Thessaloniki, Northern Greece. Four treatments ( B12: 12 buds on 6 spurs; B24: 24 buds on 12 spurs; M12: 12 buds on 2 canes; M24: 24 buds on 4 canes) combining two bud load levels (12 or 24 count nodes) and two pruning types (short spurs or long canes) were applied to 'Xinomavro' vines in complete block randomized design. Measurements included vine water status, gas exchange, canopy characteristics, yield components, and berry composition. Bud load and pruning type significantly influenced vine canopy development, microclimate, and yield components. Short pruning with high bud load (B24) resulted in denser canopies and higher yields, while cane pruning (M12 and M24) led to more open canopies and improved berry quality indicators. Treatment effects on berry composition were inconsistent across years but showed a tendency for higher anthocyanin and total phenol content in cane-pruned vines. The study demonstrates that pruning type (short or long fruiting units) may have a greater impact on vine growth, yield, and berry composition than bud load alone in 'Xinomavro' vines. Cane pruning appears to be a more effective strategy for achieving vine balance and potentially improving grape quality under the given experimental conditions.

The growing use of drones in precision agriculture highlights the need for enhanced operational efficiency. Despite the ability of computer vision based on deep learning has made remarkable progress in the past ten years, when it comes to segmentation task on UAVs, there is always a conflict between the demand of high precision and low inference latency. Due to such a dilemma, we propose the IRB-YOLO, an efficiency model based on Inverted Residual Block, devoting to provide constructive strategies in real-time detection tasks of UAV camera. The working details of this paper are as follows: (1) This paper innovates with a IR-Block(Inverted Residual Block), integrated into a refined YOLOv8-seg structure to create IRB-YOLO. This model specializes in pixel-level classification of UAV-acquired RGB images, facilitating the creation of exact maps to guide agricultural strategies. (2)When it comes to the experiments on a Vatica dataset with any other light-weight segmentation model, IRB-YOLO achieve at least a 3.3% increase in mAP. Further validation using a diverse species dataset confirms its robust generalization. (3)Without overloading the complex attention mechanism and deeper and deeper network, a stem that incorporates efficient feature extraction components, inverted residual block, can still possess outstanding modeling capabilities. IRB-YOLO builds a bridge between academic research and edge deployment of drones, making it applicable in real-world scenarios.

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

The corrosion inhibition effects of Drimia maritima (L.) Stearn sin. Urginea matima (L.) Backer on three different materials, i.e. as-cast Al-7 wt.% Si alloy, SAE 1020 low carbon steel and commercially pure Al samples, into a stagnant and naturally aerated 0.5 M NaCl solution are evaluated. For this purpose, both the potentiodynamic polarization curves and electrochemical impedance spectroscopy with equivalent circuit are utilized. It is found that inhibition effect in-creases up to certain minor Drimia maritima content. Adsorption isotherms (e.g. Langmuir and Temkin) have indicated that all three examined material comprise physical adsorption mecha-nism. Al-Si alloys have attained inhibition efficiency of about 96% at 25 oC with 1250 ppm of Drimia maritima, and ~43% with 625 ppm at 45 oC. On the other hand, the cp. Al and SAE 1020 samples attain ~ 89% and 68% with 1250 ppm and 500 ppm at 25 oC, respectively. This clearly in-dicates that the dosage of Drimia maritima green inhibitor into NaCl solution posses certain sus-ceptibility for each distinctive material examined. Impedance parameters obtained by using CNLS (complex non-linear least squares simulations) are correlated and discussed.

Toxoplasma gondii is a protozoan and the etiologic agent of toxoplasmosis causes high mortality in immunocompromised individuals and newborns. Despite the medical importance of toxoplasmosis, few drugs are available for its treatment, which are associated with side events and parasite resistance. Here, we show a screening of molecules present in Covid-Box as a way of discovering new hits with anti-T. gondii activity. Covid-Box contains 160 molecules with known or predicted activity against SARS-CoV-2. Our analysis selected 23 Covid-Box molecules that can inhibit the tachyzoite forms of the RH strain of T. gondii in vitro by more than 70% at 1 µM after seven days of treatment. The inhibitory curves showed that most of these molecules inhibited the proliferation of tachyzoites with IC50 values below 0.80 µM; Cycloheximide and (-)-Anisomycin were the most active drugs, with IC50 values of 0.02 μM. Cell viability assays showed that the compounds are not toxic at active concentrations, and most are highly selective for parasites. Overall, all 23 compounds were selective, and for three of them (Apilimod, Midostaurin, and Salinomycin), this is the first report of activity against T. gondii. To better understand the effect of the drugs, we analyzed the effect of six of them on the ultrastructure of T. gondii using transmission electron microscopy. The main changes observed in parasite morphology after treatment with the selected drugs were changes in cell division and parasite organelles.

Oxidative stress and chronic inflammation create a perpetual cycle in the elderly, where impaired immune function amplifies susceptibility to oxidative damage, and oxidative stress further weakens the immune response. This cycle is particularly detrimental to the respiratory system of the elderly, which is an easy target for constant exogenous harmful attacks during cold/flu season or under heavy air pollution. Herbal medicines that protect respiratory function are seen as safer alternatives to conventional therapies; however, there is limited availability of scientifically validated, safe, and effective natural supplements for these conditions. In this study, we evaluated a standardized bioflavonoid composition, UP446, which contains bioactives from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, as a natural and nutritional supplement for its antioxidative and immunoregulatory effects in oxidative stress-accelerated aging and chemically induced immune suppression mouse models. Immunosenescence was induced by continual subcutaneous injection of D-galactose (D-Gal) at a dose of 500 mg/kg/day in CD-1 mice. UP446 was administered orally at doses of 100 mg/kg and 200 mg/kg starting in the fifth week of immunosenescence induction. The study lasted a total of ten weeks. All mice received a quadrivalent influenza vaccine 14 days before the end of the study. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis.Cyclophosphamide (Cy)-induced immunosuppression was triggered by three consecutive injections of cyclophosphamide at 80 mg/kg/day, followed by oral administration of UP446 for 18 days at doses of 100 mg/kg and 200 mg/kg. Blood was collected from each animal at necropsy, and serum was isolated for IgA and IgG ELISA analysis. UP446 was found to improve immune response, as evidenced by stimulation of innate (NK cells) and adaptive immune responses (T cells and cytotoxic T cells), an increase in antioxidant capacity (glutathione peroxidase), preservation of vital immune organs (the thymus), and a reduction in NFκB. UP446 also increased serum levels of IgA and IgG. The findings presented in this report demonstrate the antioxidative, anti-inflammatory, and immune-regulatory activities of UP446, suggesting its potential use in respiratory conditions involving immune stress due to aging, oxidative stress, and/or pathogenic challenges.

Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We investigated the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Children aged &lt; 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range undergoing cardiac surgery without DHCA were included as the control group. All patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician. Seventeen of 25 DHCA and six of 10 control patients completed the BSTID assessment. The groups showed no preoperative, operative, or postoperative significant differences. In adjusted multivariable analysis, prematurity and age at assessment were significant changing predictors of each of the BSTID components (p &lt; 0.001), other than the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Use of DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes if DHCA has a long duration.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Soil water balance (SWB) in woody crops is sometimes difficult to estimate with one-dimensional models because these crops do not completely cover the soil and usually have a deep root system, particularly when cropped under rainfed conditions in a Mediterranean climate. In this study, the actual crop evapotranspiration (ETc act) is estimated with the soil water balance model SIMDualKc which uses the dual-Kc approach (relating the fraction of soil cover with the crop coefficients) to improve the estimation of the water requirements of a rainfed vineyard, using data from a deep soil profile. The actual basal crop coefficient (Kcb act) obtained using the SIMDualKc model was compared with the Kcb act estimated using the A&amp;P approach, which is a simplified approach based on measurements of the fraction of ground cover and crop height. Spectral vegetation indices derived from Landsat-5 satellite data were used to determine the fraction of ground cover (fc VI) and thus, the density coefficient (Kd). The SIMDualKc model was calibrated using soil water content (SWC) measurements down to a depth of 1.85 meters, which significantly improved the conditions for using a SWB estimation model. The test of the model was performed using a different SWC dataset. A good agreement between simulated and field measured SWC was observed for both data sets along the crop season, with RMSE&lt;12.0 mm, NRMSE &lt;13%. The calibrated Kcb values were 0.15, 0.60 and 0.52 for the initial, mid-season, and end season, respectively. The ratio between actual (ETc act) and crop evapotranspiration (ETc) was quite low between veraison and maturity (mid-season), corresponding to 36%, indicating that the rainfall was not sufficient to satisfy the vineyards water requirements. Spectral vegetation indices used to compute fc VI were unable to fully track the plants’ conditions when water stress. However, ingestion of data from remote sensing showed promising results that could be used to support decisions making in irrigation scheduling. Further studies on the use of the A&amp;P approach using remote sensing data are required.

Integrating optical coherence tomography (OCT) into the pre-surgical stage of cataract management holds significant clinical and economic potential, particularly in low-to-middle-income countries like Kazakhstan. This study aimed to evaluate these impacts by prospectively recruiting 124 patients, aged 70±8 years, from two ophthalmology surgical centers in Almaty, Kazakhstan. Patients undergoing phacoemulsification of cataracts with monofocal intraocular lens (IOL) implantation between January and December 2022 were divided into two groups: the OCT group (n=75) received pre-operative OCT, while the Control group (n=49) did not. Visual acuity (VA) was measured pre- and post-surgery, and the cost-effectiveness of the surgical strategies was analyzed. The OCT group experienced a significantly greater improvement in VA (-0.647±0.232 logMAR) compared to the Control group (-0.543±0.244 logMAR), with a notable interaction between time and group (F(df) = 217.2, p &lt; 0.001). Additionally, pre-existing concomitant diseases were diagnosed in 25.3% of cases in the OCT group and 28.6% in the Control group. The economic analysis revealed that the integration of OCT facilitated multiple surgeries in one appointment, thereby reducing overall costs. These findings suggest that implementing OCT in the pre-surgical stage of cataract management can significantly enhance visual outcomes and decrease the cost of ophthalmology services in Kazakhstan.

Objective-Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Method- This cross-sectional study was conducted on 326 women of reproductive age using hormonal contraceptives for a week to one year referred to as "hormonal contraceptive (HC) users" (n=165), and those using non-hormonal methods and not using contraceptives referred to as "HC non-users" (n=161). Beck's depression inventory (BDI-II) was used to measure depression. Result-There was no discernible difference in mean Beck's depression inventory score and degree of depression between the two groups. However, individual symptoms of depression such as sadness(p=0.01), reduced libido(p=0.0002) feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly high in the HC user group. Conclusion- We conclude that there was no significant difference in mean depression scores between groups. However, few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Graphene oxide (GO) is considered as one of the promising adsorbents for the removal of various heavy metal contaminants in aquatic environment, due to its beneficial structural, chemical and electronic properties. Using the density functional theory (DFT) approach, we investigate the reactivity of a model GO nanoparticule (C30H14O15) toward neutral and charged lead (Pb) and cadmium (Cd) atoms. We found the model metal-free GO to have a high chemical reactivity. To study the adsorption of the metal atoms on the GO nanoparticle, we have used a single and doubly-adsorbed neutral (Pb0 and Cd0) and charged (Pb2+, Cd2+) atoms. After identified possible adsorption sites on the GO, we found that a single charged metal ion binds more strongly than a neutral atom of the same type. To determine the possibility of multiple adsorptions of GO nanoparticle, two metal atoms of the same species are co-adsorbed on its surface. Our calculations reveals a site-dependent adsorption energy such that when two atoms of the same specie are adsorbed at sites Si and Sj , the binding energy per atom depends on the whether one of the two atoms is adsorbed firstly on the Si or Sj sites. It is also found that the binding energy per atom for two co-adsorbed atoms of the same specie is less than the binding energy of a singly-adsorbed atom which suggests that atoms may become less likely to be adsorbed on the GO nanoparticle when their concentrations increase. This applies to both neutral and charged atoms. We adduce the origin of this observation to be interplay between metal-metal interaction on the one hand and GO-metal on the other, with the former resulting in a less binding for the charged adsorbed metals in particular, due to repulsive interaction between two positively charged ions. The frontier molecular orbitals analysis and the calculated global reactivity descriptors of the respective GO- metal complexes revealed that all the GO-metal complexes have a smaller HOMO-LUMO gap (HLG) relative to that of pristine metal-free GO nanoparticle. This suggests that although the GO-metal complexes are stable, they are less stable compared to metal-free GO nanoparticles. The negative values of the chemical potentials obtained for all the GO-metal complexes further confirms their stability. Our work calculates parameters that will be crucial to rational design of GO nanoparticles for Pb abd Cd ions contaminants removal, and may find application in water purification for example.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern part of the hemisphere, its use has moved and flourished in the Western Nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. Passing the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.