International students were – and continue to be – particularly vulnerable to the negative consequences of the COVID-19 pandemic. 625 international students in Israel completed an online survey assessing risk and protective factors (socio-demographics, health status, COVID-19 related experiences/concerns, financial difficulties, academic challenges/experiences, social support, and coping) for student’s depression, perceived need for help, and seeking help from the university. Approximately 15% of participants had moderately-severe or severe depression. Over half needed at least a little help, but only 19.7% had asked for help. Depression symptoms were related coping (β=-.34) and health (β=.12). Need for help was related to being a postdoc (β=-0.26) and experiencing food insecurity (β=0.20). Universities need to develop services which address international students’ unique needs during global crises.

Rocky Mountain or Brazilian spotted fever, caused by Ricketsia ricketssi, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Rapid detection are essential for a better prognosis and survival rate of the infected individual. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. Therefore, this review aimed to identify methods for antibody or antigen detection, its gaps, and evolution over time. A search was conducted to find all studies in the Pubmed database that described antibody or antigen detection for Ricketsia ricketsii infection. Initially, a total of 403 articles were screened. Of these articles, only 19 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as low specificity using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective Ricketsia ricketssi infection diagnosis.

Background: Since there is no cure for amyotrophic lateral sclerosis (ALS) currently, it is very important for searching diagnostic biomarkers and novel treatments to reduce the severity of this disease; one of these treatment approaches is stem cell transplantation. This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing molecular data. Methods: In this single-centre, open-label, phase II clinical trial, retrospective study, fifteen confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6) , MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment of molecular investigation by evaluating specific microRNAs expression (Mir206, 133a-3p, 338-3p) in the patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up. Statistical analysis includes paired T-test or Wilcoxon signed ranks. Results: No serious adverse effects were reported following stem cell transplantation. Besides, the mentioned microRNA expression slightly increased but still non-significant (P>0.05). Conclusions: Although Our study demonstrated non-signifying results. However, the still increasing of these MircRNAs in serum and CSF overall, can indicate that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

To examine the effect of synchronous dance movements on social bonding and perceived closeness between generations, 168 young (20-45 years) and older (65-90 years) participants were randomly assigned to six dyad conditions. These included dancing synchronously or asynchronously with an in-age-group or an out-age-group unfamiliar partner for 11 minutes. Participants completed social bonding and groups’ closeness questionnaires. To assess variation across individuals’ and dyads’ measurements, a generalized estimating equations modeling analysis was conducted. In line with the first two hypotheses, synchronized dance increased social bonding, and young adults showed enhanced perception of closeness between generations. Hypothesis 3 that synchronous dance with out-age-group members would foster greater perceived closeness compared to in-age-group members was not confirmed. Surprisingly, results indicated that asynchronous movements with the in-age-group led to a higher degree of closeness between generations than asynchronous movements with the out-age-group. The study offers new directions for practitioners in welfare, nursing, and therapy fields, particularly for engaging young adults in intergenerational dance interventions.

We report the application of a recently proposed approach for modeling biological systems using a maximum entropy production rate principle in lieu of having in vivo rate constants. The method is applied in four steps: (1) a new ODE-based optimization approach based on Marcelin’s 1910 mass action equation is used to obtain the maximum entropy distribution, (2) the predicted metabolite concentrations are compared to those generally expected from experiment using a loss function from which post-translational regulation of enzymes is inferred, (3) the system is re-optimized with the inferred regulation from which rate constants are determined from the metabolite concentrations and reaction fluxes, and finally (4) a full ODE-based, mass action simulation with rate parameters and allosteric regulation is obtained. From the last step, the power characteristics and resistance of each reaction can be determined. The method is applied to the central metabolism of Neurospora crassa and the flow of material through the three competing pathways of upper glycolysis, the non-oxidative pentose phosphate pathway, and the oxidative pentose phosphate pathway are evaluated as a function of the NADP/NADPH ratio. It is predicted that regulation of phosphofructokinase (PFK) and flow through the pentose phosphate pathway are essential for preventing an extreme level of fructose 1, 6-bisphophate accumulation. Such an extreme level of fructose 1,6-bisphophate would otherwise result in a glassy cytoplasm with limited diffusion, dramatically decreasing the entropy and energy production rate and, consequently, biological competitiveness.

Digitalization have force emerging markets (EMs) firms operating in resource-constrained environment to adopt market-driven strategies, particularly frugal innovation, to provide affordable, optimize processes and high-value solutions. However, understanding the mechanisms behind developing frugal innovation capability (FIC) at the firm level in diverse EMs remains limited. From the perspective of the Resource-based View, this study added to the existing body of knowledge by exploring how strategic orientation (entrepreneurial orientation (EO) and market orientation (MO)) and organizational ambidexterity (OA) impact the development of FIC in EMs. The study utilized a cross-sectional survey in data collection with 386 valid respondents from Tanzanian manufacturing firms to empirically validate our theoretical predictions. The results show that both EO and MO have strong and positive association with OA and the development of FIC in EMs. In addition, OA partially mediate the relationship of both EO and MO with the development of FIC. Furthermore, our results indicate that MO exerts a more significant impact on the development of FIC than EO in EMs. Managers of manufacturing firms in EMs can use these findings to review their strategic decisions and their exploitative and exploratory approaches to enhance supply chains, develop cost-effective technologies, and produce affordable offerings that cater to the preferences of price-conscious consumers in the digitalization age.

The number of physical devices connected to the Internet such as vehicles, household appliances and other "things" has been steadily increasing in recent years, thus forming the basis for the Internet of Things (IoT). IoT ecosystem extends beyond country borders and application domains, combining thousands of versatile devices that differ in terms of their structures, capabilities, and available resources. It is therefore not surprising that the landscape of wireless communication technologies and the degree of IoT devices available today is excessively broad and diverse. Interference between networks leads to frame collisions and consequent packet loss. Frame collisions occur when two or more packets overlap in time and frequency and use the same Long Range (LoRa) parameters, i.e. the same Spreading Factor (SF), Bandwidth (BW) and Carrier Frequency (CF). When most devices use the same configuration, collision probability is higher. The probability of frame collisions is also affected by traffic characteristics, particularly the periodicity of the transmission and the payload size. Larger payload sizes and more frequent transmissions accumulate with higher Time on Air (ToA) and channel occupancy [1]. Transmission powers and the location of the gateways also influences this situation. The aim of this experimental work is to verify the effects of collisions and interference in Long Range Wide Area Network (LoRaWAN), regarding the periodicity of transmissions and the payload sizes in a context of an inter-SF interference scenario. And to validate measuring tools like Received Signal Strength Indicator (RSSI), ToA and Packet Delivery Ratio (PDR) in the reliability of a network. We validate our conclusions by analyzing ToA according with RSSI and different data sizes, the RSSI for different SFs and different data sizes and finally the packet loss through the PDR for a better understanding of the reliability of packet transmission in our link. In the end we conclude that in an environment with inter-SF interference, the choice of SFs and packet lengths impacts ToA. When dealing with multiple devices near gateways, different SFs and varying packet lengths can lead to increased latency and longer ToA. Consequently, the risk of packet loss becomes more significant, especially if the signal-to-interference ratio (SIR) is low. This limitation will therefore affect scalability, particularly in Non-Line-Of-Sight (NLOS) scenarios.

Obstructive sleep apnea (OSA) is a common sleep disorder that is associated with a wide variety of health conditions, including cardiovascular, cerebrovascular, metabolic, neoplastic, and neurocognitive manifestations. OSA as a chronic condition is mainly characterized by repeated upper airway obstructions during sleep that cause episodes of intermittent hypoxia (IH), resulting in tissue hypoxia-reoxygenation cycles. Decreased arterial oxygen pressure (PaO₂) and hemoglobin saturation (SatO₂) stimulate reflex responses to overcome the obstruction. The prevalence of OSA is significant worldwide, and an underrated problem when focusing on women during pregnancy. The physiological changes associated with pregnancy, especially during its latest stages, are related with a higher prevalence of OSA events in pregnant mothers, and associated with an increased risk of hypertension, pre-eclampsia and diabetes, among other deleterious consequences. Furthermore, OSA during pregnancy can interfere with normal fetal development and is associated with growth retardation, preterm birth, or low term weight. Carotid body overstimulation and hypoxia-reoxygenation episodes contribute to cardiovascular disease and oxidative stress, which can harm both mother and fetus and have long-lasting effects that can reach into adulthood. Because IH is the hallmark of OSA, this review examines the literature available about the impact of gestational intermittent hypoxia (GIH) on the respiratory system at maternal, fetal, and offspring levels. Offering the latest scientific data about OSA during pregnancy, we may help to tackle this condition with lifestyle changes and therapeutic approaches, that could influence the mothers, but also impact adult health problems, mostly unknown, inherited from these hypoxic episodes in the uterus.

This longitudinal study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n=40; 56.78±6.38 years). Participants were divided into two groups: one rowed in fixed seat rowing (FSR) boats (n=20; 56.35±4.89 years) and the other in sliding seat rowing (SSR) boats (n=20; 57.20±7.7 years). Both groups engaged in two 75-minute sessions per week for 24 weeks. Significant improvements were observed in both groups in resting heart rate (FSR: -10.65 bpm; SSR: -8.45 bpm), heart rate at the beginning of the 6-minute walk test (6MWT) (FSR: -10.7 bpm; SSR: -11.25 bpm), and heart rate at the end of the test (FSR: -13.85 bpm; SSR: -20.35 bpm). Blood pressure improved significantly in both diastolic blood pressure (FSR: -12.35 mmHg; SSR: -19.25 mmHg) and systolic blood pressure (FSR: -13 mmHg; SSR: -16.95 mmHg). Additionally, both groups increased the distance covered in the 6MWT (FSR: +63.05 m; SSR: +93.65 m). These results suggest that a rowing training program is a viable and safe activity for female breast cancer survivors, improving cardiac function, blood pressure, and cardiorespiratory capacity, particularly in sliding seat boats.

Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15- 20 % of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is by analysis of tumor biopsies for HER2 expression and amplification. Previously patients were either defined as HER2-positive or negative, however, with approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 and lacking HER2 amplification have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is mo-lecular imaging with radiotracers. In case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Affibody-based radiotracers are clinically validated molecules with favorable characteristics for imaging. In this article we summarize the HER2-targeted therapeutic landscape, describe the experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as novel diagnostic tool in breast cancer and beyond.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

There is evidence that behavioral risk factors such as western type diet, and life style can predispose to oxidative stress, deficiency in antioxidant status, hyperglycemia, dyslipidemia and increase in inflammation in tissues of various organs: beta cells of the pancreas, LDL receptors in the hepatocytes, endothelium, neurons, osteocytes and gut. Further studies indicate that diets rich in antioxidant flavonoids, omega-3 fatty acids and fiber in foods were inversely associated whereas western-type foods were positively associated with risk of mortality due to cardiovascular diseases (CVDs). One important cause for beneficial effects of diet may be certain foods and nutrients such as vegetables, fruits and whole grains that are rich in fiber and flavonoids, known to produce liters og molecular hydrogen in the gut. It seems that, high-fiber diets, prebiotic and probiotics can produce greater hydrogen, which acts as an antioxidant and may inhibit free radical generation. Recent studies indicate that molecular hydrogen can inhibit hydroxyl and nitrosyl radicals and can directly act as antioxidant in the cells and tissues, which can cause marked decline in oxidative stress and inflammation leading to significant decline in CVDs and metabolic diseases. Clinical and experimental studies indicate that hydrogen therapy such as hydrogen rich water can provide benefits in the management of CVDs and metabolic diseases. Larger studies are necessary to verify the role of hydrogen administration in CVDs.

Background: Long-range transport of dust aerosol has intense impacts on the atmospheric environment over wide areas. Methods: The annual and seasonal changes in meteorological parameters associated with the occurrence of dust storms were studied. The features of an intense dust storm and its transport characteristics were studied during June 7th to June 9th 2010 in Ahvaz city. Temporal and spatial distribution of Middle Eastern dust storm event was analyzed by models of HYSPLIT and WRF/Chem, and in- situ observations. Results: A disagreement between the occurrences of dust storms, temperature, relative humidity and rainfall, show the major source of dust storms over Ahvaz city are neighboring countries. Using HYSPLIT results, the dust particles are mainly transported from north western region of Iraq and eastern Syria to downward areas including Ahvaz city. The arrived Dust aerosols mixed with local anthropogenic emissions, led to the highest PM10 concentration of 4200 ppm. The model results were found to well reproduce temporal and spatial distribution of mineral dust concentrations according to in-situ measurements. Conclusion: The performance of WRF/Chem was acceptable for simulation of temporal and spatial distributions of dust storm events. Therefore, it can be taken as a reference in daily air quality forecasting.

This paper investigates the influence of microorganisms and clay minerals on the deterioration process of ancient Egyptian murals in the Al-Qurna region, situated on the west bank of Thebes (Luxor), Egypt. To achieve this objective, an extensive examination of building materials (including bedrock, building stone, mortars, and plasters) from various tombs within the study area was conducted. The investigation employed a multidisciplinary approach, combining micro-biological analysis with advanced techniques such as X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) as well as petrographic examination. These methods were employed to identify the composition of the materials and to assess the masonry structure’s response to deformation caused by endogenous factors, particularly clay minerals. Additionally, mycological analyses were performed using a swabbing cotton sterile technique, revealing the presence of several species, including Ascosphera apis, Aspergillus tamarii, Aspergillus ochraceus, Doratomyces sp, and Eurotium repens. Notably, swelling clays—such as smectite, illite, and chlorite—along with mixed layers of illite-smectite and illite-vermiculite were detected in the studied samples. The presence of such deleterious clay minerals and fungi imperils wall painting preservation, causing discoloration, surface alteration, physical decay, and structural instability. Informed conservation strategies must address these threats for sustained integrity.

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.

Background: Infantile haemangiomas (IH) may require treatment with propranolol. Sleep disturbances are the most fre-quently reported side effects. Monitoring drug adverse events necessitates repeated hospital visits, despite the SARS-CoV-2 pandemic. Objectives: To explore the effectiveness of a new electronic questionnaire in identifying sleep disturbances as adverse events to treatment and potential confounders. To evaluate the response rate to the questionnaire. To report the propor-tion of patients on propranolol with sleep disturbances. Methods: In an observational, prospective cohort study, caregivers provided clinical information at office visits and via an electronic questionnaire after an 8-week treatment course and at treatment interruption. Adverse drug reaction (ADR) reporting forms were evaluated for causality assessment. Results: The questionnaire response rate was 91%, and the completion rate was 100%. The prevalence of sleep disturb-ances as adverse reactions was 59%. Sleep disorders were more frequent during sleep regression phases and in subjects who fell asleep with physical contact with caregivers or bed-sharing with parents. Conclusion: The application of this questionnaire allows for identifying sleep-adverse events associated with propranolol in IH and potential confounders. Counselling on sleep hygiene is recommended before treatment onset

Heterodimeric approach has emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. This study aimed to develop and compare six alternative routes for stereoselective synthesis of heterobivalent conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic approach, considered such factors as efficiency, complexity, synthesis and purification characteristics, as well as yields of the target compounds has been made. Optimal conditions for the stereoselective synthesis of heterobivalent ligands to PSMA and GRP, which could serve as molecular platforms for the targeted delivery of therapeutic and/or diagnostic agents to these receptors, were determined. For synthesized heterobivalent ligand 26^x and heterobivalent conjugate with DOTA 27 complete signal assignment in ¹H, ¹³C, and ¹⁵N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra.

The use of pesticides such as rotenone can lead to toxicity, dysfunction and neuronal death in humans. The Copaifera Reticulata Ducke Oil-Resin (CPOR) is widely used by the natives of the Amazon, however, studies on its potential neuroprotective effect are lacking. This study investigated the cytoprotective effect of CPOR on total cell cultures of the ventral midbrain (VMC), hippocampus (HC) and cerebral cortex (CCC) exposed to rotenone at different concentrations. The total cell cultures of VMC, HC and CCC were exposed for 72 or 24 hours to rotenone, CPOR and rotenone + CPOR. Cell viability was measured using the MTT test and compared using one-way ANOVA. Exposure to rotenone reduced the cell viability of CMV, HC and CCC. Exposure to CPOR reduced the cell viability of CMV. The cell viability of CMV exposed simultaneously to rotenone and CPOR was higher compared to rotenone alone. The cell viability of HC exposed simultaneously to rotenone and CPOR was higher than that exposed to rotenone. CMVs are more vulnerable to rotenone toxicity and more sensitive to CPOR. Considering simultaneous exposure, CPOR revealed a possible neuroprotective effect against rotenone damage only for VMC and HC.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

Cryopreservation, storing biological material in liquid nitrogen (LN, −196 °C), offers a valuable option for the long-term conservation of non-orthodox seeds and vegetatively propagated species in the sector of agrobiodiversity and wild flora. Although large-scale cryobanking of germplasm collections has been increasing worldwide, the wide application of cryopreservation protocol in wild flora is hampered by difficulties in vitro propagation and a lack of universal cryopreservation protocols, among others. This study established a systematic approach to developing an in vitro culture and droplet-vitrification cryopreservation procedure for shoot tips of Scrophularia kakudensis. The standard procedure includes two-step preculture with 10% sucrose for 31 h and with 17.5% sucrose for 16 h, osmoprotection with loading solution C4-35% (17.5% glycerol + 17.5% sucrose, w/v) for 30 min, cryoprotection with A3-80% (33.3% glycerol + 13.3% dimethyl sulfoxide + 13.3% ethylene glycol + 20.1% sucrose, w/v) at 0 °C for 60 min, and cooling and rewarming using aluminum foil strips. After unloading, a three-step regrowth procedure starting with an ammonium-free medium with growth regulators was essential for developing normal plantlets from cryopreserved shoot tips. Liquid overlay on the gelled medium two weeks after inoculation resulted in vigorous growth during subcultures. Moreover, liquid overlay increased LN regeneration by up to 80%, i.e., 23% higher than no liquid overlay.

The Midwestern region of the United States has been experiencing periodic forage shortages due to frequent droughts, a growing livestock population, and reliance on traditional farming practices. This study evaluated the dry matter yield (DMY), forage nutritive value, water use efficiency (WUE), and economic viability of forage soybean [Glycine max (L.) Merr.] in a no-till winter wheat-based rainfed cropping system in the Midwest, USA. The research aimed to identify alternative summer forage crops that are drought-resilient, require lower inputs, mitigate seasonal gaps, and provide higher DMY and forage nutritive value compared to traditional forages. A four-year field experiment in a randomized complete block design with four replications assessed these parameters at various growth stages and planting dates. Results showed that forage soybean had a high DMY (~13 Mg ha-1), especially when optimally planted and harvested at the R3 stage. Forage nutritive value, including crude protein (CP), in vitro dry matter digestibility (IVDMD), and relative feed value (RFV), was highest at early vegetative stages (V2-V3), meeting livestock nutritional requirements. Forage soybean also demonstrated good WUE (21 kg ha-1 mm-1), making it suitable for water-limited regions. Economic analysis indicated substantial net profits ($322 per hectare), confirming its economic viability. The study concludes that forage soybean is a promising summer forage option for Midwest growers, offering high-quality forage, efficient water use, and economic benefits. Further research, particularly animal feeding trials, is recommended to validate its potential for widespread adoption in cropping systems.

Ti6Al4V samples obtained by selective laser melting were subjected to acid treatment, chemical oxidation in hydrogen peroxide solution and subsequent thermochemical treatment. The effect of temperature and time of acid etching of Ti6Al4V samples on surface roughness, morphology, topography and chemical and phase composition after the thermochemical treatment was studied. The surfaces were characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and contact profilometry. Pore and protrusion sizes were measured. Acid etching modified the elemental composition and surface roughness of the alloy. Temperature had a greater influence on the morphology, topography and surface roughness of samples than time. Increases in roughness values were observed when applying successive chemical oxidation and thermochemical treatment compared to the values observed on surfaces with acid etching. After the thermochemical treatment, the samples with acid etching at a temperature of 80 °C showed a multiscale topography. In addition, a network-shaped structure was obtained on all surfaces, both on their protrusions and pores previously formed during the acid etching.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

The article presents the issues related to the operation and modelling of the ship main propulsion steam boiler. Such objects are used widely in seagoing ships especially the very large crude oil carriers as a main propulsion turbine feed. The advantages of such along with simple construction thus great reliability make oil feed boilers an excellent source of power for chosen type of the large ships. It must be pointed out that a lot of research work was done in the previous years regarding automatic control of boiler automation but since then this technology was not in the focus of the researchers. In the future the fossil fuels will become less important than they are now, but the control techniques of boilers would eventually change due to different fuel parameters therefore, development of such is necessary. The article presents the results of research collected in real ship boilers during their operation and then, based on the results, a digital model of such an object was created. This model was implemented into Hardware-In-Loop which is the initial step for preparing the full model (including sensors etc.) of a steam heated boiler. Theoretical background along with chosen simulation and experimental results of control implemented into HIL were presented to validate assumptions...

Many medicinal plants and their essential oils are used to treat or prevent diseases without the risk of mutagenicity, carcinogenicity, or teratogenicity. Eucalyptus essential oils are commonly used as preservatives, flavoring agents, and in various consumer goods. Eucalyptus leaves are being widely studied due to their volatile essential oils, including 1,8-cineole, p-cymene, α and β-pinene, limonene, citronellal, citral, eudesmol, terpinen-4-ol, terpineol, α–phellanderene, and 9β-sitosterol. Among these compounds, 1,8-cineole is the most abundant. Eucalyptus leaves are rich in flavonoids and phenolic compounds and are thus a great source of antioxidants. 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays are used to measure antioxidant capacity. The antioxidant activity of Eucalyptus essential oil is stronger than that of standard antibiotics like Erythromycin, Cefixime, and Gentamicin due to the presence of significant terpenoids in addition to phenolic chemicals and flavonoids. The lower the IC₅₀ value, the higher the antioxidant potential. Phenolic compounds and flavonoids are often associated with beneficial health outcomes, including anti-inflammatory and antioxidant effects, anti-cancer properties, reduced risk of cardiovascular diseases, prevention of age-related neurodegenerative diseases, and prevention of Alzheimer’s disease. Flavonoids also play an essential role in plants, including protecting against reduction, fertility, reproduction, and infection. Due to their anti-inflammatory, anti-oxidative, and immune-modulatory properties, flavonoids are crucial for pharmacological, medical, and nutraceutical applications.

Currently, conventional spark-ignition engines face challenges in meeting the ever-growing demands of customers and increasingly stringent regulations regarding pollutant emissions. A combination of innovative strategies and carbon-neutral fuels is deemed necessary in order to further reduce fuel consumption and minimize engine emissions. The present work aims to assess the performance of combustion strategies using low-carbon content fuel, such as methanol M100, ignited by a plasma-assisted igniter (PAI) under ultra-lean conditions. The experimental campaign is conducted on a single-cylinder research engine at different engine speeds and low loads, moving up to the engine lean stable limits. To determine the benefits brought by the proposed strategy, referred to as M100-PAI, the obtained outcomes are compared with the ones obtained using market gasoline E5 ignited by the PAI system and conventional spark. The synergy between M100 (methanol) and Plasma Assisted Ignition (PAI) in internal combustion engines yielded notable benefits. This combination significantly improved combustion stability if compared to the other combinations tested, by extending the lean stable limit to λ=2.0, reducing cycle-to-cycle variability, and facilitating faster flame front acceleration, resulting in enhanced homogeneity. These enhancements, obtained with the combination M100-PAI, contributed to higher fuel efficiency showing a 10% efficiency gain over the combination E5-gasoline spark ignition.

As the global arid climate intensifies and the groundwater becomes increasingly scarce, drought stress has become a major challenge to plant growth and development worldwide, especially causing yield reduction and extinction of cultivated crops. In a large number of drought resistance studies, DNA methylation has been found dynamically associated with response to drought stress in plants by regulating gene expression and developments in plants, but the specific mechanisms are not yet clear. In this article, the current advances of research have been summarized on DNA methylation response to drought stress in various plant species, in terms of methylation detection methods, mechanisms of pattern changes (DNA de novo methylation, DNA maintenance methylation, and DNA demethylation), and its response to drought stress. With Most of the studies showed significant changes in genome or gene promoter methylation levels in plants subjected to drought stress, but the identification of the genes and pathways involved is still in the minority. The aim is to provide references for in-depth research on the response of plants to drought stress through epigenetics, and to uncover drought resistance genes regulated by DNA methylation, specific signaling pathways, and molecular mechanisms of action.

Background/Objectives: Determining the outcome of epilepsy is crucial for making proactive and timely treatment decisions, as well as for counseling patients. Recent research efforts have focused on using various imaging techniques and EEG for prognostication; however, there is insufficient evidence regarding the role of blood parameters. Our study aimed to investigate the additional prognostic value of routine blood parameters in predicting epilepsy outcomes. Methods: We analyzed data from 1,782 patients who underwent routine blood tests within 90 days of their first visit and had a minimum follow-up duration of three years. The etiological types were structural (35.1%), genetic (14.2%), immune (4.7%), infectious (2.9%), and unknown (42.6%). The outcome was defined as the presence of seizures in the last year. Results: Initially, a multivariate analysis was conducted based on clinical variables, MRI, and EEG data. This analysis revealed that sex, age of onset, epileptiform discharge, structural etiology, and the number of antiseizure medications were related to the outcome, with an area under curve (AUC) of 0.708. Among the blood parameters, fibrinogen, bilirubin, uric acid, and aPTT were significant, with AUCs of 0.602, 0.597, 0.455, and 0.549, respectively. Including these blood parameters in the analysis slightly improved the AUC to 0.713. Conclusions: Some blood parameters were found to be related to the final outcome, potentially paving the way to understanding the mechanisms of epileptogenesis and drug resistance.

The emergence of acquired resistance to EGFR-TKIs is almost inevitable even after a remarkable clinical response. Secondary mutations such as T790M and C797S are responsible for the resistance to 1st/2nd generation (1/2G) TKIs and 3G TKIs, respectively. To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as explored resistance mechanisms to a 4G TKI. First, we compared the efficacies of seven TKIs including a 4G TKI, BI4020, against Ba/F3 cell models that simulate resistant tumors after frontline osimertinib treatment failure because of a secondary mutation. We also established acquired re-sistant cells to BI4020 by chronic drug exposure. Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib). BI4020 inhibited the growth of C797S-positive cells; however it was not effective against L718Q-positive cells. Erlotinib was active against all Ba/F3 cells tested. In the analysis of resistance mechanisms of BI4020 resistant (BIR) cells, none harbored secondary EGFR mutations. HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020. HCC4006BIR and H1975BIR cells exhibited epithelial to mesenchymal transition. This study suggests that erlotinib may be more suitable than 4G TKIs to overcome sec-ondary mutations after front-line osimertinib. We found that off-target mechanisms that cause re-sistance to earlier generation TKIs will also cause resistance to 4G TKIs.

Background: Atrial fibrillation (AF) is increasingly recognised in paediatric patients and presents unique management challenges. We aimed to investigate the prevalence, management strategies, and outcomes of AF in this population. Methods: This retrospective analysis was conducted at a tertiary paediatric cardiology centre, including patients aged ≤18 years who were diagnosed with AF between January 2015 and December 2023. Demographic details, clinical manifestations, treatments, and outcomes were also analysed. Patients with documented AF episodes were in-cluded. Descriptive statistics were used to assess the treatment efficacy, recurrence, and complications. Results: The study included 36 patients (mean age, 15 years; 58% male). Of these, 52.8% had acquired heart disease, 16.7% had congenital anomalies, and 16.7% had lone AF. The initial treatment involved electrical cardioversion (53.3%) and pharmacological conversion with amiodarone (46.7%). Over 80% of the patients received rhythm control therapy, and 63.9% were placed on oral anticoagulation, primarily for rheumatic and congenital heart diseases. The success rate of rhythm control was 50% with an AF recurrence rate of 3.8%. Ischaemic stroke was the most common complication (n=3) occurring in patients with underlying heart disease. Conclusion: AF in paediatric patients is predominantly associated with rheumatic and congenital heart diseases, although a notable proportion of patients present with lone AF. Despite the high intervention and antiarrhythmic therapy rates, neurological complications, particularly in those with underlying heart disease, remain a significant concern. These findings highlight the need for further com-prehensive studies to understand better the aetiology, risk factors, and management of paediatric AF.

Chromobacterium species are common in tropical and subtropical zones in environmental water samples and believed to «tropical» species. Here we describe an environmental case of resident Chromobacterium vaccinii in biofilms associated with Carex spp. roots in Moscow region, Russia (warm-summer humid continental climate zone). We performed broad characterization of individual properties as well as surrounding context for better understanding the premise of C. vaccinii survival during winter season. Genome properties of isolated strains propose some insights into adaptation to habit and biofilm mode of life, including social cheaters carrying ΔluxR mutation. Isolated C. vaccinii differs with previously described strains in some biochemical properties and some basic characteristics like fatty acid composition as well as unique genome features. Despite potential to modulate membrane fluidity and presence of several genes responsible for cold shock response, isolated C. vaccinii didn`t survive during exposure to 4 °C, while in initial complex biofilm it was able to survive for months in vitro at 4 °C. Surrounding bacterial community within the same biofilm with C. vaccinii represented a series of psychrophilic bacterial species which may share resistance to low temperatures with other species within biofilm and provide C. vaccinii opportunity to survive during cold winter season.

Hydrologic studies on rainfall-runoff have been extensively conducted in many regions around the globe to fulfill various desirable needs with a purpose of effective and proper planning and managing water resources for present and future uses, whereas such study is not well drawn much attention to river catchments of Tonle Sap Lake Basin in Cambodia, which may prevail to water insecurity. The Stung Sreng catchment, which is one among them considered to be a significant basin for water resources management in Cambodia, is remarkably increasing under intolerable pressures in water resources development. This study was to apply HEC-HMS (Hydrological Engineering Center-Hydrological Model System) model to predict streamflow of Stung Sangker catchment, located in Tonlesap Lake Basin in Cambodia. The result showed that the calibration was good at monthly basis. The model performance was given by Nash-Sutcliffe Efficiency criteria followed by 0.44 for daily and 0.71 for monthly basis, respectively. Moreover, the Percent Bias (PBIAS) for daily and monthly simulation was 4.13% and 3.56%, indicating a satisfactory model fit. The HEC-HMS conceptual model can be used to simulate flow of Stung Sangke catchment on a continuous time scale particularly monthly basis. The result also indicated that there was a clear seasonal variation in monthly water availability, especially during both wet and dry season.

Self-esteem, the evaluation of one's own worth or value, is a critical aspect of psychological well-being and mental health. In this paper, we propose an active inference account of self-esteem, casting it as a sociometer, or an inferential capacity to interpret one's standing within a social group. This approach allows us to explore the interaction between an individual's self-perception and the expectations of their social environment.When there's a mismatch between these perceptions and expectations, the individual needs to adjust their actions or update their self-perception to better align with their current experiences. We also consider this hypothesis in relation to recent research on affective inference, suggesting that self-esteem enables the individual to track and respond to this discrepancy through affective states such as anxiety or positive affect. By acting as an inferential sociometer, self-esteem allows individuals to navigate and adapt to their social environment, ultimately impacting their psychological well-being and mental health.

This paper proposes an optimization method for the scheduling of a multi-energy virtual power plant supply-demand balance in the power market environment of Jiangxi Province. The objective of this method is to enhance the operational efficiency of the power grid, reduce energy costs, and facilitate economical and efficient energy distribution in the power market. The method comprehensively considers the characteristics and uncertainties of renewable energy sources such as solar and wind energy, and incorporates advanced multi-objective optimization algorithms. Additionally, real-time market price feedback is integrated to achieve accurate allocation of power supply and demand. Through a case study of a multi-energy virtual power plant in Jiangxi Province, this paper examines the optimal combination model for various energy sources within VPP, and analyzes the impact of different market environments on supply-demand balance. The results demonstrate that the proposed scheduling optimization method significantly improves economic benefits while ensuring grid stability. Compared with traditional power supply models, it reduces average electricity costs by 15% and increases renewable energy utilization efficiency by 20%.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

This paper comprehensively explores the integration of cloud computing and advanced recommendation systems, emphasizing their pivotal roles in enhancing user experiences and operational efficiencies across digital platforms. It reviews the evolution of recommendation algorithms, highlighting their application in diverse domains such as e-commerce and media. The study evaluates the performance of advanced models like UniLLMRec against traditional counterparts using datasets from news and e-commerce domains. Additionally, the paper discusses the infrastructure architecture of cloud computing, demonstrating its capability to support scalable and efficient data processing. Through experimental insights and methodology, the research underscores the transformative impact of cloud technologies on optimizing recommendation system performance, thereby advancing digital engagement and competitiveness.

The presence and localization of plant metabolites are indicative of physiological processes, e.g., under biotic and abiotic stress conditions. Further, the chemical composition of plant parts is related to their quality as food or for medicinal applications. Mass spectrometry imaging (MSI) has become a popular analytical technique for exploring and visualizing the spatial distribution of plant molecules within a tissue. This review provides a summary of mass spectrometry methods used for mapping and identifying metabolites in plant tissues. We present the benefits and the disadvantages of both vacuum and ambient ionization methods, considering direct and indirect approaches. Finally, we discuss the current limitations in annotating and identifying molecules and perspectives for future investigations.

Governments worldwide are actively committed to achieving their carbon emission reduction targets, and one avenue under exploration is harnessing the potential of hydrogen. Blending hydrogen with natural gas is emerging as a promising strategy to reduce carbon emissions, as it burns cleanly without emitting carbon dioxide. This blending could significantly contribute to emissions reduction in both residential and commercial settings. However, a critical challenge associated with this approach is the potential for Hydrogen Embrittlement (HE), a phenomenon wherein the mechanical properties of pipe steels degrade due to the infiltration of hydrogen atoms into the metal lattice structure. This can result in sudden and sever failures when the steel is subjected to mechanical stress. To effectively implement hydrogen-natural gas blending, it is imperative to gain a comprehensive understanding of how hydrogen affects the integrity of pipe steel. This necessitates the development of robust experimental methodologies capable of monitoring the presence and impact of hydrogen within the microstructures of steel. Key techniques employed for this assessment include microscopic observation, hydrogen permeation tests, and tensile and fatigue testing. In this study, samples from two distinct types of pipeline steels used in the natural gas distribution network underwent rigorous examination. To induce hydrogen absorption, an electrochemical charging process is employed in a solution rich in H+ ions. This charging process, accomplished by a potentiostat applying a constant current, prompts the hydrogen evolution reaction at the steel specimen, acting as the cathode of the charging cell. Immediate tensile and fatigue testing following the charging process enables the evaluation of mechanical properties in comparison to non-charged samples. Different charging current densities are employed to simulate various hydrogen blend scenarios. The findings from this research indicate that charged samples exhibit a discernible decline in fatigue and tensile properties. This deterioration is attributed to embrittlement and reduced ductility stemming from the infiltration of hydrogen into the steel matrix. The extent of degradation in fatigue properties is correlated not only to the hydrogen content but also to the hydrogen permeability and diffusion rate influenced by steel’s microstructural features, with higher charging current densities indicating a more significant presence of hydrogen in the natural gas pipeline blend.

Background: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to under-stand how these elements continue to affect young populations in the post-pandemic era. Methods: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7–19 years, to ensure age and gender representation. The survey included par-ent ratings and adolescent (11–19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). Results: Of the 4,525 valid responses, 1,831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents' mental health problems, whereas self-report tended to underestimate them. Conclusions: Persistent mental health problems and gender disparities high-light the need for a public health approach. This should include accessible support services, resili-ence building, targeted support for vulnerable families and gender-specific interventions.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

Type 2 diabetes (T2DM) presents an enormous global healthcare challenge, especially among rural communities due to limited access. To overcome this, many low- and middle-income countries are resorting to task shifting, using community health workers (CHWs) for diabetes management. However, its successful implementation depends on the practice behaviours and knowledge of these workers. This cross-sectional study from rural South India aimed to evaluate the proficiency of 275 CHWs in diabetes screening and management. A customized questionnaire, developed through experts and government was used to evaluate the practice behaviours and knowledge. Analytical methodologies consisted of descriptive statistics, logistic regression, and mosaic plots for comprehensive data interpretation. Results showed significant deficiencies of mean correct practice behaviours at 48 and 50% respectively. The identified gaps included diabetes diagnosis, HbA1c testing, diet, self-management, complications screening and risk assessment. In several areas, correct practice behaviour was reported by a relatively large number of CHWs despite incorrect answers to the related knowledge questions such as referral to the health centres, self-management and calculation of diabetes risk assessment. Addressing these deficiencies requires a thorough needs assessment and tailored training for improved diabetes management by CHWs. Training of CHWs, should not only identify prior knowledge and/or behaviour but also their interrelationship to help create a robust and flexible set of practice behaviours.

The current study evaluated the effect of powder fractions based on particle size on the chemical composition of macronutrients such as proteins and sugars, on phytochemical properties (total content of polyphenolic compounds, vitamin C and antioxidant activity), on preservation capaci-ty (water activity), reconstitutability properties (water absorption capacity and water solubility index) and physicochemical properties (particle size distribution and moisture content) of black-thorn berries (Prunus spinosa) powders. The fruits were separated from the plant material and seeds, dried and then ground using a FRITSCH PULVERISETTE 19 universal mill for hard mate-rials. Eight fractions were obtained after sieving on seven sieves with different mesh sizes, such as: 1 mm, 0.8 mm, 0.630 mm, 0.450 mm, 0.315 mm, 0.200 mm, 0.125 mm. The grinding/sieving pro-cedure was effective in separating Prunus spinosa powder into sufficiently different size classes. The maximal moisture content and water activity were 5.61% and 0.250 respectively, show the good preservation from a microbiological point of view and ensure prevention the oxidation of bi-ologically active compounds of blackthorn berries powders. For samples with reduced particle sizes, reconstitutability was greatly improved. Total phenolic content, protein content, carbohy-drates and antioxidant activity showed significant improvements for some particle size classes compared to the unsieved sample. Vitamin C presented a semnificative content for the fraction with particle large sizes, precisely because they did not undergo intense degradation processes. Therefore, the technique of grinding and successive sieving proved effective in enhancing the physicochemical and functional characteristics of powdered blackthorn berries, particularly for smaller particles.

This study sought to investigate steel frames’ performance with dual lateral loader system (Frame bending + bracings of divergent and convergent) in near and far filed to fault. In order to this, four categories of steel frame with dual system with 8, 10 and 12 story are designed with average formation based on existing seismic regulation in 2800 standard of Iran and tenth chapter of national regulations of construction (planning and performing steel construction). Time history non-linear dynamic analysis under the effect of near and far field earthquakes has been done on plan’s models. Then the maximum of floors’ dislocation, floors’ drift, roof dislocation, base shear and energy curves of frames are shown and compared with each other. All non-linear time history analyses have been accomplished using PERFORM 3D software.

Considering that emotional events diversify as one ages, this study formulates the Salient Episodic Memory Aggregation Hypothesis, which claims that aging induces homogenization of episodic memory and consequently increases the salience of emotional episodes. To test this hypothesis, the study focused on sadness episodic memory and conducted a web-based survey and a combined analysis consisting of natural language processing, machine learning, and network graph analysis. A sample of 2,954 adults aged between their 20s and over 70s participated in this study. They were asked to describe a sad event they had experienced and assess the psychological properties of the recalled episodes. After isolating and lemmatizing episodic words using natural language processing, vocabulary frequency was counted for each generation, and network graph analysis based on machine learning was performed to compare the structures of sadness episodes between generations. As a result, there were mainly two types of episodic words for which frequencies either declined or increased with age. The network structures of episodic words for the older generations possessed higher proximity (shortest path length) to higher concentrations of episodic words. These findings support the current hypothesis, indicating that the nature of sadness episodes differ between generations, and that older people have more aggregated episodic memory structures.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

The industrial metaverse paradigm is generally a virtual environment that integrates various technologies such as augmented reality (AR) and mixed reality (MR) to enhance business operations and processes. It aims to streamline workflows, reduce error rates, improve efficiency, and provide a more engaging experience for employees. The promise of the industrial Metaverse to drive sustainability and resource efficiency is compelling. Utilizing advanced technologies like the Industrial Metaverse is essential for staying competitive in today’s rapidly evolving business environment. However, the environmental impact of the technologies underpinning the industrial metaverse, like data centres and network infrastructure, should not be overlooked. The ecological footprint of these technologies must be considered in the sustainability equation. Researchers have warned that by 2025, without sustainable AI practices, AI will consume more energy than the human workforce, significantly offsetting carbon-zero gains. As the metaverse persists in evolving and gaining momentum, it will be necessary for companies to prioritize sustainability and explore new ways to balance technological advancements with environmental stewardship. However, recent studies have conjectured that the Metaverse holds the potential to reduce carbon emissions, as digital replacements for physical goods become more prevalent and physical activities like mobility and construction are reduced. However, the specific extent to which this substitution can alleviate environmental concerns remains understudied, presenting a knowledge gap in understanding the real-world impact of digital replacements. Thus, the objective of this paper is to provide a comprehensive review of the industrial metaverse as well as explore the environmental impact of the industrial metaverse. The methodological approach is that of integrative literature review design wherein multiple sources from web science and databases such as ACM library, IEEE Library, and Google Scholar, were analysed to provide a comprehensive understanding of the developments in the industrial metaverse. Specifically, firstly by considering the Industrial metaverse architecture we elucidate the concept of the "industrial metaverse" and the associated enabling technologies. Secondly, an exploration through discussion, of the prevalent use cases and deployment of the emerging industrial metaverse. Thirdly, exploration of the impact of the industrial metaverse on the environment. In the fourth instance, we address novel security and privacy risks as well as upcoming research challenges, keeping in mind that the industrial metaverse is based on a strong data fabric. Results point to the Industrial Metaverse as having both positive and negative environmental effects by energy consumption, e-waste, and pollution. Overall research, however, indicates that most industrial metaverse applications have a positive environmental impact and subsequently trend toward sustainability. Ultimately for sustainability in the industrial metaverse, enterprises may consider utilizing renewable energy sources and cloud services. Furthermore, examining the effects of products on the environment as well as creating a circular economy.

A topological representation theory of chiral spin liquid is proposed to unify the integral and fractional quantum Hall fluid based on hyperbolic geometry, knot lattice and Thurston's train track theory. The integral and fractional Hall resistivity obeys an exact unified equation, $R_{xy} = (h/e^2)B_{e}$, $B_{e} = (n+\nu)^{-1}$, with respect to the bulk energy gap ${\Delta}E = {\hbar{e}B_{e}}/{Mc}$. The Wen-Zee matrix formulation of topological fluid for quantum Hall effect is constructed by topological surgery and train track. The chirality of spin liquid is spontaneously distinguished by Jones polynomial. The integral Chern number for Hall conductance is fractionalized by generalizing Thurston's train track to folding laminations in three dimensions, which spontaneously bring fractional quantum Hall fluid and anyons into three dimensions and provided an theoretical explanation on the competing fractional quantum Hall states. The many body system of interacting fermions or bosons are mapped into many interacting liquid droplets that interwind into knot lattice, which provide an effective topological representation for superfluid and superconductor, the strange metal state in superconductor is explained by topological dislocation and topological surgery. The Kauffman decomposition rule in knot theory is extended to describe the topological relations between different two dimensional manifolds, which further reveals the non-trivial relationship between the partition functions of pairing fermions and free electrons. The minimal energy state is the most stable topological state, even thought it maybe shares the same topological number with the excited states. The topological representation theory predicts a circular motion of electrons in hyperbolic space, that is implementable and testable by inhomogeneous magnetic field in three dimensions. The folding lamination representation of topological quantum fluid provides an promising implementation of string theory in high energy physics.

This work continues the review and illustrative application to energy systems of the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” (4th-BERRU-PM) methodology. The 4th-BERRU-PM methodology uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, in-cluding fourth (and higher) order sensitivities of computed model responses with respect to model parameters. The 4th-BERRU-PM methodology yields the fourth-order MaxEnt posterior distribution of experimentally measured and computed model responses and parameters, in the combined phase-space of model responses and parameters. The 4th-BERRU-PM methodology encompasses fourth-order sensitivity analysis (SA) and uncertainty quantification (UQ), which were reviewed in the accompanying work (Part 1), as well as fourth-order data assimilation (DA) and model calibration (MC) capabilities, which will be reviewed and illustrated in this work (Part 2). The applicability of the 4th-BERRU-PM methodology to energy systems is illustrated by using the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark, which is modeled using the linear neutron transport Boltzmann equation, involving 21976 im-precisely known parameters. This benchmark is representative of “large-scale computations” such as those involved in the modeling of energy systems. The result (“response”) of interest for the PERP benchmark is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. The impact of the high-order sensitivities of the response with respect to the PERP model parameters is quantified for “high-precision” parameters (2% standard deviations) and “medium-precision” parameters (5% standard deviations). Analyzing the best-estimate results with reduced uncertainties for the 1st- through 4th-order moments (mean values, covariance, skewness, and kurtosis) produced by the 4th-BERRU-PM methodology for the PERP benchmark indicates that, even for systems mod-eled by linear equations (e.g., the PERP benchmark), retaining only first-order sensitivities is insufficient for reliable predictive modeling (including SA, UQ, DA, MC). At least second-order sensitivities should be retained in order to obtain reliable predictions.

The study of Internet of Vehicle (IoV) based on Fog Computing (FC) and Artificial Intelligent (AI) has attracted more and more attention. However, there are still many problems require to investigate such as time-critical, scalability, load-balancing, energy consumption, and so on. Focusing on these problems, we proposed an AI-based Vehicle-to-Everything (V2X) model for tasks and resource offloading model for IoVs network, which ensures reliable low-latency communication efficient tasks offloading in IoV network by using Software Defined Vehicular based FC (SDV-F) architecture. To fit to time-critical data transmission task distribution, the proposed model reduces unnecessary task allocation at the fog computing layer by proposing an AI-based task-allocation algorithm in IoV layer to implement task allocation of each vehicle. By applying AI technologies of Reinforcement Learning (RL), Markov decision process, and Deep Learning (DL), the proposed model intelligently makes decision on maximizing resource utilization at the fog layer, and minimizing the average end-to-end delay of time-critical IoV applications. The experiment demonstrates the proposed model can efficiently distribute the fog layer tasks while minimizing the delay.

Abstract: Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- or/and post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight pathological, blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction ( qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes including neurogenesis, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weight measurement showed a significant reduction of the testes, kidneys, heart, liver, and epididymides although no abnormal changes from pathological examination. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl, Abhd14b and downregulation of Hspa1b, P4ha1, and Banp genes in both hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p, miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8Gy or below may not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposure with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or expanding once a nuclear accident or leakage occurs.

Crohn’s disease (CD) is a chronic inflammatory disease associated with a significant burden in terms of quality of life and health care costs and is frequently associated with several complications, including the development of intestinal strictures. Stricturing CD requires a careful multidisciplinary approach involving medical therapy and surgery, still posing a continuous management challenge; in this context, endoscopic treatment represents a valuable, in-between opportunity as a minimally invasive strategy, endorsed by extensive yet heterogeneous evidence and evolving research and techniques. This review summarizes current knowledge on the role of therapeutic endoscopy in stricturing CD, focusing on evidence gaps, recent updates, and novel techniques intended for optimizing efficacy, safety, and tailoring of this approach in the view of precision endoscopy.

Gastric cancer is the 5th most common disease in the world and the 4th most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy, however there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patient’s plasma. And we attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patient’s plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2%, and found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5'end-motif analysis.

Exosomes, nanoscale extracellular vesicles, are a hot area of investigation in the biomedical field, as they have been shown to play a crucial role in the physiology of numerous tissues, including bone. This study explores the landscape of exosome-based bone regeneration research using infometric techniques. By relying on BERTopic, an advanced topic modeling algorithm, we analyzed a comprehensive corpus of scientific literature to identify key themes and trends in exosome research in the bone regeneration field. We then extracted significant concepts from the abstracts of the corpus and we used them to create knowledge graphs using GPT 3.5 turbo Large Language Model, to map the distribution of information within this domain. The resulting ide-oscape highlights the key ideas that aggregate most of the recent research in the area, from mesenchymal stem cell-derived exosomes to engineered exosome-integrated biomaterials. This exploration provides a holistic view of the field and uncovers its emerging trends, providing useful insight to guide future research directions.

Biochemical compositions of black carpenter ants (Camponotus pennsylvanicus) were analyzed using standard methods. The proximate composition (%) were as follows: crude protein (22.50), crude fibre (1.46), carbohydrate by difference (30.86) and energy (35.4Kcal). The predominant mineral was potassium and nickel was the least. The antinutritional properties (mgkg^-1) ranged as follows: Oxalate (1.35), phytate (62.79), and tannins (0.72). The results suggested that the ant may be a good source of nutrition.

Plant-based proteins, like those derived from hemp and rapeseed can significantly contribute to a balanced diet and human daily nutritional requirements by providing essential nutrients such as protein, fiber, vitamins, minerals, and antioxidants. According to numerous recent research papers the consumption of plant-based proteins has been associated with numerous health benefits, including reduced risk of chronic diseases such as heart disease, diabetes, and certain cancers. Plant-based diets are often lower in saturated fat and cholesterol and higher in fiber and phytonutrients, which can support overall health and well-being. Present research investigates the nutritional attributes, functional properties, and potential food applications of hemp and rapeseed protein for a potential use in new food product development, with a certain focus on identifying anti-nutritional factors and bioactive compounds. Through comprehensive analysis, anti-nutritional factors and bioactive compounds were elucidated, shedding light on their impact on protein quality and digestibility. The study also delves into the functional properties of hemp and rapeseed protein, unveiling their versatility in various food applications. Insights from this research contribute to a deeper understanding of the nutritional value and functional potential of hemp and rapeseed protein, paving the way for their further utilization in innovative food products with enhanced nutritional value and notable health benefits.

The high radio frequency polarization imaging of non-thermal emission from active galactic nuclei (AGN) is a direct way to probe the magnetic field strength and structure in the immediate vicinity of supermassive black holes (SMBHs) and is crucial in testing the jet-launching scenario. To explore the the magnetic field configuration at the base of jets in blazars, we took advantage of the full polarization capabilities of the GMVA (Global Millimeter VLBI Array). With an angular resolution of ~50 micro-arcseconds at 86 GHz, one could reach scales down to ~900 Schwarzschild radii (for a 10^9 solar mass black hole). We present here the preliminary results of our study on the blazar BL Lac. Our results imply that on sub-mas scales the core and central jet of BL Lac is significantly polarized with two distinct regions of polarized intensity. We also noted a great morphological similarity between the 7mm/3mm VLBI images at very similar angular resolution.

Lipoprotein (a) is a highly atherogenic, lipid particle whose concentration is genetically determined, and represents an independent risk factor for cardiovascular disease. On the other hand, metabolic syndrome represents a cluster of interconnected cardiovascular risk factors (obesity, insulin resistance, arterial hypertension, dyslipidemia) that are a direct consequence of an unhealthy lifestyle. Some evidence suggests a connection between each component of metabolic syndrome and high levels of lipoprotein (a). Still, the exact mechanisms are not fully understood and may involve complex interactions between various metabolic pathways. High levels of lp(a) are associated with insulin resistance, a key feature of type 2 diabetes mellitus and obesity. Although there is no significant association between lp(a) and other lipid levels (LDL-C, HDL-C, triglycerides), studies have shown a strong synergistic effect of genetically elevated LDL-C and Lp (a) on the development of cardiovascular events. Also, there is supporting evidence that hypertensive patients with high levels of lp(a) have higher cardiovascular risk, there is no direct association between hypertension and lp (a). Treatment of metabolic syndrome is often long-term and challenging but very important to reduce the overall cardiovascular risk, especially in individuals with higher levels of Lp (a), in whom the risk of developing cardiovascular disease is much higher.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

This paper describes the load capacity of short fiber-reinforced polymer lugs with Ti-6Al-4V selective laser-melted bushings with the original embedded element surface roughness and after sandblasting and vibratory finishing. Lugs are an important part of pin-joints. Adhesion between PA6 and SLM produced titanium is not fully studied. The cohesive zone material Mode II model parameters were calibrated experimentally by extruding a cylindrical bushing along the lug axis. The values of the maximum equivalent tangential contact stress were fitted for cases with investigated embed element roughness. The critical fracture energy for tangential slip was also estimated. Validation of the constructed CZM Mode II models with the results of strength experiments was performed. In both the experiment and the calculation, greater bushing roughness provides greater lug load-bearing capacity. The presented models can be used for the preliminary evaluation of SFRP PA6 parts with titanium embedded elements bearing capacity.

Ultrathin Bi₂Se₃-NbN bilayers comprise a simple proximity system of a topological insulator and an s-wave superconductor for studying gating effects on topological superconductors. Here we report on 3 nm thick NbN layers of weakly connected superconducting islands, overlayed with 10 nm thick Bi₂Se₃ film which facilitates enhanced proximity coupling between them. Resistance versus temperature of the most resistive bilayers shows insulating behavior but with signs of superconductivity. We measured the magnetoresistance (MR) of these bilayers versus temperature with and without a magnetic field H normal to the wafer (MR=[R(H)-R(0)]/\{[R(H)+R(0)]/2\}), and under three electric gate-fields of 0 and ±2 MV/cm. The MR results showed a complex set of gate sensitive peaks which extended up to about 30 K. The results are discussed in terms of vortex physics, and the origin of the different MR peaks is identified and attributed to flux-flow MR in the isolated NbN islands and the different proximity regions in the Bi₂Se₃ cap-layer. The dominant MR peak was found to be consistent with enhanced proximity induced superconductivity in the topological edge currents regions. The high temperature MR data suggest a possible pseudogap phase or a highly extended fluctuation regime.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group), and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota, with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days, and examined 16.71% weight loss at 300 days after treatment. In the whole subjects, 60.4%, 21.3% and 6.3% achieved weight reductions exceeding 5%, 10% and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p=0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In vivo, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

The widespread adoption of IoT networks has revolutionized modern life thanks to their diverse range of applications. With their increased usage, the need to transfer data securely has never been more vital. Often IoT devices are battery-driven and possess limited processing and storage capabilities. In response to those limitations, there has been a shift towards the implementation of resource-efficient and lighter protocols. This research aims to evaluate how lightweight key establishment through Object Security for Constrained RESTful Environments (OSCORE) and Ephemeral Diffie-Hellman Over COSE (EDHOC) can enhance cybersecurity in IoT networks where resources are limited. The study aims to explore different key management approaches and the effects of certificates on security, efficiency, and power consumption. The research methodology consists of the practical implementation of the protocols in a physical system where factors such as the impact of hardware acceleration on computational overhead and overall power consumption will be assessed. Furthermore, the study will verify the cost of resources and overall efficiency, evaluating them against real-world scenarios. The expected contributions of this study are insights into the tradeoffs between security, power consumption, and efficiency in resource-limited IoT environments.

Growing concerns about the greenhouse effect, global warming, and adverse climate changes primarily stemming from carbon dioxide (CO2) emissions in traditional Portland cement (OPC) used in civil engineering construction, have prompted a shift toward eco-friendly alternatives like geopolymer cement (GPC). Over the last few decades, significant advancements have been made in developing environmentally sustainable pavement construction materials such as GPC to mitigate global CO2 emissions. The success of geopolymer cement (GPC) as an eco-friendly alternative to OPC has garnered attention for its potential to lower carbon emissions and enhance durability. This is attributed to the sustainable production method of GPC, where industrial cementitious waste materials (such as fly ash (FA), metakaolin (MK), mine tailings (MT), slag, etc.) are combined with an eco-friendly alkaline activator and water through the geopolymerization process. Numerous studies on geopolymer concrete indicate that, like OPC, GPC exhibits comparable mechanical properties, including strength, fire resistance, chemical resistance, and durability. This review explores the properties and applications of GPC as a sustainable material in pavement construction, exploring key studies and advancements in geopolymer technology, particularly its suitability for pavement applications. The assessment covers the mechanical properties, long-term performance, and environmental impact of geopolymer-based pavements, providing a comprehensive overview to inform policymakers, engineers, and researchers about the viability of geopolymer-based materials as a sustainable solution for modern pavement construction.

Three neutral Pt(II) complexes with diphenylamino-modified 2-phenylpyridine derivatives as cy- clometalating ligands and acetylacetone as the ancillary ligand exhibit aggregation-induced phosphorescent emission (AIPE) properties in THF/H2O. The crystal structures of the complexes highlight the contributions of non-covalent Pt···Pt interactions and hydrogen bonds to the AIPE properties. These AIPE-active Pt(II) complexes 1-3 have been successfully applied to detect picric acid (PA) in aqueous media, affording the lowest limit of detection at 70 nM. Furthermore, three Pt(II) complexes are able to detect PA in common water samples. The quenching of luminescence in the detection can be attributed to photo-induced electron transfer.

Recognition, decoding and tracking of vortex patterns is of increasing importance in many fields reaching from astronomical observation of distant galaxies to turbulence phenomena in liquids or gases. Currently, coherent light beams with orbital angular momentum (OAM) are of particular interest for optical communication, metrology, micro-machining or particle manipulation. One common task is to identify characteristic spiral patterns in pixelated intensity maps at real-world signal-to-noise ratios. Recently, Fast Fourier Transform (FFT) was applied to the quantitative analysis of spiral interference patterns of OAM beams. Our study considers this approach in more detail. It is demonstrated that specific information can be extracted by combining conformal mapping by polar transform with determining one- or two-dimensional angular frequency spectra either in spatially fixed or scanning mode. Results of proof-of-principle experiments are presented.

Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel Salmonella typhimurium (ST) vector expressing the bacterial collagenase Streptomyces omiyaensis trypsin (SOT), a serine protease known to hydrolyze collagens I and IV, which are predominantly found in PDAC. Utilizing aggressive models of PDAC, we show that ST-SOT selectively degrades intratumoral collagen leading to enhancement of immune checkpoint blockade (ICB) therapy in tumor-bearing mice. Ultimately, we found that ST-SOT treatment significantly modifies the intratumoral immune landscape to generate a microenvironment more conducive to ICB.

Introduction: Diagnosing and managing Borrelia miyamotoi disease (BMD) is challenging due to its symptom overlap with Lyme disease (LD) and the lack of reliable laboratory diagnostics for BMD. This case study demonstrates the use of phage-based PCR (phb-PCR) to identify B. miyamotoi in a patient who had been bitten by ticks. Case presentation: A female patient aged 46 presented with joint and muscle pain, myalgic encephalomyelitis/chronic fatigue syndrome, and cognitive impairment after multiple tick bites in Europe. The patient was assessed for LD at the National Reference Centre in Strasbourg using Enzyme-linked immunosorbent assay (ELISA) and immunoblot. Additional diagnostics involved screening for Bartonella and Anaplasma antibodies using indirect immunofluorescence, and tests for antinuclear antibodies to check for autoimmune conditions. All serological and immunological tests yielded negative results. However, the phb-PCR identified B. miyamotoi. Consequently, the patient received treatment for BMD with a regimen of intravenous ceftriaxone, oral azithromycin, and additional intravenous vitamin and mineral therapy. Post-treatment evaluations showed significant improvements in pain levels, cognitive abilities, and fatigue. Conclusion: This case highlights the importance of direct diagnostic methods like phb-PCR for identifying BMD when serological tests fail. Clinicians should consider B. miyamotoi testing for accurate and timely management of complex TBDs.

Staphylococcus aureus is an opportunistic human pathogen and a leading cause of bloodstream infections. It can acquire different antibiotic resistance genes, leading to treatment failure. Aim: We elaborate on the genomic characteristics; antibiotic resistance, virulence, pathogenicity, phylogenomics and clonal diversity of S. aureus implicated in bloodstream infections. Six multidrug-resistant (MDR) S. aureus, three methicillin-resistant S. aureus (MRSA) and three methicillin-sensitive S. aureus obtained from blood cultures underwent whole genome sequencing and bioinformatics analysis. All isolates carried different permutations and combinations of resistance genes including, blaZ, mecA, aac(6')-aph (2''), ant(9)-Ia, ant(6)-Ia, mepR, fosB, norA, norC, lmrS, arlS, arlR, mgrA, kdpD and sdrM. We found 6 spa types (t9475, t355, t045, t1265, t1257, and t7888) with varying profiles of virulence genes responsible for immune invasion, enterotoxins, adhesion/biofilm, haemolysins, and leukotoxins. Panton-Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types IVd(2B) and I(1B) were identified. Isolates belonged to four multilocus sequence types (MLSTs), the most common of which was ST5 (n=3). The STs were clustered into two clonal complexes CC5 and CC8. We found two MRSA clones typed as ST5-CC5-t045-SCCmec_I(1B), and the human-associated MRSA endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). The insertion sequences IS30 and IS6 associated with virulence were found in two isolates. The presence of virulent MDR S. aureus in bloodstream infections poses a clinical concern because of limited treatment options and increased risk of mortality.

This study aimed to translate and validate the Genomic Nursing Concept Inventory (GNCI) in Greek, analyze the genomic knowledge of nurses in Crete, Greece, and explore potential factors that could affect it. This cross-sectional study included 324 nurses from public hospitals and primary care units between July and December 2022. The GNCI is a 31-item questionnaire that evaluates genomic nursing concepts, but it has not been translated and validated in Greek. The translation process included independent forward translations, reconciliation, and back-translation. To evaluate internal consistency, Cronbach’s alpha was used, and Confirmatory Factor Analysis (CFA) was conducted to determine the fit of the model. Multiple linear regression analysis was performed to examine the associations between the demographic variables and GNCI scores. The internal consistency of the GNCI was acceptable (Cronbach’s alpha= 0.622). The CFA indicated that the one-factor model had an adequate fit (SRMR = 0.076, CD = 0.677, CFI = 0.744). The mean GNCI score was moderate (0.35±0.14). Regression analysis suggested that only gender could affect GNCI scores, with female nurses scoring higher than male nurses (p>0.001). In conclusion, the Greek version of the GNCI is a reliable tool for assessing genomic knowledge among Greek nurses.

Several series of new polymers were synthesized: binary copolyesters of vanillic (VA) and hydroxybiphenylcarboxylic (HBCA) acids, as well as ternary copolyesters additionally containing hydroxybenzoic acid (HBA) and obtained via three different ways (in solution, in melt and in solid state). The high values of logarithmic intrinsic viscosities and insolubility of several samples proved its high molecular weights. It has been shown that the use of vanillic acid leads to the production of copolyesters with a relatively high glass transition temperature (about 130°C). Thermogravimetric analysis revealed onset of weight loss temperatures of ternary copolyesters occurred at 330-350 °C, the temperature of 5% mass loss is in the range of 390-410 °C. Two-stage thermal destruction is observed for all aromatic copolyester of vanillic acid: decomposition begins with VA units at 420-480 °C, and then decomposition of more heat-resistant units demonstrated above 520 °C. The copolyesters are thermotropic and exhibit a typical nematic type of liquid crystalline order. Mechanical characteristics of copolyesters are close to those for semi-aromatic copolyesters, but are much lower than typical values for fully aromatic thermotropic polymers. Thus, vanillic acid is a mesogenic monomer suitable for the synthesis of thermotropic fully aromatic and semi-aromatic copolyester, but resulting processing temperature must not exceed 280°C.

Aortic transection, a near-complete tear through the layers of the aorta, is a critical condition often resulting from trauma such as motor vehicle collisions. The urgency of managing aortic transection underscores the critical need for effective interventions. We report the case of a male in his early 50’s with no significant medical history who presented to the emergency department following a motor vehicle collision, sustaining multiple injuries including a descending thoracic aortic transection. Rapid diagnostic assessment confirmed the severity of the injury, necessitating immediate intervention. Endovascular aortic repair (EVAR) was successfully employed, highlighting its efficacy in managing acute aortic injuries. The patient responded well to treatment, underscoring the importance of timely intervention in improving patient outcomes. This case emphasizes the critical role of rapid diagnostic assessment and endovascular intervention in managing life-threatening thoracic aortic injuries, particularly in the acute setting.

There are various approaches to managing polyethylene terephthalate waste, including methods for recycling PET. However, at present, only the cleanest wastes that can already be efficiently recycled using known methods are considered in the scientific literature. The study aims to look at other forms of polyethylene terephthalate waste that pose a challenge: low quality PET flakes, polyester tire cord, PET dust and prepolymer waste. The waste was characterized by FTIR spectroscopy, viscosimetry, differential scanning calorimetry, laser diffraction and sieve analysis. The findings describe the composition and properties of various forms of polyethylene terephthalate waste. Low quality PET flake waste and polyethylene terephthalate dust have been shown to be suitable for all chemical recycling methods. When recycling waste polyester tire cord, it is difficult to completely separate the rubber, so its presence in the final product must be taken into account. The most promising way to process a prepolymer is its depolymerization by hydrolysis, alcoholysis or glycolysis to produce monomers for the synthesis of PET, similar in properties to the primary one.

Mesenchymal stem cells (MSCs), whose main function is tissue repair, use collagen to restore the structural integrity of damaged tissue, maintaining its organization through concomitant remodelling. The non-enzymatic glycation of collagen is likely to compromise its communication with MSC, which indeed underlies various pathological conditions such as late complications of diabetes and aging. However, data on the effect of more early stages of collagen glycation on the MSC interaction are lacking. This study focused on the fate of in vitro glycated rat tail collagen (RTC) in contact with MSCs after its pre-exposure to glucose for 1 or 5 days. Using human adipose tissue-derived MSCs (ADMSCs), we showed that their interaction with glycated collagen is significantly altered, manifested morphologically by reduced cell spreading, less formation of focal adhesions, and weaker development of the actin cytoskeleton, further confirmed by ImageJ morphometric analysis. This suggests a poorer recognition of early glycated collagen by integrin receptors, possibly due to steric hindrance of their binding sites. These morphological events were also accompanied by greatly reduced fibril-like reorganization of adsorbed FITC-collagen (a sign of impaired remodeling), complemented by reduced sensitivity to proteases. The latter was confirmed in two ways: measuring directly FITC-collagen degradation by the attached cells and quantifying the proteolysis reduction upon exogenous addition of collagenase in a cell-free system. The mechanism of the observed effects is unclear, although differential scanning calorimetry confirmed the presence of weak structural changes in glycated collagen. All this led us to conclude that the reason for the morphological changes of ADMSCs is the impaired interaction with early-glycated collagen due to the hindrance of complementary sequences for integrins, which certainly also affects the mechanical remodeling of collagen. However, the impaired collagenolytic activity, together with the observed small changes in the thermal transition profile, undoubtedly indicate some internal changes in the structural organization of the collagen molecule occurring even at this early stage of glycation, which in turn contributes further to the impaired MSC remodeling activity.

Although mammography has been the gold standard for early detection of breast cancer, if a woman has dense breast tissue, a false negative diagnosis may occur. Breast ultrasound, whether hand-held or automated, is a useful adjunct to mammography but adds extra time and cost. The primary aim was to demonstrate that our second-generation Aceso system, which combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform, is able to produce improved quality images that provide clinically meaningful results. Aceso was first tested using two industry standards: a CDMAM phantom to assess the FFDM images; and the CIRS 054GS phantom to evaluate the ABUS images. In addition, 25 women participated in a clinical trial: 14 were healthy volunteers while 11 were patients referred by the breast clinic at Groote Schuur Hospital. The CDMAM phantom results showed the FFDM results were better than EUREF’s standard of “acceptable” and were approaching “achievable”. The ABUS results showed lateral and axial spatial resolution of 0.5 mm and adequate depth penetration of 80 mm. Our second-generation Aceso system, with its improved quality of clinical FFDM and ABUS images, has demonstrated its potential for early detection of breast cancer in a busy clinic.

The environmental Kuznets curve (EKC) hypothesis posits an inverted U-shaped relationship between economic growth and environmental degradation. However, there is no consensus regarding the EKC hypothesis among countries and regions of different income groups. In this study, we analyze the EKC hypothesis for 158 countries and 44 regions from 1990 to 2020, categorizing them into different income groups based on the World Bank's income classification (low, lower-middle, upper-middle, and high-income countries). Our findings reveal mixed patterns in the EKC across different income levels, highlighting the heterogeneous relationship between economic growth and carbon emissions and showing differentiated patterns among different income levels. While a rise in income for high-income countries should be reflected in a shift toward fewer carbon emissions, for lower-income countries, growth is still associated with rising emissions. This underscores the urgent need for policy interventions that decouple economic development from environmental degradation. A balanced approach to economic growth, which prioritizes carbon neutrality across all stages of development, by tailoring environmental and economic strategies to address CO2 emissions effectively, should be adopted, recognizing the different developmental stages and income levels of countries and regions.

While many studies have described the association between cognitive decline and eating habits, little attention has been paid to its association with cheese intake. In this cross-sectional study of 1,035 community-dwelling women aged ≥ 65, we investigated the association between intake/type of cheese and cognitive function. The anthropometry, functional ability, and the frequency of food intake, including cheese, were assessed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a score of 20–26 was defined as mild cognitive decline (MCD). We found that MMSE score was significantly different between the presence of cheese intake (cheese intake: 28.3±1.9; non-cheese intake: 27.8±2.2) and between the type of cheese consumed (Camembert cheese: 28.7±1.3; others: 28.3±1.9). After adjusting for confounders, multiple logistic regression revealed four significant independent variables for MCD: Camembert cheese intake (odds ratio [OR] = 0.448, 95% confidence interval [CI] = 0.214–0.936), age (OR = 1.114, 95% CI = 1.059–1.171), usual walking speed (OR = 0.2620, 95% CI = 0.109–0.621), and repetitive saliva swallowing test scores (OR = 0.865, 95% CI = 0.750–0.995). Our results, while based on cross-sectional data from Japanese community-dwelling older women, demonstrated that Camembert cheese intake is significantly associated with MCD.

Protein dynamics play a crucial role in biological function, encompassing motions ranging from atomic vibrations to large-scale conformational changes. Recent advancements in experimental techniques, computational methods, and artificial intelligence have revolutionized our understanding of protein dynamics. Nuclear magnetic resonance spectroscopy provides atomic-resolution insights, while molecular dynamics simulations offer detailed trajectories of protein motions. The integration of machine learning, exemplified by AlphaFold2, has accelerated structure prediction and dynamics analysis. These approaches have revealed the importance of protein dynamics in allosteric regulation, enzyme catalysis, and intrinsically disordered proteins. The shift towards ensemble representations of protein structures and the application of single-molecule techniques have further enhanced our ability to capture the dynamic nature of proteins. Understanding protein dynamics is essential for elucidating biological mechanisms, designing drugs, and developing novel biocatalysts, marking a significant paradigm shift in structural biology and drug discovery.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of DNA-aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with AGE-Apt or control aptamer for 6 weeks and then sacrificed. Plasma glucose, testicular AGEs, and RAGE gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice; the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited the seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing the AGE–RAGE-induced oxidative stress and inflammation in the testes of DM mice.

An increasing need for better agricultural practices that are sustainable to provide increased yields of crops for the ever increasing food demand to be met for the growing world population is a current necessity. It is estimated by the UN that in 2050 the world’s populace may be as much as 9.8 billion global, yet, farmers still face several obstacles, which includes soil degradation, extreme temperatures, and drought which as increasingly becoming more severe with climate changes. Plant health monitoring is a method that will help to increase awareness about plant enhancing by studying how to increase crop yields while decreasing the environmental impacts. The use of low-cost, controlled environments, soil quality, water levels, and pathogenic and pests attacks can be regularly monitored. Currently, several diagnostic technologies and portable point-of-use methods and technologies are employed for detection of diseases, although, the current available lab-based methods used for plant’s diagnostics test are inadequate for plant point-of-use monitoring. The promotion of use of these point of use methods will enable pathogen detection, poor plant growth, unsuitable environmental conditions and nutrient use efficiency allowing for immediate and timely corrective actions to ensure minimal damage to the plants with maximal yield. Increase in the use of sustainable agri practices are required for ensuring higher yields with minimal inputs and that are non-destructive to the land and the use of improved methodologies and technologies will be useful tools for achieving sustainable agriculture.

Traditional path planning algorithms have drawbacks in unmanned vehicle path planning, such as low efficiency, unsuitability for dynamic environments, and high computational complexity. To address these issues, this paper proposes a dynamic path planning method for unmanned vehicles that combines the A* algorithm with an improved Dynamic Window Approach (DWA). Firstly, a collision risk function is incorporated into the DWA algorithm to evaluate scores based on the braking distance corresponding to the current vehicle speed and the distance to obstacles, determining whether timely braking or obstacle avoidance is feasible. The earlier the braking or obstacle avoidance, the higher the score, thereby enhancing the evaluation algorithm of the DWA. Secondly, the key points extracted by the A* algorithm are used as temporary target points for the DWA algorithm, reducing the eight search directions to five. Finally, the key points of the A* algorithm’s path are set as the temporary end points for the DWA algorithm, integrating the two algorithms to plan a smoother curved path that can avoid unknown and dynamic obstacles. Simulation data demonstrates that compared to traditional artificial potential field methods, RRT, and Dijkstra’s algorithm, the new fusion algorithm reduces time by 11.71 seconds, a decrease of 6.9%, and shortens path length by 3.093 meters, a reduction of 4.16%, while increasing average linear velocity by 2.9%. The proposed algorithm ensures smoother paths while also making paths more rational and efficient

Leishmaniasis, comprising cutaneous and mucocutaneous forms, is a parasitic disease caused by Leishmania species via sandfly bites, leading to skin ulcers and mucosal damage. Traditional treatments include antiparasitic drugs such as pentavalent antimonials, amphotericin B, and miltefosine, with immunotherapy and chemotherapy being explored for enhanced efficacy and reduced relapse. Mucocutaneous leishmaniasis (ML) balances IFN-γ and IL-10, affecting severity, while cutaneous leishmaniasis (CL) shows varied IFN-γ/IL-10 ratios influencing prognosis. Cytokines and chemokines are diagnostic and prognostic markers in CL. Research into neutrophils and the NLRP3 inflammasome informs Th1/Th2 response regulation. Live attenuated LdCen-/- parasites and genetically modified vaccines show promise, with miR-21 as a potential efficacy biomarker. Understanding cytokine networks is crucial for new treatment strategies.

The COVID-19 pandemic remains a serious public health problem globally. During winter flu seasons, more aggressive SARS-CoV-2 infections with fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and cellular tropism for their replication in the human respiratory tract. However, it is still unclear how the two pathogens interplay to ensure their survival in the same lung microenvironment. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence on how influenza co-infection mechanistically modifies the disease outcome in COVID-19. This mini-review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

Studies were initiated to find new effective fungicides to use under field conditions to identify novel options for improved disease management in sugar beet. Cercospora-leaf spot (CLS) of sugar beet, caused by Cercospora beticola Sacc., is a major foliar disease of sugar beet in all sugar beet growing areas, worldwide. The disease is now dominant in almost all sugar beet growing areas of Europe, including Hungary. The epidemic spread of this disease can cause up to 50% yield loss. The use of fungicides has been being an integral part of the control of CLS of sugar beet, due to lack of efficacy from non-chemical alternatives. In recent decades, the emergence of resistant strains in C. beticola Sacc. populations have reduced the efficacy of some fungicides (Quinoine inside Inhibitors (QoI) – FRAC Group 11; and DeMethylation-Inhibitors (DMI) – FRAC Group 3) because of repeated use over many uears. Resistance of CLS to fungicides belonging to different groups of active substances has been described in many countries of the world, including Hungary. The picolinamides are a new distinct group of fungal respiration inhibitors (Inhibition of Complex III) belonging to Quinoine inside Inhibitors (QiI). Two novel fungicides from the group of picolinamides (Qil – FRAC Group 21) – fenpicoxamid and florylpicoxamid– were tested and evaluated over two seasons, in vegetation period of 2020 and 2021 for controlling CLS of sugar beet in Hungary. Both fungicides were applied as straight formulated products at a range of dose rates, and they showed very effective control of CLS compared to the untreated control check plots and the reference fungicide product difenoconazole. The results consistently showed all tested dose rates of fenpicoxamid and florylpicoxamid provided effective control against CLS of sugar beet in addition to a clear dose response curve. Disease severity, in terms of area under the disease progress curve values (AUDPC), was significantly correlated with yield decrease, while no significant context existed between disease severity and sugar content of the roots. Additionally, the results showed in two investigated years, the efficacy of both picolinamide fungicides applied at 75 g ai/ha provided significantly better % control on CLS of sugar beet than the DMI fungicide difenoconazole applied at 100 g ai/ha dose rate. Fenpicoxamid is already registered in Europe in cereals and label extension is planned in sugar beet and other crops. Florylpicoxamid is not yet registered in Europe but is beginning to be approved in countries across the globe in a range of crops and is continuously under evaluation for potential markets.

In recent years the field of computer science has experienced great changes, due to the incredible advances in the field of artificial intelligence. Deep Learning models are responsible for most of them since the biggest milestones occurred in 2012 when AlexNet won the image classification challenge called ImageNet. These models have demonstrated great performances in different types of complex tasks like image restoration, medical diagnosis or object recognition. Their disadvantages are related to their high data dependency, which forces experts in the field to follow a precise methodology to obtain accurate models. In this paper, we describe a complete workflow that begins with the management of the raw data until the in-depth interpretation of the performance of the models. This should be taken as a high-level consultation document describing good practices that should be applied. Apart from the step-by-step methodology, we present different use cases that correspond to the two main problems of the field: classification and regression.

The crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete Aphanomyces astaci (Ap. astaci), which was introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish Austropotamobius pallipes. The aquatic mould is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for A. pallipes. However, this changed in 1987 when a mass mortality event was linked to the pathogen marking the pathogen's introduction to the region. Fortunately, the plague did not establish and was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Ap. astaci. Since then, the pathogen has appeared across the island. Between 2015 and 2023, Ap. astaci was detected in 18 Irish water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland exists without its natural host species. The uneven distribution of various genetic lineages strongly suggests human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, Ap. astaci’s introductions into Ireland, its rapid spread, the genotypes documented, the issue of non-indigenous crayfish species in Ireland and management efforts.

The effect of high temperature (HT) stress on nicotine biosynthesis in Nicotiana attenuata was examined. Nicotine content was measured in mature leaves, young sink leaves and in roots from well-watered plants grown at 25 °C as controls and from plants exposed to 38 °C and 43 °C temperatures applied for 24, 48, 72 and 96-hr duration. At 38 °C, all leaf nicotine levels were significantly less than control plants for up to 72-hr exposure but rose sharply thereafter to levels significantly greater than controls with 96-hr exposure. In contrast, plants exposed to 43 °C never exhibited a reduction in leaf nicotine content and showed a significant increase in content with just 48-hr exposure. When radioactive 11CO2 was administered to plants, HT stress significantly reduced fixation. Furthermore, radiocarbon flux analysis revealed that ‘new’ C partitioning (as 11C) into the [11C]-amino acid pool was significantly reduced with HT stress as were yields of [11C]-aspartic acid, an important amino acid in nicotine biosynthesis, and its beta-amido counterpart [11C]-asparagine significantly reduced. In contrast, [12C]-aspartic acid levels appeared unaffected at 38 °C but were significantly elevated at 43 °C relative to controls. Additionally, [12C]-asparagine levels were significantly elevated at both stress temperatures. Finally, leaf total soluble protein (TSP) was reduced 39% with long exposures to both stress temperatures. However, Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which was 41% TSP appeared unaffected by HT stress. Altogether, these results support the theory that plant proteins other than Rubisco degrade at elevated temperatures freeing up essential amino acids supporting the nicotine biosynthetic machinery, and while feedback might downregulate de novo amino acid synthesis from ‘new’ C resources, more than likely plant C/N rebalancing caused by HT reductions in C input restricted N uptake, which in turn, limited this process.

The anterior cruciate ligament (ACL) injury is the most serious injury in judo. Therefore, its prevention is of great importance. The main mechanism of injury is the collapse of the knee in valgus, which usually occurs when there are deficits of strength and neuromuscular control of the core, external rotators and hip abductors, as well as limitations of ankle and hip mobility. In most sports there is a difference in the prevalence of this injury between both sexes, being more common in women. Therefore, in the present study we observed this possible intersexual disparity in the difference of movement patterns among elite judokas according to their sex, in order to identify those athletes with a higher risk of ACL injury. In addition, it was not observed differences between sexes in the performance of the Single Leg Squat test (SLS test); There was worse neuromuscular control of the non-dominant leg in men and women; No differences were observed in in the range of motion of ankle dorsiflexion and hip external rotation between men and women, but there were differences in internal rotation, a movement whose restriction may be related to an increased risk of ACL injury.

Background: Primary lymphedema is a chronic condition caused by a developmental abnormality of the lymphatic system and its malfunction. Different surgical options such as physiologic and excisional procedures have been proposed. The aim of this study was to present a complete algorithm for the treatment of primary lower extremity lymphedema: Primary LYmphedema Multidisciplinary Approach (P-LYMA). Methods: Nineteen patients were treated according to the P-LYMA. Patients underwent pre- and post-operative complex decongestive therapy (CDT). Different physiologic and excisional procedures were performed independently or in combination. The primary outcome was the circumferential reduction rate (CRR). The Lymphedema Quality of Life Score (LeQOLiS), reduction in the number of episodes of cellulitis, length of stay, and complications were recorded. Results: The mean CRR calculated was 72.8±19.6% after twelve months. The episodes of cellulitis per year decreased from a mean of 1.9±0.8 preoperative to 0.4± 0.6 throughtout follow-up. Two patients experienced minor complications. Mean hospitalization time was 5 days. Patients’ quality of life (LeQOLi score) drastically improved from 70.4±11.6 to 24.2 ±13.9 at twelve months post-op. Conclusion: The P-LYMA algorithm allows to maximize surgical results and improve the quality-of life in patients who suffer from primary lymphedema. CDT is mandatory to optimize results.

In this paper, an iterative procedure to find the solution of a nonlinear structural model is introduced. The model presents different multiplicities where parameters are randomly selected within a solvability region. To achieve this aim, a class of multipoint fixed-point iterative schemes for single roots is modified to find multiple roots, reaching the fourth order of convergence. Complex discrete dynamics techniques are employed to select the members with the most stable performance. The structural problem, as well as some academic problems involving multiple roots, are solved numerically to verify the theoretical analysis, robustness and applicability of the proposed scheme.