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

This study examines the impact of executives implicated in fraud on firms' investment decisions using AAERs in the US, aiming to address the underexplored aspect of rationalization within the fraud triangle. Executives implicated in fraud often display abnormal attitudes to justify accounting irregularities, prompting an investigation into how abnormal investment decisions are used for rationalizing fraud, given their critical role in a firm's long-term sustainability. Analysis of AAERs spanning from 1981 to 2013 reveals that implicated executives, particularly CEOs and CFOs, tend to make abnormal investment decisions, and that collusive fraud exacerbates this behavior. Notably, such executives lean towards overinvestment, particularly in R&D expenditures, to hide or justify fraud; the duration of fraud amplifies its impact on investment decisions. By shedding light on the rationalization aspect of the fraud triangle, this research contributes valuable insights for investors, regulators, and academia emphasizing the significance of public disclosure of fraud to enhance transparency in capital markets and the importance of ethics-focused education in accounting to prevent corporate fraud.

Background: Obesity and Type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity plays a key role in these diseases through biological mechanisms. This study examined the effect of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. Methods: A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. Results: HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Conclusions: Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed HFS diet for 7 mo. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance of lipogenic and antioxidant enzymes, measurement of liver 2-OG, and mitochondrial function were assessed in rats and we studied the effect of HFS with functional foods. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of HFS diet in Wistar rats caused oxidative stress, hepatic steatosis and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. Addition of functional foods to the diet modified the gut microbiota, reducing B. producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. In order to use 2-OG as biomarker, this metabolite was measured in healthy subjects or with MASLD and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis.

In 2023, we proposed the modified Delay and Doppler Profiler (mDDP) as an inter-carrier interference (ICI) countermeasure for underwater acoustic OFDM mobile communications in a multipath environment. However, the performance improvement in computer simulation and pool experiments was not significant. In a subsequent study, the accuracy of the Channel Transfer Function (CTF), which is the input for the mDDP channel parameter estimation, was considered insufficient. Then a 2-step mDDP was devised. This paper presents simulations of underwater OFDM communications using 1- to 3-step mDDPs. The simulation conditions are a two-wave multipath environment where the receiving transducer moves at a speed of 0.3 m/sec and is subjected to a Doppler shift in the opposite direction. As NumCOL, the number of taps in the multi-tap equalizer which removes ICI, was increased, Bit Error Rate (BER) of 0.016 at NumCOL = 1 was significantly reduced by a factor of approximately 40 to BER of 0.00041 at NumCOL = 41 for the 2-step mDDP.

The cDNA sequences of the common gonadotrophic hormone α-subunit (ag-GTHα) and 13 of the specific follicle-stimulating hormone β-subunit (ag-FSHβ) of the giant Amazonian fish Ara-14 paima gigas, have been previously isolated by our research group. A synthesis of ag-FSH in HEK293 15 cells and its purification and preliminary characterization were also carried out. In the present work, 16 ag-FSH was obtained and purified from the same host cells and an extensive physical chemical 17 characterization was performed via RP-HPLC, HPSEC and MALDI-TOF-MS. Ag-FSH, when com-18 pared to human FSH (hFSH), showed a higher hydrophobicity by RP-HPLC and a higher molecular 19 mass (MM) via HPSEC. The same higher MM was also confirmed via MALDI-TOF-MS: 35,353 Da 20 for ag-FSH against 31,969 Da for hFSH. Its immunological activity was also confirmed via an hFSH 21 ELISA, in comparison with the highly purified pituitary preparation of hFSH-AFP7298A, from the 22 National Hormone and Pituitary Program (NHPP-USA). Finally, an in-vitro bioassay, based on the 23 stimulated release of 11-ketotestosterone (11-KT) from immature A. gigas testis, quantified its bio-24 logical activity in comparison with human chorionic gonadotropin (hCG) and with the WHO Inter-25 national Standard of recombinant hFSH (NIBSC-08/282) This suggests that injections of ag-FSH in 26 A. gigas and ag-FSH cDNA Gene Therapy applications should improve the reproductive functions 27 of this threatened species.

Turbidity is an important indicator of water quality in hydrology. More traditional ways to monitor turbidity can provide reliable results. However, they are prone to human error, have elevated costs, and lack real-time monitoring capacity. Addressing these hindrances, in this work we combine spectral bands and indices from Sentinel-2 with several machine learning paradigms, namely XGBoost, Random Forests, GMDH, Support Vector Regression, k-Nearest Neighbors and Least Absolute Shrinkage and Selection Operator to model turbidity, using data from twelve monitoring stations encompassing the Mississippi River, USA. Results show that considering the individual monitoring stations, the ML paradigms for turbidity modeling were satisfactory at locations with a larger range and standard deviation values, achieving a mean R2 value of 59.5%. Tree-based models were the best overall approach, often ranking as the best or second-best performing model. When all the samples from the monitoring stations were used, the XGBoost provided superior output for turbidity modeling, reaching an R2 equal to 75.7%. A comprehensive comparison with the literature found values showed that the models implemented using this study’s methodology could provide competitive results, deeming it as an alternative for turbidity modeling from remote sensing data.

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

The solvent extraction of gold(III) by undiluted 2-ethylhexanol or dissolved in toluene from HCl solution has been investigated. The numerical analysis of gold distribution data suggests the formation of HAuCl4·L and HAuCl4·2L (L= 2-ethylhexanol) species in the organic phase with formation constants K11= 38 and K12= 309, respectively. The results derived from gold(III) distribution have been implemented in a solid-supported liquid membrane system. The influence of several variables on gold transport was considered: feed and receiving phases stirring speeds, HCl and gold concentrations in the feed phase and carrier concentration in the membrane phase as well as the presence of base metals (Fe,Cu,Ni) and PGMs in the feed phase. Also, diffusional resistances to mass transfer are estimated. Gold is recovered as zero valent nanoparticles.

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P<0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

Our investigation focused on the degradation of perfluorooctanoic acid (PFOA) and 6:2 fluorotelomer sulfonamide alkyl betaine (6:2 FTAB, Capstone B), using UV photolysis under various pH conditions. Initially, we used PFOA as a reference, finding a 90% decomposition after 360 minutes at the original (unadjusted) pH 5.6, with a decomposition rate constant of (1.08 ± 0.30) × 10-4 sec-1 and a half-life of 107 ± 2 minutes. At pH 4 and 7, degradation averaged 85% and 80%, respectively, while at pH 10, it reduced to 57%. For 6:2 FTAB at its natural pH 6.5, almost complete decomposition occurred. The primary UV transformation product was identified as 6:2 fluorotelomer sulfonic acid (6:2 FTSA), occasionally accompanied by shorter-chain perfluoroalkyl acids (PFAA). Interestingly, the overall decomposition percentages were unaffected by pH for 6:2 FTAB, though pH influenced rate constants and half-lives. In PFOA degradation, direct photolysis and reaction with hydrated electrons were presumed mechanisms, excluding the involvement of hydroxyl radicals. The role of superoxide radicals remains uncertain. For 6:2 FTAB, both direct and indirect photolysis were observed, with potential involvement of hydroxyl, superoxide radicals, and/or other reactive oxygen species (ROS). Clarification is needed regarding the role of eaq- in the degradation of 6:2 FTAB.

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. Background: This study offers an approach on histopathological and immunohistochemical placental observations from SARS-CoV-2 positive mothers compared negative ones. Methods: Out of 44 examined placentas, 24 were collected from patients with SARS-CoV-2 infection during pregnancy and 20 without infection. Results: The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblast and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV), thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%) and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), chorioamnionitis (5%) and two cases of meconium (19%). Our results were consistent with literature. Conclusions: This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p=0.01) and fibrin deposition (p=0.01). Further research is necessary to establish whether SARS-CoV-2 is the cause of vascular pathologies during pregnancy.

The Dirac and Klein-Gordon equations have proven to be some of the most accurate theories for describing particle behaviour and have laid the foundations of Relatavistic Quantum Mechanics. We extend the formulations to consider a 5 Dimensional spacetime with two time dimensions (as first conceptualised by Sajjad Zahir) and extend the notions to Quantum Field Theory to arrive at the behaviour of particles through the Dirac and Klein-Gordon counterparts of the 5 Dimensional spacetime. The implications of this to anti-matter are discussed.

Little is known about the long-term durability of the induced immune response in subjects af-fected by obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody response after BNT162b2 vaccine booster dose, com-paring individuals with abdominal obesity (AO) with those without, discerning between indi-viduals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, 21 days after vaccine dose-1 and at one, three, six and nine months after dose-2 and at one and three months after booster dose. Nucleocapsid antibodies were assessed at baseline and at the end of the study to detect SARS-CoV-2 infection. To evaluate the three-months difference in absolute variation of IgG-TrmicericS levels from booster dose we used multivariable linear regression that showed interaction between AO and SARS-CoV-2 infection status (p=0.016). AO is associated with higher absolute IgG-TrimericS variation in prior infected individuals, regardless of possi-ble confounders and IgG-TrimericS levels at booster dose (p=0.0125). No interaction was evinced using BMI in the same regression model (p=0.418). The robust response in the development of antibodies after booster dose, observed in people with OA and previous infection, may support the recommendations to undergo the booster dose also in this population group.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

The drug delivery systems receive more and more attention for the control and treatment of many diseases due to their increased number in recent years. The main aims of this study were to develop and to characterize a polyurethane drug delivery system that it is intended to be used for the transmembrane transport of nucleosides. Three different samples have been synthesized based on aliphatic diisocyanates (hexamethylene diisocyanate, isophorone diisocyanate and lysine diisocyanate) as organic phase, respectively a mixture of polyethylene glycol, polycaprolactone diol and low molecular weight diols as aqueous phase. The samples were characterized by pH, refractivity index and solubility measurements, drug loading efficacy and release investigations, thermal behavior, Zetasizer, cells viability and irritation tests on mice skin. The results indicate the obtaining of different populations of neutral acido-basic particles with size between 132 and 190 nm; the Zeta potential values and SEM images show a medium tendency to form clusters, while UV-Vis evaluations indicate an almost 70% encapsulation efficacy, a prolonged release (45% of encapsulated substance is released in the first 5 days) and around 70% of particles have penetrated an artificial membrane in the first 24h. The synthesized products can be tested in further clinical trials, the currently tests on cells culture and mice skin revealing no side effects.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

The SARS-CoV-2 Hydra with many heads (variants) has been causing the COVID-19 pandemic for 3 years. The appearance of every new head (SARS-CoV-2 variant) causes a new pandemic wave. The last in the series is the XBB.1.5 “Kraken” variant. In the general public (social media) and in the scientific community (scientific journals), during the last several weeks since the variant has appeared, the question was raised of whether the infectivity of the new variant will be greater. This article attempts to provide the answer. Analysis of thermodynamic driving forces of binding and biosynthesis leads to the conclusion that infectivity of the XBB.1.5 variant could be increased to a certain extent. The pathogenicity of the XBB.1.5 variant seems to be unchanged compared to the other Omicron variants.

The Hunga Tonga-Hunga Ha’apai underwater volcano (20.57°S, 175.38°W) violently erupted on 15 January 2022. The volcanic plume evolution during its initial stages is delineated by using Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)-2 radio occultation (RO) measurements. The bending angle (BA) anomaly over the Tonga volcanic plume (within 200 km from the eruption center) at 5:17 UTC on 15 January shows a prominent peak at higher stratospheric heights. The top of the BA anomaly revealed that negative to positive change occurred at ~38 km indicating the first height where the RO line-of-sight encounters the volcanic plume. The BA anomaly further revealed an increase of ~50% at ~36 km and confirms the volcanic plume reached above ~36 km. Further, the evolution of BA perturbations within 24 hours after the initial explosion is also discussed. From collocated RO profiles with the volcanic plume, we find a clear descending of the peak altitude of the BA perturbation from ~36 km to ~30 km within 24 hours after the initial eruption. The results from the study will provide some insights into advancing our understanding of volcanic cloud dynamics and their implementation in volcanic plume modeling.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

We have proposed a simple algorithm to retrieve the total ozone column and snow properties (spectral albedo and effective light absorption path) using the high spatial resolution single – view MSI/S-2 measurements over Antarctica.

A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented..

We report diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a rare, hereditary neurodegenerative disease of childhood, in a four and a half year old girl, the first child of non-consanguineous parents with no family history. Despite extensive efforts by the parents, her clinical condition remained undiagnosed and without management, until recently. Our published “Bottom-up Approach”, based on comprehensive and multidisciplinary clinical, pathological, radiographical and genetic evaluations, played key role in diagnosis of the disease. Detailed analyses involving Next Generation Sequencing confirmed a missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene. In silico analyses predicted it to be highly pathogenic. Further family screening (including her both unaffected parents and asymptomatic, one year old younger sister) of the identified variation through Sanger Sequencing, revealed a perfect autosomal recessive segregation in the family. This study is the first case report on classic CLN2 from Jammu and Kashmir-India. This study is also indicating the effectiveness of our “Bottom-up Approach” in understanding rare disorders in low resource regions and the importance of timely diagnosis. Like in the proband, had diagnosis been established a bit early, the family might have benefitted at least with reference to their second child through counselling programmes.

The aim of this study was the reconstruction of SARS-CoV-2 evolutionary dynamics in time and space in Italy and Europe between February and June 2020. The cluster analysis showed that pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 entered Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, the reconstructed ancestral scenario suggests a central role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.

The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

Pratylenchus loosi is an important root-lesion nematode that cause damage to tea plantations in Iran and all over the world. The present study reports on the characterization and evolution of three ß-1,4-engoglucanase genes Pl-eng-2, Pl-eng-3 and Pl-eng-4. The gene structure of Pl-eng-2 was fully determined with the predicted signal peptide and devoid of the linker domain and carbohydrate-binding domain, while Pl-eng-3 and Pl-eng-4 were only partially sequenced. The transcription of Pl-eng-2 was localized in the secretory esophageal glands of all life stages, but it was upregulated in male and females stages. Exon/intron structures of Pl-eng-2, Pl-eng-3 and Pl-eng-4 confirmed that they resulted from gene duplication followed by sequence and gene structure diversification with loss of linker domain and carbohydrate-binding domain during evolution. Phylogenetic analysis further confirmed that nematode endoglucanases resulted from horizontal gene transfer of a bacterial gene as Pl-eng-3 showed sister relationships with CelB cellulase of Bacillus subtilis. Silencing Pl-eng-2 by in vitro RNA interference, produced a 60% decrease of the transcript level. The reproductive ability of silenced P. loosi showed a 35% reduction of eggs and larval stages compared to untreated nematodes suggesting that this gene is involved in the early steps of invasion.

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS-CoV, SARS-CoV-2 does not bind human DPP4.

In this work, pure TiO₂ and binary nanocomposites of Fe₃O₄/TiO₂ and Ag/TiO₂ were synthesized in order to improve photocatalytic performance of these samples for degradation of 2, 4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, SEM/EDX, and elemental mapping were employed to reveal the crystal structure, morphology and property of the nanocomposites. XRD data demonstrated that the prepared samples are purely in TiO₂ anatase phase and cubic spinel Fe₃O₄ exist in the synthesized nanocomposite. We calculated the TiO₂ crystal size from XRD patterns, in the range of 8.35-11.09 nm. The presence of Ag, Fe, O, and Ti atoms in the synthesized nanocomposites was confirmed by SEM/EDX. We obtained 30.43, 32.02 and 42.40 % degradation of 2, 4-DCP (100 ml 2, 4-DCP 40 ppm and 0.01 g catalyst) for pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively, after 180 min of irradiation under visible light. Similar conditions were employed for 2, 4-DCP degradation under UV irradiation, we obtained 53.05, 51.00 and 71.50 % degradation of 2, 4-DCP pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively. Thus, the synthesized binary nanocomposites exhibited higher photocatalytic activity compared to pure TiO₂ under visible light.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).

The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection in host cells induces mitochondrial dysfunction, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.

Since the COVID-19 caused by SARS-CoV-2 break out in Wuhan China from Dec. 2019, it has spread to hundreds of countries up to now. Scientists from all over the world have paid tremendous efforts to research and try to control the disease. Previous studies suggested that some of the wild animals could be intermediate hosts between humans and origination of SARS-CoV-2, and some companion animals of humans can be infected by SARS-CoV-2, which raised our curiosity about cross-infection of SARS-CoV-2 between animals and humans. Thus, we select some kinds of animals that might have contact with humans to estimate the susceptibility to SARS-CoV-2 in different animals by evolutionary analysis of their receptors for SARS-CoV-2. The results show that some companion animals of the Felidae family like the cat has a higher infection possibility while the species of the Rodent family like the rat and mouse having close contact with humans show an opposite result, which consist with recent animal experiments and researches. These should raise concerns about cross-infection between human and companion animals or animals having close contact with humans which might turn animals into depositaries of the coronavirus even after control of SARS-CoV-2 spreading and cause second or more waves of infections after social reopening. Another side of our results stands by the opinion that bioinformatic analysis can be consistent with experiments in some respects so that we can prevent unnecessary sacrifice of laboratory animals in future experiments.

The severity of the global COVID-19 pandemic, with a high transmission rate, 2.6-4.7% lethality and a huge economic impact, poses an urgent need for efficient medical treatments and vaccines. Currently, there are only non-specific treatments to assist the patients in acute respiratory distress during the inflammatory step following the preliminary infection by SARS-CoV-2. Clinical trials of drug repurposing were quickly launched at the international level. Specific treatments such as the transfusion of plasma from patients who have recovered into infected patients or the use of specific inhibitors of the viral RNA-polymerase complex are promising strategies to block infection. To complete the therapeutic arsenal, we believe that the opportunity of targeting the SARS-CoV-2 genome by RNA therapy should be deeply investigated. In the present paper, we propose to design specific antisense oligonucleotides targeting transcripts encoding viral proteins associated to replication and transcription of SARS-CoV-2, aiming to block infection. We designed antisense oligonucleotides targeting the genomic 5’ untranslated region (5’-UTR), open reading frames 1a and 1b (ORF1a and ORF1b) governing expression of the replicase/transcriptase complex, and the gene N encoding the nucleoprotein that is genome-associated. To maximize the probability of efficiency, we predicted the antisense oligonucleotides by using two design methods: i) conventional antisense oligonucleotides with 100% phosphorothioate modifications (ASO); ii) antisense locked nucleic acids GapmeR. After binding the viral RNA target, the hetero-duplexes antisense oligonucleotide-RNA are cleaved by RNAse H1. Nine potent ASO candidates were found and we selected five of them targeting ORF1a (3), ORF1b (1) and N (1). Nine GapmeR candidates were predicted with excellent properties and we retained four of them targeting 5’-UTR (1), ORF1a (3), ORF1b (1) and N (1). The most potent GapmeR candidate targets the 5’-UTR, a key genomic domain with multiple functions in the viral cycle. By this open publication, we are pleased to share these in silico results with the scientific community in hopes of stimulating innovation in translational research in order to fight the unprecedented COVID-19 pandemic. These antisense oligonucleotide candidates should be now experimentally evaluated.

SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.

Injuries to the ligaments of the knee are extremely common among athletes who participate in high-risk sports, or any sport that requires frequent cutting motions, jumping, or contact. In order to determine the best way to heal these injuries, it is important to understand not just the pathology of the injury, but also the biomechanical factors that are affected, including stability and steadiness. While many studies have been done to examine the stability of healthy knees, there is little to no existing literature on stability of knees afflicted by injury. In order to surpass this obstacle, static steadiness and dynamic stability data was collected using the Lockhart Monitor phone application and Xsens accelerometers, respectively, both before and after completion of a course of physical therapy in a patient with a grade 2 medial collateral ligament (MCL) tear. These results were then used to determine the degree to which the prescribed physical therapy protocol was effective in healing the MCL, which can be useful for tweaking the individual protocol for future conservative treatment and management of the injury.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and three group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analysed using thematic analysis. Two overarching themes were identified. These were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice respectively: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients); and balancing expectations and pre-conceptions of self-management (providers). Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients were in need of support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers with respect to communication and uptake of self-management advice.

In the recent past about 40 botulinum neurotoxin (BoNT) subtypes belonging to serotypes A, B, E, and F pathogenic to humans were identified among hundreds of independent isolates. BoNTs are the etiological factors of botulism and represent potential bioweapons, but are also recognized pharmaceuticals for efficient counteraction of hyperactive nerve terminals in a variety of human diseases. The detailed biochemical characterization of subtypes as the basis for development of suitable countermeasures and possible novel therapeutic applications is lagging behind the increase in new subtypes. Here we report the primary structure of a ninth subtype of BoNT/F. Its amino acid sequence diverges by at least 8.4% at the holotoxin and 13.4% on the enzymatic domain level from all other known BoNT/F subtypes. We found that BoNT/F9 shares the scissile Q⁵⁸/K⁵⁹ bond in its substrate vesicle associated membrane protein 2 with the prototype BoNT/F1. Comparative biochemical analyses of four BoNT/F enzymatic domains showed that the catalytic efficiencies decrease in the order F1 > F7 > F9 > F6 and vary by up to factor eight. K_M values increase in the order F1 > F9 > F6 ≈ F7, whereas k_cat decreases in the order F7 > F1 > F9 > F6. Comparative substrate scanning mutagenesis studies revealed a unique pattern of crucial substrate residues for each subtype. Based upon structural coordinates of F1 bound to an inhibitor polypeptide the mutational analyses suggest different substrate interactions in the substrate binding channel of each subtype.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Abstract: Background: Surgery on varicose veins (crossectomy and stripping) leads to recurrence and has clinical and socio-economic repercussions. Their etiopathogenesis has yet to fully under-stood. Objective: Study the expression of endoglin and other molecules involved in the neovascu-larisation process in patients suffering from this disease. Methods: 43 patients that have undergone surgery for varicose veins (24 primary and 19 recurrent). They were identified on the venous wall (proximal -saphenofemoral junction- and distal), via real-time RT-PCR, and in serum, via ELISA: Endoglin (Eng), Vascular Endothelial Growth Factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLT1), (VEGFR2 or FLK), and the Hypoxia-Inducible Factor (HIF-1A). All the patients signed a con-sent form. Results: The recurrent group recorded a higher expression of Eng, VEGF-A, VEGFR1 and VEGFR2 at the level of proximal venous wall compared to the primary group. HIF-1A did not record any differences. As regards the determination of the distal venous wall, no markers recorded differ-ences between the groups. Among the serum determinations, only sFLT1 recorded a significant drop among the patients with recurrent varicose veins. Conclusions: Patients with recurrent vari-cose veins record a higher expression of endoglin and other markers of angiogenesis in proximal veins. Endoglin in the blood (sEng) has not proven to be of any use in recurrent varicose veins.

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker to assess safety during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). Results: We retrieved 94 QTc intervals [during TH (n=50, until day 3) or subsequent normothermia (n=44, day 4-7)] in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We added a relevant non-maturational covariate (TH, °C dependent) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Soil sodicity is a major constraint to seedling emergence and crop production, potentially reducing plant growth due to physical and chemical constraints. Examining responses to ion imbalances may assist in the identification of genotypes tolerant to chemical constraints in sodic soils and improve productivity. We evaluated the performance of four wheat (Triticum aestivum. L) genotypes in solutions with five sodium adsorption ratios (SARs) ranging from 0 to 60. For all four genotypes, seedling emergence and shoot dry matter (DM) decreased significantly with increasing SAR. A significant positive correlation was observed between Ca concentration in roots, as well as both root and shoot DM for all genotypes. At SAR values &gt;20, a more tolerant genotype (EGA Gregory), had higher Ca concentrations in root tissues, while a more sensitive genotype (Baxter) exhibited Na-induced Ca deficiency. Thus, selection for genotypes that are able to accumulate Ca in roots in sodic conditions may be a useful trait for selecting genotypes tolerant of soils with high ESP values. However, for soils that restrict plant growth at ESP (SAR) values of 6-10%, it is likely that growth is restricted by physical constraints rather than by a Na-induced Ca deficiency.

Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency. In this study we assess the prevalence of restless sleep disorder, as well as that of periodic leg movements during sleep (PLMS) in these children. Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery or tracheostomy were included. Three groups were compared, children with PLMS index&gt;5, children with restless sleep disorder (RSD), and children with neither elevated PLMS index nor RSD. During the study, 2,577 sleep studies were conducted. Ninety-two studies fit our criteria and were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; after polysomnography 18% were found to have PLMS index &gt;5/hour, 14% fit the criteria for RSD. There were no statistically significant differences in polysomnographic parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). There was elevated frequency of RSD and elevated PLMS in children with history of prematurity that might be linked to the increased risk of iron deficiency in premature infants. These new results add new knowledge on the prevalence of RSD in these children.

This paper investigates the photocatalytic characteristics of Ag Nanowire (AgNW)/TiO2 and AgNW/TiO2/Graphene oxide (GO) nanocomposites. Samples were synthesized by the direct coating of TiO2 particles on the surface of silver nanowires. As-prepared AgNW/TiO2 and AgNW/TiO2/GO nanocomposites were characterized by electron microscopy, X-ray diffraction, UV/visible absorption spectroscopy, and infrared spectroscopy. Transmission electron microscope (TEM) images confirmed the successful deposition of TiO2 nanoparticles on the surface of AgNWs. The photocatalytic activity of synthesized nanocomposites was evaluated using Rhodamine B (RhB) in an aqueous solution as the model organic dye. Results showed that synthesized AgNW/TiO2/GO nanocomposite has superior photocatalytic activities when it comes to the decomposition of RhB.

The current study sets out to develop an empirical line method (ELM) radiometric calibration framework for reducing atmospheric contributions in UAS imagery and for producing scaled remote sensing reflectance imagery. Using a MicaSense RedEdge camera flown on a custom-built octocopter, the research reported herein finds that atmospheric contributions have an important impact on UAS imagery. Data collected over the Lower Pearl River Estuary in Mississippi during five week-long missions covering a wide range of environmental conditions was used to develop and test a simplified ELM radiometric calibration framework designed specifically for the reduction of atmospheric contributions to UAS imagery in studies with limited site accessibility or data acquisition time constraints. The framework was effective in reducing atmospheric and other external contributions to UAS imagery. Unique to the proposed radiometric calibration framework is the radiance to reflectance conversion conducted externally from the calibration equations which allows for the normalization of illumination independent from the time of UAS image acquisition and from the time of calibration equations development. This paper presents the simplified ELM radiometric calibration framework that can be used as a time-effective calibration technique to reduce errors in the UAS imagery.

Multispectral and 3D LiDAR remote sensing data sources are valuable tools for characterizing the 3D vegetation structure and thus understanding the relationship between forest structure, biodiversity and microclimate. This study focuses on mapping riparian forest species in the canopy strata using a fusion of Airborne LiDAR data and multispectral multi-sources and multi-resolution satellite imagery; Sentinel-2 and Pleiades at tree level. The idea is to assess the contribution of each data source in the tree species classification at the considered level. The data fusion was processed at feature-level and decision level. At feature level, LiDAR 2D attributes were derived and combined with vegetation indices. At decision level, LiDAR data was used for 3D tree crown delimitation providing unique trees or groups of trees that are used as a support for the species classification. Data augmentation techniques were used to improve the training process. Best results were obtained by the fusion of Sentinel-2 time series and LiDAR data with a Kappa of 0.66 thanks to red-edge based indices that better discriminate vegetation species and the temporal resolution of Sentinel-2 images that allows monitoring the phenological stages helping to discriminate the species.

Three new compounds (1, 11 and 12), together with 32 known ones, were isolated from the root bark of Morus alba L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR and HRESIMS data analysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature. All the isolates were evaluated for their cytotoxic activities against human gastric cancer HGC27 cells by CCK-8 assay. Among them, compounds 5, 8, 10 and 30 exhibited cytotoxic activities on HGC27 cells with IC50 values of 10.24 ± 0.89 μM, 28.94 ± 0.72 μM, 6.08 ± 0.34 μM and 33.76 ± 2.64 μM, respectively. Furthermore, compound 10 was confirmed to reduce proliferation ability, increase apoptosis rate and inhibit cell migration pathway by annexin V/PI double staining experiment, transwell experiment and western blot analysis.

Based upon a radically new approach, this paper describes a 2-box absolute flow model that calculates the CO₂ transfer between the atmosphere and a terrestrial / ocean mixing reservoir. Given the inputs of anthropogenic fossil fuel emissions (CO2ff), atmospheric CO₂ mixing-ratio and nuclear weapons bomb yields, the model calculates atmospheric d¹³C and Δ¹⁴C time-series, with the level of agreement for d¹³C being to within ± 0.05 ‰, for Δ¹⁴C to within ± 3‰, spanning 200 years. The model contains only seven internal parameters which are varied to optimize the fit. Yet according to conventional wisdom, this model should not work. It is commonly held that the ¹³C and ¹⁴C isotopic forms of carbon bypass seawater carbonate chemistry, resulting in very different absorption properties (Revelle factor) as compared to ¹²C. This study rejects this assumption, and uses the same residence time and reservoir mixing properties for all isotopes. The paper includes an analysis justifying why the isotopic bypass of the Revelle factor is not significant. The study describes the use of the model to track CO2ff takeup using two separate measures, a) the amount of molecular CO2ff remaining in the atmosphere and b) the amount of atmospheric growth attributable to CO2ff, thereby resolving discrepancies in published values.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

The characteristics of the Sentinel-2 mission with a decametric resolution and frequent acquisitions allow to improve the identification of crops. The majority of the studies on crop classification using RS were targeted at herbaceous and gramineous crop classes while fewer results were obtained on woody crops which present a strong variability in management practices that make their identification difficult. Thus, this study aimed to propose a rapid, accurate, and cost-effective analytical approach for the delineation of fruit orchards (OC), vineyards (VY), and olive groves (OL) in the Mediterranean (Southern France) considering two locations. A classification based on phenology metrics (PM) de-rived from temporal Sentinel-2 time series was developed to perform the classification. The PM were computed by fitting a double logistic model on temporal profiles of vegeta-tion indices to delineate OC, VY, and a DC class gathering all remaining surfaces. The generated PM were introduced in a random forest (RF) algorithm to identify woody crops across the two sites. The method was tested on different vegetation indices, the best results being obtained with the leaf area index (LAI). To delineate OL in the DC class, the tem-poral features of the green chlorophyll vegetation index (GCVI) were found to be the most appropriated with a typical drop of the signal during the mid-season (DOY 150-250). As a final result, we obtained an overall accuracy ranging from 89-96% and Kappa of 0.86-0.95 by considering each study site and year (2016-2021), separately. This accuracy is much better than applying the RF algorithm on the LAI times series, which led to a Kappa rang-ing between 0.3 and 0.52 and demonstrates the interest of using phenological traits rather than the raw time series of the RS data. The method can be well reproduced from one year to another. Moreover, it is possible to apply the classification model of a given year to an-other, keeping good accuracy. This is an interesting feature to reduce the burden of col-lecting ground truth information. On the contrary, the use of a classification model cali-brated in one site and applied to another led to a strong degradation of the classification accuracy. Woody crop phenology is dependent on site climatic conditions as well as the cultivar and management practices that can differ from one site to another.

Phylogenetic trees of coronaviruses are difficult to interpret because they undergo frequent ge-nomic recombination. Here, we propose a new method, named coloured genomic bootstrap (CGB) barcodes, to highlight the polyphyletic origins of human sarbecoviruses and understand their host and geographic ori-gins. The results indicate that SARS-CoV and SARS-CoV-2 contain genomic regions of mixed an-cestry originating from horseshoe bat (Rhinolophus) viruses. First, different regions of SARS-CoV share exclusive ancestry with five Rhinolophus viruses from Southwest China (RfYNLF/31C: 17.9%; RpF46: 3.3%; RspSC2018: 2.0%; Rpe3: 1.3%; RaLYRa11: 1.0%) and 97% of its genome can be related to bat viruses from Yunnan (China), supporting its emergence in Rhinolophus species of this province. Second, different regions of SARS-Cov-2 share exclusive ancestry with eight Rhi-nolophus viruses from Yunnan (RpYN06: 5.8%; RaTG13: 4.8%; RmYN02: 3.8%), Laos (RpBA-NAL103: 3.3%; RmarBANAL236: 1.7%; RmBANAL52: 1.0%; RmBANAL247: 0.7%), and Cam-bodia (RshSTT200: 2.3%), and 98% of its genome can be related to bat viruses from northern Laos and Yunnan, supporting its emergence in Rhinolophus species of this region. Although CGB barcodes are very useful to retrace the origins of human sarbecoviruses, further investigations are needed to better apprehend the diversity of coronaviruses in bats from Cambo-dia, Laos, Myanmar, Thailand and Vietnam.

Complex modeling has received significant attention in recent years and is increasingly used to explain the statistical phenomenon with increasing and decreasing fluctuations such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which ends up a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID database, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains of Wuhan, Beijing, New York, German, and UK variant B.1.1.7) were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2 for which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolvement of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS>SARS-CoV-1>SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

We are witnessing the severe third outbreak mediated by coronaviruses affecting global public health with unprecedented economic consequences. A better understanding of its phylogenetics, exploration of sequence features and mutational changes could unveil its genealogy to gain insights into the mechanism of transmission and development of possible interventions. Our comparative genomic analyses of >160 isolates of SARS-CoV-2 reveal phylogenetic kinship with other coronaviruses and emergence of evolutionary divergence in clinical isolates. t-SNE-based clustering revealed different clades but no continent specific clusters. Amino acid substitutions at RBD of spike protein provide possible reasons for rapid transmission. Few proteins specific to SARS-CoV-2 were identified which could have implications as therapeutic targets and diagnostic biomarkers. Virtual screening identified repurposed drugs, known nutraceuticals, for specific interventions. These phylogenetic observations reveal the ancestry and computational studies reveal the emergency measures to interject this emerging pathogen that pose threat to whole of mankind.

The recurrent coronavirus outbreaks in China (SARS-CoV and its relative, SARS-CoV-2) have raised speculations that perhaps Asians are somehow more susceptible to these coronaviruses. Here, we test this possibility based on an analysis of the lung-specific expression of ACE2, which encodes the known cell-entry receptor of both SARS-CoV and SARS-CoV-2. We show that ACE2 expression is not affected during tumorigenesis, supporting that the abundant transcriptomes in cancer genomic studies can be informatively used to study ACE2 expression among diverse individuals without cancer. We find that ACE2 expression in the lung increases with age, but is not associated with sex. Further, Asians do not differ from other populations for ACE2 expression and do not harbor unique genetic polymorphisms in the ACE2 locus. Thus, beyond illustrating an innovative method for assessing the potential impacts of demographic factors for non-cancer diseases from large-scale cancer sample datasets, our statistically robust findings emphasize that individuals of all races require the same level of personal protection against SARS-CoV-2.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors BAP1, NF2 and P16 may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess therapies using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.

In pig production, pigs often show more aggressive behavior after mixing, which adversely affects animal welfare and growth performance. The Jumonji and structural domain-rich AT interaction domain 2 (JARID2) gene plays an important role in neurodevelopment in mice and various psychiatric disorders in humans. The JARID2 gene may impact the aggressive behavior of pigs. By observing the behavior of 500 weaned pigs during the first 72 hours after mixing, the ear tissue samples of the 12 most aggressive and 12 least aggressive pigs were selected for DNA resequencing based on the intensity of their aggressive behavior. Large group correlation analysis indicated that the rs3262221458 site located in the 3'-UTR region of the porcine JARID2 gene has a strong relationship with aggressive behavior of weaned pigs. Pigs with the mutant TT genotype of rs3262221458 have more aggressive behavior than those pigs with the GG and GT genotypes. The dual luciferase assay indicated that the luciferase activity of the plasmids containing the G allele of rs326221458 was significantly less than plasmids conaining the T allele of rs326221458 and control groups. The binding abiltiy of miR-9828-3p to sequences containing the T allele was less than sequences containing the G allele. The overexpression of miR-9828-3p in porcine neuroglial cells (PNGCs) and PK15 cells significantly decreased the mRNA and protein levels of the JARID2 gene. In addition, miR-9828-3p inhibited the proliferation of PNGCs. After inhibiting miR-9828-3p, the mRNA and protein expression levels of JARID2 increased, and the proliferation of PNGCs showed an opposite trend to the cells that forced expression of miR-9828-3p. In addition, interference with the JARID2 gene by siRNA can effectively inhibit the proliferation of PNGCs. In summary, we found that the rs326221458 locus regulates the expression of the JARID2 gene by affecting the binding of miR-9828-3p and the JARID2 gene, thereby affecting the aggressive behavior of weaned pigs after mixing.

In this paper, we present an innovative technique that improves the convergence order of iterative schemes that do not require the evaluation of Jacobian matrices. Using this procedure, we achieve a remarkable increase in the order of convergence, raising it from p to p + 3 units, which results in a remarkable improvement in the overall performance. We have conducted comprehensive numerical tests in various scenarios to validate the theoretical results, showing the efficiency and effectiveness of the new Jacobian-free schemes.

Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.

Knowledge regarding egg morphology can aid the selection of postharvest fumigants for insect control. Accordingly, scanning electron microscopy (SEM) was used to examine eggs of spotted lanternfly (SLF), Lycorma delicatula (White) (Hemiptera: Pentatomidae), a pest recently invasive to the mid-Atlantic region of the United States. As the overwintering life stage of SLF, eggs are deposited on a variety of refugia, including many forestry products that can be distributed geographically via travel, commerce, and/or trade. For fumigation to control SLF, and potentially translate into a viable strategy for limiting the spread of SLF by subject pathways, the fumigant must permeate the chorion to react with biomolecules and/or disrupt cellular processes. SLF chorion was characterized by a porous network of aeropyles localized around the operculum, in cranial and caudal relation to the developing nymph, as well as an interstice between the operculum edge and the opercular rim. The confirmation of chorionic ultrastructure that allows for ready gas exchange warrants further investigation of fumigation efficacy, even for those “non-reactive” fumigants, such as phosphine and hydrogen cyanide, which must overcome the suppression of cellular processes coincident with overwintering.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

A lightweight image encryption algorithm based on chaos induction via a 5-dimensional hyperjerk oscillator (5DHO) is presented. First, the dynamics of our 5DHO network is investigated and shown to exhibit up to five coexisting hidden attractors in the state space that depend exclusively on the system’s initial values. Further, a simple implementation of the circuit was used to validate its ability to exhibit chaotic dynamical properties. Second, an Arduino UNO platform is used to confirm the usability of our oscillator in digital implementation of the system. Finally, an efficient image encryption application is executed using the proposed chaotic networks based on the use of permutation-substitution sequences. The superior qualities of the proposed strategy are traced to the dynamic set of keys used in the substitution process which heralds the generation of the final ciphered image. Based on the results obtained from the entropy analysis (7.9976), NPCR values (99.62), UACI tests (33.69) and encryption execution time for 512x512 images (0.1179 sec), the proposed algorithm is adjudged to be fast and robust to differential and statistical attacks relative to similar approaches.

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

Abstract: Viremia in coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is often only discussed in passing and there are very few references detailing its structural mechanisms. In addition to viremia in the classic closed cardiovascular system, the lymphatic system is discussed in relation to a possible “lympho-viremia”. The cells that comprise each of these separate but interacting systems will be examined and include endothelial cells, erythrocytes, leukocytes (monocytes/monocyte-derived macrophages and resident tissue macrophages) (lymphocytes) (neutrophils) and thrombocytes -platelets. The SARS-CoV-2 virus has been identified in multiple extrapulmonary target organs at autopsy in those with severe COVID-19 requiring intensive care. Vulnerable COVID-19 patients may suffer from multiple storms including viral/virion storm, redox storm, cytokine storm and thrombo-embolic storm. Therefore, it is important that the possible mechanisms of viremia be explored in greater detail and how these mechanisms might affect intravascular blood components, extracellular tissue interstitium and organ structural remodeling and function. While the co-morbidity of T2DM does not increase the risk of acquiring COVID-19, it is commonly accepted that T2DM increases the risk for COVID-19 admissions to hospitals, assisted ventilation, morbidity and mortality. Importantly, the co-existence of T2DM and COVID-19 may have synergistic detrimental outcomes.

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

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Woodland strawberry (Fragaria vesca L.) is an underutilized plant species, appreciated by consumers for its qualitative features. Utilizing technical means of production, such as plant biostimulants, that can increase crop productivity and quality could be highly important in woodland strawberry cultivation. The scope of the present study was to appraise the influence of two biostimulants (Trichoderma atroviride and plant protein hydrolysate) - used either alone or combined - on plant performance and economic profitability of two woodland strawberry genotypes (‘Alpine’ and ‘Regina delle Valli’). Overall, data showed that ‘Alpine’ had the highest productive performances, whereas ‘Regina delle Valli’ revealed the highest fruit qualitative traits. T. atroviride inoculation and V-PH application significantly boosted plant marketable yield (+20.5% for T. atroviride and +12.9% for V-PH), total sugars (+1.9% for Trichoderma and +1.4% for V-PH) and anthocyanins (+14.1% for T. atroviride and +9.8% for V-PH) compared to non-treated plants. Plants supplied with both biostimulants had higher marketable yield (+34.8%), mean fruit weight (+6.0%), fruit dry matter (+13.8%), total sugars (+3.5%), ascorbic acid (+12.7%), flavonoid (+26.3%) and anthocyanins (+29.9%) compared to non-treated plants. Furthermore, our study revealed that the highest fruit polyphenols concentration was recorded in both genotypes treated with the combination of biostimulants and in ‘Regina delle Valli’ sprayed with V-PH, whereas the highest antioxidant activity was found in ‘Regina delle Valli’ fruit when plants were supplied with both biostimulants. Our study pointed out that the application of microbial and non-microbial biostimulants, especially in combination, might be an useful strategy for improving performances of underutilized species and, therefore, encourage its cultivation, valorisation and economic profitability (+10195.3 €/ha when plants were exposed to both biostimulants).

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

Theoretical studies propose an association between family violence and low self-control in adolescence, yet empirical findings of this association are inconclusive. The aim of the present research was to systematically summarize available findings on the relation between family violence and self-control across adolescence. We included 27 studies with 143 effect sizes, representing more than 25,000 participants of eight countries from early to late adolescence. Applying a multi-level meta-analyses, taking dependency between effect sizes into account while retaining statistical power, we examined the magnitude and direction of the overall effect size. Additionally, we investigated whether theoretical moderators (e.g., age, gender, country), and methodological moderators (cross-sectional/longitudinal, informant) influenced the magnitude of the association between family violence and self-control. Our results revealed that family violence and self-control have a small to moderate significant negative association (r = -.191). This association did not vary across gender, country, and informants. The strength of the association, however, decreased with age and in longitudinal studies. This finding provides evidence that researchers and clinicians may expect low self-control in the wake of family violence, especially in early adolescence. Recommendations for future research in the area are discussed.

Prior work has suggested that discrimination and immigration-related stress may impede mental health care seeking and utilization among Latinx populations. These effects may be more nuanced as both discrimination and immigration-related stress may increase symptomology, particularly posttraumatic stress disorder (PTSD) and depression. Both symptoms may in turn prompt attempts to seek care. The current study examined the direct effects of discrimination and immigration-related stress on care access, as well as potentially indirect effects with PTSD and depression symptoms as mediators. Interviews and online surveys were completed with 234 Latinx residents of the Midwest assessing everyday discrimination, discrimination in healthcare, PTSD symptoms, depression symptoms, current mental health utilization, and previous unsuccessful attempts to seek care. Direct effects of discrimination and immigration-related stress were largely unrelated to care access variables. Discrimination in healthcare settings predicted both unsuccessful attempts to seek care and current use, but this effect was positive. The indirect effect was largely supported, but only for PTSD symptoms and not depression. Results indicate further investigation is necessary to understand the direct effects of discrimination on care access. Further, discrimination and immigration-related stress may indirectly prompt attempts to seek mental health care.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

After 2010, the source model of the microSelectron HDR Afterloader System was slightly modified from the previous model. Granero et al. named the modified source model “mHDR-v2r (revised model mHDR-v2)” and the previous model “mHDR-v2”. They concluded that the dosimetric differences arising from the dimensional changes between the mHDR-v2 and mHDR-v2r designs were negligible at almost all locations (within 0.5 % for r ≥ 0.25 cm), the two-dimensional anisotropy function difference between the two sources is found 2.1 % at r = 1.0 cm when compared with the results of the other experimental group. To confirm this difference, we performed a full Monte Carlo simulation without the energy fluence approximation. This is useful near the radiation source where charged-particle equilibrium does not hold. The two-dimensional anisotropy function of the TG-43U1 dataset showed a few percent difference between the mHDR-v2r and mHDR-v2 sources. There was no agreement in the immediate vicinity from the source (0.10 cm and 0.25 cm), when compared to Granero et al. in mHDR-v2r sources. The differences in these two-dimensional anisotropy functions were identified.

The objective of this study was to evaluate the glycemic index and the satiety response of three Mexican kinds of honey. The values of fructose ranged from 272.40-395.10 g/kg, while the glucose value ringed 232.20-355.50 g/kg. The ratio F/G of sample honey was 1.45, 1.00, and 1.17 for Highland, Multifloral, and Avocado honey, respectively. Twenty-six participants completed this study, which was previously approved by the ethics committee of the Facultad de Salud Pública y Nutrición (CE 2/2018-19). Highland and Avocado honey is classified as medium-GI (69.204.07 and 66.365.74, respectively), while Multifloral honey is classified as high-GI (74.245.98). The Highland honey presented the best satiety response. The difference in IG values and the effect of the satiety response of Highland honey could be explained by the different fractions of carbohydrates in samples and other components such as phytochemicals.

Brain-Computer Interface (BCI) systems can assist physically challenged people to interact with their surroundings and improve the quality of their lives. Decoding human thoughts is a powerful technique that can assist paralyzed people who have lost their speech production ability. Speaking is a combined process involving synchronizing the brain and the oral articulators. This paper proposed a high-accuracy brain wave pattern recognition based on inner speech using a novel feature extraction method. Only eight EEG electrodes were used in this study, and they were set on selected spots on the scalp. Support Vector Machine (SVM) was employed to decode the recorded EEG dataset into four internally spoken words which are: Up, Down, Left, and Right. The proposed approach achieved overall classification accuracy that ranges between 96.20% to 97.5%. In addition, more performance evaluation metrics were estimated to test the reliability of classifying the EEG-based inner speech data, and we obtained 97.61%, 97.50%, and 97.73% for F1-score, recall, and precision respectively. Furthermore, the Area Under Curve of the Receiver Operating Characteristic (AUC-ROC) proved the strength of the proposed approach for classifying the specified inner speech commands by achieving a macro-average amount of 99.32%. The inner speech classification method using electroencephalography proposed in this work can clinically help improve communication for patients with problems including speech disorder, mutism, cognitive development, executive function, and psychopathology.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

The incidence of venous thromboembolism is estimated at around 3% of cancer patients. However, a majority of incidental pulmonary embolism (iPE) can be overlooked by radiologists in asymptomatic patients, performing CT scans for disease surveillance, which may significantly impact the patient's health and management. Routine imaging in oncology is usually reviewed with delayed hours after the acquisition of images. Nevertheless, the advent of AI in radiology could reduce the risk of diagnostic delay of iPE by an optimal triage immediately at the acquisition console. This study aimed to determine the accuracy rate of an AI algorithm (CIN A-iPE) in detecting iPE and the duration until the management of cancer patients in our center in addition to describing the characteristics of patients with a confirmed pulmonary embolism (PE). MATERIALS AND METHODS This is a retrospective analysis of the role of Avicenna's CE-certified and FDA-cleared CINA-iPE algorithm in oncology patients treated at Gustave Roussy Cancer Campus. The results obtained from the AI algorithm were compared with the attending radiologist's report and analyzed by both a radiology resident and a senior radiologist. In case of any discordant results, the reason for this discrepancy was further investigated. The duration between the exact time of the CT scan and analysis was assessed as well as the duration from the result’s reporting and the start of active management. RESULTS Out of 3047 patients, 104 alerts were detected for iPE (prevalence of 1.3%) while 2942 had negative findings. 36 of the 104 patients had confirmed PE while 68 alerts were false positives. Only one patient reported as negative by the AI tool was deemed to have a PE by the radiologist. The sensitivity and specificity of the AI model were 97.3% and 97.74% while the PPV and NPV were 34.62% and 99.97% respectively. Most causes of FP were artifacts (22 cases, 32.3%) and lymph nodes (11 cases, 16.2%). Seven patients experienced delayed diagnosis, requiring them to return to the ER for treatment after being sent home following their scan. The remaining patients received prompt care immediately after their testing with a mean delay time of 8.13 hours. CONCLUSION The addition of an AI system for the detection of unsuspected PEs on chest CT scans in routine oncology care demonstrated a promising efficacy in comparison to human performance. Despite a low prevalence, the sensitivity and specificity of the AI tool reached 97.3% and 97.7% respectively with detection of all the reported clinical PEs except one single case. This study describes the potential synergy between AI and radiologists for an optimal diagnosis of iPE in routine clinical cancer care.

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacte-rial and parasitic infections, most notably coccidiosis in poultry and in ruminants. We have in-vestigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. It induced distinct alterations in the parasite mitochondrion within 24h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC50) of 1.1 nM and the high selec-tivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ antici-pated to have better physicochemical properties than DCQ were assessed in vitro. One such com-pound RMB060 displayed an exceedingly low IC50 of 0.07 nM when applied concomitantly with infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6h after commencement of treatment. After 48h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features remi-niscent of bradyzoites. Exposure of infected cultures to 300 nM RMB060 for 52 days did not re-sult in complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. Treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.

Cryopreservation has been used extensively for cattle in Bangladesh, albeit no study was conducted on the cryopreservation techniques of buffalo. This study compares two freezing methods and the effects of diluters on the semen quality of buffalo. In the first freezing protocol, semen was frozen in two-step: from 37 °C to 5 °C for 30 minutes in a BLRI-developed equilibration chamber and from 5 oC to -120 oC in a Styrofoam box using liquid nitrogen vapor from different distances (0.5, 1.5, 1.6, 2 and 3 inches). At the same time semen was frozen in a programmable freezer in three steps. The semen samples were then evaluated for motility and morphological quality by CASA. In another experiment, the efficacy of one locally developed diluter-Tris-fructose-egg yolk-based (TFE) and three commercial diluters (Andromed, Triladyl and Steridyl) were evaluated. The highest number of motile sperms (62.67±1.12; P< 0.01) and progressive motility (38.97±1.10; P < 0.001) was observed at 1.6 inches above liquid nitrogen. There was no significant difference in overall motility, progressive and slow motility between semen cryopreserved in the cheap nitrogen vapor technique (57.49±5.67, 38.70± 4.04 and 3.83± 0.63, respectively) and expensive automated technique (65.94±4.65, 45.54 ± 3.64 and 2.43± 0.36, respectively). The highest recovery rate and conception rate were observed in semen diluted with TFE (82.4% and 80%, respectively). Hence, the cryopreservation technique using nitrogen vapor and TFE diluent is cost-effective and suitable for freezing buffalo semen that would produce superior semen for artificial insemination.

The hazard and the carcinogenic risks due to the exposure to some potentially toxic elements by the Santiago Island (Cape Verde) population where calculated, considering soil ingestion, inhalation and dermal contact as exposure pathways. The topsoil of Santiago Island is enriched in Co, Cr, Cu, Ni, V, Zn, Mn and Cd to upper crust values. Hazard indices (HI) were calculated for these metals and As exposures, of Santiago Island population and the calculations were performed for children and adults. For children HI are higher than 1 for Co, Cr and Mn. So there is indication of potential non-carcinogenic risk for children, due to the high Co (HI=2.995), Cr (HI=1.329) and Mn (HI=1.126), values in soils. For the other elements and for adults there is no potential non-carcinogenic risk. Cancer risk was calculated for As, Cd, Cr and Ni exposures, for adults and children and the results are always lower than the carcinogenic target risk of 1x10-6, for As, Cd, and Ni. However, cancer risk are higher than the carcinogenic target risk for Cr, for adults. Regarding As, for children the fraction due to Riskingestion represents 51.6%, while Riskinhalation represents 48.0% and Riskdermalcontact represents only 0.4% of total risk. For adults Riskinhalation represents 81.3%, Riskingestion represents 16.6% and Riskdermal contact represents 2.1%. These results reflect the higher daily ingestion dose for children and the higher inhalation rate and higher dermal contact surface for adults. For the other elements and for adults the cancer risk due to Cr, Ni and Cd inhalation is always higher than for children, reflecting the higher inhalation rate for adults.

In this study, we test the performance of a compact gas chromatograph with photoionization detector (GC-PID) and optimize the configuration to detect ambient (sub-ppb) levels of benzene, toluene, ethylbenzene, and xylene isomers (BTEX). The GC-PID system was designed to serve as a relatively inexpensive (~$10k) and field-deployable air toxic screening tool alternative to conventional benchtop GCs. The instrument uses ambient air as a carrier gas, and consists of a Tenax-GR trap preconcentrator, a gas sample valve, two capillary columns, and a photoionization detector (PID) with a small footprint and low power requirement. The performance of the GC-PID has been evaluated in terms of system linearity and sensitivity in field conditions. The BTEX-GC system demonstrated the capacity to detect BTEX at levels as high as 500 ppb with a linear calibration range of 0-100 ppb. A detection limit lower than 1 ppb was found for all BTEX compounds with a sampling volume of 1 L. No significant drift in the instrument was observed. A time-varying calibration technique was established that requires minimal equipment for field operations and optimizes the sampling procedure for field measurements. With an analysis time of less than 15 minutes, the compact GC-PID is ideal for field deployment of background and polluted atmospheres for near-real time measurements of BTEX. The results highlight the application of the compact and portable GC-PID for community monitoring and screening of air toxics.

Kersting’s groundnut is an important source of protein and essential nutrients that contribute to food security in West Africa. However, the crop is still underexploited by the populations and under-researched by the scientific community. This study aimed to investigate the genetic diversity and population structure of 217 Kersting’s groundnut accessions from five origins using 886 DArTseq markers. Gene diversity was low and ranged from 0.049 to 0.064. The number of private alleles greatly varied among populations (42–192) and morphotypes (40–339). Moderate to very high levels of selfing and inbreeding were observed among populations (s=56–85%, F_IS=0.389–0.736) and morphotypes (s=57–82%, F_IS=0.400–0.691). Moreover, little to very high genetic differentiations were observed among populations (0.006≤F_IS≤0.371) and morphotypes (0.029≤F_IS≤0.307). Analysis of molecular variance partitioned 38.5% of the genetic variation among and 48.7% within populations (P<0.001). Significant isolations by distance were detected between populations (R²=0.612, P=0.011) and accessions (R²=0.499, P<0.001). Discriminant analysis of principal components and neighbour joining consistently distinguished eight distinct clusters. These data provide a global picture of the existing genetic diversity for Kersting’s groundnut and will guide the choice of breeding strategies to increase production.

Objective: Rheumatoid Arthritis (RA) is a chronic inflammatory disease affecting the synovium and articular cartilage that initiates joint damage. RA associates with a change in many inflammatory biomarkers. The present study aims to measure the levels of inflammatory adipocytokines (chemerin and visfatin) and their ratio in addition to some related biomarkers in RA patients group in comparison to healthy control group and find out their efficacy in diagnosis of RA.Methods: The study included 60 RA patients and 30 healthy control group. Serum visfatin and chemerin were measured by using ELISA technique, while other biomarkers were determined spectrophotometrically. Multivariate general linear model analysis and Receiver operating curve was used to study the opportunity of using chemerin and visfatin as diagnostic tools for RA.Results: The results indicated that there was a significant increase (p<0.05) in all lipid profile components, except HDLc that decreased, in RA patients in comparison with healthy control group; while significant decrease (p<0.001) in high density lipoprotein-cholesterol of RA patients in comparison with control group. Serum chemerin, visfatin, C-reactive protein, and uric acid levels were significantly higher (p<0.05) in RA patients than those of control group. The results showed a relatively good sensitivity and specificity of chemerin (sensitivity=88.1, specificity=75.9) at a concentration=187.88ng in diagnosis of RA.Conclusions: chemerin is able to diagnose RA efficiently but this diagnoses, due to relatively small specificity, may interfere with other inflammatory disorders. However, with adjuvant with other diagnostic parameters, chemerin may represent a useful addition in diagnosis of RA.

The UK economy is overly reliant on unsustainable production and consumption practices, depleting finite resources at rates that will increase production costs, business risk and economic instability. This over-consumption produces emissions and waste that cause climate change and environmental degradation, impacting on the wellbeing of people in the UK and beyond. The Resource Recovery from Waste programme (RRfW) promotes a transition towards waste and resource management in a circular economy that restores the environment, creates societal benefits and promotes clean growth by engaging relevant actors in the transition process. RRfW collaborates with academia, government, and industry to co-produce a shared vision and approach to realise such a transition. Reflecting insights from RRfW’s government engagement, this article presents a positive outlook for changing the UK economy and society. It envisions a long-term future for waste and resource management that maximises the value of materials by circulating them in the economy for as long as possible. Four themes and an approach are proposed, including recommendations for regulatory instruments and a stable policy framework. It recommends further collaborative research to capitalise on opportunities for economic growth, innovation and resilient infrastructure whilst contributing to quality jobs and welfare in all four UK nations.

DC residential distribution system (RDS) consisted by DC living home will be a significant integral part in the future green transmission. Meanwhile, the increasing number of distributed resources and intelligent devices will change the power flow between main grid and demand sides. The utilization of distributed generations (DGs) requires an economic operation, stability, environmentally friendly in the whole DC system. This paper not only presents an optimization schedule and transactive energy (TE) approach through centralized energy management system (CEMS), but a control approach to implement and ensure DG output voltages to various DC buses in DC RDS. Based on data collection, prediction and a certain objection, the expert system in CEMS can work out the optimization schedule, after this, the voltage droop control for steady voltage is aligned with the command of unit power schedule. In this work, a DC RDS is as a case study to demonstrate the process, the RDS is associated with unit economic models, cost minimization objective is proposed to achieve based on real-time electrical price. The results show that the proposed framework and methods will help the targeted DC residential system to reduce the total cost and reach stability and efficiency.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as mobile phase comprising of acetonitrile-0.1M KH₂PO₄ pH 6.5-0.1M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59% v/v/v/v) delivered at a flow rate of 1.0 ml/min. The stationary phase consisted of reverse-phase XTerra^® (250 mm× 4.6 mm i.d., 5 µm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50-150% (r²=0.997). The limits of detection and quantification were found to be 0.02% (20 µg) and 0.078% (78 µg) respectively with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Mechanistic models have been used for centuries to describe complex interconnected processes, including biological ones. As the scope of these models has widened, so have their computational demands. This complexity can limit their suitability when running many simulations or when real-time results are required. Surrogate machine learning models can be used to approximate the behaviour of complex mechanistic models, and once built, their computational demands are several orders of magnitude lower. This paper provides an overview of the relevant literature, both from an applicability and a theoretical perspective. For the latter, the paper focuses on the design and training of the underlying machine learning models. Application-wise, we show how machine learning surrogates have been used to approximate different mechanistic models. We present a perspective on how these approaches can be applied to models representing biological processes with potential industrial applications (e.g., metabolism and whole-cell modelling) and show why surrogate machine learning models may hold the key to making the simulation of complex biological models possible using a typical desktop computer.

Electric arc furnace oxidizing slag (EAF) has a high density of 3.0~3.7 t/m3 and therefore has a high bulk density when mixed with concrete. Extensive research has been conducted on the use of concrete with high unit volume weight as heavyweight concrete for radiation shielding concrete. In this study, to examine the possibility of developing a radiation shielding concrete, the physical properties of normal concrete, magnetite concrete, EAF concrete, and EAF concrete with added iron powder, were compared. Also, their radiation shielding performance was assessed through shielding tests against X-rays and γ-rays. While the unit volume weight of EAF concrete (3.21 t/m3) appeared lower than that of magnetite concrete (3.5 t/m3), the compressive strength of EAF concrete was greater than those of magnetite and normal concretes. The radiation shielding ratio of magnetite concrete was observed to be 93.9% from the X-ray shielding test, followed by 91.2% of EAF concrete, and 73.7% of normal concrete, indicating a linear relationship with unit volume weight. From the γ-ray shielding test, the performance of EAF and magnetite concretes appeared to be similar. Based on the excellent physical properties and radiation shielding performance of EAF concrete, its potential applicability as radiation shielding concrete was confirmed.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of HR-HPV infection in female population has led to the discovery of several cases of double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate high risk (HR) HPV infections in women with double cervix within the National Cervical Cancer Screening program of the Lazio Region (Italy). From June 2021 to March 2024 a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervixes and analyzed separately. Twenty-seven women with double cervix were identified (0.019%): 20 women were tested as negative for both cervices, while the remaining four (namely A, B, C and D) resulted positive. By genotyping, the following results were obtained: A) both samples showed genotype 31; B) one cervix was negative while the other showed genotype 58. C) one cervix was positive for HPV 18 and 31 while for 18, 31 and 33 in the other. D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition, where the presence HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

Directive 2018/844/EU on energy efficiency claims almost 80% of final energy consumption in EU is used within the buildings. Subsequent Directive (EU) 2023/1791 introduced in 2023 expected 68% of the World population living in urban areas. Both Directives enhanced the role of energy management (EM) applied on the city buildings. The study introduces the development of energy management in Czech municipalities between the years 2009 and 2023. The main goal of this article is to present selected results of the unique national survey focused on the energy management in Czech municipalities conducted in 2023 and compare it with results of national surveys implemented in 2009 and 2018. The main method is the evaluation of deep survey conducted among the municipal representatives or energy managers in the past with the new survey conducted in 2023. The results show that EM became notably more important issue for the most Czech municipalities. The number of cities implementing EM significantly grew and the number of city energy managers increased too. On the other hand, the used potential of energy savings triggered by establishing EM is insufficient. This article should be applied to stress power of municipal EM in performing energy efficiency and RES projects and encouraging government to support municipal energy managers in their complex role.

The search for graphene or few layer graphene production methods that are simple, allow mass production and yield good quality material continues to provoke intense investigation. The present work contributes through the study of the aqueous exfoliation of four types of graphene sources, namely graphite and graphite nanoflakes with different morphologies and geographical origin. The exfoliation was achieved in an aqueous solution of a soluble pyrene derivative that was synthesized to achieve maximum interaction with the graphene surface at low concentration (5 x 10-5 M). The yield of bilayer and few layer graphene obtained was quantified by Raman spectroscopic analysis and the adsorption of the pyrene derivative on the graphene surface was studied by thermogravimetric analysis and X-ray diffraction. The whole procedure was rationalized with the help of molecular modeling.

The windowpane oyster Placuna placenta, lives in brackish coastal waters and has long been economically important to the Philippines because of its durable and translucent shell, which is used as a glass substitute and material for making windowpanes and handicrafts. There has been considerable degradation of the windowpane oyster fishery in past decades. Moreover, there are waste and under-exploited by-products such as the meat, which though nutritious and edible, currently has a very low value; its use being confined to dishes consumed by families in the fishing community. Historically there are instances of excellent practice in terms of regulating the windowpane oyster fishery, while in recent times there have been local initiatives to restore this and to develop high value food products from the meat. These initiatives have, however, never been followed through at a provincial or national level. Research on other molluscs and marine organisms highlights that these also contain high value pharmaceutical products. This review compiles evidence to establish the groundwork for an essential and comprehensive multidisciplinary research program centred around the windowpane oyster, which would ensure a high value for all parts of the oyster, including those currently discarded. By fostering a sustainable and circular economy within this fishery sector and its associated industry, its economic value would be amplified. This is particularly important for oyster harvesters in the Philippines, who often find themselves at the economic ladder's lower rungs. By integrating the principles of a circular economy, this initiative would not only aim to uplift the economic prospects of these harvesters but in doing so would drive the restoration of the windowpane oyster to its former range.