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The spike (S) protein is one of the three proteins forming the coronaviruses' viral envelope. The S protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has a spatial structure similar to the S proteins of other mammalian coronaviruses, except for a unique receptor-binding domain (RBD), which is a significant inducer of host immune response. Recombinant SARS-CoV-2 RBD is widely used as a highly specific minimal antigen for serological tests. Correct exposure of antigenic determinants has a significant impact on the accuracy of such tests-the antigen has to be correctly folded, contain no potentially antigenic non-vertebrate glycans, and, preferably, should have a glycosylation pattern similar to the native S protein. Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. RBDv1 contained a native viral signal peptide, RBDv2 -human tPA signal peptide. We transfected a CHO DG44 cell line, selected stably transfected cells, and performed a few rounds of methotrexate-driven amplification of the genetic cassette in the genome. For the RBDv2 variant, a high-yield clonal producer cell line was obtained. We developed a simple purification scheme that consistently yielded up to 30 mg of RBD protein per liter of the simple shake flask cell culture. Purified proteins were analyzed by polyacrylamide gel electrophoresis in reducing and non-reducing conditions and gel filtration; for RBDv2 protein, the monomeric form content exceeded 90% for several series. Deglycosylation with PNGase F and mass spectrometry confirmed the presence of N-glycosylation. The antigen produced by the described technique is suitable for serological tests and subunit vaccine studies.

Recombinant human follicle stimulating hormone (FSH), produced in Chinese hamster ovary (CHO) cells, is widely used for treatment of fertility disorders and is subject to biosimilars development. Cell lines with high specific productivities may simplify the FSH production process. Here, we used our previously established expression system based on vector p1.1 to create new cell lines secreting heterodimeric FSH protein. To this end, we linked open reading frames of both FSH subunits by the wild-type internal ribosome entry site from the encephalomyocarditis virus (EMCV IRES). Intact and double-negative for the dihydrofolate reductase CHO cells were stably transfected by the FSH-coding plasmids. Stably transfected intact cells showed higher level of the FSH secretion and were utilized for subsequent methotrexate-driven transgene amplification, which doubled their productivity. The excess of the free α-subunit was corrected by transfecting the cells by the additional p1.1-based plasmid encoding the β-subunit of the FSH. Clonal cell lines obtained secreted mostly the heterodimeric FSH and possessed specific productivities up to 12.3±1.7 pg/cell/day. Candidate clonal cell line C-P1.3-FSH-G4 maintained a constant specific productivity for at least 2 months of culturing without the section pressure. The resulting FSH protein conformed to the international pharmaceutical quality criteria as evidenced by the receptor binding kinetics, distribution pattern of hormone isoforms and biological activity. In conclusion, our expression system offers a simple and cost-effective approach to production of FSH.

OBJECTIVE:Results of the screening of disease causative mutations in congenital hypothyroidism (CH) vary significantly, depending on the sequence strategy, patients' inclusion criteria and bioinformatics. The objective was to study the molecular basis of severe congenital hypothyroidism, using the next generation sequencing (NGS) and the recent guidelines for assessment of sequence variants. DESIGN:243 patients with CH (TSH levels at neonatal screening or retesting greater than 90 mU/l) and 56 control subjects were included in the study. METHODS:A custom NGS panel targeting 12 CH causative genes was used for sequencing. The sequence variants were rated according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS:In total, 48 pathogenic, 7 likely pathogenic and 57 variants of uncertain significance were identified in 92/243 patients (37.9%), while 4 variants of uncertain significance were found in 4/56 control subjects (7.1%). 13.1% (12/92) of the cases showed variants in 'thyroid dysgenesis' (TD) genes: TSHR, n = 6; NKX2-1, n = 2; NKX2-5, n = 1; PAX8, n = 3. The variants in 'dyshormonogenesis' (DH) genes were found in 84.8% (78/92) of cases: TPO, n = 30; DUOX2, n = 24; TG, n = 8; SLC5A5, n = 3; SLC26A4, n = 6; IYD, n = 1. 8 patients showed oligonenic variants. The majority of variants identified in DH genes were monoallelic. CONCLUSIONS:In contrast to earlier studies demonstrating the predominance of TD in severe CH, the majority of variants identified in our study were in DH genes. A large proportion of monoallelic variants detected among DH genes suggests that non-mendelian mechanisms may play a role in the development of CH.

The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK). Phosphoproteomic and site-directed mutagenesis analyses of lamin B1 isolated from control and MMS-treated nuclei identified T575 as a JNK site phosphorylated after stress. A new phospho-T575 specific anti-peptide antibody confirmed increased interphase cellular T575 phosphorylation after cell exposure to certain stress conditions, enabling us to conclude that lamin B1 acts as an interphase kinase target, releasing Oct-1 to execute a protective response to stress.

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

Factor XIIa (fXIIa) is a serine protease that triggers the coagulation contact pathway and plays a role in thrombosis. Because it interferes with coagulation testing, the need to inhibit fXIIa exists in many cases. Infestin-4 (Inf4) is a Kazal-type inhibitor of fXIIa. Its specificity for fXIIa can be enhanced by point mutations in the protease-binding loop. We attempted to adapt Inf4 for the selective repression of the contact pathway under various in vitro conditions, e.g., during blood collection and in 'global' assays of tissue factor (TF)-dependent coagulation. First, we designed a set of new Inf4 mutants that, in contrast to wt-Inf4, had stabilized canonical conformations during molecular dynamics simulation. Off-target activities against factor Xa (fXa), plasmin, and other coagulation proteases were either reduced or eliminated in these recombinant mutants, as demonstrated by chromogenic assays. Interactions with fXIIa and fXa were also analyzed using protein-protein docking. Next, Mutant B, one of the most potent mutants (its Ki for fXIIa is 0.7 nM) was tested in plasma. At concentrations 5-20 μM, this mutant delayed the contact-activated generation of thrombin, as well as clotting in thromboelastography and thrombodynamics assays. In these assays, Mutant B did not affect coagulation initiated by TF, thus demonstrating sufficient selectivity and its potential practical significance as a reagent for coagulation diagnostics.

The goal of this study was to evaluate the capacity for mass spectrometry of blood plasma to diagnose impaired glucose tolerance (IGT). For this study, blood plasma samples from control subjects (n = 30) and patients with IGT (n = 20) were treated with methanol and low molecular weight fraction were then analyzed by direct infusion mass spectrometry. A total of 51 metabolite ions strongly associated with IGT were detected. The area under a receiver operating characteristic (ROC) curve (AUC) for diagnosing IGT that was based on an analysis of all these metabolites was 0.93 (accuracy 90%, specificity 90%, and sensitivity 90%). The associated reproducibility was 85%. The metabolites identified were also consistent with risk factors previously associated with the development of diabetes. Thus, direct infusion mass spectrometry of blood plasma metabolites represents a rapid, single-step, and reproducible method for the analysis of metabolites. Moreover, this method has the potential to serve as a prototype for clinical analyses that could replace the currently used glucose tolerance test with a more patient-friendly assay.

Background: The IRONMAN® (IM) triathlon is a popular multi-sport, where age group athletes often strive to qualify for the IM World Championship in Hawaii. The aim of the present study was to investigate the location of the fastest IM racecourses for age group IM triathletes. This knowledge will help IM age group triathletes find the best racecourse, considering their strengths and weaknesses, to qualify., Objective: To determine the fastest IM racecourse for age group IM triathletes using descriptive and predictive statistical methods., Methods: We collected and analyzed 677,702 age group IM finishers' records from 228 countries participating in 444 IM competitions held between 2002 and 2022 across 66 event locations. Locations were ranked by average race speed (performance), and countries were sorted by number of records in the sample (participation). A predictive model was built with race finish time as the predicted variable and the triathlete's gender, age group, country of origin, event location, average air, and water temperatures in each location as predictors. The model was trained with 75% of the available data and was validated against the remaining 25%. Several model interpretability tools were used to explore how each predictor contributed to the model's predictive power, from which we intended to infer whether one or more predictors were more important than the others., Results: The average race speed ranking showed IM Vitoria-Gasteiz (1 race only), IM Copenhagen (8 races), IM Hawaii (18 races), IM Tallinn (4 races) and IM Regensburg (2 races) in the first five positions. The XG Boost Regressor model analysis indicated that the IM Hawaii course was the fastest race course and that male athletes aged 35 years and younger were the fastest. Most of the finishers were competing in IM triathlons held in the US, such as IM Wisconsin, IM Florida, IM Lake Placid, IM Arizona, and IM Hawaii, where the IM World Championship took place. However, the fastest average times were achieved in IM Vitoria-Gasteiz, IM Copenhagen, IM Hawaii, IM Tallin, IM Regensburg, IM Brazil Florianopolis, IM Barcelona, or IM Austria with the absolutely fastest race time in IM Hawaii. Most of the successful IM finishers originated from the US, followed by athletes from the UK, Canada, Australia, Germany, and France. The best mean IM race times were achieved by athletes from Austria, Germany, Belgium, Switzerland, Finland, and Denmark. Regarding environmental conditions, the best IM race times were achieved at an air temperature of ∼27°C and a water temperature of ∼24°C., Conclusions: IM age group athletes who intend to qualify for IM World Championship in IM Hawaii are encouraged to participate in IM Austria, IM Copenhagen, IM Brazil Florianopolis, and/or IM Barcelona in order to achieve a fast race time to qualify for the IM World Championship in IM Hawaii where the top race times were achieved. Most likely these races offer the best ambient temperatures for a fast race time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Knechtle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Skin lesion segmentation plays a pivotal role in the diagnosis and treatment of skin diseases. By using deep neural networks to segment lesion areas, doctors can more accurately assess the severity of health-related conditions of patients and promptly implement appropriate treatment measures, thereby enhancing treatment outcomes and improving the quality of life (QoL) of patients. However, existing segmentation networks still face challenges in balancing segmentation performance and efficiency. To address this issue, a novel network, named AFCF-Net, is proposed in this paper for skin lesion segmentation tasks. Firstly, the proposed network employs a newly designed spatial channel feature calibration convolution (SCFCConv) to enhance its ability to perceive spatial and channel features. Secondly, AFCF-Net utilizes newly designed feature symmetric fusion convolution (FSFConv) in skip connections to selectively fuse features from different levels, thereby enhancing its sensitivity to texture, edges, and other detailed features. In addition, a feature attention recombination module (FARM) is added to the bottleneck of the proposed network to comprehensively acquire and utilize contextual information at different scales, thus improving the network's generalization ability. Finally, a newly designed multi-level feature aggregation branch is introduced as an additional decoder for AFCF-Net to supplement key features lost during the original decoding process. Experiments, conducted on four skin image datasets, demonstrate that the proposed AFCF-Net network achieves better segmentation performance with fewer parameters and computational resources, compared to state-of-the-art segmentation networks. Additionally, AFCF-Net exhibits stronger generalization ability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to develop image-analysis-based classification models for distinguishing individuals younger and older than 30 using the medial clavicle. We extracted 2D images of the medial clavicle from multi-slice computed tomography (MSCT) scans from Clinical Hospital Center Split (n = 204). A sample was divided into a training (164 images) and testing (40 images) dataset. The images were loaded into the Orange Data Mining 3.32.0., and transformed into vectors using the pre-trained neural network Painters: A model trained to predict painters from artwork images. We conducted Principal Components Analysis (PCA) to visualize regularities within data and reduce data dimensionality in classification. We employed three classifiers that provided >80% accuracy: Support Vector Machine (SVM), Logistic Regression (LR), and Neutral Network Identity SGD (NNI-SGD). We used 5-fold cross-validation (CV) to obtain optimal variables and performances and validated data on the independent test set, with a standard posterior probabilities (pp) threshold of 0.5 and 0.95. The explainability of the model was accessed visually by analyzing clusters and incorrectly classified images using anthropology field knowledge. Based on the PCA, clavicles clustered into categories under 30 and 40 years, between 40 and 55 years, and over 80 years. The overall accuracy with standard pp ranged from 82.5% to 92.5% for CV and 82.5% to 92.5% for the test set. The posterior probability of 0.95 provided classification accuracy up to 100% but with a lower proportion of images that could be classified. The study showed that image analysis based on a pre-trained deep neural network could contribute to distinguishing clavicles of individuals younger and older than 30., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ivković et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p<0.001), opportunistic infections after TPT completion (aPRR 4.31 (aPRR 2.58-7.2), p<0.001), a history of TB active TB disease (aPRR 1.60 (1.06-2.41), p = 0.026), and chronic illness during or after TPT (aPRR 1.68 (1.03-2.73), p = 0.038). To reduce the development of TB disease post TPT thereby improving the effectiveness of TPT, ART adherence should be emphasized to resolve viral suppression and active management of chronic and opportunistic infections. Further clinical management consideration and research is needed for PLHIV who receive TPT but have a previous history of TB disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Turinawe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Tennis is a globally popular sport known for its numerous health benefits. However, it also underscores the physical demands and potential injuries associated with high-performance play. This review emphasizes the role of kinetic chains in executing powerful movements and discusses common injuries, particularly in the upper limbs due to the sport's overhead nature. It highlights the importance of effective rehabilitation methods for swift recovery and long-term performance enhancement in high-performance tennis players., Aims: The review aims to investigate the relationship between age, sex, and injury prevalence among high-performance tennis players to inform injury prevention strategies., Methodology: This review protocol will provide a description on effective rehabilitation methods to tennis players, aiding coaches, physiotherapists and physicians. Methodologically, this systematic review will develop following the PRISMA guidelines, focusing on articles published between 2011 and 2024, with eligibility criteria specified. Data collection involved screening titles and abstracts, removing duplicates, and assessing full texts for eligibility. Data extraction will include information on authors, publication year, evidence level, participant demographics, injuries, treatments, etc. The GRADE framework will be used for evidence quality assessment, and NIH criteria were applied for study quality assessment., Trial Registration: Prospero registration number: CRD42023453182., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodríguez-González et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression., Materials and Methods: We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution., Results: Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19)., Conclusion: High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Slomka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The rapid population growth in urban areas has led to an increased frequency of lost and unclaimed items in public spaces such as public transportation, restaurants, and other venues. Services like Find My iPhone efficiently track lost electronic devices, but many valuable items remain unmonitored, resulting in delays in reclaiming lost and found items. This research presents a method to streamline the search process by comparing images of lost and recovered items provided by owners with photos taken when items are registered as lost and found. A photo matching network is proposed, integrating the transfer learning capabilities of MobileNetV2 with the Convolutional Block Attention Module (CBAM) and utilizing perceptual hashing algorithms for their simplicity and speed. An Internet framework based on the Spring Boot system supports the development of an online lost and found image identification system. The implementation achieves a testing accuracy of 96.8%, utilizing only 0.67 GFLOPs and 3.5M training parameters, thus enabling the recognition of images in real-world scenarios and operable on standard laptops., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Self-reported unmet healthcare needs are a useful indicator of access to healthcare, but there is little research from low- and middle-income countries. This study sought to investigate the prevalence and determinants of unmet needs arising from wait times, distance/transportation and financial affordability in Bulgaria using European Health Interview Survey data. We explored associations between individual characteristics and the probability of reporting unmet need by fitting logistic regression models to the data. Unaffordability-related unmet needs were the most cited barrier to access. The largest proportion of people reported unmet dental care needs (14%) or unmet needs due to unaffordability of medicines (8%); distance/transportation problems were the least cited reason (3%). People with poor physical and mental health had a substantially higher probability of experiencing unmet needs. Those with a disability, less disposable income, less social support and lower educational attainment were also more likely to report unmet healthcare needs. People who lived in rural areas experienced specific barriers to access, most notably from distance or transportation issues. Unmet healthcare needs lead to inefficiencies for the healthcare system and are more prevalent among already disadvantaged societal groups. Ensuring better access to healthcare is therefore important from both the efficiency and equity perspectives., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Maslyankov, Hernández. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to determine the validity and between-day reliability of the mean velocity (MV), peak velocity (PV), mean power (MP), and peak power (PP) provided by the Vitruve linear position transducer at different submaximal loads in the free-weight and Smith machine back squat using GymAware as a reference point. Fourteen male sports science students (free-weight back squat one-repetition maximum [1RM]: 132.5 ± 28.5 kg, Smith machine back squat 1RM: 163.9 ± 30.4 kg) performed six experimental sessions, twice per week with 72 hours of rest. The first two included the assessment of the 1RM of both exercises. In the four remaining, both linear position transducers were simultaneously used to record MV, PV, MP, PP of each repetition during an incremental load test (i.e., 20, 40, 60, 80, 90% 1RM) with three minutes of rest between sets. Vitruve displayed both fixed and proportional bias for certain relative loads across all variables. Vitruve did not meet the validity criteria for all (MV, PP) or at least two (MP, PV) relative loads (Coefficient of variation [CV] > 10%; Pearson correlation < 0.70; Effect size > 0.60). MV, PV, MP, and PP recorded by Vitruve displayed acceptable reliability (CV < 10%) with superior reliability observed during a Smith Machine compared to free-weight back squat, and for velocity compared to power variables. Considering GymAware as a reference point, Vitruve was not valid for measuring velocity and power outcomes. Acceptable validity was observed only for PV in the Smith machine back squat, while the other variables-regardless of relative loads and exercise modes-were mostly inaccurate. All variables demonstrated acceptable reliability, with greater reliability noted in the Smith machine compared to the free-weight back squat exercise mode., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ruiz-Alias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Extensive research has delved into the impact of environmental circumstances on the pacing and performance of professional marathon runners. However, the effects of environmental conditions on the pacing strategies employed by marathon participants in general remain relatively unexplored. This study aimed to examine the potential associations between various environmental factors, encompassing temperature, barometric pressure, humidity, precipitation, sunshine, cloud cover, wind speed, and dew point, and the pacing behavior of men and women. The retrospective analysis involved a comprehensive dataset comprising records from a total of 668,509 runners (520,521 men and 147,988 women) who participated in the 'Berlin Marathon' events between the years 1999 and 2019. Through correlations, Ordinary Least Squares (OLS) regression, and machine learning (ML) methods, we investigated the relationships between adjusted average temperature values, barometric pressure, humidity, precipitation, sunshine, cloud cover, wind speed, and dew point, and their impact on race times and paces. This analysis was conducted across distinct performance groups, segmented by 30-minute intervals, for race durations between 2 hours and 30 minutes to 6 hours. The results revealed a noteworthy negative correlation between rising temperatures and declining humidity throughout the day and the running speed of marathon participants in the 'Berlin Marathon.' This effect was more pronounced among men than women. The average pace for the full race showed positive correlations with temperature and minutes of sunshine for both men and women. However, it is important to note that the predictive capacity of our model, utilizing weather variables as predictors, was limited, accounting for only 10% of the variance in race pace. The susceptibility to temperature and humidity fluctuations exhibited a discernible increase as the marathon progressed. While weather conditions exerted discernible influences on running speeds and outcomes, they did not emerge as significant predictors of pacing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Weiss et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The sex difference in athletic performance has been thoroughly investigated in single sport disciplines such as swimming, cycling, and running. In contrast, only small samples of long-distance triathlons, such as the IRONMAN® triathlon, have been investigated so far., Aim: The aim of the study was to examine potential sex differences in the three split disciplines by age groups in 5-year intervals in a very large data set of IRONMAN® age group triathletes., Methods: Data from 687,696 (553,608 men and 134,088 women) IRONMAN® age group triathletes (in 5-year intervals from 18-24 to 75+ years) finishing successfully between 2002 and 2022 an official IRONMAN® race worldwide were analyzed. The differences in performance between women and men were determined for each split discipline and for the overall race distance., Results: Most finishers were in the age group 40-44 years. The fastest women were in the age group 25-29 years, and the fastest men were in the age group 30-34 years. For all split disciplines and overall race time, men were always faster than women in all groups. The performance difference between the sexes was more pronounced in cycling compared to swimming and running. From the age group 35-39 years until 60-64 years, the sex differences were nearly identical in swimming and running. For both women and men, the smallest sex difference was least significant in age group 18-24 years for all split disciplines and increased in a U-shaped manner until age group 70-74 years. For age groups 75 years and older, the sex difference decreased in swimming and cycling but increased in running. Considering the different characteristics of the race courses, the smallest performance gaps between men and women were found in river swimming, flat surface cycling and rolling running courses., Conclusions: The sex difference in the IRONMAN® triathlon was least significant in age group 18-24 years for all split disciplines and increased in a U-shaped manner until age group 70-74 years. For 75 years and older, the sex difference decreased in swimming and cycling but increased in running., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Knechtle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper reports the activity concentrations of 137Cs, 90Sr, 239+240Pu, 241Am, and 3Н in the form of tritiated water (НТО) and organically bound tritium (ОBТ) in the tissues and organs of roe deer (Capreolus pygargus Pal., 1771) that inhabit the 'Degelen' test location of the Semipalatinsk Test Site. Tissues and organs were sampled from six deer by killing. The activity concentrations of specific radionuclides in the samples were measured using γ-, α-, and β-spectrometry. The radionuclide activity concentrations in the tissues and organs showed considerable variation, for example, 0.6-170 Bq kg-1 for 137Cs and 0.3-2.8×103 Bq kg-1 for 90Sr. The activity concentrations of radionuclides in animal muscular tissue did not exceed permissible values for the meat of wild animals. The tissues and organs in the roe deer were arranged as follows in descending order of their ability to accumulate 137Cs and 90Sr: for 137Cs, muscular tissue-kidneys-lungs-spleen-heart-liver-bone tissue; for 90Sr, bone tissue-liver-lungs-muscular tissue-spleen-heart-kidneys. The activity concentrations of 241Am and 239+240Pu did not exceed the minimum detectable activity. Therefore, no quantitative values could be determined for 241Am, and the 239+240Pu activity concentration could be derived for only one sample: 0.5±0.1 Bq kg-1 (liver). The distribution pattern of these radionuclides in the tissues and organs of the roe deer could not be determined because of insufficient data. The HTO volumetric activity in the tissues and organs of the examined animals ranged from 2.6×10-2 to 77 kBq l-1; activity concentration of OBT, 3.0×10-2 to 16 kBq kg-1; and OBT-to-HTO ratios, 2.0×10-3 to 5.3×102. This ratio can serve as an indicator of how long the examined animals stay in radioactively contaminated ecosystems. Within the 'Degelen' site, the activity concentrations of 90Sr and tritium, in the form of HTO and OBT, are expected to be high in the bone tissues, soft tissues, and organs, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Panitskiy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Colon polyps represent a common gastrointestinal form. In order to effectively treat and prevent complications arising from colon polyps, colon polypectomy has become a commonly used therapeutic approach. Accurately segmenting polyps from colonoscopy images can provide valuable information for early diagnosis and treatment. Due to challenges posed by illumination and contrast variations, noise and artifacts, as well as variations in polyp size and blurred boundaries in polyp images, the robustness of segmentation algorithms is a significant concern. To address these issues, this paper proposes a Double Loss Guided Residual Attention and Feature Enhancement Network (DLGRAFE-Net) for polyp segmentation. Firstly, a newly designed Semantic and Spatial Information Aggregation (SSIA) module is used to extract and fuse edge information from low-level feature graphs and semantic information from high-level feature graphs, generating local loss-guided training for the segmentation network. Secondly, newly designed Deep Supervision Feature Fusion (DSFF) modules are utilized to fuse local loss feature graphs with multi-level features from the encoder, addressing the negative impact of background imbalance caused by varying polyp sizes. Finally, Efficient Feature Extraction (EFE) decoding modules are used to extract spatial information at different scales, establishing longer-distance spatial channel dependencies to enhance the overall network performance. Extensive experiments conducted on the CVC-ClinicDB and Kvasir-SEG datasets demonstrate that the proposed network outperforms all mainstream networks and state-of-the-art networks, exhibiting superior performance and stronger generalization capabilities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite developing new diagnostics, drugs, and vaccines, treating tuberculosis (TB) remains challenging. Monitoring inflammatory markers can contribute to more precise diagnostics of TB, identifying its active and latent forms, or monitoring its treatment success. We assessed alterations in plasma levels of 48 cytokines in 20 patients (17 males) with active pulmonary TB compared to age-matched healthy controls (n = 18). Blood samples were collected from individuals hospitalised with TB prior to commencing antibiotic therapy, after the first week, and following the third week. The majority of patients received treatment with a combination of four first-line antituberculosis drugs: rifampicin, isoniazid, ethambutol, and pyrazinamide. Plasmatic cytokine levels from patients three times and controls were analyzed using a Bio-Plex Pro Human Cytokine Screening Panel. The results showed significantly higher levels of 31 cytokines (p<0.05) than healthy controls. Three-week therapy duration showed significantly decreased levels of nine cytokines: interferon alpha-2 (IFN-α2), interleukin (IL) 1 alpha (IL-1α), IL-1 receptor antagonist (IL-1ra), IL-6, IL-10, IL-12 p40, IL-17, leukemia inhibitory factor (LIF), and tumor necrosis factor alpha (TNF-α). Out of these, only levels of IL-1α and IL-6 remained significantly elevated compared to controls. Moreover, we have found a negative correlation of 18 cytokine levels with BMI of the patients but no correlation with age. Our results showed a clinical potential for monitoring the levels of specific inflammatory markers after a short treatment duration. The reduction in cytokine levels throughout the course of therapy could indicate treatment success but should be confirmed in studies with more individuals involved and a longer observation period., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2024 Krivošová et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present study intended to determine the nationality of the fastest 100-mile ultra-marathoners and the country/events where the fastest 100-mile races are held. A machine learning model based on the XG Boost algorithm was built to predict the running speed from the athlete's age (Age group), gender (Gender), country of origin (Athlete country) and where the race occurred (Event country). Model explainability tools were then used to investigate how each independent variable influenced the predicted running speed. A total of 172,110 race records from 65,392 unique runners from 68 different countries participating in races held in 44 different countries were used for analyses. The model rates Event country (0.53) as the most important predictor (based on data entropy reduction), followed by Athlete country (0.21), Age group (0.14), and Gender (0.13). In terms of participation, the United States leads by far, followed by Great Britain, Canada, South Africa, and Japan, in both athlete and event counts. The fastest 100-mile races are held in Romania, Israel, Switzerland, Finland, Russia, the Netherlands, France, Denmark, Czechia, and Taiwan. The fastest athletes come mostly from Eastern European countries (Lithuania, Latvia, Ukraine, Finland, Russia, Hungary, Slovakia) and also Israel. In contrast, the slowest athletes come from Asian countries like China, Thailand, Vietnam, Indonesia, Malaysia, and Brunei. The difference among male and female predictions is relatively small at about 0.25 km/h. The fastest age group is 25-29 years, but the average speeds of groups 20-24 and 30-34 years are close. Participation, however, peaks for the age group 40-44 years. The model predicts the event location (country of event) as the most important predictor for a fast 100-mile race time. The fastest race courses were occurred in Romania, Israel, Switzerland, Finland, Russia, the Netherlands, France, Denmark, Czechia, and Taiwan. Athletes and coaches can use these findings for their race preparation to find the most appropriate racecourse for a fast 100-mile race time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Knechtle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The body mass index (BMI), defined as weight in kilograms divided by height in meters squared, has been widely used to assess thinness and obesity in all age groups, including children and adolescents. However, the validity and utility of BMI as a reliable measure of nutritional health have been questioned. This study discusses the mathematical conditions that support the validity of BMI based on population statistics. Here, we propose a condition defined as allometric uni-scaling to ensure the validity of BMI as an objective height-adjusted measure. Any given centile curve, including the median curve, in a weight-for-height distribution should be approximated using power-law functions with the same scaling exponent. In contrast, when the scaling exponent varies depending on the position of the centile curve, it is called allometric multi-scaling. By introducing a method for testing these scaling properties using quantile regression, we analyzed a large-scale Japanese database that included 7,863,520 children aged 5-17 years. We demonstrated the remarkable multi-scaling properties at ages 5-13 years for males and 5-11 years for females, and the convergence to uni-scaling with a scaling exponent close to 2 as they approached 17 years of age for both sexes. We confirmed that conventional BMI is appropriate as an objective height-adjusted mass measure at least 17 years of age, close to adulthood, for both males and females. However, the validity of BMI could not be confirmed in younger age groups. Our findings indicate that the growth of children's weight-for-height relation is much more complex than previously assumed. Therefore, a single BMI-type formula cannot be used to assess thinness and obesity in children and adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ogata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Peru, one-third of transgender women (TW) are estimated to be living with HIV. While TW are recognized as a priority population, their sexual partners are an at-risk hidden population with unmet needs for HIV services. We conducted a study examining the practices and preferences for HIV services among partners of transgender women (PTW), as compared to TW, to better understand the needs of PTW and inform HIV service delivery for them in Peru., Methods: Between July-October 2022 we conducted a cross-sectional mixed methods study among PTW and TW in Lima, Peru. Using an explanatory sequential design, we administered online surveys to PTW (n = 165) and TW (n = 69), then interviewed a subset of participants (n = 20: 16 PTW, 4 TW). We quantitatively and qualitatively described PTW practices/perspectives on HIV testing and treatment and compared them to TW practices/preferences; we also compared practices/preferences among PTW based on their relationship with TW., Results: Overall, PTW and TW shared similar experiences and preferences for HIV testing/treatment, but fewer PTW reported accessing non-traditional HIV testing options and PTW expressed less strong preferences for HIV services. PTW practices/preferences varied by type of relationship with TWs. Surveys and interviews highlighted a need to prioritize efficiency for HIV testing, eliminate gender/sexuality-based discrimination in healthcare settings, increase privacy when delivering HIV services, and increase awareness of pre-exposure prophylaxis., Conclusion: PTW identified many aspects related to the location, convenience, and privacy of HIV services as important. Next steps could include a discrete choice experiment to further clarify priorities for HIV services for PTW in Peru., Competing Interests: The authors have declared no competing interests., (Copyright: © 2024 Kazmirak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polyamines (PAs), including putrescine (Put), spermidine (Spd), and spermine (Spm), are essential polycations with wide-ranging roles in cellular functions. PA levels decline with age, making exogenous PA supplementation, particularly Spd, an intriguing prospect. Previous research in honey bees demonstrated that millimolar Spd added to their diet increased lifespan and reinforced oxidative resilience. The present study is aimed to assess the anti-aging effects of spermidine supplementation at concentrations of 0.1 and 1 mM in honey bees, focusing on autophagy and associated epigenetic changes. Results showed a more pronounced effect at the lower Spd concentration, primarily in the abdomen. Spd induced site-specific histone 3 hypoacetylation at sites K18 and 27, hyperacetylation at K9, with no change at K14 in the entire body. Additionally, autophagy-related genes (ATG3, 5, 9, 13) and genes associated with epigenetic changes (HDAC1, HDAC3, SIRT1, KAT2A, KAT6B, P300, DNMT1A, DNMT1B) were upregulated in the abdomens of honey bees. In conclusion, our findings highlight profound epigenetic changes and autophagy promotion due to spermidine supplementation, contributing to increased honey bee longevity. Further research is needed to fully understand the precise mechanisms and the interplay between epigenetic alterations and autophagy in honey bees, underscoring the significance of autophagy as a geroprotective mechanism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kojić et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Francisella tularensis, the causative agent of tularemia, is divided into three subspecies. Two of these, subspecies holarctica and tularensis, are highly pathogenic to humans and consequently relatively well studied. The third subspecies, mediasiatica, is rarely isolated and remains poorly studied. It is distributed in the sparsely populated regions of Central Asia and Siberia. Curently this subspecies is not known to have been responsible for human infections in spite of its high virulence in laboratory animals. Subspecies mediasiatica is currently divided into three subgroups-MI, present in Central Asia, MII, present in southern Siberia, and MIII represented by a unique strain, 60(B)57, isolated in Uzbekistan in 1960. We describe here the unexpected observation that MIII strain 60(B)57 is avirulent and immunogenic. We observed that infection with this strain protected mice from challenge 21 days later with a virulent subsp. mediasiatica strain. With an increase of this interval, the protection for mice was significantly reduced. In contrast, guinea pigs were protected from challenge with strains of the subspecies holarctica and mediasiatica (but not subsp. tularensis) 90 days after infection with 60(B)57. We performed genome assembly based on whole genome sequencing data obtained using the Nanopore MinION for strain 60(B)57 and two subsp. mediasiatica strains representing the Central Asian MI and Siberian MII phylogenetic subgroups. The prmA gene is truncated due to a nonsense mutation in strain 60(B)57. The deletion of gene prmA has previously been shown to induce a loss of virulence in Francisella novicida the closest model organism suggesting that the observed mutation might the cause of the avirulence of strain 60(B)57., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Timofeev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen's Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration, this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR-182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary., Competing Interests: the authors have declared that no competing interests exist., (Copyright: © 2024 Stefanović et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Workers with occupational exposure to respirable silica dust, such as casual labourers at road construction sites (RCSs), are known to be at high risk of developing pulmonary tuberculosis (TB). There is limited literature about the burden of PTB among this subpopulation with high occupational exposure to silica dust at road construction sites. We aimed to determine the prevalence of PTB among casual labourers working at road construction sites in central Uganda., Methods: We enrolled 297 participants via consecutive sampling in a cross-sectional study between September 1st and September 30th, 2022, at four road construction sites in four districts in central Uganda. A structured questionnaire was administered, and the PTB patients were identified by using GeneXpert and/or computer-aided detection for TB (CAD4TB). The data were analysed with STATA version 17.0. Descriptive statistics adjusted for clustering were used to summarize the data, and the relationships between PTB and independent variables were assessed by using a mixed effects modified Poisson regression model to estimate the adjusted prevalence ratios., Results: Most participants were males (95.6% [284/297]), and the median age was 29 years (interquartile range [IQR]: 25-33). The prevalence of PTB among casual labourers was 2.4% (95% CI: 1.9, 2.8). Not being vaccinated with BCG (3.45, 95% CI: 1.02, 11.61), alcohol use (2.70, 95% CI: 1.52, 4.80) and staying in shared rooms (8.13, 95% CI: 4.37, 15.12) were positively associated with having PTB., Conclusion: There is a high prevalence of PTB among casual labourers working at road construction sites in central Uganda. Individuals who had never been vaccinated with BCG, alcohol users and those staying in shared rooms were at an increased risk of having PTB. We recommend routine screening of casual labourers at road construction sites to optimize active TB case finding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahimbisibwe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Due to the increase in life expectancy and high-energy traumas, anterior column acetabular fractures (ACFs) are also increasing. While open reduction and internal fixation (ORIF) is still the standard surgical procedure, minimally invasive, percutaneous fixation of osteoporotic acetabulum fractures (AF) are growing in popularity. The aim of this biomechanical study was to evaluate the biomechanical competence following antegrade fixation with a standard screw versus a cannulated compression headless screw., Methods: Eight anatomical osteoporotic composite pelvises were given an anterior column fracture. Two groups of eight specimens each (n = 8) for fixation with either a 6.5 mm cannulated compression headless screw in group Anterior Acetabulum Canulated Compression Headless Screw (AACCH), or with a 6.5 mm partially threaded cannulated screw in group Anterior Acetabulum Standard Screw (AASS) where compared. Each specimen was biomechanically loaded cyclically at a rate of 2 Hz with monotonically increasing compressive load until failure. Motions were assessed by means of optical motion tracking., Results: Initial construct stiffness trended higher in group AACCH at 152.4 ± 23.1 N/mm compared to group AASS at 118.5 ± 34.3 N/mm, p = 0.051. Numbers of cycles and corresponding peak load at failure, were significantly higher in group AACCH at 6734 ± 1669 cycles and 873.4 ± 166.9 N versus group AASS at 4440 ± 2063 cycles and 644.0 ± 206.3 N, p = 0.041. Failure modes were breakout of the screws around the proximal entry point., Conclusion: From a biomechanical perspective, group AACCH was associated with superior biomechanical competence compared to standard partially threaded cannulated screws and could therefore be considered as valid alternative for fixation of anterior acetabulum fractures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Berk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The quantification of peak locomotor demands has been gathering researchers' attention in the past years. Regardless of the different methodological approaches used, the most selected epochs are between 1-, 3-, 5- and 15-minutes time windows. However, the selection of these time frames is frequently arbitrary. The aim of this study was to analyse the peak locomotor demands of short time epochs (15, 30, 45, and 60 seconds) in women's football, with special emphasis over the high-speed metrics. During two seasons, the match physical performance of 100 female football players was collected with Global Positioning System units (STATSports Apex). Peak locomotor demands for the selected variables were calculated by using a 1-second moving average approach. For statistical procedures, linear mixed modelling was used, with total distance, high-speed running distance (>16 km∙h-1), sprint distance (>20 km∙h-1), and acceleration and deceleration distance (±2.26 m∙s-2) considered as the dependent variables and the epoch lengths (15, 30, 45, and 60 seconds) considered as the independent variables. A novel finding was the high ratio observed in the 15 seconds epochs of high-speed running distance and sprint distance (77.6% and 91.3%, respectively). The results show that most peak high-speed demands within 60 seconds are completed within just 15 seconds. Thus, intensity-related variables, such as high-speed metrics, would be better contextualised and adapted into training practices if analysed in shorter epoch lengths (15-30 seconds), while longer periods might be used for volume-related metrics (i.e., total distance), depending on the purpose of the analysis., Competing Interests: The authors have read the journal’s policy and have the following competing interests: IB is affiliated with CIFI2D, which is financed by the Portuguese Foundation for Science and Technology (https://doi.org/10.54499/UIDB/05913/2020) outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2024 Baptista et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We have previously shown that polygenic risk scores (PRS) can improve risk stratification of peripheral artery disease (PAD) in a large, retrospective cohort. Here, we evaluate the potential of PRS in improving the detection of PAD and prediction of major adverse cardiovascular and cerebrovascular events (MACCE) and adverse events (AE) in an institutional patient cohort. We created a cohort of 278 patients (52 cases and 226 controls) and fit a PAD-specific PRS based on the weighted sum of risk alleles. We built traditional clinical risk models and machine learning (ML) models using clinical and genetic variables to detect PAD, MACCE, and AE. The models' performances were measured using the area under the curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), and Brier score. We also evaluated the clinical utility of our PAD model using decision curve analysis (DCA). We found a modest, but not statistically significant improvement in the PAD detection model's performance with the inclusion of PRS from 0.902 (95% CI: 0.846-0.957) (clinical variables only) to 0.909 (95% CI: 0.856-0.961) (clinical variables with PRS). The PRS inclusion significantly improved risk re-classification of PAD with an NRI of 0.07 (95% CI: 0.002-0.137), p = 0.04. For our ML model predicting MACCE, the addition of PRS did not significantly improve the AUC, however, NRI analysis demonstrated significant improvement in risk re-classification (p = 2e-05). Decision curve analysis showed higher net benefit of our combined PRS-clinical model across all thresholds of PAD detection. Including PRS to a clinical PAD-risk model was associated with improvement in risk stratification and clinical utility, although we did not see a significant change in AUC. This result underscores the potential clinical utility of incorporating PRS data into clinical risk models for prevalent PAD and the need for use of evaluation metrics that can discern the clinical impact of using new biomarkers in smaller populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Omiye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic was characterised by rapid waves of disease, carried by the emergence of new and more infectious SARS-CoV-2 virus variants. How the pandemic unfolded in various locations during its first two years has yet to be sufficiently covered. To this end, here we are looking at the circulating SARS-CoV-2 variants, their diversity, and hospitalisation rates in Estonia in the period from March 2000 to March 2022., Methods: We sequenced a total of 27,550 SARS-CoV-2 samples in Estonia between March 2020 and March 2022. High-quality sequences were genotyped and assigned to Nextstrain clades and Pango lineages. We used regression analysis to determine the dynamics of lineage diversity and the probability of clade-specific hospitalisation stratified by age and sex., Results: We successfully sequenced a total of 25,375 SARS-CoV-2 genomes (or 92%), identifying 19 Nextstrain clades and 199 Pango lineages. In 2020 the most prevalent clades were 20B and 20A. The various subsequent waves of infection were driven by 20I (Alpha), 21J (Delta) and Omicron clades 21K and 21L. Lineage diversity via the Shannon index was at its highest during the Delta wave. About 3% of sequenced SARS-CoV-2 samples came from hospitalised individuals. Hospitalisation increased markedly with age in the over-forties, and was negligible in the under-forties. Vaccination decreased the odds of hospitalisation in over-forties. The effect of vaccination on hospitalisation rates was strongly dependent upon age but was clade-independent. People who were infected with Omicron clades had a lower hospitalisation likelihood in age groups of forty and over than was the case with pre-Omicron clades regardless of vaccination status., Conclusions: COVID-19 disease waves in Estonia were driven by the Alpha, Delta, and Omicron clades. Omicron clades were associated with a substantially lower hospitalisation probability than pre-Omicron clades. The protective effect of vaccination in reducing hospitalisation likelihood was independent of the involved clade., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Päll et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety., Objective: Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence., Methods: This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable., Results: Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated., Conclusion: The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fernandes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adapters and Low-Rank Adaptation (LoRA) are parameter-efficient fine-tuning techniques designed to make the training of language models more efficient. Previous results demonstrated that these methods can even improve performance on some classification tasks. This paper complements existing research by investigating how these techniques influence classification performance and computation costs compared to full fine-tuning. We focus specifically on multilingual text classification tasks (genre, framing, and persuasion techniques detection; with different input lengths, number of predicted classes and classification difficulty), some of which have limited training data. In addition, we conduct in-depth analyses of their efficacy across different training scenarios (training on the original multilingual data; on the translations into English; and on a subset of English-only data) and different languages. Our findings provide valuable insights into the applicability of parameter-efficient fine-tuning techniques, particularly for multilabel classification and non-parallel multilingual tasks which are aimed at analysing input texts of varying length., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Razuvayevskaya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted people who use drugs (PWUD). This study explored relationships between drug use, COVID-19 testing, vaccination, and infection. This cross-sectional study was conducted in Miami, Florida between March 2021 and October 2022 as part of the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative and the Miami Adult Studies on HIV (MASH) cohort. Users of cannabis, cocaine/crack, heroin/fentanyl, methamphetamines, hallucinogens, and/or prescription drug misuse in the previous 12 months were considered PWUD. Sociodemographic data, COVID-19 testing history, and vaccination-related beliefs were self-reported. Vaccinations were confirmed with medical records and positivity was determined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Statistical analyses included chi-square tests and logistic regression. Of 1,780 participants, median age was 57 years, 50.7% were male, 50.2% Non-Hispanic Black, and 66.0% reported an annual income less than $15,000. Nearly 28.0% used drugs. PWUD were less likely than non-users to self-report ever testing positive for SARS-CoV-2 (14.7% vs. 21.0%, p = 0.006). However, 2.6% of participants tested positive for SARS-CoV-2, with no significant differences between PWUD and non-users (3.7% vs. 2.2%, p = 0.076). PWUD were more likely than non-users to experience difficulties accessing testing (10.2% vs. 7.1%, p = 0.033), vaccine hesitancy (58.9% vs. 43.4%, p = 0.002) and had lower odds of receiving any dose of a COVID-19 vaccine compared to non-users (aOR, 0.63; 95% CI, 0.49-0.81; p<0.001). PWUD presented with greater difficulties accessing COVID-19 testing, greater vaccine hesitancy, and lower odds of vaccination. Testing and immunization plans that are tailored to the needs of PWUD and consider access, trust-building campaigns, and education may be needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tamargo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive., Methodology: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data., Results: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic., Conclusion: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Musiime et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)