bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a home quantitative sensory testing tool-kit to assess changes in sensory and pain processing: a study in healthy young adults
Authors: Ocay Don Daniel , Lobo Kimberly , Kim Angela , Halpin Meghan , Berde Charles B. 
Published: July 2024

Abstract
Quantitative sensory testing (QST) is a set of methods for quantifying somatosensory functioning. Limitations of laboratory-based QST (LQST) include high cost, complexity in training, lack of portability, and time requirements for testing. Translating QST to a home setting could facilitate future research and clinical care. The objective of this study was to develop a home QST (HQST) tool-kit that is cost-effective, easy to use, and detects changes in sensory and pain processing. Thirty-two young healthy adults underwent sensory testing on their nondominant forearm using standard in-person LQST, followed by “simulated HQST” using video guidance in a separate room from the investigator before and after application of either a lidocaine or capsaicin cream. We observed good agreement between HQST and LQST scores, with significant correlations observed between the pinprick, pressure, cold and heat measures (|ρ| range = 0.36-0.54). The participants rated the HQST protocol as highly acceptable and safe but can be improved in future implementations. Home QST was able to detect hypoesthesia to vibration after lidocaine cream application (P = 0.024, d = 0.502) and could detect hypoalgesia and hyperalgesia to pressure and heat pain sensitivity tests after application of lidocaine and capsaicin creams, respectively (P-value range = <0.001-0.036, d-value range = 0.563-0.901). Despite limitations, HQST tool-kits may become a cost-effective, convenient, and scalable approach for improving sensory profiling in clinical care and clinical research.
Vitamin D Status and Cardiovascular Disease in College Athletes After SARS-CoV-2 Infection
Authors: Hollabaugh William L. , Hymel Alicia , Pennings Jacquelyn S. , Clark Daniel E. , Soslow Jonathan H. , Karpinos Ashley R. 
Published: July 2024

Objective:
To evaluate the association between vitamin D status and CV disease after COVID-19 in college athletes.

Design:
Retrospective cohort study.

Setting:
National College Athletic Association Division-I college athletes from a single academic institution.

Patients:
A total of 157 athletes (60 female; median age: 20 years) from 9 sports with a positive SARS-CoV-2 test, cardiac magnetic resonance imaging (CMR), and vitamin D level.

Independent Variables:
Serum 25-hydroxyvitamin D level (primary); age, sex (regression models).

Main Outcomes Measures:
Differences in age, sex, race, ethnicity, myocarditis, pericarditis, and CMR metrics by vitamin D status were analyzed. Regression models were used to assess the relationship between vitamin D status and CMR metrics accounting for age and sex.

Results:
Low vitamin D (LVD) was found in 33 (21.0%) of athletes, particularly Black males (P < 0.001). Athletes with LVD had higher biventricular and lower mid-ventricular extracellular volumes, but these differences were not significant when corrected for age and sex. Athletes with LVD had higher left ventricle (LV) mass (P < 0.001) and LV mass index (P = 0.001) independent of age and sex. Differences in global circumferential strain were noted but are likely clinically insignificant. Vitamin D status did not associate with myocarditis and pericarditis (P = 0.544).

Conclusions:
LVD is common in athletes, particularly in Black males. Although athletes with LVD had higher LV mass, cardiac function and tissue characterization did not differ by vitamin D status. Future studies are needed to determine if the differences in LV mass and LV mass index by vitamin D status are clinically significant. This study suggests that vitamin D status does not impact the development of myocarditis or pericarditis after COVID-19 infection.
Gender Diversity Among Reconstructive Microsurgery Studies Based on the Relative Citation Ratio
Authors: Falcon Dominick J. , Bustos Valeria P. , Mahmoud Amir-Ala , Lee Bernard T. 
Published: July 2024

Background
Gender disparities in plastic surgery authorship have been previously described in the literature. The relative citation ratio (RCR) index is a new metric that normalizes citation rates for field and time, which can be utilized to compare authors. This study aims to evaluate differences in gender authorship in reconstructive microsurgery (RM) papers, as well as the impact of gender on the RCR index.

Methods
A PubMed query isolated RM studies between 2002 and 2020 across the 3 highest impact PS journals. Author names and RCR information were collected from NIH iCite. The likely gender was adjudicated by using NamSor-Software. Unpaired Wilcoxon rank-sum and chi-square tests were used to assess differences between groups.

Results
Of 1146 articles (2172 authors), there was a significant difference between the proportion of females as senior authors compared to first authors (P < 0.001). Overall, females represented 15.4% of all authors, 19.7% of first authors, and 11.3% of senior authors. Males had a significantly higher weighted RCR (P < 0.0001) and number of publications (P < 0.0001), which remained significant when stratified by first and senior author. Female authors collectively had a higher mean RCR (P = 0.008) and among first authors (P < 0.0001), with no significant difference among senior authors (P = 0.47).

Conclusion
A considerably greater number of males are publishing in reconstructive microsurgery compared to females, with significantly more males being senior authors compared to first authors. Males had higher weighted RCR scores and publications compared to females. This study suggests that equity in gender authorship within the field is yet to be achieved.
Representation of Racial Diversity on US Plastic Surgery Websites: A Cross-sectional Study
Authors: Escobar-Domingo Maria J. , Mahmoud Amir-Ala , Lee Daniela , Taritsa Iulianna , Foppiani Jose , Hernandez Alvarez Angelica , Schuster Kirsten , Lin Samuel J. , Lee Bernard T. 
Published: July 2024

Background
The racial diversity portrayed in plastic and reconstructive surgery (PRS) media is an important indicator of an inclusive environment for potential patients. To evaluate the degree to which PRS websites demonstrate inclusivity, we assessed the racial composition of both patients and plastic surgeons depicted on the most visited academic and private PRS websites to determine the extent to which racial diversity is represented.

Methods
A cross-sectional study was conducted in September 2023. The 10 most visited websites in each state were identified. Sociodemographic characteristics including race and sex of patients and plastic surgeons, as well as the type of practice, were collected. Race was classified according to individuals' Fitzpatrick Phototypes into White and non-White. Differences in patient and surgeon representation were compared to the 2020 US Census and the 2020 ASPS demographics using χ2 tests. Subgroup analyses were conducted to identify differences by type of practice and region.

Results
We analyzed a total of 2,752 patients from 462 websites belonging to 930 plastic surgeons. PRS websites were predominantly from private practices (93%). Regarding patient representation, 92.6% were female, 7.4% were male, 87.6% were White, and 12.4% were non-White. The surgeon population on the studied webpages was 75.1% male, 92.1% White, and 7.8% non-White. Statistically significant differences were found in the patient population when compared to the 2020 national (P < 0.001) and regional (P < 0.001) US Census demographics and the 2020 ASPS Statistics Report (P < 0.001). Although minority representation was significantly higher on academic websites compared to private practice (22.9% vs. 12.1%; P = 0.007), both were significantly lower than the percentage of minority patients undergoing PRS.

Conclusions
This study illuminates racial disparities in the representation of racial groups among patients and plastic surgeons in the most frequented plastic surgery websites. Moreover, it underscores the imperative to bolster racial diversity within the digital content of both private and academic PRS websites. Greater racial representation can foster a more inclusive perception of the plastic surgery field, which may potentially broaden access to care and enrich the professional landscape.
Control of Modular Tissue Flows Shaping the Embryo in Avian Gastrulation
Authors: Serrano Nájera Guillermo , Plum Alex M. , Steventon Ben , Weijer Cornelis J. , Serra Mattia 
Published: July 2024

AbstractAvian gastrulation requires coordinated flows of thousands of cells to form the body plan. We quantified these flows using their fundamental kinematic units: one attractor and two repellers constituting its Dynamic Morphoskeleton (DM). We have also elucidated the mechanistic origin of the attractor, marking the primitive streak (PS), and controlled its shape, inducing gastrulation flows in the chick embryo that are typical of other vertebrates. However, the origins of repellers and dynamic embryo shape remain unclear. Here, we address these questions using active matter physics and experiments. Repeller 1, separating the embryo proper (EP) from extraembryonic (EE) tissues, arises from the tug-of-war between EE epiboly and EP isotropic myosin-induced active stress. Repeller 2, bisecting the anterior and posterior PS and associated with embryo shape change, arises from anisotropic myosin-induced active intercalation in the mesendoderm. Combining mechanical confinement with inhibition of mesendoderm induction, we eliminated either one or both repellers, as predicted by our model. Our results reveal a remarkable modularity of avian gastrulation flows delineated by the DM, uncovering the mechanistic roles of EE epiboly, EP active constriction, mesendoderm intercalation and ingression. These findings offer a new perspective for deconstructing morphogenetic flows, uncovering their modular origin, and aiding synthetic morphogenesis.
stormTB: A web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments
Authors: Visintainer Roberto , Fochesato Anna , Boaretti Daniele , Giampiccolo Stefano , Watson Shayne , Levi Micha , Reali Federico , Marchetti Luca 
Published: July 2024

AbstractIntroductionTuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability. Drug-specific models are often tied to commercial software and developed on various platforms and languages, potentially hindering access and complicating the comparison of different compounds.MethodsThis work introduces stormTB: SimulaTOr of a muRine Minimal-pbpk model for anti-TB drugs. It is a web-based interface for our minimal physiologically based pharmacokinetic (mPBPK) platform, designed to simulate custom treatment scenarios for tuberculosis in murine models. The app facilitates visual comparisons of pharmacokinetic profiles, aiding in assessing drug-dose combinations.ResultsThe mPBPK model, supporting 11 anti-TB drugs, offers a unified perspective, overcoming the potential inconsistencies arising from diverse modeling efforts. The app, publicly accessible, provides a user-friendly environment for researchers to conduct what-if analyses and contribute to collective TB eradication efforts. The tool generates comprehensive visualizations of drug concentration profiles and pharmacokinetic/pharmacodynamic indices for TB-relevant tissues, empowering researchers in the quest for more effective TB treatments. stormTB is freely available at the link:https://apps.cosbi.eu/stormTB.
Structurally targeted mutagenesis identifies key residues supporting α-synuclein misfolding in multiple system atrophy
Authors: Reis Patricia M. , Holec Sara A. M. , Ezeiruaku Chimere , Frost Matthew P. , Brown Christine K. , Liu Samantha L. , Olson Steven H. , Woerman Amanda L. 
Published: July 2024

ABSTRACTMultiple system atrophy (MSA) and Parkinson’s disease (PD) are caused by misfolded α-synuclein spreading throughout the central nervous system. While familial PD is linked to several point mutations in α-synuclein, there are no known mutations associated with MSA. Our previous work investigating differences in α-synuclein misfolding between the two disorders showed that the familial PD mutation E46K inhibits replication of MSA prions bothin vitroandin vivo, providing key evidence to support the hypothesis that α-synuclein adopts unique strains in patients. Here, to further interrogate α-synuclein misfolding, we engineered a panel of cell lines harboring both PD-linked and novel mutations designed to identify key residues that facilitate α-synuclein misfolding in MSA. These data were paired within silicoanalyses using Maestro software to predict the effect of each mutation on the ability of α-synuclein to misfold into one of the reported MSA cryo-electron microscopy conformations. In many cases, our modeling accurately identified mutations that facilitated or inhibited MSA replication. However, Maestro was occasionally unable to predict the effect of a mutation on MSA propagationin vitro, demonstrating the challenge of using computational tools to investigate intrinsically disordered proteins. Finally, we used our cellular models to determine the mechanism underlying the E46K-driven inhibition of MSA replication, finding that the E46/K80 salt bridge is necessary to support α-synuclein misfolding. Overall, our studies use a structure-based approach to investigate α-synuclein misfolding, resulting in the creation of a powerful panel of cell lines that can be used to interrogate MSA strain biology.
Loss of conserved noncoding elements likely shaped the evolution of regressed phenotypes in cavefish
Authors: Lal Mohan , Bhattacharya Jui , Sandhu Kuljeet Singh 
Published: July 2024

AbstractThe Mexican cavefish, Astyanaxmexicanus, is a captivating model for probing cave adaptations, showcasing pronounced divergence in traits like vision, brain morphology, behaviour, pigmentation, and hypoxia tolerance compared to its surface-dwelling counterpart. Very few protein-coding variants are identified in cave-morphs, and the vast phenotypic gap between the two morphs remains inadequately explained. We investigated the noncoding genomes of teleosts and found that 3,343 conserved non-coding elements (CNEs) were independently lost in cave-morphs. These CNEs, confirmed in Zebrafish, displayed enhancer-associated histone modifications, possessed binding sites of neuronal transcription factors and interacted with cognate genes through chromatin loops. Genes crucial for eye and nervous system development were located adjacent to CNEs lost in cave morphs. Notably, these flanking genes were gradually downregulated during embryonic development of cave-morphs, contrasting with surface morphs. These insights underscore how compromised developmental pathways, stemming from the loss of distal regulatory elements, contribute to the regression of phenotypes in cave morphs.Article SummaryDespite availability of genome sequences and allied datasets, the genetic underpinning of regressed traits of cavefish remains enigmatic. By aligning the genome sequences of teleosts, we identified thousands of noncoding elements specifically lost in cavefish, exhibited enhancer-associated hallmarks, and were enriched with the binding sites of neuronal transcription factors. Their cognate genes were associated with eye and nervous system development, and exhibited developmental downregulation in cavefish. This study highlights how the loss of regulatory elements impacted the cavefish evolution and adaptation.
BacTermFinder: A Comprehensive and General Bacterial Terminator Finder using a CNN Ensemble
Authors: Taheri Ghahfarokhi Seyed Mohammad Amin , Peña-Castillo Lourdes 
Published: July 2024

AbstractA terminator is a DNA region that ends the transcription process. Currently, multiple computational tools are available for predicting bacterial terminators. However, these methods are specialized for certain bacteria or terminator type (i.e., intrinsic or factor-dependent). In this work, we developed BacTermFinder using an ensemble of Convolutional Neural Networks (CNNs) receiving as input four different representations of terminator sequences. To develop BacTermFinder, we collected roughly 41k bacterial terminators (intrinsic and factor-dependent) of 22 species with varying GC-content (from 28% to 71%) from published studies that used RNA-seq technologies. We evaluated BacTermFinder’s performance on terminators of five bacterial species (not used for training BacTermFinder) and two archaeal species. BacTermFinder’s performance was compared with that of four other bacterial terminator prediction tools. Based on our results, BacTermFinder outperforms all other four approaches in terms of average recall without increasing the number of false positives. Moreover, BacTermFinder identifies both types of terminators (intrinsic and factor-dependent) and generalizes to archaeal terminators. Additionally, we visualized the saliency map of the CNNs to gain insights on terminator motif per species. BacTermFinder is publicly available athttps://github.com/BioinformaticsLabAtMUN/BacTermFinder.
Independent genetic mapping experiments identify diverse molecular determinants of host adaptation in a generalist herbivore
Authors: Villacis-Perez Ernesto , Graeve Femke De , Beer Berdien De , Alshami Seham Ali , de Jong Rick , Meyer Tim De , Leeuwen Thomas Van 
Published: July 2024

AbstractInteractions between plants and herbivores promote evolutionary change. Studying the evolution of herbivore mechanisms aimed to cope with diUerent host plant species is a critical intersection between evolutionary biology and sustainable pest management. Generalist herbivores are of particular interest, as hybridization between genetically distinct populations can increase the standing genetic variation and therefore the adaptive potential of the species.Tetranychus urticaeis a generalist arthropod known for its adaptive potential, evidenced in its immense host range and ability to develop metabolic resistance to xenobiotics. However, the molecular underpinnings associated with the potential of host adaptation and the consequences of host adaptation in this and many other pests remain elusive. Here, we use two independent, empirical approaches to identify and map the genetic basis of host plant performance and adaptation in genetically distinct populations ofT. urticae. In the first approach, we subject a genetically diverse mite population to tomato selection and map genomic regions linked to the phenotypic evolution of increased reproductive performance. In the second approach, we map genomic regions responsible for performance on tomato by comparing the genomes of pooled individuals from a F2 backcross between populations with high and low reproductive performance. Both approaches revealed specific and shared genomic regions associated with host plant performance and adaptation and key candidate genes were identified. Our findings highlight the power of spider mite genetic approaches to identify the complex genetic basis of host adaptation in a generalist herbivore.
Soil microbial responses to multiple global change factors as assessed by metagenomics
Authors: Rodríguez del Río Álvaro , Rillig Matthias C. 
Published: July 2024

ABSTRACTAnthropogenic activities impose multiple concurrent pressures on soil ecosystems at a global scale, but the response of soil microbes to multiple concurrent global change (GC) factors is poorly understood. Here, we applied 10 GC treatments individually and in random combinations of 8 factors to soil samples, and monitored their bacterial and viral composition by metagenomic analysis. The application of multiple GC factors selects for particular prokaryotic and viral communities different from the effects of any individual factor, favoring, for instance, potentially pathogenic unknown mycobacteria and novel viruses. At the functional level, multiple GC factors select for sessile and non-biofilm-forming bacteria which are metabolically diverse and show a high load of antibiotic resistance genes. Finally, we show that novel genes are also relevant for understanding microbial response to GC. Our study indicates that multiple GC factors impose directional selective pressures on soil prokaryotes and viruses not observed at the individual GC factor level, and improves our understanding of how GC interactions shape microbial communities.
Targeting prostate cancer by new bispecific monocyte engager directed to prostate-specific membrane antigen
Authors: Das Gargi , Ptacek Jakub , Havlinova Barbora , Nedvedova Jana , Barinka Cyril , Novakova Zora 
Published: July 2024

AbstractProstate cancer (PCa) ranks as the second leading cause of cancer-related deaths among men in the United States. Prostate-specific membrane antigen (PSMA) represents a well-established biomarker of PCa and its levels correlate positively with the disease progression, culminating at the stage of metastatic castration-resistant prostate cancer. Due to its tissue-specific expression and cell surface localization, PSMA shows superior potential for precise imaging and therapy of PCa. Antibody-based immunotherapy targeting PSMA offers the promise of selectively engaging the host immune system with minimal off-target effects.Here we report on the design, expression, purification, and characterization of a bispecific engager, termed 5D3-CP33, that efficiently recruits macrophages to the vicinity of PSMA-positive cancer cells mediating PCa death. The engager was engineered by fusing the anti-PSMA 5D3 antibody fragment to a cyclic peptide 33 (CP33) selectively binding the Fc gamma receptor I (FcγRI/CD64) on the surface of phagocytes. Functional parts of 5D3-CP33 engager revealed nanomolar affinity for PSMA and FcγRI/CD64 with dissociation constants of KD= 3 nM and KD= 140 nM, respectively. At a concentration as low as 0.3 nM, the engager was found to trigger production of reactive oxygen species by U937 monocytic cells in the presence of PSMA-positive cells. Moreover, flow cytometry analysis demonstrated antibody-dependent cell-mediated phagocytosis of PSMA-positive cancer cells by U937 monocytes when exposed to 0.1 nM 5D3-CP33. Our findings illustrate that 5D3-CP33 effectively and specifically activates monocytes upon PSMA-positive target engagement, resulting in the elimination of tumor cells. The 5D3-CP33 engager can thus serve as a promising lead for the development of new immunotherapy tools for the efficient treatment of PCa.