bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship Between the Electrically Evoked Stapedius Reflex Threshold and Stimulus Burst Duration in Pediatric Cochlear Implant Users: Preliminary Data
Authors: Walkowiak Adam , Kontides Alejandra , Takanen Marko , Obrycka Anita , Skarżyński Piotr , Skarżyński Henryk , Lorens Artur 
Published: November 2024

Introduction
The electrically evoked stapedius reflex threshold (eSRT) is an objective measure that helps to fit cochlear implants (CIs). The primary aim of this study was to investigate the relationship between different burst durations to elicit eSRT in pediatric CI users.

Materials and Methods
Different stimuli burst durations (100–500 ms) were applied to observe the effect in the reflex determination in 11 pediatric CI users. Reflexes were measured in electrode contacts #2, #6, #9, and #11. Testing was conducted at 9 months after CI activation.

Results
Burst duration and electrode contact site both had a significant effect on eSRT (p < 0.001). The lowest eSRT thresholds were obtained with the longest burst duration. The highest stimulation level was required to elicit a reflex at basal electrode contacts. No significant effect was found for the interaction between electrode contact site and burst duration.

Discussion
Burst durations of 100 ms yielded significantly larger eSRT thresholds than 300- and 500-ms burst durations. Thresholds obtained with the longest (i.e., traditional) burst durations reflected maximum comfortable loudness (MCL) levels typically found at early post-activation stages. In contrast, 100-ms burst yielded threshold levels similar to MCLs that have stabilized. We therefore consider both short (100 ms) and longer (300 or 500 ms) bursts useful in the clinical practice.

Conclusion
The best burst duration to use depends on the interval: longer burst durations are useful for estimating MCLs for earlier intervals, whereas shorter burst durations are useful for later intervals. These findings may help clinicians optimize fittings in cases where using behavioral responses is problematic.
Medicaid Policy and Hepatitis C Treatment Among Rural People Who Use Drugs
Authors: Stopka Thomas J. , Whitney Bridget M. , de Gijsel David , Brook Daniel L. , Friedmann Peter D. , Taylor Lynn E. , Feinberg Judith , Young April M. , Evon Donna M. , Herink Megan , Westergaard Ryan , Koepke Ruth , Havens Jennifer R. , Zule William A. , Delaney Joseph A. , Pho Mai T. 
Published: November 2024

Background:
Restrictive Medicaid policies regarding hepatitis C virus (HCV) treatment may exacerbate rural health care disparities for people who use drugs (PWUD). We assessed associations between Medicaid restrictions and HCV treatment among rural PWUD.

Methods:
We compiled state-specific Medicaid treatment policies across 8 US rural sites in 10 states and merged these with participant survey data. We hypothesized that local restrictions regarding prescriber type, sobriety, and fibrosis estimates were associated with HCV treatment outcomes. We conducted a cross-sectional, ecological analysis of treatment restrictions and HCV treatment outcomes using bivariate analyses to characterize differences between PWUD who initiated HCV treatment and unadjusted logistic regressions to assess associations between restrictions and treatment.

Results:
Among 944 participants, 111 (12%) reported receiving HCV treatment. Participants receiving treatment were older [median age (interquartile range): 42 (34–53) vs. 35 (29–42), P<0.001], more likely to receive disability support (32% vs. 20%, P=0.002), and less likely to be Medicaid-insured (57% vs. 71%, P < 0.001). More PWUD in states without any restrictions reported receiving treatment (17% vs. 11%, P=0.08) and achieving HCV cure/clearance (42% vs. 30%, P=0.01) than in states with restrictions. Restrictions were associated with lower odds of receiving HCV treatment (odds ratio=0.61, 95% CI: 0.35–1.06, P=0.08). Sensitivity analyses showed a similar association with HCV cure/clearance (odds ratio=0.60, 95% CI: 0.40–0.91, P=0.02).

Conclusions:
We identified significant unadjusted associations between Medicaid restrictions and receipt of HCV treatment and cure, which has substantial implications for health outcomes among rural PWUD. Lifting remaining Medicaid restrictions will be critical to achieving HCV elimination.
Spontaneous recovery of active shoulder external rotation in patients with brachial plexus birth injury
Authors: Hyttinen Maria , Rönkkö Henrikki , Paavilainen Pasi , Helminen Mika , Jokihaara Jarkko 
Published: November 2024

Background:
Brachial plexus birth injuries (BPBI) occur as a result of a difficult delivery. External rotation of shoulder (ER) is usually one of the last movements which may recover. There is no consensus about the predicting factors for spontaneous recovery or the optimal timing for surgical treatment of ER in BPBI patients. The aim of our retrospective study was to describe spontaneous recovery of active ER and evaluate predicting factors for the recovery.

Methods:
We screened 562 patients and identified a consecutive cohort of 103 BPBI patients, who had no active ER at the age of 3 months. We systematically collected clinical data on recovery. In addition, we assessed whether early recovery of elbow flexion, shoulder abduction or Narakas grade at 1 month predicts ER recovery.

Results:
Fifty-two (51%) patients spontaneously recovered ER, 44% of whom were recovered by the age of 1 year, 83% by 1.5 years, 92% by 2 years and 98% by 3 years. A breakpoint in the slope of the curve showing proportion of recovered patients occurred at 2 years of age. Recovery of active ER was significantly associated with early elbow flexion and Narakas grade at 1 month, but not with early active shoulder abduction.

Conclusions:
Most spontaneous recovery of ER in patients with BPBI occurs until 2 years of age, which thus can be considered a meaningful follow-up period for spontaneous recovery of ER. This information should be considered when making decision about peripheral nerve transfer surgery to improve ER in BPBI.
Evidence of 18F-FDG Utility in Rare Case of Metastatic Anal Melanoma With Prolonged Survival
Authors: Ranes Jennifer Marie Catherine , Ormaza Vera Ana Jamileth , Flynt Lesley 
Published: November 2024

Abstract
A 43-year-old woman presented with an anorectal mass at which time excision was performed, and biopsy revealed anorectal mucosal melanoma (AM), anal subtype. Postexcision, 18F-FDG PET/CT identified residual melanoma, confirmed on biopsy. Recurrence was monitored every 3 months using 18F-FDG, which identified a perirectal lymph node 2.5 years later positive for metastatic melanoma. Given the rarity of AM and often delayed diagnosis, patients often present with metastases, resulting in poor prognosis. This unique case of metastatic AM with prolonged survival of 7 years to date supports the implementation of 18F-FDG in the diagnostics and monitoring of AM.
Patterns of trauma-induced coagulopathy in injured children: A principal component analysis investigating endothelial, coagulation, and platelet biomarkers
Authors: Morgan Katrina M. , Feeney Erin V. , Spinella Philip C. , Gaines Barbara A. , Leeper Christine M. 
Published: November 2024

BACKGROUND
Trauma-induced coagulopathy is common and associated with poor outcomes in injured children. Our aim was to identify patterns of coagulopathy after injury using endothelial, platelet, and coagulation biomarkers, and associate these phenotypes with relevant patient factors and clinical outcomes in a pediatric trauma cohort.

METHODS
Principal component (PC) analysis was performed on data from injured children between 2018 and 2022. Laboratories included endothelial markers (syndecan-1, thrombomodulin, tissue factor, and vascular endothelial growth factor), international normalized ratio, platelet count, rapid thromboelastography maximum amplitude, and base deficit. Variables were reduced to PCs; PC scores were generated for each subject and used in logistic regression with outcomes including mortality, blood transfusion, shock (pediatric-adjusted shock index), and patient characteristics including age, sex, injury mechanism, and traumatic brain injury.

RESULTS
In total, 59 children had complete data for analysis. Median (interquartile range) age was 10 (4–14) years, 31% female, 21% penetrating mechanism, and median (interquartile range) injury severity score of 16 (9–21). Principal component analysis identified two significant PCs accounting for 67% of overall variance. PC1 included syndecan-1, thrombomodulin, vascular endothelial growth factor, international normalized ratio, and base deficit; PC1 scores were associated with mortality, blood transfusion, and shock (all p < 0.001). PC2 included tissue factor, platelet count, and rapid thromboelastography maximum amplitude; PC2 scores were associated with age (ρ = −0.42, p = 0.001) but no studied clinical outcome. Neither PC was significantly associated with sex, injury mechanism, or traumatic brain injury.

CONCLUSION
Principal component analysis detected two distinct biomarker patterns in injured children involving the domains of the endothelium, coagulation, and platelets. The first phenotype was associated with poor clinical outcomes, while the second was associated with age. This supports the concept that pediatric trauma-induced coagulopathy elicits a heterogeneous response, and suggests that there may be a prognostic value to these phenotypes that warrants further investigation.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Context-dependent effects of ivermectin residues on dung insects: Interactions with environmental stressors, size, and sex in a sepsid fly (Sepsis neocynipsea)
Authors: Walker Jill , Mathews Benjamin J. , Rohner Patrick T. 
Published: November 2024

AbstractInsects associated with livestock dung frequently encounter veterinary medication residues. These residues often have negative effects on insect survival, reproduction, and ecosystem functioning and may contribute to the rapid decline in temperate insect populations. Ivermectin is an antiparasitic drug widely used to treat parasites in livestock. While it has long been recognized that ivermectin effects insect survival, the potential interactive effects between ivermectin exposure and other ecologically relevant abiotic stressors remain poorly understood. Here, we study these effects in the black scavenger flySepsis neocynipsea, which depends on cow dung for reproduction. Using a fully factorial design, we test whether the effects of ivermectin exposure on adult survival interact with heat and desiccation stress, and whether these effects depend on size and sex. Ivermectin exposure had strong negative impacts on adult survival, but its effects were stronger in females and large individuals. While heat stress also had a strong effect on adult survival, the combined effects of heat and ivermectin exposure were less severe than the expected additive effects of both stressors applied independently, suggesting some cross-resistance. We did not find an interaction between ivermectin and desiccation stress. Taken together, our findings highlight how the complex interactions between insecticides and abiotic stressors could drive changes in coprophagous insect populations and their ecological functions across different ecosystems and climates.
Learning multi-cellular representations of single-cell transcriptomics data enables characterization of patient-level disease states
Authors: Liu Tianyu , De Brouwer Edward , Kuo Tony , Diamant Nathaniel , Missarova Alsu , Wang Hanchen , Hao Minsheng , Bravo Hector Corrada , Scalia Gabriele , Regev Aviv , Heimberg Graham 
Published: November 2024

AbstractSingle-cell RNA-seq (scRNA-seq) has become a prominent tool for studying human biology and disease. The availability of massive scRNA-seq datasets and advanced machine learning techniques has recently driven the development of single-cell foundation models that provide informative and versatile cell representations based on expression profiles. However, to understand disease states, we need to consider entire tissue ecosystems, simultaneously considering many different interacting cells. Here, we tackle this challenge by generatingpatient-levelrepresentations derived from multi-cellular expression context measured with scRNA-seq of tissues. We develop PaSCient, a novel model that employs a multi-level representation learning paradigm and provides importance scores at the individual cell and gene levels for fine-grained analysis across multiple cell types and gene programs characteristic of a given disease. We apply PaSCient to learn a disease model across a large-scale scRNA-seq atlas of 24.3 million cells from over 5,000 patients. Comprehensive and rigorous benchmarking demonstrates the superiority of PaSCient in disease classification and its multiple downstream applications, including dimensionality reduction, gene/cell type prioritization, and patient subgroup discovery.
Uncovering Bifurcation Behaviors of Biochemical Reaction Systems from Network Topology
Authors: Huang Yong-Jin , Okada Takashi , Mochizuki Atsushi 
Published: November 2024

AbstractThe regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited knowledge of reaction kinetics, bifurcation behaviors in biological systems remain largely underexplored. To address this, we developed a mathematical method, Structural Bifurcation Analysis (SBA), which decomposes the system into substructures and determines important aspects of bifurcation behaviors—such as substructures responsible for bifurcation conditions, bifurcation-inducing parameters, and bifurcating variables—solely from network topology. We establish a direct relationship between SBA and classical bifurcation analysis, enabling the study of systems even in the presence of conserved quantities. Additionally, we provide a step-by-step bifurcation analysis for general use. We applied our method to the macrophage M1/M2 polarization system. Our analysis reveals that the network structure strongly constrains possible patterns of polarization. We also clarify the dependency of the M1/M2 balance on gene expression levels and predict the emergence of intermediate polarization patterns under gene deletions, including SOCS3, which are experimentally testable.
A deletion at the X-linkedARHGAP36gene locus is associated with the orange coloration of tortoiseshell and calico cats
Authors: Toh Hidehiro , Au Yeung Wan Kin , Unoki Motoko , Matsumoto Yuki , Miki Yuka , Matsumura Yumiko , Baba Yoshihiro , Sado Takashi , Nakamura Yasukazu , Matsuda Miho , Sasaki Hiroyuki 
Published: November 2024

AbstractThe X-linkedorange(O) locus in domestic cats controls an unknown molecular mechanism that causes the suppression of black-brownish pigmentation in favor of orange coloration. The alternating black-brownish and orange patches seen in tortoiseshell and calico cats are considered as classic examples of the phenotypic expression of random X-chromosome inactivation (XCI) occurring in female mammals. However, theOgene in the cat genome has not been identified, and the genetic variation responsible for the orange coloration remains unknown. We report here that a 5.1-kilobase (kb) deletion within an intron of the X-linkedARHGAP36gene, encoding a Rho GTPase activating protein, is closely and exclusively associated with orange coloration. The deleted region contains a highly conserved putative regulatory element, whose removal presumably cause alteredARHGAP36expression. Notably,ARHGAP36expression in cat skin tissues is linked to the suppression of many melanogenesis genes, potentially shifting pigment synthesis from eumelanin to pheomelanin. Furthermore, we find evidence that the gene undergoes XCI in female human and mouse cells, and XCI-dependent CpG island methylation consistent with random XCI in female domestic cats. The 5.1-kb deletion seems widespread in domestic cats with orange coat coloration, suggesting a single origin of this coat color phenotype.
Fungal-derived tRNAs are expressed and aminoacylated in orchid mitochondria
Authors: Warren Jessica M. , Ceriotti Luis F. , Sanchez-Puerta M. Virginia , Sloan Daniel B. 
Published: November 2024

AbstractPlant mitochondrial genomes (mitogenomes) experience remarkable levels of horizontal gene transfer (HGT), including the recent discovery that orchids anciently acquired DNA from fungal mitogenomes. Thus far, however, there is no evidence that any of the genes from this interkingdom HGT are functional in orchid mitogenomes. Here, we applied a specialized sequencing approach to the orchidCorallorhiza maculataand found that fungal-derived tRNA genes are transcribed, post-transcriptionally modified, and aminoacylated. In contrast, all the transferred protein-coding sequences appear to be pseudogenes. These findings show that fungal HGT has altered the composition of the orchid mitochondrial tRNA pool and suggest that these foreign tRNAs function in translation. The exceptional capacity of tRNAs for HGT and functional replacement is further illustrated by the diversity of tRNA genes in theC. maculatamitogenome, which also include genes of plastid and bacterial origin in addition to their native mitochondrial counterparts.
Host traits and environmental variation shape gut microbiota diversity in wild threespine stickleback
Authors: Härer Andreas , Kurstjens Emma , Rennison Diana J. 
Published: November 2024

AbstractBackgroundDespite the growing recognition of the importance of gut microbiota in host ecology and evolution, our understanding of the relative contributions of host-associated and environmental factors shaping gut microbiota composition within and across wild populations remains limited. Here, we investigate how host morphology, sex, genetic divergence, and environmental characteristics influence the gut microbiota of threespine stickleback fish populations from 20 lakes on Vancouver Island, Canada.ResultsOur findings reveal substantial variation in gut microbiota composition and diversity among populations, with host traits exerting a stronger influence on bacterial alpha diversity than environmental characteristics. Host morphology, which is indicative of trophic ecology, was linked to gut microbiota divergence among populations, suggesting that dietary specialization may play a role in shaping the stickleback gut microbiota. Within and across populations, we only observed a weakly defined core microbiota and limited sharing of ASVs among hosts, indicating that gut microbiota composition is individualized. Additionally, we detected sex-dependent differences in microbial diversity, opening avenues for future research into the mechanisms driving this variation.ConclusionsIn sum, our study emphasizes the need to consider both host-associated and environmental factors in shaping gut microbiota dynamics and highlights the complex interplay between host organisms, their associated microbial communities, and the environment in natural settings. Ultimately, these insights enhance our understanding of host-microbiota interactions and their eco-evolutionary implications.
Cellular behavior analysis from live-cell imaging of TCR T cell–cancer cell interactions
Authors: Verma Archit , Yu Changhua , Bachl Stefanie , Lopez Ivan , Schwartz Morgan , Moen Erick , Kale Nupura , Ching Carter , Miller Geneva , Dougherty Tom , Pao Ed , Graf William , Ward Carl , Jena Siddhartha , Marson Alex , Carnevale Julia , Van Valen David , Engelhardt Barbara E 
Published: November 2024

ABSTRACTT cell therapies, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cells, are a growing class of anti-cancer treatments. However, expansion to novel indications and beyond last-line treatment requires engineering cells’ dynamic population behaviors. Here we develop the tools forcellular behavior analysisof T cells from live-cell imaging, a common and inexpensive experimental setup used to evaluate engineered T cells. We first develop a state-of-the-art segmentation and tracking pipeline,Caliban, based on human-in-the-loop deep learning. We then build theOccidentpipeline to collect a catalog of phenotypes that characterize cell populations, morphology, movement, and interactions in co-cultures of modified T cells and antigen-presenting tumor cells. We use Caliban and Occident to interrogate how interactions between T cells and cancer cells differ when beneficial knock-outs ofRASA2andCUL5are introduced into TCR T cells. We apply spatiotemporal models to quantify T cell recruitment and proliferation after interactions with cancer cells. We discover that, compared to a safe harbor knockout control,RASA2knockout T cells have longer interaction times with cancer cells leading to greater T cell activation and killing efficacy, whileCUL5knockout T cells have increased proliferation rates leading to greater numbers of T cells for hunting. Together, segmentation and tracking from Caliban and phenotype quantification from Occident enable cellular behavior analysis to better engineer T cell therapies for improved cancer treatment.
Chaperonin TRiC bridges radial spokes for folding proteins locally translated in mammalian sperm flagella
Authors: Meng Xueming , Li Luan , Lin Cheng , Zhu Yun , Feng Yanyan , Zhou Xuehai , Tong Yujie , Wang Shanshan , Yin Guoliang , Liu Ruimin , Sun Fei , Yan Xiumin , Zhu Xueliang , Cong Yao 
Published: November 2024

AbstractAs animals evolved from external to internal fertilization, sperm flagella, which once transiently propelled sperm in water to reach nearby eggs, developed to beat for days or even longer within the female reproductive tract. How flagella were remodeled accordingly remains unclear. Unlike externally fertilizing zebrafish and sea urchin, mammalian sperm flagella feature a unique barrel-shaped bridge between axonemal radial spokes RS1 and RS2, though its components and function remain unknown. Here, using cryo-EM and cryo-ET combined with mass spectrometry and immunofluorescence staining, we reveal that this RS1-RS2 barrel (RRB) in mammalian sperm flagella is a group II chaperonin TRiC/CCT. We purified and resolved the unforeseen cryo-EM structure of TRiC from bovine sperm flagella, discovering that flagella TRiC contains the testis-specific CCT6B subunit. Additionally, we resolved the cryo-ET map of mouse sperm flagella RSs, containing the RRB, achieving unprecedented local resolution of 10-14 Å. Thein-situRRB map displays two extra densities within its chambers in a polarized manner, suggesting the presence of folding substrates and a co-chaperone (likely phosducin-like 2). Notably, mammalian flagella also contain components of translation machineries and actively synthesize proteins. Our results suggest that the RRB TRiC folds locally translated proteins to sustain mammalian flagella, providing new insights into flagellar remodeling in internally fertilizing species. Our findings also shed lights on male fertility and potential treatments for infertility.