bluuebunny/crossref_metadata_2025_split huggingface dataset:
Underdiagnosis Bias of Chest Radiograph Diagnostic AI can be Decomposed and Mitigated via Dataset Bias Attributions
Authors: Kobayashi Yuta , Zhang Haoran , Singh Harvineet , Gichoya Judy Wawira , Joshi Shalmali 
Published: January 2025

ABSTRACTInequitable diagnostic accuracy is a broad concern in AI-based models. However, current characterizations of bias are narrow, and fail to account for systematic bias in upstream data-collection, thereby conflating observed inequities in AI performance with biases due to distributional differences in the dataset itself. This gap has broad implications, resulting in ineffective bias-mitigation strategies. We introduce a novel retrospective model evaluation procedure that identifies and characterizes the contribution of distributional differences across protected groups that explain population-level diagnostic disparities. Across three large-scale chest radiography datasets, we consistently find that distributional differences in age and confounding image attributes (such as pathology type and size) contribute to poorer model performance across racial subgroups. By systematically attributing observed underdiagnosis bias to distributional differences due to biases in the data-acquisition process, or dataset biases, we present a general approach to disentangling how different types of dataset biases interact and compound to create observable AI performance disparities. Our method is actionable to aid the design of targeted interventions that recalibrate foundation models to specific subpopulations, as opposed to methods that ignore systematic contributions of upstream data biases on inequitable AI performance.
Community Informed Approach for Designing Seasonal Malaria Chemoprevention Delivery in Semi-Nomadic Population in Turkana Central Sub-County, Kenya: Results from Baseline Mixed-Methods Study
Authors: Kostandova Natalya , Kafu Catherine , Chepkwony Tabitha J. , Ambani George , Abel Lucy , Rotich Beatrice , Kirui Joseph Kipkoech , Kimachas Emmah , Robie Emily , Lowoi Kaman , Ekai David , Lokoel Gilchrist , Orinda Omalo , Hulle Suzanne Van , Mgeni Robert , O’Meara Wendy Prudhomme , Wesolowski Amy , Genberg Becky , Menya Diana 
Published: January 2025

AbstractFollowing the expansion of the World Health Organization’s guidelines on eligibility for the seasonal malaria chemoprevention (SMC), the government of Kenya prepared to implement SMC for a first time in Turkana Central Sub-County in 2024. To inform design of SMC, we conducted a baseline qualitative and quantitative study. Using a stratified cluster sampling approach, we enrolled 198 households with children 6 months - 5 years old, and tested all individuals one year and older using a Rapid Diagnostic Test (RDT) and polymerase chain reaction (PCR). We carried out 82 key informant interviews, 31 focus group discussions with community health workers, elders, and caretakers of children, and 60 In-depth interviews with caretakers. Malaria prevalence was 21% [9%-42%] as reported by RDT and 21% [11%-38%] by PCR. Prevalence varied across villages, with the highest positivity of 73% by PCR. While SMC was perceived positively, challenges identified included physical access (households far from village centers, pastoralists, children living in the streets); stigma (children living with disabilities, households with members struggling with alcohol use); and acceptability (traditionalists, highly educated households). This study found that while malaria burden is high in the region, SMC may be a feasible approach to reduce its burden and transmission. However, implementation of SMC should be tailored, with a combination of centralized distribution supplemented by door-to-door and outreach to pastoralists and people in the interior. Using existing grassroots structures, such as Tree of Men and religious and group leaders, and intensive mobilization will be critical for success of this intervention.
Foxg1 and companions: not only transcription factors
Authors: Mallamaci Antonello , Artimagnella Osvaldo , Liuzzi Gabriele 
Published: January 2025

ABSTRACTHere, moving from our most recent results on Foxg1 biology, we firstly summarize available information about a few, special pleiotropic effectors of neurodevelopmental interest, involved in control of both transcription and post-transcriptional steps of gene expression. Next, upon further scanning of literature, we report evidence that, not strictly limited to neurodevelopmental processes, such functional pleiotropy also applies to other transcription factors, involved in physiology and homeostasis. Besides, by systematic mining of a major public protein-protein interaction database, we collect robust evidence that an involvement of “canonical” transcription factors in post-transcriptional control of gene expression may be a pervasive phenomenon, characterizing hundreds of effectors. Finally, we discuss the biological meaning of these findings and propose three evolutionary mechanisms that may have conspired to such unexpected scenario.
Modulation of Common Synaptic Inputs and Motor Unit Recruitment Threshold in Triceps Surae Muscles: Effects of Ankle Position
Authors: Yu Xin Sienna , Levine Jackson T. , Pons José L. 
Published: January 2025

AbstractThe objective of this study was to investigate how altering muscle length by changing ankle position affects force control, motor unit recruitment, and motor unit coherence within and across triceps surae muscles. Sixteen healthy young adults performed isometric plantarflexion (PF) at three ankle positions with the ankle plantarflexed at 20° (PF20°), at the neural position (PF0°) and dorsiflexed at 20° (DF20°). High-density surface electromyography was used to record the medial and lateral heads of the gastrocnemius muscle (GM and GL), and the medial and lateral portions of the soleus muscle (SL and SM). Motor unit cumulative spike trains (MUCST) were used to calculate intramuscular, intermuscular, and Force-MUCST coherence in the delta (0-5 Hz), alpha (5-15 Hz), and beta (15-35 Hz) frequency bands. Changing the ankle position from a shortened to lengthened position resulted in increased GM-SM coherence in the delta and alpha bands and improved force steadiness, while intramuscular coherence and Force-MUCST coherence decreased in the alpha band. However, there were minimal changes in beta band coherence. Motor unit recruitment thresholds of GM and SL were reduced with muscle lengthening, while GL showed greater thresholds at lengthened positions, and SM was unaffected by ankle position. These findings highlight the role of inhibitory inputs associated with changes in muscle length and the modulation of these inputs by neighboring synergistic muscles. This study reveals a neuromuscular control strategy that modulates common synaptic inputs and motor unit recruitment of triceps surae to maintain force output during isometric plantarflexions at varying muscle lengths.Key pointsWhen comparing isometric contractions at different ankle joint angles, a lengthened position resulted in greater shared common inputs between the medial head of the gastrocnemius and the medial compartment of the soleus in delta and alpha frequency bands during submaximal force production.Increased muscle length resulted in improved force steadiness, as well as reduced common synaptic inputs within each triceps surae muscle and coupling between force output and neural drive in the alpha band.Shifting the ankle position from a shortened to a lengthened position resulted in a reduced motor unit recruitment threshold of GM and SL. However, GL exhibited an opposite pattern, showing higher recruitment thresholds at lengthened positions, while SM was not affected by changes in muscle length.This study reveals a neuromuscular control strategy that integrates afferent feedback and muscle mechanical properties while modulating common descending inputs to synergistic plantarflexors.
Injury-Specific Muscle Regeneration: A Computational Blueprint for Cellular and Cytokine Drivers
Authors: Haase Megan , Comlekoglu Tien , Petrucciani Alexa , Sego T.J. , Peirce Shayn M. , Blemker Silvia S. 
Published: January 2025

AbstractSkeletal muscle regeneration is crucial for maintaining muscle health and mobility, making it a key research focus. Common experimental models of muscle injury used to study this process in vivo include cardiotoxin injury (CTX), freeze-induced (FI) injury, and eccentric contraction (EC) injury. While the response to injury varies across these models, these variations are often overlooked in experimental designs. The cellular dynamics throughout the time course of muscle regeneration differ significantly between these injury types, presenting challenges for both experimental investigation and literature analysis. To enhance understanding of how regeneration responses differ across injury types, we extend our previously validated computational model of skeletal muscle regeneration to simulate muscle fiber remodeling during regeneration following CTX, FI, and EC injuries. We further validate our model against multiple literature-derived metrics of regeneration for each injury type. Analysis of model outcomes reveals that recovery from each injury type is sensitive to unique combinations of cells and cytokines acting at different critical time points, exerting the greatest influence on regeneration at 28 days post-injury. Notably, the cytokines responsible for satellite cell (SSC) recruitment, proliferation, and differentiation required for regeneration vary across injury types, driven by biological redundancy and feedback mechanisms. Specifically, for EC injuries, cross-sectional area (CSA) recovery was predominantly associated with hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A) during the early stages of regeneration, with SSC dynamics playing a critical role throughout. FI injuries demonstrated a consistent reliance on HGF across all phases, with additional influences from transforming growth factor beta (TGF-β), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and SSC dynamics in later stages. CTX injuries showed early dependence on TGF-β, with significant contributions from SSC, TNF-α, VEGF-A, and fibroblast dynamics over time. Our findings emphasize the importance of considering the molecular and cellular mechanisms relevant to each injury type used in pre-clinicalin vivostudies, and motivates the development of therapeutic strategies that are designed for specific injury types to optimize recovery outcomes.
Optimizing fungicide deployment in a connected crop landscape while balancing epidemic control and environmental sustainability
Authors: Radici Andrea , Martinetti Davide , Bevacqua Daniele 
Published: January 2025

SummaryBioaggressors cause significant losses in crop production, and the efficacy of control methods, primarily based on chemical compounds, comes with considerable environmental and health costs. Plant protection practices implemented locally undermine the mobility of bioaggressors, which can spread between fields, connecting different crop populations. As a consequence, the yield in a given field depends also on the management of connected fields. In this study, we evaluate the efficiency of different fungicide deployment strategies across a national-scale agriculture landscape, balancing the conflicting objectives of maximizing crop production and reducing fungicide use. We use a climate-driven metapopulation model describing the dynamics of the peach (Prunus persica)-brown rot (caused byMoniliniaspp.) pathosystem in continental France. Fungicide deployment strategies are based on indices or algorithms, considering network topology, epidemic risk, territory, and stochastic sampling, which prioritize sites to be treated first. Eventually, we focus solely on the objective of maximizing harvest revenue, assuming that untreated fruit can be marketed at higher prices. The optimal strategy depends on the treatment allocation threshold: if up 20% of the area is treated, epidemic risk provides the most effective prioritization. If more than 40% of the area can be treated, a combination of random sampling and risk-based prioritization proves optimal. When considering a single objective, we find that the higher the consumer’s willingness to pay for untreated fruit, the larger the proportion of untreated sites becomes. Fungicide use could be avoided if untreated fruit were sold at 2.9 times the price of treated fruit.
Metformin inhibits nuclear egress of chromatin fragments in senescence and aging
Authors: Kumazawa Takuya , Xu Yanxin , O’Brien Tara C. , Lee Ji-Won , Wang Yu , Cetinbas Murat , Sadreyev Ruslan I. , Bardeesy Nabeel , Cheng Chia-Wei , He Bin , Dou Zhixun 
Published: January 2025

AbstractChronic inflammation is a hallmark of aging and contributes to many age-associated diseases. Metabolic intervention is a strategy to modulate inflammation. However, the connection between inflammation and metabolism during aging remains poorly understood. A mechanism driving chronic inflammation involves cytoplasmic chromatin fragments (CCFs), which appear in senescent cells and aged tissues, activating the cGAS-STING pathway. The size of the CCFs exceeds the capacity of the nuclear pore complex, raising the question of how chromatin fragments enter the cytoplasm. Here, we report that chromatin fragments exit the nucleus via nuclear egress, a membrane trafficking process at the nuclear envelope that shuttles large complexes from the nucleus to the cytoplasm. Inactivating critical nuclear egress ESCRT-III or Torsin proteins results in accumulation of chromatin fragments at the nuclear membrane, thereby impairing the activation of cGAS-STING and senescence-associated inflammation. Notably, nuclear egress of CCFs is inhibited by glucose limitation or metformin treatment. This is due to AMPK phosphorylation and autophagic degradation of the ESCRT-III component, ALIX. Metformin treatment in naturally aged mice downregulates ALIX protein and blocks cGAS activation and chronic inflammation in the small intestine. Together, our study defines a central mechanism linking nutrient sensing and chronic inflammation, two distinct hallmarks of aging, and suggests a new approach to suppress age-associated inflammation by targeting the nuclear egress of chromatin fragments.
Intra-tumor microbiome-based tumor survival indices predict immune interaction and drug sensitivity on pan-cancer scale
Authors: Gao Yan , Zhang Haohong , Chu Dongliang , Ning Kang 
Published: January 2025

AbstractGrowing research evidence indicates a substantial influence of the intra-tumor microbiome on tumor outcome. However, there is currently no consistent criterion for identifying the association of microbes with tumor progression and response to treatment across various types of cancer. In this study, we concentrate on the intra-tumor microbiome and develop the Tumor Microbiome Survival Index (TMSI), a measure indicative of cancer patient’ survival risk. Our indices revealed notable distinctions between two stratified risk groups for each of the 10 cancer types and could precisely predict patients’ overall survival. For each type of cancer, our findings unveiled two distinct gene expression profiles and shed light on the varying patterns of immune and stromal cell enrichment between the two risk groups. Additionally, we noted that the high-TMSI group exhibited substantially elevated IC50 values for a number of drugs, indicating that individuals in the low-TMSI group might experience superior therapeutic effects from chemotherapy. These findings illuminate the complex dynamics between the tumor microbiome, the patient’s immune reaction, and medical outcomes, thus shedding light on microbiome-based personalized therapeutic interventions.HighlightsThe TMSI model generates a survival risk score based on the intra-tumor microbiome.The TMSI model predicts survival rates accurately across multiple cancer types.Molecular-level analysis highlights distinct immune interactions with tumor microbes.High-TMSI groups showed altered drug sensitivity and implying potential differences in treatment response.
Atypical scene-selectivity in the retrosplenial complex in individuals with autism spectrum disorder
Authors: Persichetti Andrew S. , Li Taylor L. , Stevens W. Dale , Martin Alex , Gilmore Adrian W. 
Published: January 2025

AbstractA small behavioral literature on individuals with autism spectrum disorder (ASD) has shown that they can be impaired when navigating using map-based strategies (i.e., memory-guided navigation), but not during visually guided navigation. Meanwhile, there is neuroimaging evidence in typically developing (TD) individuals demonstrating that the retrosplenial complex (RSC) is part of a memory-guided navigation system, while the occipital place area (OPA) is part of a visually-guided navigation system. A key identifying feature of the RSC and OPA is that they respond significantly more to pictures of places compared to faces or objects – i.e., they demonstrate scene-selectivity. Therefore, we predicted that scene-selectivity would be weaker in the RSC of individuals with ASD compared to a TD control group, while the OPA would not show such a difference between the groups. We used functional MRI to scan groups of ASD individuals and matched TD individuals while they viewed pictures of places and faces and performed a one-back task. As predicted, scene-selectivity was significantly lower in the RSC, but not OPA, in the ASD group compared to the TD group. These results suggest that impaired memory-guided navigation in individuals with ASD may, in part, be due to atypical functioning in the RSC.Lay summaryThe retrosplenial complex (RSC), a cortical region that is part of a neural system that supports our ability to form map-like mental representations of the environment and use them to navigate (i.e., memory-guided navigation), exhibits atypical responses to images of places in individuals with autism spectrum disorder (ASD). These results are a first step towards understanding the neural mechanisms responsible for understudied behavioral impairments in memory-guided navigation in individuals with ASD.
Transcriptomic plasticity in hybrid schistosomes can contribute to their zoonotic potential
Authors: Aparicio Nelia Luviano , Mathieu-Bégné Eglantine , Kincaid-Smith Julien , Rey Olivier , Picard Marion , Chaparro Cristian , Allienne Jean-François , Rognon Anne , Polack Bruno , Vallée Isabelle , Thomas Myriam , Fontaine Jean-Jacques , Boissier Jérôme , Toulza Eve 
Published: January 2025

AbstractHybrids betweenSchistosoma haematobiumandS. bovisare linked to both human and animal infections, highlighting the complex interspecies interactions that contribute to the spread of schistosomiasis. Additionally,S. boviscan infect multiple ruminant hosts, facilitating cross- species transmission and increasing the risk of zoonotic outbreaks. In this study, we investigated transcriptomic plasticity as a potential mechanism enabling hybrid schistosomes to adapt to alternative definitive hosts. We focused on two contexts: 1) introgressedS.haematobium × S. bovishybrids, which demonstrated higher virulence in sheep compared to parentalS. bovis, and 2)S. bovisinfecting different host species. Our analysis uncovered 366 differentially expressed genes (DEGs), representing 4% of the total protein-coding genes, between introgressed hybrids and parentalS. bovisin sheep. We also identified transcriptomic changes inS. bovisacross different mammalian hosts (hamster and sheep), with around 30% of the total genes differentially expressed, demonstrating thatS. bovisparasites display a high transcriptomic plasticity, allowing them to infect different definitive hosts. Shared enriched biological processes during introgression and host change include nuclear-transcribed mRNA catabolic processes, inner mitochondrial membrane organization, microtubule-based movement, response to endoplasmic reticulum stress, and sensory perception. These findings suggest that transcriptomic plasticity inS. bovisand hybrid worms enhance their ability to adapt and infect diverse host species, potentially increasing their zoonotic potential. This raises concerns for schistosomiasis epidemiology, as this plasticity could expand the parasite’s transmission capacity and complicate control efforts.
An optimised protocol for the relative quantification of ATP and polyphosphates in the microalgaChlamydomonas reinhardtii
Authors: Israelievitch Eliora , Boulouis Alix 
Published: January 2025

AbstractBackgroundPolyphosphates (polyP) and ATP are phosphate-containing metabolites present in prokaryotes and eukaryotes. PolyP has a wide variety of functions including phosphate and cation storage. ATP is a central metabolite in cellular bioenergetics and the phosphate providing substrate of polyP. In the green microalgaChlamydomonas reinhardtii, polyP synthesis is suggested to buffer ATP concentration, and the role of polyP in energetic metabolism requires further investigation. In this aim, relative quantification of both metabolites is needed. Because ATP and polyP half-lives differ greatly, harvesting generates biases in this relative quantification in current methods. For this reason, we present here a joint protocol optimised to compromise between maximal yield and specific constraints of both assays.MethodsThe optimised method quantifies ATP and polyP from the sameC. reinhardtiicell extract after neutral phenol-chloroform extraction. Cells are directly pipetted from the culture to the phenol-chloroform- EDTA extraction mix. After a second chloroform extraction, ATP is quantified directly from the extract, while polyP measurement requires purification by ethanol precipitation. We used one-way analysis of variance or Kruskall-Wallis testing and appropriate post hoc testing to evaluate statistical effects in our results.ResultsWe show that he polyP/ATP ratio of the reference strain CC-4533 in exponential mixotrophic growth is around 65. While the optimised protocol performs as well as specific protocols for either ATP or polyP, the dispersion of the polyP/ATP ratio is twice better than for the separate metabolites. Direct sampling from the culture works better than centrifugation and filtration to maintain physiological conditions and high polyP yield. Using spiking with ATP and polyP, we show that ATP and longer chain polyP are fully recovered but not very short chain polyP. Finally, we show that the polyP chain length distribution extracted from CC-4533 is very broad, reaching up to several thousand P with a mean around 200 P.DiscussionOur protocol improves the precision of relative quantification of ATP and polyP by using neutral phenol-chloroform extraction and allows polyP/ATP ratio calculation from low-density samples and without normalisation. It can be applied to other microorganisms or cells, in a variety of physiological and stress conditions.