bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomics with super-voxel segmentation improves HPV prediction accuracy significantly in oropharyngeal cancer
Authors: Altinok Oya , Schabath Matthew B. , Guvenis Albert 
Published: December 2024

AbstractHuman papillomavirus (HPV) status has been shown to be prognostic among patients with oropharyngeal cancer (OPC); Specifically, patients with HPV-positive tumors often have a superior prognosis and response to treatment compared to HPV-negative tumors which may be attributed greater tumor heterogeneity. This study assessed if analyzing tumor subregions (i.e., habitats) using super-voxel segmentation can effectively capture intratumor heterogeneity and improve predicting HPV positivity compared to a conventional whole-tumor approach. Using publicly available data from The Cancer Imaging Archive (TCIA) of 192 patients (85% HPV positive) with OPC, we utilized radiomics to predict HPV status comparing a super-voxel segmentation approach and a whole tumor approach. For the subregion approach, the number of supervoxels (subregions) generated per patient varied based on tumor size (mean = 30 supervoxels/patient [SD = 10]). 18 radiomic features were extracted from each supervoxel based on gray-level frequency distribution and aggregated using variance to summarize heterogeneity. For the whole tumor approach, the same radiomic features were generated across the entire tumor without sub-segmentation. As such, 18 radiomic features were utilized to predict HPV status in both models. The dataset was divided into a training set (70%) and an independent test set (30%). An optimizable ensemble model based on a decision tree with GentleBoost was applied to both the subregion and the whole tumor models to predict HPV status from radiomics features. The proposed super-voxel-based approach yielded an AUC of 0.94 in the training set and 0.91 in the test set which outperformed whole tumor analysis (AUC of 0.77 and 0.75, respectively). These findings demonstrate the value of incorporating heterogeneity measure and super-voxel segmentation in oropharyngeal cancer radiomics, which enable a significantly more accurate prediction of the HPV Status.
Trends, correlates, and recent pattern of antibiotic misuse in acute rotavirus diarrhea in urban and rural Bangladesh
Authors: Saqeeb Kazi Nazmus , Tafsir Hasan S. M. , Khan Soroar Hossain , Khan Md Alfazal , Faruque ASG , Ahmed Tahmeed 
Published: December 2024

AbstractBackgroundThe indiscriminate use of antibiotics in pediatric populations has emerged as a critical global public health concern. A notable example of this is the misuse of antibiotics for treating rotavirus infections, particularly in developing countries. Despite this, there is a dearth of comprehensive research from this region. To address this gap, this study systematically examined the trends and factors associated with antibiotic misuse for acute rotavirus diarrhea among children aged 6-23 months in Bangladesh over a 15-year period. The study also explored sources of prescription, and types of antibiotics utilized in both urban and rural settings of Bangladesh.MethodsData from the icddr,b’s Diarrhea Disease Surveillance System (DDSS) were analyzed for 4870 children with laboratory-confirmed acute rotavirus diarrhea treated at Dhaka (urban) and Matlab (rural) hospitals between 2004 and 2018. Relevant sociodemographic and epidemiological data was obtained from the database. To assess changes in antibiotic use over the years chi-square test for trend was employed. Separate logistic regression models specific to each site were developed to identify factors linked to antibiotic use in cases of rotavirus diarrhea.ResultsOver the study period, the percentage of children with rotavirus diarrhea treated with antibiotics significantly rose in both urban (from 43% to 75.5%) and rural (from 35% to 69%) settings (p<0.001). In urban areas, a majority of children (57.5%) received antibiotics at a physician’s clinic for their illness, whereas almost all rural children (86.3%) obtained antibiotics from a pharmacy before being treated at icddr,b. Macrolides were identified as the most frequently prescribed antibiotics (46.6% in urban areas and 38% in rural areas). The urban regression model, revealed that factors such as severity of illness (OR = 1.8; 95% CI 1.5, 2.2), mother’s education (OR = 2.1; 95% CI 1.6, 2.8), father’s education (OR = 1.8; 95% CI 1.4, 2.3), household monthly income > $100 (OR = 1.5; 95% CI 1.2, 1.9), and the distance from home to the nearest health facility (OR = 1.4; 95% CI 1.1, 1.9) were all significantly positively correlated with the use of antibiotic among children suffering from rotavirus diarrhea. Similar results were observed in the rural regression model.ConclusionsThe increasing trend of antibiotic misuse for rotavirus diarrhea in Bangladesh, coupled with the tendency of healthcare providers to prescribe antibiotics inappropriately and the higher incidence of misuse among affluent, educated families, is alarming. Future research is therefore imperative to elucidate the hindrances and catalysts to the prudent administration of antibiotics across diverse societal groups, encompassing both healthcare personnel and family members.
Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) for pain prevention in patients with limb amputation: a protocol for a systematic review and meta-analysis
Authors: del Moral Preciado Jesús , Gámiz David Gurpegui , Calatayud Bernardo Hontanilla 
Published: December 2024

ABSTRACTIntroductionRegenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) are two reinnervation techniques which have shown clear superiority over classical amputation. It is mainly due to a lower incidence of painful neuromas, residual limb pain and phantom limb pain associated with these new procedures.However, they have never been compared to each other. Neither has their effectiveness been evaluated based on patients demographics, age, sex, comorbidities (diabetes, coronary heart disease, peripheral arterial disease, chronic kidney disease, congestive heart failure), amputations cause, type of amputation, amputation level, previous surgeries and if there was or not previous nerve division into fascicles. Therefore, the objective of this systematic review and meta-analysis is to compile all the evidence to date and provide a comprehensive view of what each technique offers.Methods and designThe review will be conducted according to this protocol, following the recommendations of the ‘Cochrane Handbook for Systematic Reviews’. A comprehensive electronic search will be performed in: Cochrane Register of Controlled Trials (CENTRAL), Web of Science, Scopus, PubMed and MedRixb. This review will include randomized, quasi-randomized, and observational studies written in English and Spanish. We will use Covidence for assessing all titles and abstracts identified during the literature search. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points.Ethics and disseminationThe proposed systematic review will collect and analyse data from published studies; therefore, it raises no ethical issues. The results of the review will be disseminated by publication in a peer-review journal and submitted for presentations at conferences.PROSPERO registration numberCRD42024617299.STRENGTHS AND LIMITATIONS OF THIS STUDY-This will be the first systematic review to include a comparison between RPNI and TMR.-Through a comprehensive search and selection of high-quality articles, the best available evidence of RPNI and TMR against classical amputation will be gathered.-Gray literature and unpublished studies will be sourced from MedRixb aiming to reduce the impact of a possible publication bias.-Exclusion of non-English/Spanish papers may lead to language bias.PICO QUESTIONPopulationAny adults (aged over 18 years) and gender with a superior or inferior limb amputation.InterventionTargeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI).ComparatorsClassical amputation.TMR vs RPNI.Outcomes1) Incidence of neuroma, 2) Incidence of residual limb pain (RLP), 3) Severity of Pain 4) Incidence of phantom limb pain (PLP), and 5) Surgical complications (dehiscence, infection, haematoma and seroma).
Uncovering the Biological Toll of Neighborhood Physical Disorder: Links to Metabolic and Inflammatory Biomarkers in Older Adults
Authors: Yu Jiao , Cudjoe Thomas K.M. , Mathis Walter S. , Chen Xi 
Published: December 2024

AbstractBackgroundNeighborhood physical disorder has been linked to adverse health outcomes, yet longitudinal assessments of its relationship with metabolic and inflammatory biomarkers in older adults remain limited. This study examined the association between patterns of neighborhood physical disorder exposure and biomarkers among older adults.MethodsWe included community-dwelling Medicare beneficiaries with 2017 biomarker data from the National Health and Aging Trends Study (n = 4,558). Neighborhood physical disorder from 2011 to 2016 was assessed using interviewer reports of neighborhood characteristics. Latent class analysis was employed to identify longitudinal patterns of exposure. Inverse probability weighted linear regression models were used to examine associations between physical disorder patterns and five biomarkers, including body mass index (BMI), waist circumference, hemoglobin A1C (HbA1c), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6).ResultsFour classes of neighborhood physical disorder emerged: stable low exposure (85%), increased exposure (4%), decreased exposure (8%), and stable high exposure (3%). Regression findings indicate that residing in neighborhoods with stable high exposure was significantly associated with higher levels of BMI (b = 0.06, p<0.05), HbA1c (b= 0.09,p<0.05), hsCRP (b = 0.21, p < 0.05), and IL-6 (b = 0.22, p < 0.05), compared to those with stable low exposure. Older adults with increased exposure and decreased exposure also exhibited elevated risks in multiple metabolic and inflammation biomarkers.ConclusionsPersistent exposure to neighborhood physical disorder is associated with higher levels of metabolic and inflammatory biomarkers, underscoring the need for targeted clinical screening and neighborhood initiatives to promote healthy aging in place.
Nucleosome Spacing Can Fine-Tune Higher Order Chromatin Assembly
Authors: Chen Lifeng , Maristany M. Julia , Farr Stephen E. , Luo Jinyue , Gibson Bryan A. , Doolittle Lynda K. , Espinosa Jorge R. , Huertas Jan , Redding Sy , Collepardo-Guevara Rosana , Rosen Michael K. 
Published: December 2024

AbstractCellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organizationin vivo. Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation. We show that as DNA linkers extend from 25 bp to 30 bp, as examplars of 10N+5 and 10N (integer N) bp lengths, chromatin condensates become less thermodynamically stable and nucleosome mobility increases. Simulations reveal that this is due to trade-offs between inter- and intramolecular nucleosome stacking, favored by rigid 10N+5 and 10N bp linkers, respectively. A remodeler can induce or inhibit phase separation by moving nucleosomes, changing the balance between intra- and intermolecular stacking. The intrinsic phase separation capacity of chromatin enables fine tuning of compaction and dynamics, likely contributing to heterogeneous chromatin organizationin vivo.
PfATP2 is an essential flippase on thePlasmodium falciparumsurface that influences parasite sensitivity to antiplasmodial compounds
Authors: Qiu Deyun , England Eleanor , Lehane Adele M. 
Published: December 2024

AbstractAntimalarials play a crucial role in the fight against malaria. However, resistance of the most virulent malaria parasite,Plasmodium falciparum, to front-line antimalarials is spreading. To identify new antimalarials, millions of compounds have been screened for their ability to inhibit the growth of blood-stageP. falciparumparasites. To gain insight into the mode of action of novel compounds and the ease by which parasites can acquire resistance to them, many have been tested in ‘in vitroevolution experiments’, in which parasites are exposed to the compound for a prolonged period of time. In a recent study, parasite resistance to two compounds, MMV007224 and MMV665852, was associated with amplification of thepfatp2gene, implicating PfATP2, a putative phospholipid flippase, as a parasite drug target or resistance determinant. These two compounds, along with MMV665794 (which is structurally related to MMV007224) had previously been reported to dysregulate pH in parasites. Here, we show that PfATP2 localises to the parasite surface and is essential for parasite growth. We demonstrate that parasites genetically engineered to overexpress PfATP2 display reduced sensitivity to MMV665794, MMV007224 and MMV665852 compared to parasites with a normal expression level of the protein, and that parasites in which PfATP2 is knocked down become hypersensitive to the three compounds. We show that PfATP2 expression level does not affect the cytosolic pH of parasites, or the potency by which MMV665794 or MMV007224 dysregulate parasite pH. We show that PfATP2-overexpressing parasites internalise a fluorescent phosphatidylserine analogue (NBD-PS) at a greater rate than parasites with a normal expression level of PfATP2, and that parasites in which PfATP2 is knocked down have a reduced rate of NBD-PS uptake. Further, we provide evidence that MMV665794 and MMV007224 inhibit both ATP- dependent and ATP-independent NBD-PS internalisation mechanisms, the former at lower concentrations. Together, our data are consistent with PfATP2 serving as a major ATP-dependent phosphatidylserine internalisation mechanism at the parasite plasma membrane, and being a target of MMV665794 and MMV007224.
Balancing Act: A Neural Trade-off Between Coherence and Creativity in Spontaneous Speech
Authors: Patel Tanvi , Macpherson Sarah E. , Hoffman Paul 
Published: December 2024

AbstractEffective communication involves a delicate balance between generating novel, engaging content and maintaining a coherent narrative. The neural mechanisms underlying this balance between coherence and creativity in discourse production remain unexplored. The aim of the current study was to investigate the relationship between coherence and creativity in spontaneous speech, with a specific focus on the interaction among three key neural networks: the Default Mode Network, Multiple Demand Network, and the Semantic Control Network. To this end, we conducted a two-part analysis. At the behavioural level, we analysed speech samples produced in response to topic cues, computing measures of global coherence (indexing the degree of connectedness to the main topic) and Divergent Semantic Integration (DSI; reflecting the diversity of ideas incorporated in the narrative). Coherence and divergence in speech were negatively correlated, suggesting a trade-off between maintaining a coherent narrative structure and incorporating creative elements. At the neural level, higher global coherence was associated with greater activation in the Multiple Demand Network, emphasising its role in organising and sustaining logical flow in discourse production. In contrast, functional connectivity analyses demonstrated that higher DSI was related to greater coupling between the Default Mode and Multiple Demand Networks, suggesting that creative speech relies on a dynamic interplay between associative and executive processes. These results provide new insights into the cognitive and neural processes underpinning spontaneous speech production, highlighting the complex interplay between different brain networks in managing competing demands of being coherent and creative.
Alternative splicing ofSORBS1affects neuromuscular junction formation and stability in myotonic dystrophy type 1
Authors: Hermitte Caroline , de Calbiac Hortense , Moulay Gilles , Mérien Antoine , Lainé Jeanne , Polvèche Hélène , Cailleret Michel , Vassilopoulos Stéphane , Kabashi Edor , Furling Denis , Martinat Cécile , Gazzola Morgan 
Published: December 2024

ABSTRACTMyotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disease characterized by a CTG repeat expansion in the 3’ untranslated region of the gene coding for thedystrophia myotonica protein kinase(DMPK). Presence of expanded CTG repeats in DMPK-mRNAs leads to the sequestration of RNA binding factors such as the Muscleblind like (MBNL) proteins resulting in widespread splicing defects contributing to progressive muscle weakness and myotonia. Here, we show that abnormal splicing ofSORBS1exon 25 found in skeletal muscle of myotonic dystrophy type 1 patients is a critical contributor to neuromuscular junction (NMJ) formation and maintenance. Forced exclusion ofSORBS1exon 25 in mice results in NMJ degeneration with marked denervation and postsynaptic destabilization. In zebrafish, misregulation ofsorbs1exon 25 results in reduced motor function and abnormal AChR cluster morphology. Finally, we observed that forcingSORBS1exon 25 exclusion in hiPSC-derived skeletal muscle cells reduces the formation of large AChR clusters upon agrin stimulation. Thus, our study identifies MBNL regulatedSORBS1alternative splicing during skeletal muscle development as a critical event for NMJ formation and maintenance. The aberrant splicing ofSORBS1exon 25 in DM1 expands our understanding of how splicing dysregulation compromises neuromuscular system communication, shedding light on the broader impact of mRNA splicing regulation on NMJ integrity.
YAP regulates periosteal expansion in fracture repair
Authors: Nijsure Madhura P , Tobin Brendan , Jones Dakota L , Lang Annemarie , Hallström Grey , Baitner Miriam , Tanner Gabrielle I , Moharrer Yasaman , Panebianco Christopher J , Seidl Elizabeth G , Dyment Nathaniel A , Szeto Gregory L , Wood Levi , Boerckel Joel D 
Published: December 2024

AbstractBone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear. Here, we show that Yes-Associated Protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) mediate periosteal expansion and periosteal cell proliferation. Bone fracture increases the number of YAP-expressing periosteal cells, and deletion of YAP and TAZ from Osterix (Osx) expressing cells impairs early periosteal expansion. Mechanistically, YAP regulates both ‘cell-intrinsic’ and ‘cell-extrinsic’ factors that allow for periosteal expansion. Specifically, we identified Bone Morphogenetic Protein 4 (BMP4) as a cell extrinsic factor regulated by YAP, that rescues the impairment of periosteal expansion upon YAP/TAZ deletion. Together, these data establish YAP mediated transcriptional mechanisms that induce periosteal expansion in the early stages of fracture repair and provide new putative targets for therapeutic interventions.
Motor sequence learning involves better prediction of the next action and optimization of movement trajectories
Authors: Kashefi Mehrdad , Diedrichsen Jörn , Pruszynski J. Andrew 
Published: December 2024

AbstractLearning new sequential movements is a fundamental skill for many animals. Although the behavioral manifestations of sequence learning are clear, the underlying mechanisms remain poorly understood. Motor sequence learning may arise from three distinct processes: (1) improved execution of individual movements independent of their sequential context; (2) enhanced anticipation of “what” movement should be executed next, enabling faster initiation; and (3) the development of motoric sequence-specific representations that encode “how” movements should be optimally performed within a sequence. However, many existing paradigms conflate the "what" and "how" components of learning, as participants often acquire both the sequence content (what to do) and its execution (how to do it). This overlap obscures the distinct contributions of each mechanism to motor sequence learning. In this study, we disentangled these mechanisms using a continuous reaching task. Performance in trained sequences was compared to random sequences to rule out improvements attributable solely to isolated movement execution. By also varying how many upcoming targets were visible we assessed the role of anticipation in learning. When participants could only see one future target, improvements were mostly due to them learning which target would come next. When they could see four future targets, participants immediately demonstrated fast movement times and increased movement smoothness, surpassing late-stage performance in the one target condition. Crucially, even with full visibility of future targets, participants showed further sequence-specific learning caused by a continuous optimization of movement trajectories. Follow-up experiments revealed that the learned sequence representations were effector-specific and encoded contextual information of four movements or longer. Our paradigm enables a clear dissociation between the "what" and "how" components of motor sequence learning and provides compelling evidence for the development of effector-specific sequence representations that guide optimal movement execution.
Integrative analysis of angiogenic signaling in obesity: capillary features and VEGF binding kinetics
Authors: Lee Yunjeong , Tukei Keith Lionel , Fang Yingye , Kuila Shobhan , Liu Xinming , Imoukhuede Princess I. 
Published: December 2024

AbstractObesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults are classified as obese. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis—primarily mediated by vascular endothelial growth factor (VEGF-A)—is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation. Systems biology approaches have advanced our understanding of VEGF-A signaling in vascular diseases, but their application to obesity is limited by scattered and sometimes contradictory data. To address this gap, we performed a comprehensive analysis of the existing literature to synthesize key findings, standardize data, and provide a holistic perspective on the adipose vascular microenvironment. The data mining revealed five key findings: (1) obesity increases adipocyte size by 78%; (2) vessel density in adipose tissue decreases by 51% in obese mice, with vessels being 47–58% smaller and 4–9 times denser in comparison with tumor vessels; (3) capillary basement membrane thickness remains similar regardless of obesity; (4) VEGF-A shows the strongest binding affinity for VEGFR1, with four times stronger affinity for VEGFR2 than for NRP1; and (5) binding affinities measured by radioligand binding assay and surface plasmon resonance (SPR) are significantly different. These consolidated findings provide essential parameters for systems biology modeling, new insights into obesity-induced changes in adipose tissue, and a foundation for developing angiogenesis-targeting therapies for obesity.