bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches for extracting daily dosage from free-text prescription signatures in heart failure with reduced ejection fraction: a comparative study
Authors: Haaker Theodorus S , Choi Joshua S , Nanjo Claude J , Warner Phillip B , Abu-Hanna Ameen , Kawamoto Kensaku 
Published: January 2025

Abstract

Objective
To compare various methods for extracting daily dosage information from prescription signatures (sigs) and identify the best performers.

Materials and Methods
In this study, 5 daily dosage extraction methods were identified. Parsigs, RxSig, Sig2db, a large language model (LLM), and a bidirectional long short-term memory (BiLSTM) model were selected. The methods were analyzed with regard to positive predictive value (PPV), sensitivity, F1-score, cost to compute, and time to finish on a sig dataset in the context of heart failure with reduced ejection fraction.

Results
The dataset consisted of 29 896 free-text sigs, which were split into training and validation sets of 70% and 30%, respectively. The BiLSTM model scored lowest with an F1-score of 0.71. The LLM GPT-4o and regular expression-based RxSig achieved the highest F1-scores with 0.98 and 0.95, respectively. The LLM outperformed RxSig in sensitivity. RxSig outperformed the LLM in PPV. Additionally, RxSig had a lower run time and no costs compared to a cost of 25 dollars.

Discussion
In practical usage, it would be preferable for an algorithm to score high on PPV and F1-score, to reduce false positive assertions of daily dosage. Additionally, long running times and high costs are not scalable for larger datasets. Thus, RxSig is likely the most scalable approach. Further research is needed to investigate the generalizability of the findings.

Conclusion
This study demonstrates that both the LLM and RxSig models excel in daily dose extraction from free-text sigs, with the RxSig model appearing to be the more scalable approach.
Case report – Hyperthermia and nuclear hypersegmentation of blood cells
Authors: Rivière C , Vimeux S , Laurens S , Deluche L , Juvin P Y , Sanson A , Metsu D 
Published: January 2025

Abstract
This case report describes a patient with a medical history of schizophrenia, found in a coma with hyperthermia, likely due to classic heatstroke. The white blood cells observed on the blood smear showed cytological abnormalities characterized by multilobed nuclei, which could be early signs of cell death. The evolution into multiorgan failure led rapidly to death.
Ischemic Stroke Complicated by Acute Decompensated Heart Failure and Its Association with Hemoglobin Levels
Authors: Yamazaki Yusuke , Shiraishi Yasuyuki , Kohsaka Shun , Ikegami Shogo , Kohno Takashi , Nagatomo Yuji , Kitamura Mitsunobu , Sakamoto Munehisa , Nomoto Michiru , Mizuno Atsushi , Takahashi Toshiyuki , Kobayashi Masatake , Higuchi Satoshi , Ieda Masaki , Yoshikawa Tsutomu ,   the West Tokyo Heart Failure Registry Investigators
Published: January 2025

AbstractBackgroundIschemic stroke (IS) is a serious complication in heart failure, particularly following hospitalization for acute decompensated heart failure (ADHF). However, its actual incidence during the acute and stable treatment phases remains unclear. Moreover, the association between IS and hemoglobin levels, which fluctuate during these phases, has not been comprehensively investigated.MethodsPatient-level data from 2018 to 2024 were extracted from a prospective multicenter cohort study that consecutively enrolled patients hospitalized with ADHF. Cerebrovascular events were confirmed by local board-certified neurologists using imaging modalities. The incidence of IS and its association with hemoglobin levels, categorized by the universal anemia definition (hemoglobin <13.0 g/dL for men and <12.0 g/dL for women) were examined in early (within 30 days) and late phases (beyond 30 days) following ADHF hospitalization. Fine–Gray models were used for early IS analyses, and Cox proportional hazards models with time-varying covariates (hemoglobin levels) were applied for late IS. Results: A total of 5,106 patients (median age 79 years; men 58%) were analyzed, and 115 (2.3%) developed IS over a median follow-up of 13 months. The incidence was higher in the early phase (median onset 7 days,p for trend=0.002). Cardioembolic stroke (61.7%) was the predominant subtype throughout phases. After covariate adjustments, higher hemoglobin levels (non-anemia) were associated with increased risk of early IS (sHR 2.05,95%CI 1.09– 3.83, p=0.03), but not with late IS (adjusted HR 1.21,95% CI 0.65–2.23, p=0.55), with restricted cubic spline further demonstrating non-linear phase-dependent differences in the impact of hemoglobin levels on IS risk.ConclusionIS occurred across phases of ADHF management, with higher incidence within 30 days after hospitalization. The relationship between hemoglobin levels and IS risk varies by phase, highlighting non-anemia as a potential marker for high-risk patients in the early phase. Incorporating hemoglobin levels into risk stratification could guide targeted screening and preventive strategies.
Using Latent Class Analysis to Identify Subgroups of Post-Operative Older Adults
Authors: McLaughlin Kevin , Bettencourt Amie , Young Daniel , Hoyer Erik , Friedman Michael , Colantuoni Elizabeth , Goeddel Lee A. , Gozalo Pedro 
Published: January 2025

AbstractObjectiveIdentify subgroups of postoperative older adults using electronic health record data.Summary of Background DataPostoperative older adults represent a vulnerable population who may benefit from tailored postoperative care pathways. Identifying clinical subgroups can inform the development of these pathways.MethodsRetrospective cohort study of postoperative adults>65 years (N=2,036) from a single healthcare system. Latent class analysis was used to identify patient subgroups based on measures of frailty, mobility, activities of daily living, and general health status. Hospital outcomes were described among each subgroup, including extended lengths of stay (LOS) (>0.5 SD beyond mean LOS by surgical category), discharge disposition (i.e., home versus non-home discharge), and utilization (weekly visit frequency) of physical therapy (PT) and occupational therapy (OT).ResultsWe identified 3 subgroups that we labeled Low Frailty-High Mobility (LF-HM), High Frailty-Low Mobility (HF-LM), and Low Frailty-Low Mobility (LF-LM), representing 15.3%, 27.6%, and 57.1% of the cohort, respectively. Discharge to home was highest among the LF-HM group (99%), followed by LF-LM (96%), and HF-LM (77%). Extended LOS was most common among the HF-LM group (27%), followed by LF-LM (18%), and LF-HM (6%). PT and OT visit frequencies were highest in the HF-LM group followed by the LF-LM and LF-HM groups.ConclusionsThis study identified 3 subgroups of postoperative older adults using routinely collected patient data. These groups may help to identify patients with increased odds of non-home discharge, extended LOS, and higher utilization of PT and OT and may inform the development of tailored postoperative care pathways for older adults.
Cohort-level analysis of humande novomutations points to drivers of clonal expansion in spermatogonia
Authors: Seplyarskiy Vladimir , Moldovan Mikhail A , Koch Evan , Kar Prathitha , Neville Matthew DC , Rahbari Raheleh , Sunyaev Shamil 
Published: January 2025

AbstractIn renewing tissues, mutations conferring selective advantage may result in clonal expansions1–3. In contrast to somatic tissues, mutations driving clonal expansions in spermatogonia (CES) are also transmitted to the next generation. This results in an effective increase ofde novomutation rate for CES drivers4–7. CES was originally discovered through extreme recurrence ofde novomutations causing Apert syndrome4. Here, we develop a systematic approach to discover CES drivers as hotspots of humande novomutation. Our analysis of 54,715 trios ascertained for rare conditions8–12, 6,065 control trios11,13–18, and population variation from 807,162 mostly healthy individuals19identifies genes manifesting rates ofde novomutations inconsistent with plausible models of disease ascertainment. We propose 15 genes hypermutable at loss-of-function (LoF) sites as candidate CES drivers. Additional 17 genes feature hypermutable missense mutations at individual positions, suggesting CES acting through gain-of-function (GoF). Among candidates are 5 of 13 known CES drivers6,7, 11 cancer drivers, and 16 members of major signaling pathways; notably, 12 genes show CES evidence in direct sperm sequencing20. CES increases the average mutation rate ∼16-fold for LoF genes in both control trios and sperm and ∼500-fold for pooled GoF sites in sperm. Positive selection in the male germline elevates the prevalence of genetic disorders and increases polymorphism levels, masking the effect of negative selection in human populations. Despite the excess of mutations in disease cohorts for 15 LoF CES driver candidates, only 5 show clear evidence of disease causality21, suggesting that CES may lead to false-positive disease associations.
Feasibility of real-time fMRI neurofeedback for rehabilitation of reading deficits in aphasia
Authors: Boukrina Olga , Yamin Abubakar , Yue Guang H , Kong Yekyung , Koush Yury 
Published: January 2025

AbstractBackgroundReading impairments, a common consequence of stroke-induced aphasia, significantly hinder life participation, affecting both functional and leisure activities. Traditional post-stroke rehabilitation strategies often show limited generalization beyond trained materials, underscoring the need for novel interventions targeting the underlying neural mechanisms.MethodThis study investigates the feasibility and potential effectiveness of real-time functional magnetic resonance imaging (fMRI) neurofeedback (NFB) intervention for reading deficits associated with stroke and aphasia. We enrolled left-hemisphere stroke survivors in the subacute recovery period and healthy controls in an fMRI NFB intervention study focusing on increasing activation within the left supramarginal gyrus (SMG), a critical region for reading supporting orthography-phonology conversion.ResultsPreliminary findings demonstrate that stroke participants showed significant improvements in reading comprehension and phonological awareness, as evidenced by marked gains on the Reading Comprehension Battery for Aphasia (RCBA) and a phonology two-alternative forced choice test. Functional MRI results indicated that stroke participants exhibited increased activation from day 1 to day 3 of NFB training within the left SMG and the broader left hemisphere reading network, particularly during challenging nonword reading tasks. Healthy controls also showed increased activation during NFB regulation and reading tasks, but these changes were outside the traditional reading network, involving regions associated with cognitive control, reward anticipation, and learning. In both stroke participants and healthy controls, we also found changes in dynamic functional connectivity of multiple resting state networks from before to after NFB training.ConclusionsAlthough preliminary, this research contributes to the development of biologically informed interventions for reading deficits in aphasia, representing an early step towards improving post-stroke rehabilitation outcomes. Future randomized controlled trials are necessary to validate these findings by including a sham NFB control group within a larger participant sample.RegistrationThe study was preregistered on ClinicalTrials.gov, NCT#NCT04875936
Pattern and association of immunoglobulin G antibodies to AMA1, GLURP, and MSP3 with protection from malaria in a cohort of Cameroonian children living in Mutengene: Anaemia a possible collateral damage?
Authors: Njua-Yafi Clarisse , Achidi Eric A. , Anchang-Kimbi Judith K. , Apinjoh Tobias O. , Mugri Regina N. , Chi Hanesh F. , Tata Rolland B. , Njumkeng Charles , Dodoo Daniel 
Published: January 2025

AbstractUnderstanding the characteristics of naturally acquired immunity in different epidemiologic settings is essential for vaccine development and testing. The relationship between antibodies against four malaria vaccine candidate antigens and protection from malaria in a cohort of Cameroonian children was assessed. Immunoglobulin (Ig)G and IgG subclasses against recombinantPlasmodium falciparumapical membrane antigen 1 (AMA1), glutamate rich protein (GLURP) R0, GLURP R2 and merozoite surface protein 3 (MSP3) in the plasma of 357 Cameroonian children were measured by sandwich ELISA at three time points (baseline, 6 months and 12 months) during which time participants were monitored for malaria.Total IgG to all four antigens correlated positively with age (0.51≤ r ≤ 0.23, p < 0.001) at all three time points. Adjusting for age, total IgG, IgG1, IgG3, IgG2 (except for MSP3 IgG2) antibody levels to all four antigens were associated with protection against malaria parasitaemia at baseline. GLURP R0 IgG (F = 35.7, p < 0.001), GLURP R2 IgG (F = 16.5, p < 0.001), AMA1-3D7 IgG2 (F = 10.8, p < 0.001) and AMA1-3D7 IgG3 (F = 4.01, p = 0.019) decreased with a corresponding decrease in malaria cases (χ2= 10.4, p = 0.034) across the three time points, contrary to the increase observed in MSP3 IgG (F = 8.9, p < 0.001) and MSP3 IgG2 (F = 44.2, p < 0.001). Increased levels of AMA1-3D7 IgG [OR = 4.13, 95% CI (1.09 – 15.65), p = 0.037] and MSP3 IgG1 [OR = 8.16, 95% CI (1.06 – 62.64), p = 0.044] were associated with susceptibility to anaemia after controlling for age and parasitaemia.Total IgG, cytophilic subclasses and IgG2 to all the antigens (except MSP3 IgG2) were associated with malaria protection while MSP3 IgG seemed to persist longer. The relationship between malaria specific antibodies and anaemia warrants further studies.
Challenges and Facilitators for Physicians and Medical Schools to Promote Social Accountability in Rural Communities: A Scoping Review and Thematic Analysis
Authors: Wasim Aghna , Abud Ali , Wang Yihan , Tavakoli Ehsan , Moreno-Gris Athena , Joshi Samar , Wang Arthur , Neasadurai Angela , Shaw Nikki 
Published: January 2025

AbstractBackgroundSocial accountability aligns the health demands and priorities of the community and the commitment of medical schools. Existing literature has proposed contextually distinctive interventions encompassing geographical initiatives, acting networks or parties, and systematic categorizations for the implementation of social accountability in a rural setting. Research concerning social accountability implementation strategies has been insufficient. This study provides an overview of the existing literature surrounding the social accountability practice of physicians and medical schools, in rural settings, through evidence of the barriers and facilitators inherent to the rural communities.MethodsThis scoping review was conducted following the Arksey and O’Malley Framework. Web of Science, MEDLINE, EMBASE, SCOPUS, and CINAHL were searched for peer-reviewed studies published since 2000.ResultsA total of 2698 abstracts were identified, 180 full-text articles were reviewed, and 53 articles met the eligibility criteria across 15 different countries. Strategies used and problems inherent in promoting social accountability across physician practice and medical education are reported.ConclusionsThis scoping review synthesizes existing evidence on the barriers and facilitators of social accountability practices in rural settings globally. The identified literature captures recurring themes of medical infrastructure inadequacy, community immersion curriculum design, targeted admission, geographical isolation, and institutional or peer support.
Engineered Living Glues for Autonomous Detection and On-Demand Treatment of Inflammatory Bowel Disease
Authors: Ge Changhao , Jiang Shanshan , Dong Xiaomin , Jiang Xiaoyu , Zhi Weiliang , Xiang Yunqing , Yang Peilang , Zhang Qian , Chen Xin , Liu Yan , Huang Shuqiang , Liu Yifan , Lin Jing , An Bolin , Huang Peng , Zhong Chao 
Published: January 2025

AbstractSmart biomaterials capable of autonomously sensing pathological conditions and executing targeted medical interventions offer therapeutic advantages over conventional passive biomaterials. However, their development remains a considerable challenge. Here, we introduce a therapeutic “living glue” for the automatic detection and on-demand treatment of inflammatory bowel disease (IBD). This living glue employs a genetically engineered, non-pathogenicEscherichia coliwith a highly sensitive blood-inducible gene circuit to monitor gastrointestinal bleeding, a key indicator of severe IBD. Upon detection, the bacteria respond by producing potent adhesive and therapeutic proteins around bleeding sites, enabling robust attachment to inflamed tissues and sustained treatment. In a dextran sulfate sodium (DSS)-induced mouse model, a single rectal administration of the living glue markedly improved weight recovery, reversed colonic shortening, and reduced intestinal bleeding. Additionally, the living glue decreased intestinal inflammation, promoted mucosal repair, and restored gut barrier integrity, demonstrating comprehensive therapeutic effects in alleviating IBD symptoms. This study highlights the potential of integrating programmable, living components into biomaterials for autonomous, targeted, and enhanced medical interventions.
Pea-Saving Partners: Bacillus and Pseudomonas combat downy mildew in pea crops
Authors: Okechukwu Emeka Chibuzor , Jimenez-Quiros Catherine , Baysal Ömür , Kocamaz Süreyya , Arıkan Burhan , Webb Anne , Wood Thomas , Arora Sanu , Domoney Claire , Studholme David J. , Tör Mahmut 
Published: January 2025

AbstractDowny mildew (DM) is a destructive disease that significantly reduces the yield and quality of important pulses (legumes) and horticultural crops, particularly during humid and cool seasons. This disease is caused by obligate and host-specific oomycete pathogens. Controlling the pathogen is challenging due to its long-term survival as spores and its rapid mutation. Use of chemical pesticides has been the most effective method to control DM pathogens, but their environmental hazards are a global concern. Current research is focused on exploring the potential of microbial biological control agents (MBCA), particularly rhizobacteria strains of the generaBacillusandPseudomonas, which have shown suppression of plant pathogens. However, to date, no MBCA has been reported to be effective against DM pathogens in pulses. We investigated the effectiveness ofBacillusandPseudomonasstrains as potential biopesticides against the pea downy mildew pathogenPeronospora viciaef. sp.pisi(Pvp). In our study,in vitrobioassays showed 100% inhibition ofPvpspore germination compared to the control.In plantaantagonism assays further demonstrated significant suppression (>80%) ofPvpsporulation in pea plants sprayed with strains ofBacillus velezensisorP. fluorescensor their filtrates. The drench application also showed significant effects where either aPseudomonasor cold-adaptedBacillusstrain was used. We observed a synergistic effect for the dual foliar application of the microbes compared to individual application (27.6 to 46.7% suppression). Furthermore, the results from the molecular biomass analysis were consistent with the results of the sporulation assays. This demonstrates the strong interactive and promotive benefits of usingBacillusandPseudomonasas biocontrol agents Based on these results, we conclude that these MBCAs could be effective in combattingPvpinfections in the field.
Ten species comprise half of the bacteriology literature, leaving most species unstudied
Authors: Jensen Paul A. 
Published: January 2025

AbstractMicrobiology research has historically focused on a few species of model organisms. Our bibliographic analysis finds extreme bias in the distribution of bacteriology research across species, with half of all papers referencing only ten species and 74% of all known species remaining unstudied. Microbiologists will need to broaden their perspective and embrace complexity to develop a complete understanding of the microbial world.
Tripartite loops reverse antibiotic resistance
Authors: Chowdhury Farhan R. , Findlay Brandon L. 
Published: January 2025

AbstractAntibiotic resistance threatens to undo many of the advancements of modern medicine. A slow antibiotic development pipeline makes it impossible to outpace bacterial evolution, making alternative strategies essential to combat resistance. In this study, we introduce cyclic antibiotic regimens composed of three drugs or “tripartite loops” to contain resistance within a closed drug cycle. We show that as bacteria sequentially evolve resistance to the drugs in a loop, they continually trade their past resistance for fitness gains, reverting back to sensitivity. Through fitness and genomic analyses, we find that tripartite loops guide bacterial strains towards evolutionary paths that mitigate fitness costs and reverse resistance to component drugs in the loops and drive levels of resensitization not achievable through previously suggested pairwise regimens. These findings open the door to sequential antibiotic regimens with high resensitization frequencies which will improve the longevity of existing antibiotics even in the face of antibiotic resistance.TOC
Machine learning segmentation tool trained on synthetic data for tracking cytoskeleton polymerisation and depolymerisation
Authors: Elangovan Karan , Spelman Tamsin A. , Dupouy Gilles , Singh Gaurav , Chaboute Marie-Edith , Jonsson Henrik 
Published: January 2025

AbstractThe cytoskeleton is important in controlling the growth and morphology of plant cells, so tracking its morphological changes is essential. Here, we develop a new machine learning based segmentation tool for microtubules (MTs), which can distinguish between polymerised and depolymerised fibres. To circumvent the low abundance of data, we trained on synthetic images of microtubules from a computational micro-tubule model, pre-processed to reproduce microscope effects and partial depolymerisation. We used this tool to investigate how the MT network in anArabidopsis thalianaroot hair cell repolymerises after depolymerisation under Oryzalin (OZ) drug treatments. Specifically, we show the network initially repolymerises from the shank region. This work demonstrates the viability of using synthetic data to train machine learning systems handling cytoskeletal image data.
Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate is Subject to Redox Modulation
Authors: Stollmaier Juana Goulart , Czarnecki B. Abigail R. , Christianson David W. 
Published: January 2025

ABSTRACTOrganoselenocyanates have attracted considerable attention in recent years due to their therapeutic potential and versatility in medicinal chemistry. Here, we report on the mechanism of inhibition by 5-phenylcarbamoylpentyl selenocyanide (SelSA-2), an analogue of the well-characterized histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, a.k.a. Vorinostat). We show that histone deacetylases 6 and 10 can promote selenocyanate hydrolysis to generate a selenolate anion, and we explore the redox chemistry of selenium as it modulates inhibitory activity through reversible formation of the diselenide. The 2.15 Å-resolution crystal structure of histone deacetylase 6 cocrystallized with SelSA-2 conclusively demonstrates that it is not the selenocyanate, but instead the selenolate anion, that is the active pharmacophore responsible for enzyme inhibition.