bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel method for detection of Aβ and Iso-D7-Aβ N-terminus-specific B cells and Iso-D7-Aβ-specific antibodies
Authors: Kolobova Elizaveta A , Petrushanko Irina Yu , Mitkevich Vladimir A , Makarov Alexander A , Grigorova Irina L 
Published: January 2025

Abstract
Alzheimer’s disease (AD) is a multifactorial systemic disease that is triggered, at least in part, by the accumulation of β-amyloid (Aβ) peptides in the brain, but it also depends on immune system-mediated regulation. Recent studies suggest that B cells may play a role in AD development and point to the accumulation of clonally expanded B cells in AD patients. However, the specificity of the clonally expanded B cells is unknown, and the contribution of Aβ-specific B cells to AD pathology development is unclear. In this study, we have developed a novel method to identify Aβ-specific B cells by flow cytometry using fluorescent tetramers. The suggested method also enables the identification of B-cell clones specific to a more pathology-provoking form of Aβ with an isomerized Asp7 residue (Iso-D7-Aβ) that accumulates in elderly people and in AD patients. The method has been verified using mice immunized with antigens containing the isomerized or non-isomerized Aβ N-terminus peptides. In addition, we describe a new method for the detection of Iso-D7-Aβ-specific antibodies, which was tested on mouse serum. These methods are of potential importance in research aimed at studying AD and may be also utilized for diagnostic and therapeutic purposes.
Weighted Q-learning for optimal dynamic treatment regimes with nonignorable missing covariates
Authors: Sun Jian , Fu Bo , Su Li 
Published: January 2025

ABSTRACT
Dynamic treatment regimes (DTRs) formalize medical decision-making as a sequence of rules for different stages, mapping patient-level information to recommended treatments. In practice, estimating an optimal DTR using observational data from electronic medical record (EMR) databases can be complicated by nonignorable missing covariates resulting from informative monitoring of patients. Since complete case analysis can provide consistent estimation of outcome model parameters under the assumption of outcome-independent missingness, Q-learning is a natural approach to accommodating nonignorable missing covariates. However, the backward induction algorithm used in Q-learning can introduce challenges, as nonignorable missing covariates at later stages can result in nonignorable missing pseudo-outcomes at earlier stages, leading to suboptimal DTRs, even if the longitudinal outcome variables are fully observed. To address this unique missing data problem in DTR settings, we propose 2 weighted Q-learning approaches where inverse probability weights for missingness of the pseudo-outcomes are obtained through estimating equations with valid nonresponse instrumental variables or sensitivity analysis. The asymptotic properties of the weighted Q-learning estimators are derived, and the finite-sample performance of the proposed methods is evaluated and compared with alternative methods through extensive simulation studies. Using EMR data from the Medical Information Mart for Intensive Care database, we apply the proposed methods to investigate the optimal fluid strategy for sepsis patients in intensive care units.
Efficacy of extracorporeal photopheresis in treating severe erosive lichen planus: a case series
Authors: Loretan Audrey , Cortes Begonia 
Published: January 2025

Abstract
There are currently no good, evidence-based recommendations for any systemic treatment of erosive lichen planus (ELP). Extracorporeal photopheresis (ECP) may be an effective treatment for recalcitrant forms of this disease. We report three patients with severe ELP who were treated with ECP. Objective clinical responses as assessed by a dermatologist, subjective responses as reported by the patients, and recorded adverse events were monitored. Each patient showed a partial response of cutaneous, oral and genital lesions. Oesophageal lesions were more resistant to the treatment. The findings in the patients reported here, in addition to the 38 other cases reported in the literature, strongly support the value of ECP in the treatment of ELP. ECP may be effective as a salvage treatment option for ELP refractory to current treatments. Owing to the lack of side-effects of ECP, in contrast to other treatments, ECP is a potentially useful treatment option when immunosuppressive drugs are contraindicated.
Mission P(D)ossible: peritoneal dialysis in difficult cases
Authors: Lehmann Kijanosh , Reubke Benjamin , Wanninger Reinhard , Lindgren Manuela , Glowka Tim R , Kielstein Jan T , Eden Gabriele 
Published: January 2025

Abstract
Indications for peritoneal dialysis (PD) have undergone a paradigm shift in recent years. Medical barriers previously viewed as contraindications for PD such as anuria, autosomal dominant polycystic kidney disease, cardiovascular diseases or advanced age are increasingly re-examined. We learned that establishing a safe, functional and durable catheter access can be established even in patients with a variety of co-morbidities. Moreover, conditions that predispose to catheter-related infections and peritonitis are not as obvious as we thought. In this case-based review we present patients who have been performing PD for a long time and in whom PD might still be viewed unfeasible. The aim of the paper is to underline the importance of PD as a kidney replacement therapy with fewer medical limits than previously thought. It is also a plaidoyer for interdisciplinary and interprofessional collaboration. This ‘Mission PD-possible’ should be accompanied by a coordinated approach aligning policy, organizational structures and financial resources.
Toxic effects of eight azole fungicides on the growth, photosynthetic activity, and oxidative stress of Raphidocelis subcapitata
Authors: Huang Yongxiang , Guo Dijie , Qin Litang , Mo Lingyun , Zhao Yuqing 
Published: January 2025

Abstract
This study investigates the 96 hours toxicity and physiological effects of eight azole fungicides on Raphidocelis subcapitata (R. subcapitata). The findings revealed significant differences in toxicity levels among these fungicides, with the hierarchy of toxicity as follows: Difenoconazole (DIF) ≈ Tetraconazole (TET) ≈ Fuberidazole (FUB) &gt; Metconazole (MET) &gt; Terrazole (TER) ≈ Triflumizole (TRI) &gt; Flutriafol (FLU) &gt; Hymexazol (HYM). Increased concentrations of azole fungicides corresponded with decreased cellular activity and inhibited algal growth, highlighting the concentration-dependent nature of toxicity. The toxicological mechanisms involved include reduced levels of chlorophyll (Chla, Chlb) and carotenoids (Car), disrupting the photosynthetic process. Additionally, exposure to these fungicides resulted in decreased total protein (TP) levels, increased reactive oxygen species (ROS) and malondialdehyde (MDA), and elevated activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT). Consequently, there was a significant rise in apoptosis rates among algal cells. These findings provide important insights for assessing the ecological impact of azole fungicides on aquatic ecosystems and aquatic life.
Dimensionality reduction for visualizing spatially resolved profiling data using SpaSNE
Authors: Zhou Yuansheng , Tang Chen , Xiao Xue , Zhan Xiaowei , Wang Tao , Xiao Guanghua , Xu Lin 
Published: January 2025

Abstract

Background
Spatially resolved profiling technologies to quantify transcriptomes, epigenomes, and proteomes have been emerging as groundbreaking methods for comprehensive molecular characterizations. Dimensionality reduction and visualization is an essential step to analyze and interpret spatially resolved profiling data. However, state-of-the-art dimensionality reduction methods for single-cell sequencing data, such as the t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), were not tailored for spatially resolved profiling data.

Results
Here we developed a spatially resolved t-SNE (SpaSNE) method to integrate both spatial and molecular information. We applied it to a variety of public spatially resolved profiling datasets that were generated from 3 experimental platforms and consisted of cells from different diseases, tissues, and cell types. To compare the performances of SpaSNE, t-SNE, and UMAP, we applied them to 4 spatially resolved profiling datasets obtained from 3 distinct experimental platforms (Visium, STARmap, and MERFISH) on both diseased and normal tissues. Comparisons between SpaSNE and these state-of-the-art approaches reveal that SpaSNE achieves more accurate and meaningful visualization that better elucidates the underlying spatial and molecular data structures.

Conclusions
This work demonstrates the broad application of SpaSNE for reliable and robust interpretation of cell types based on both molecular and spatial information, which can set the foundation for many subsequent analysis steps, such as differential gene expression and trajectory or pseudotime analysis on the spatially resolved profiling data.
Elevated LINC00115 expression correlates with aggressive endometrial cancer phenotypes via JAK/STAT pathway modulation
Authors: Zhao Zheqi , Liu Yangyang , Wang Mengyao , Wei Aiwu 
Published: January 2025

Abstract
This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors. In vivo models confirmed that LINC00115 overexpression accelerates tumor growth and metastasis. Our study is the first to identify LINC00115 as a key activator of the JAK/STAT pathway through direct interaction with KH-type Splicing Regulatory Protein (KHSRP), a previously unrecognized mechanism in EC. This finding provides new insights into lncRNA-mediated signaling regulation and highlights LINC00115 as a novel biomarker and promising therapeutic target for EC, offering a theoretical basis for developing targeted therapies.
Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023
Authors: Wade Alioune , Sene Seynabou D , Caspar Emanuelle , Diallo Fatoumata , Platon Lucien , Thiebaut Lucas , Pouye Mariama N , Ba Aboubacar , Thiam Laty Gaye , Fall Magal , Sadio Bacary Djilocalisse , Desamours Ife , Guerra Noemi , Hagadorn Kelly , Amambua-Ngwa Alfred , Bei Amy K , Vigan-Womas Ines , Ménard Didier , Mbengue Alassane 
Published: January 2025

Abstract

Background
Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.

Objective
To assess the proportion of P. falciparum parasites carrying molecular signatures associated with antimalarial resistance (PfKelch13, Pfmdr1, Pfcrt, dhfr and dhps) in isolates collected at Kédougou using multiplex amplicon deep sequencing.

Methods
Venous blood samples were collected from patients diagnosed with P. falciparum infection over a 3-year period (2021, 2022 and 2023). Parasite DNA was extracted, and multiplex amplicon sequencing was used to investigate gene polymorphisms.

Results
Analysis of PfKelch13 did not reveal any non-synonymous mutations. Pfcrt mutations were present in 45% of the samples, mainly K76T (44%) and I356T (36%). The dominant Pfmdr-1 allele was Y184F (62%). The sextuple mutant 51I/59R/108N + 436A/437G/613S dhfr/dhps was observed in 10% of the samples.

Conclusion
The absence of PfKelch13 mutants suggests that ACT efficacy remains uncompromised, although clinical outcome studies are required to confirm this. Analysis of Pfcrt and Pfmdr-1 shows that CQ-R alleles, probably from previous CQ use, are slowly decreasing. Likewise, the detection of the dhfr/dhps sextuple mutant highlights the need to monitor sulfadoxine-pyrimethamine resistance and the emergence of 581G. There is therefore a need for continued antimalarial resistance surveillance in Senegal.
Assessing Artificial Intelligence (AI) Implementation for Assisting Gene Linking (at the National Library of Medicine)
Authors: Islamaj Rezarta , Wei Chih-Hsuan , Lai Po-Ting , Huston Melanie , Coss Cathleen , Kochar Preeti Gokal , Miliaras Nicholas , Mork James G , Rodionov Oleg , Sekiya Keiko , Trinh Dorothy , Whitman Deborah , Wallin Craig , Lu Zhiyong 
Published: January 2025

Abstract

Objectives
The National Library of Medicine (NLM) currently indexes close to a million articles each year pertaining to more than 5300 medicine and life sciences journals. Of these, a significant number of articles contain critical information about the structure, genetics, and function of genes and proteins in normal and disease states. These articles are identified by the NLM curators, and a manual link is created between these articles and the corresponding gene records at the NCBI Gene database. Thus, the information is interconnected with all the NLM resources, services which bring considerable value to life sciences. National Library of Medicine aims to provide timely access to all metadata, and this necessitates that the article indexing scales to the volume of the published literature. On the other hand, although automatic information extraction methods have been shown to achieve accurate results in biomedical text mining research, it remains difficult to evaluate them on established pipelines and integrate them within the daily workflows.

Materials and Methods
Here, we demonstrate how our machine learning model, GNorm2, which achieved state-of-the art performance on identifying genes and their corresponding species at the same time handling innate textual ambiguities, could be integrated with the established daily workflow at the NLM and evaluated for its performance in this new environment.

Results
We worked with 8 biomedical curator experts and evaluated the integration using these parameters: (1) gene identification accuracy, (2) interannotator agreement with and without GNorm2, (3) GNorm2 potential bias, and (4) indexing consistency and efficiency. We identified key interface changes that significantly helped the curators to maximize the GNorm2 benefit, and further improved the GNorm2 algorithm to cover 135 species of genes including viral and bacterial genes, based on the biocurator expert survey.

Conclusion
GNorm2 is currently in the process of being fully integrated into the regular curator’s workflow.
Challenges Facing the Appeal to Practical Wisdom in Medicine and Beyond
Authors: Miller Christian B 
Published: January 2025

Abstract
As work on practical wisdom and medicine accelerates, now is a good time to outline some important challenges that any approach to developing an account of this virtue faces. More specifically, I develop five challenges having to do with the existence and nature of practical wisdom, and whether it connects with objective and general normative truths. The main goal is to provide a guide to the challenges themselves and some of the options available for tackling them, rather than trying to resolve them here.
Perianal abscess complicated by histiocytic necrotizing lymphadenitis postoperatively: a case report
Authors: Zhang Liman , Yang Jie , Wang Lili , Zhang Tianpeng , Ju Fei , Wu Yanjang 
Published: January 2025

Abstract
Histiocytic necrotizing lymphadenitis (HNL) is a rare condition presenting with lymphadenopathy and fever. We report a case of a 61-year-old male with a history of perianal abscess surgery who developed HNL postoperatively. The patient was treated with corticosteroids, leading to resolution of fever and alleviation of symptoms. This case emphasizes the need for clinical vigilance for HNL in patients with a history of perianal abscess surgery and postoperative fever with lymph node enlargement.
Study protocol for the development of a pouch anal and vaginal fistula core outcome measurement set (PAVFCOMS)
Authors: Anand Easan , Joshi Shivani , Reza Lillian , Sahnan Kapil , Lung Phillip , Hart Ailsa , Tozer Phil 
Published: January 2025

Abstract
Pouch-related fistulae, such as pouch-anal and pouch-vaginal fistulae, are serious complications that impact ⁓5% of patients undergoing ileoanal pouch surgery, frequently leading to pouch failure. Research on treatment options is limited by small studies with inconsistent outcome reporting. To address this, the Pouch Anal and Vaginal Fistula Core Outcome Set (PAVFCOS) was developed, identifying seven key outcomes through stakeholder consensus. This study aims to create a core outcome measurement set (PAVFCOMS) to standardize how outcomes are measured in pouch fistula treatment, in line with Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. PAVFCOMS will incorporate validated patient-reported (PROMs) and clinician-reported (ClinROMs) outcome measures to provide a standardized tool for future clinical research. The study follows a two-phase process per COSMIN guidance. Phase one involves a systematic review to identify and assess current measurement instruments used in pouch fistula research and has been prospectively registered on PROSPERO (CRD42024505563). The second phase uses a Delphi process with international stakeholders, including patients, surgeons, gastroenterologists, radiologists and nurses, to reach consensus on the final measurement set. This will identify measurement instrument gaps and select the best available tools for each outcome. Reporting will adhere to ACCORD guidelines. This is the first international consensus to establish a core outcome measurement set for pouch fistula research. Standardized outcome measurement will enhance trial quality and facilitate stronger systematic reviews and meta-analyses. A key strength of this study is its patient-centred approach, ensuring the relevance of outcomes to the patient community, reflecting their lived experiences with pouch fistulae.
Performance of chest CT-based artificial intelligence models in distinguishing pulmonary mucormycosis, invasive pulmonary aspergillosis, and pulmonary tuberculosis
Authors: Li Yun , Chen Deyan , Zhang Youwen , Liu Shuyi , Liang Lina , Tan Lunfang , Yang Fan , Li Yuyan , Peng Chengbao , Ye Feng , Zhang Xia , Hu Guodong , Chen Huai , Zheng Jinping 
Published: January 2025

Abstract
In clinical practice, differentiating among pulmonary mucormycosis (PM), invasive pulmonary aspergillosis (IPA), and pulmonary tuberculosis (PTB) can be challenging. We aimed to evaluate the performance of chest CT-based artificial intelligence (AI) models in distinguishing among these three diseases. Patients with confirmed PM, IPA, or PTB were retrospectively recruited from three tertiary hospitals. Two models were developed: the unannotated supervised training (UST) model, trained with original CT images and the annotated supervised training (AST) model, trained with manually annotated lesion images. A network questionnaire with 20 cases was designed to assess the performance of clinicians. Sensitivity, specificity, and accuracy were calculated for both models and clinicians. A total of 61 PM cases, 136 IPA cases, and 155 PTB cases were included in the study. In the internal validation set, both models had an accuracy of 66.1%. The UST model had sensitivities of 27.3%, 73.9%, and 76.0% for PM, IPA, and PTB, while the AST model had sensitivities of 9.1%, 69.6%, and 88.0% for the same conditions. In the external validation set, both models had an accuracy of 57.6%. The UST model had sensitivities of 0, 85.7%, and 53.3% for PM, IPA, and PTB, respectively, while AST model had sensitivities of 0, 42.9% and 83.3%. A total of 112 clinicians had an accuracy of 42.9%, with sensitivities of 31.5%, 43.4%, and 48.0% for PM, IPA, and PTB. We demonstrated that two AI models showed comparable performance in diagnosing three diseases. Both models effectively detected IPA and PTB but struggled to identify PM.
Reionization morphology and intrinsic velocity offsets allow transmission of Lyman-α emission from JADES-GS-z13-1-LA
Authors: Qin Yuxiang , Wyithe J Stuart B 
Published: January 2025

ABSTRACT
We investigate the detectability of Lyman-$\alpha$ (Ly $\alpha$) emission from galaxies at the onset of cosmic reionization, aiming to understand the conditions necessary for detecting high-redshift sources like JADES-GS-z13-1-LA at $z=13$. By integrating galaxy formation models with detailed intergalactic medium (IGM) reionization simulations, we construct high-redshift galaxy catalogues to model intrinsic Ly $\alpha$ profiles and assess their transmission through the IGM. For a galaxy with $M_{\rm UV}\sim -18.5$ like JADES-GS-z13-1-LA, our fiducial model predicts a Ly $\alpha$ transmission of ${\sim }13$ per cent and there is a probability of observing Ly $\alpha$ emission with an equivalent width $\gt 40$ Å of up to 10 per cent. We also explore how variations in the UV ionizing escape fraction, dependent on host halo mass or specific star formation rate, impact Ly $\alpha$ detectability. Our findings reveal that reionization morphology significantly influences detection chances – models where reionization is driven by low-mass galaxies can boost the detection probability to as much as 12 per cent, while those driven by massive galaxies tend to reduce ionized regions around faint emitters, limiting their detectability. Our findings remain robust when further accounting for stochastic star formation with the detection probability still spanning 3 per cent to 12 per cent. This study underscores the interplay between reionization morphology and intrinsic galaxy properties in interpreting high-redshift Ly $\alpha$ observations.
Faithful Interpretation of Protein Structures through Weighted Persistent Homology Improves Evolutionary Distance Estimation
Authors: Bou Dagher Léa , Madern Dominique , Malbos Philippe , Brochier-Armanet Céline 
Published: January 2025

Abstract
Phylogenetic inference is mainly based on sequence analysis and requires reliable alignments. This can be challenging, especially when sequences are highly divergent. In this context, the use of three-dimensional protein structures is a promising alternative. In a recent study, we introduced an original topological data analysis method based on persistent homology to estimate the evolutionary distances from structures. The method was successfully tested on 518 protein families representing 22,940 predicted structures. However, as anticipated, the reliability of the estimated evolutionary distances was impacted by the quality of the predicted structures and the presence of indels in the proteins. This paper introduces a new topological descriptor, called bio-topological marker (BTM), which provides a more faithful description of the structures, a topological analysis for estimating evolutionary distances from BTMs, and a new weight-filtering method adapted to protein structures. These new developments significantly improve the estimation of evolutionary distances and phylogenies inferred from structures.