bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid tapering pace in microscopic polyangiitis and granulomatosis with polyangiitis in Japanese real-world practice: A propensity score-matched retrospective cohort study from the J-CANVAS registry
Authors: Nishioka Ryo , Omura Satoshi , Nakagomi Daiki , Abe Yoshiyuki , Kadoya Masatoshi , Takizawa Naoho , Nomura Atsushi , Kukida Yuji , Kondo Naoya , Yamano Yasuhiko , Yanagida Takuya , Endo Koji , Hirata Shintaro , Matsui Kiyoshi , Takeuchi Tohru , Ichinose Kunihiro , Kato Masaru , Yanai Ryo , Matsuo Yusuke , Shimojima Yasuhiro , Okazaki Ryota , Takata Tomoaki , Ito Takafumi , Moriyama Mayuko , Takatani Ayuko , Miyawaki Yoshia , Ito-Ihara Toshiko , Kawaguchi Takashi , Yajima Nobuyuki , Kida Takashi , Kawahito Yutaka , Mizushima Ichiro 
Published: December 2024

ABSTRACT

Objective
To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice.

Methods
We retrospectively examined the Japan Collaborative Registry of Antineutrophil Cytoplasmic Antibodies-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens. Relapse-free survival rates were compared after propensity score matching.

Results
Of 364 eligible patients, 113 (31.0%) received standard tapering and 251 slower tapering. After matching, 87 pairs no significant difference was observed in relapse-free survival (P = .506). Regarding the reduced regimen, there were so few patients (14/364, 3.8%) that statistical analysis was not performed.

Conclusions
The glucocorticoid tapering for MPA and GPA in Japanese real-world practice was found to be generally slower than the standard regimen revealing a huge evidence-practice gap. Additionally, slower tapering did not improve relapse-free survival and might cause unnecessary glucocorticoid exposure.
Defining gene ends: RNA polymerase II CTD threonine 4 phosphorylation marks transcription termination regions genome-wide
Authors: Kopczyńska Magda , Saha Upasana , Romanenko Anastasiia , Nojima Takayuki , Gdula Michał R , Kamieniarz-Gdula Kinga 
Published: December 2024

Abstract
Defining the beginning of a eukaryotic protein-coding gene is relatively simple. It corresponds to the first ribonucleotide incorporated by RNA polymerase II (Pol II) into the nascent RNA molecule. This nucleotide is protected by capping and maintained in the mature messenger RNA (mRNA). However, in higher eukaryotes, the end of mRNA is separated from the sites of transcription termination by hundreds to thousands of base pairs. Currently used genomic annotations only take account of the end of the mature transcript – the sites where pre-mRNA cleavage occurs, while the regions in which transcription terminates are unannotated. Here, we describe the evidence for a marker of transcription termination, which could be widely applicable in genomic studies. Pol II termination regions can be determined genome-wide by detecting Pol II phosphorylated on threonine 4 of its C-terminal domain (Pol II CTD-T4ph). Pol II in this state pauses before leaving the DNA template. Up to date this potent mark has been underused because the evidence for its place and role in termination is scattered across multiple publications. We summarize the observations regarding Pol II CTD-T4ph in termination regions and present bioinformatic analyses that further support Pol II CTD-T4ph as a global termination mark in animals.
Homologous recombination shapes the architecture and evolution of bacterial genomes
Authors: Torrance Ellis L , Diop Awa , Bobay Louis-Marie 
Published: December 2024

Abstract
Homologous recombination is a key evolutionary force that varies considerably across bacterial species. However, how the landscape of homologous recombination varies across genes and within individual genomes has only been studied in a few species. Here, we used Approximate Bayesian Computation to estimate the recombination rate along the genomes of 145 bacterial species. Our results show that homologous recombination varies greatly along bacterial genomes and shapes many aspects of genome architecture and evolution. The genomic landscape of recombination presents several key signatures: rates are highest near the origin of replication in most species, patterns of recombination generally appear symmetrical in both replichores (i.e. replicational halves of circular chromosomes) and most species have genomic hotspots of recombination. Furthermore, many closely related species share conserved landscapes of recombination across orthologs indicating that recombination landscapes are conserved over significant evolutionary distances. We show evidence that recombination drives the evolution of GC-content through increasing the effectiveness of selection and not through biased gene conversion, thereby contributing to an ongoing debate. Finally, we demonstrate that the rate of recombination varies across gene function and that many hotspots of recombination are associated with adaptive and mobile regions often encoding genes involved in pathogenicity.
Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small-cell lung cancer better preserves white matter networks compared to conventional PCI
Authors: Colaes Rob , Blommaert Jeroen , Lambrecht Maarten , de Ruiter Michiel B , Pullens Pim , de Ruysscher Dirk , Belderbos José , Sunaert Stefan , Schagen Sanne B , Deprez Sabine 
Published: December 2024

Abstract

Background
Hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) is proposed to reduce neurocognitive decline, while preserving the benefits of PCI. We evaluated whether (HA-)PCI induces changes in white matter (WM) microstructure and whether sparing the hippocampus has an impact on preserving brain network topology. In addition, we evaluated associations between topological metrics with hippocampal volume and neuropsychological outcomes.

Methods
In this multicenter randomized phase 3 trial (NCT01780675), small-cell lung cancer (SCLC) patients underwent neuropsychological testing and diffusion tensor imaging (DTI) before, 4 months (33 PCI, 37 HA-PCI) and 1 year (19 PCI, 17 HA-PCI) after (HA-)PCI. Changes in WM microstructure were investigated using whole-brain voxel-based analysis of fractional anisotropy (FA) and mean diffusivity (MD). Both hippocampal and whole-brain graph measures were used to evaluate the topological organization of structural networks. Correlation analysis was performed to associate topological metrics with neuropsychological outcomes and hippocampal volume.

Results
Both HA-PCI and PCI were associated with decreased FA in major WM tracts, such as the corpus callosum, at 4 months and 1 year post-treatment. While these FA decreases did not differ significantly between treatment groups, only PCI demonstrated increased MD over time. In addition, PCI showed decreased global efficiency and increased characteristic path length over time when compared with HA-PCI. Significant correlations were found between whole-brain graph measures and neuropsychological outcomes.

Conclusion
While both techniques induce important changes in the WM microstructure, HA-PCI might better preserve the topological organization of brain networks than PCI. The neuroprotective role of hippocampal sparing still needs further investigation.
Validation of the EORTC QLQ-C30 and QLQ-BN20, including WHO performance status interrater reliability, for evaluation of patients with intracranial meningiomas
Authors: Nilsson Robert F , Ström Erik , Bergenheim A Tommy , Sjöberg Rickard L , Lindvall Peter , Holmgren Klas 
Published: December 2024

Abstract

Background
The EORTC questionnaires QLQ-C30 and QLQ-BN20 are commonly used to evaluate health-related quality of life in patients with meningiomas but have not undergone a disease-specific validation. The study aimed to address this issue and to determine the interrater reliability of WHO performance status (PS) assessments in these patients.

Methods
This population-based study included prospectively enrolled intracranial meningiomas treated at Umeå University Hospital between October 14, 2010, and December 31, 2021, followed up until March 30, 2023. Patients were assessed by the EORTC questionnaires before and at 3 months after surgery. WHO PS categorized as high (0–1) or low (2–5) were evaluated for interrater reliability and used together with sick-leave status to determine the questionnaires’ clinical validity. Remaining psychometric properties of the questionnaires were analyzed by conventional methods.

Results
Of 513 eligible surgeries, 454 (88.5%) had responded to at least 1 questionnaire. WHO PS interrater agreement was 94.4%. The EORTC questionnaires’ ability to distinguish between clinically distinct groups was high. Items correlated better with their own scale than others (most r &gt; 0.70). Items measuring various aspects of the same construct showed good internal consistency (nearly all α &gt; 0.70). Questionnaire responsiveness to symptom changes over time was acceptable. Several scales displayed floor and ceiling effects.

Conclusions
The EORTC QLQ-C30 and QLQ-BN20 are overall valid instruments to evaluate patients with intracranial meningiomas but require awareness of certain limitations when specific functions and symptoms are addressed. WHO PS assessments can be applied to meningioma patients with high reproducibility between observers.
Diet–Gut Microbiota Relations: Critical Appraisal of Evidence From Studies Using Metagenomics
Authors: Lotankar Mrunalini , Houttu Noora , Mokkala Kati , Laitinen Kirsi 
Published: December 2024

Abstract
Diet may influence the gut microbiota and subsequently affect the host’s health. Recent developments in methods analyzing the composition and function of the gut microbiota allow a deeper understanding of diet–gut microbiota relationships. A state-of-the-art methodology, shotgun metagenomics sequencing, offers a higher taxonomic resolution of the gut microbiota at the bacterial species and strain levels, and more accurate information regarding the functional potential of gut microbiota. Here, the available evidence on the relationship between diet and gut microbiota was critically reviewed, focusing on results emerging from recent metagenomics sequencing studies applied in randomized controlled trials and observational studies. The PubMed and Embase databases were used to search publications between January 2011 and September 2023. Thus far, the number of studies is limited, and the study designs and methods utilized have been variable. Nevertheless, the cumulative evidence from interventions relates to dietary fiber as a modifier of bacterial species, such as Anaerostipes hadrus and Faecalibacterium prausnitzii. Furthermore, observational studies have detected associations between different dietary patterns and food groups with certain microbial species. Utilization of metagenomics sequencing is becoming more common and will undoubtedly provide further insights into diet–gut microbiota relationships at the species level as well as their functional pathways in the near future. For reproducible results and to draw reliable conclusions across various studies on diet–gut microbiota relationships, there is a need for harmonization of the study designs and standardized ways of reporting.
The lifecycle and evolution of new regimens on the National Comprehensive Cancer Network Guidelines for newly diagnosed multiple myeloma
Authors: Mohyuddin Ghulam Rehman , Almasri Jehad , Goodman Aaron , Haslam Alyson , Prasad Vinay 
Published: December 2024

Abstract

Introduction
Prior studies have evaluated the level of evidence behind treatment options listed in the National Comprehensive Cancer Network (NCCN) guidelines, but no study has categorized the life cycle of regimens listed in the NCCN guidelines. We longitudinally assessed the life cycle for each regimen for newly diagnosed multiple myeloma. We track the date of first clinical data, the date of regimen addition to NCCN guidelines, the date phase 3 data (if performed) were reported, and the results of phase 3 trials.

Methods
We systematically examined NCCN guidelines from January 2000 to April 2021. The primary objective of our study was to assess the life cycle of each drug/regimen listed on the NCCN guidelines. We systematically examined the following aspects for each regimen: (1) the inception of prospective clinical data, (2) its inclusion in the NCCN guidelines, (3) the completion of a randomized trial (if done), (4) the presence of an overall survival benefit in such trials, and (5) the removal of a regimen from NCCN guidelines (if done) and its corresponding timeline.

Results
Twenty-one regimens were added across 50 NCCN guideline document iterations during a 22-year period. The median time from when clinical data were first presented to when a regimen was first listed in the guidelines was 15 months. Phase 3 studies were conducted for 17 regimens (80%), with a surrogate endpoint (response rate or progression-free survival) as endpoint for all trials, other than one. The median time from a regimen being included in the NCCN guideline to its phase 3 data publication was 43 months. The primary endpoint was met for 13 trials (81%). No regimen was removed for a phase 3 endpoint not being met. Six regimens (38%) showed overall survival benefit. Five (23%) regimens were removed from NCCN guidelines, with none being due to failure in phase 3 testing.

Conclusion
Myeloma NCCN guidelines remain relevant and current, adding new regimens with promising early-phase data, and removing regimens that become obsolete over time. However, this process is inconsistent and may benefit from standardization.
Effects of Educational Interventions Designed to Develop Physical Therapist Learners’ Clinical Reasoning: A Systematic Review
Authors: Fu Wing , Baldwin Tobi F , Brechter Jacklyn H , Erickson Mark R , Kobal Kara , LaFay Vicki , Miller Teresa M , Morales Jaclyn 
Published: December 2024

Abstract

Objective
The objective of this systematic review was to investigate the effects of educational interventions designed to develop physical therapist learners’ clinical reasoning across the full continuum of professional development.

Data Sources
A systematic search was conducted of 6 databases, the entire Journal of Physical Therapy Education collection, and the reference lists of included articles through March 2022.

Study Selection
English-language primary relevant research studies of all research designs were included while grey literature was excluded.

Data Extraction and Synthesis
Two reviewers independently extracted data from and determined risk of bias of each of the 40 included studies. Disagreements were resolved by consensus or use of a third reviewer. A narrative synthesis summarized and explained the quantitative data. Meta-analysis was not possible due to data heterogeneity. Qualitative data were synthesized using thematic analysis.

Main Outcome(s) and Measure(s)
Main outcomes were effects of the educational interventions per the Kirkpatrick model.

Results
Forty articles met the inclusion criteria. Twenty-two of the 33 studies with quantitative data involving student or practicing physical therapists reported statistically significant positive outcomes. Three major themes emerged from thematic analysis of 23 studies: perceived educational gain, valued elements of educational interventions, and identified challenges to learning.

Conclusions and Relevance
Educational interventions that appeared to have a positive impact on learning outcomes were identified. However, the available research lacks rigor for the authors to develop evidence-based guidelines to support the development of clinical reasoning in physical therapist learners. Given the importance of clinical reasoning, high quality studies are warranted. This comprehensive systematic review appeared to be the first one in the profession to have investigated the effects of educational interventions designed to develop learners’ clinical reasoning across the entire professional development. Educators and researchers may benefit from the findings to develop educational interventions and future studies.
The impact of an online, lifestyle intervention programme on the lives of patients with a rheumatic and musculoskeletal disease: a pilot study
Authors: van Slingerland Kim , Kranenburg Laura J C , Wilmsen Nathalie , Coles Emma , Dolhain Radboud J E M , de Jong Pascal H P 
Published: December 2024

Abstract

Objectives
To evaluate the short- and long-term effects of an online, interactive, multifactorial lifestyle intervention programme (Leef! Met Reuma) on health risk and all ICHOM-recommended patient-reported outcome measures (PROMs) in patients with an inflammatory arthritis (IA), osteoarthritis (OA) or fibromyalgia (FM).

Methods
Patients with an IA, OA or FM could register for the lifestyle intervention programme. The programme consists of a 3-month intensive part followed by a 21-month aftercare period and focuses on four pillars, namely nutrition, exercise, relaxation and sleep. Health risk and PROMs are collected 3-monthly during the first 6 months and 6-monthly during the next 18 months. Health risk includes self-reported weight, waist circumference and BMI. Following PROMs were included: pain, morning stiffness severity, fatigue, Health Assessment Questionnaire, quality of life, perceived stress, sleep disturbance and impact on life. Descriptive statistics were used to assess the change in health risk and PROMs during the intensive part of the programme and aftercare period.

Results
Of the 264 patients studied, 88, 105 and 71 were diagnosed with IA, OA and FM, respectively. Health risk significantly improved in all three diagnosis groups during the intensive part of the programme. The mean BMI reduction was −1.36 (0.26), −1.22 (0.23) and −1.48 (0.33), whereafter it stabilized in the aftercare period. All PROMs showed a similar trend.

Conclusion
An online, interactive lifestyle intervention programme has a positive long-term effect, even after 2 years of follow-up, on health risk and all PRO domains in patients with an IA, OA and FM.
PAI‐1 promotes human endometrial stromal decidualization via inhibiting VEGFR2/PI3K/AKT signaling pathway mediated F‐actin reorganization
Authors: Zhao Huishan , Liu Juan , Yin Shuyuan , Bao Hongchu 
Published: December 2024

AbstractDecidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI‐1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure. This study will explore the dynamic expression changes of PAI‐1 in the endometrium during the menstrual cycle and its molecular mechanism affecting endometrial decidualization. Our findings indicated that the abundance of PAI‐1 increased in the mid‐secretory phase and attached a peak in the decidual phase in the endometrium of women with regular menstrual cycles. In human endometrial stromal cells (HESCs), PAI‐1 knockdown attenuated endometrial decidualization by upregulating VEGFR2/PI3K/AKT signaling pathway and impaired the F‐actin reorganization. Furthermore, axitinib (a VEGFR2 inhibitor) was used to inhibit the VEGFR2 protein activity and the results suggested that it eliminated the effects of PAI‐1 on PI3K/AKT signaling pathways and F‐actin remodeling. In addition, the interaction between PAI‐1 and KNG1 was confirmed by coimmunoprecipitation assay in HESCs. Altogether, PAI‐1‐KNG1 may enhance the decidualization of endometrium by inhibiting VEGFR2/PI3K/AKT signaling pathway‐mediated F‐actin reorganization in healthy females.
Identification of apigenin as a multi‐target inhibitor against SARS‐CoV‐2 by computational exploration
Authors: Huang Juanjuan , Jin Yixuan , Wu Runze , Xie Hanxi , Yang Ming , Jia Jiwei , Wang Guoqing 
Published: December 2024

AbstractMulti‐target strategy can serve as a valid treatment for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but existing drugs most focus on a single target. Thus, multi‐target drugs that bind multiple sites simultaneously need to be urgently studied. Apigenin has antiviral and anti‐inflammatory properties. Here, we comprehensively explored the potential effect and mechanism of apigenin in SARS‐CoV‐2 treatment by a network algorithm, deep learning, molecular docking, molecular dynamics (MD) simulation, and normal mode analysis (NMA). KATZ‐based VDA prediction method (VDA‐KATZ) indicated that apigenin may provide a latent drug therapy for SARS‐CoV‐2. Prediction of DTA using convolution model with self‐attention (CSatDTA) showed potential binding affinity of apigenin with multiple targets of virus entry, assembly, and cytokine storms including cathepsin L (CTSL), membrane (M), envelope (E), Toll‐like receptor 4 (TLR4), nuclear factor‐kappa B (NF‐κB), NOD‐like receptor pyrin domain‐containing protein 3 (NLRP3), apoptosis‐associated speck‐like protein (ASC), and cysteinyl aspartate‐specific proteinase‐1 (Caspase‐1). Molecular docking indicated that apigenin could effectively bind these targets, and its stability was confirmed using MD simulation and NMA. Overall, apigenin is a multi‐target inhibitor for the entry, assembly, and cytokine storms of SARS‐CoV‐2.
Covert Critical Illness Encephalopathy: Impairments That Escape Detection by Guideline Recommended, Protocolized Assessments
Authors: Shirodkar Ruhi , Bourgeois Isaac J. , Kim Minjee , Kimchi Eyal Y. , Liotta Eric M. , Maas Matthew B. 
Published: December 2024

Objectives:
To determine whether cognitive impairments of important severity escape detection by guideline-recommended delirium and encephalopathy screening instruments in critically ill patients.

Design:
Cross-sectional study with random patient sampling.

Setting:
ICUs of a large referral hospital with protocols implementing the Society of Critical Care Medicine’s ICU Liberation Bundle.

Patients:
Patients with a heterogeneous mix of primary organ system conditions leading to critical illness and with no abnormal findings scored in Confusion Assessment Method for the ICU (CAM-ICU) screening, Richmond Agitation-Sedation Scale (RASS) 0, and Glasgow Coma Scale (GCS) 15, indicating they were alert, fully oriented, and following commands with no delirium or findings to indicate subsyndromal delirium.

Interventions:
None.

Measurements and Main Results:
We evaluated 50 patients, age 54 ± 16 years. Trained critical care nurses assessed patients at regular intervals using the CAM-ICU, RASS, and GCS per a protocol. We performed a battery of psychometric cognitive tests using the NIH Toolbox. Executive functions linked to attention and inhibitory control, and processing speed were 1.5 sd below population norm (both p < 0.01). Working memory and cognitive flexibility were also significantly, but less severely, impaired (p < 0.01 and p = 0.026). Nearly two-thirds (64%) of the patients scored at least 1.5 sd worse than demographically adjusted means in two or more cognitive domains, a commonly used diagnostic criterion for cognitive impairment.

Conclusions:
Substantial cognitive impairment is present among critically ill patients with no abnormalities detected by standard delirium and encephalopathy assessments.