bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn’s Disease Recurrence
Authors: Bachour Salam P. , Shah Ravi S. , Joseph Abel , Syed Hareem , Ali Adel Hajj , Rieder Florian , Barnes Edward L. , Axelrad Jordan , Holubar Stefan D. , Regueiro Miguel , Cohen Benjamin L. , Click Benjamin H. 
Published: November 2023

Goals:
Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis.

Background:
Postoperative biologic prophylaxis reduces postoperative Crohn’s disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated.

Study:
Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy.

Results:
Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation.

Conclusion:
In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.
Disparities in Rates of Multitarget Stool DNA Test Completion for Colorectal Cancer Screening
Authors: Dong Jeffrey , Said Hyder , Miller Samuel J. , Systrom Hannah K. , Feuerstein Joseph D. 
Published: November 2023

Goals:
The aim was to assess patient adherence to multitarget stool DNA testing as well as factors associated with adherence.

Background:
In the United States, disparities in colorectal cancer screening exist along racial and socioeconomic lines. While some studies suggest that stool-based screening tests may help reduce the screening gap, the data for multitarget stool DNA testing is unclear.

Study:
We conducted a single-center retrospective cohort study on multitarget stool DNA testing ordered between April 2020 and July 2021. We calculated the proportion of patients who completed testing and used multivariate logistic regression to identify covariates associated with test adherence.

Results:
Among 797 patients ordered for multitarget stool DNA testing, 481 patients (60.4%) completed testing. Adherence rates by patient subgroups ranged from 35.8% to 78.1%. Higher test adherence was found in Asian patients (odds ratio 2.65, 95% CI 1.36-5.18) and those who previously completed colorectal cancer screening (OR 1.45, 95% CI 1.01-2.09), while Black patients (OR 0.58, 95% CI 0.39-0.87), patients with resident primary care physicians (OR 0.34, 95% CI 0.21-0.56), and patients contacted through an outreach program (OR 0.47, 95% CI 0.25-0.87) had lower adherence.

Conclusions:
A significant proportion of patients ordered for multitarget stool DNA testing did not complete testing. Differences in adherence rates among patient subgroups may be reflective of underlying disparities in health care access.
Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection
Authors: Feuerstadt Paul , Crawford Carl V. , Tan Xing , Pokhilko Victoria , Bancke Lindy , Ng Samson , Guthmueller Beth , Bidell Monique R. , Tillotson Glenn , Johnson Stuart , Skinner Andrew M. 
Published: November 2023

Goals:
To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables.

Background:
RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI.

Study:
Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570). Treatment-emergent adverse events were summarized for the double-blind treatment period within 8 weeks.

Results:
Treatment differences between RBL and placebo at 8 weeks were similar to the total population for most subgroups. Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses >14 days versus ≤14 days and higher for antibiotic washout periods of 3 days versus ≤2 days. The largest reductions in the rate of rCDI with RBL versus placebo were observed for participants with a 3-day CDI antibiotic washout period and participants with ≥4 previous CDI episodes. Most RBL-treated participants experienced TEAEs that were mild or moderate in severity and related to preexisting conditions.

Conclusion:
This analysis provides further evidence of RBL efficacy and safety across subgroups, including those at high risk for rCDI.
Cold Versus Hot Endoscopic Mucosal Resection for Sessile Serrated Colorectal Polyps ≥10 mm
Authors: Malik Talia F. , Mohan Babu P. , Deliwala Smit , Kassab Lena L. , Chandan Saurabh , Sharma Neil R. , Adler Douglas G. 
Published: November 2023

Introduction:
We performed a systematic review and meta-analysis studying the efficacy and safety of cold versus hot endoscopic mucosal resection (EMR) for resection of sessile serrated polyps (SSPs) ≥10 mm.

Methods:
Multiple databases were searched until January 2023 for studies reporting outcomes of cold versus hot EMR for SSPs ≥10 mm. The primary outcome was the residual SSP rate. Secondary outcomes included technical success rate, R0 resection rate, and adverse events. We used standard meta-analysis methods using the random-effects model, and I
2% was used to assess heterogeneity.

Results:
Thirteen studies were included in the final analysis. In all, 1896 SSPs were included with a mean polyp size of 23.7 mm (range, 15.9 to 33). A total of 1452 SSPs were followed up for a median follow-up duration of 15.3 months (range, 6 to 37). The pooled residual SSP rate for cold EMR was 4.5% (95% CI: 1.0-17.4), and 5.1% (95% CI: 2.4-10.4) for hot EMR (P=0.9). The pooled rates of technical success, R0 resection, immediate bleeding, and perforation were comparable. Hot EMR was significantly associated with lower piecemeal resection (59.2% vs. 99.3%, P<0.001), higher en-bloc resection (41.4% vs. 1.4%, P<0.001), and delayed bleeding rate (4% vs. 0.7%, P=0.05) compared to cold EMR.

Conclusions:
Cold EMR has similar efficacy compared to hot EMR for resection of SSP ≥ 10 mm, despite limitations in piecemeal R0 resection rate reporting. Although hot EMR was associated with a higher rate of en-bloc resection, it also showed an increased risk of delayed bleeding compared to cold EMR.
Thrombotic microangiopathy – the importance of a multidisciplinary approach
Authors: Tran Minh-Ha , Patel Samir , Desai Sheetal , Ciurea Stefan , Lee Benjamin J. , Hanna Ramy 
Published: November 2023

Purpose of review
The purpose of this review is to highlight the importance of a multidisciplinary thrombotic microangiopathies (TMA) Team. This goal will be accomplished through review of the complement system, discuss various causes of thrombotic microangiopathies (TMA), and aspects of their diagnosis and management. In so doing, readers will gain an appreciation for the complexity of this family of disorders and realize the benefit of a dedicated multidisciplinary TMA Team.

Recent findings
TMA causes derive from multiple specialty areas, are difficult to timely recognize, pose complex challenges, and require multidisciplinary management. Hematopoietic stem cell transplant-associated TMA (TA-TMA) and TA-TMA related multiorgan dysfunction syndrome (TA-TMA MODS) are areas of burgeoning research; use of complement testing and eculizumab precision-dosing has been found to better suppress complement activity in TA-TMA than standard eculizumab dosing. Newer tests are available to risk-stratify obstetric patients at risk for severe pre-eclampsia, whose features resemble those of TA-TMA MODS. Numerous disorders may produce TMA-like findings, and a systematic approach aids in their identification. TMA Teams elevate institutional awareness of increasingly recognized TMAs, will help expedite diagnostic and therapeutic interventions, and create pathways to future TMA-related research and facilitate access to clinical trials.

Summary
Establishment of a TMA-Team is valuable in developing the necessary institutional expertise needed to promptly recognize and appropriately manage patients with TMA.
Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma
Authors: Xu Hanli , Gao Huixia , Wang Chanjuan , Cheng Xiyu , Li Zhigang , Lei Cui , Huang XiaoTong , Li Weijing , Yue Zhixia , Tian Shuo , Zhao Xiaoxi , Xue Tianlin , Xing Tianyu , Li Jun , Wang Ying , Duan Yanlong , Wang Tianyou , Zhang Ruidong 
Published: November 2023

Background:
Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM.

Methods:
OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L::AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR.

Results:
In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L::AHI1 and GRIK1::NSDHL, which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction.

Conclusions:
Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.
Altered structural connectivity and functional brain dynamics in individuals with heavy alcohol use
Authors: Singleton S. Parker , Velidi Puneet , Schilling Louisa , Luppi Andrea I. , Jamison Keith , Parkes Linden , Kuceyeski Amy 
Published: November 2023

AbstractHeavy alcohol use and its associated conditions, such as alcohol use disorder (AUD), impact millions of individuals worldwide. While our understanding of the neurobiological correlates of AUD has evolved substantially, we still lack models incorporating whole-brain neuroanatomical, functional, and pharmacological information under one framework. Here, we utilize diffusion and functional magnetic resonance imaging to investigate alterations to brain dynamics inN= 130 individuals with a high amount of current alcohol use. We compared these alcohol using individuals toN= 308 individuals with minimal use of any substances. We find that individuals with heavy alcohol use had less dynamic and complex brain activity, and through leveraging network control theory, had increased control energy to complete transitions between activation states. Further, using separately acquired positron emission tomography (PET) data, we deploy anin silicoevaluation demonstrating that decreased D2 receptor levels, as found previously in individuals with AUD, may relate to our observed findings. This work demonstrates that whole-brain, multimodal imaging information can be combined under a network control framework to identify and evaluate neurobiological correlates and mechanisms of AUD.
Exploring SureChEMBL from a drug discovery perspective
Authors: Gadiya Yojana , Shetty Simran , Hofmann-Apitius Martin , Gribbon Philip , Zaliani Andrea 
Published: November 2023

AbstractIn the pharmaceutical industry, the patent protection of drugs and medicines is accorded importance because of the high costs involved in the development of novel drugs. Over the years, researchers have analyzed patent documents to identify freedom-to-operate spaces for novel drug candidates. To assist this, several well established public patent document data repositories have enabled automated methodologies for extracting information on therapeutic agents. In this study, we delve into one such publicly available patent database, SureChEMBL, which catalogues patent documents related to life sciences. Our exploration begins by identifying patent compounds across public chemical data resources, followed by pinpointing sections in patent documents where the chemical annotations were found. Next, we exhibit the potential of compounds to serve as drug candidates by evaluating their conformity to drug-likeness criteria. Lastly, we examine the drug development stage reported for these compounds to understand their clinical success. In summary, our investigation aims at providing a comprehensive overview of the patent compounds catalogued in SureChEMBL, assessing their relevance to pharmaceutical drug discovery.
The contribution of diverse and stable functional connectivity edges to brain-behavior associations
Authors: Matkovič Andraž , Murray John D. , Anticevic Alan , Repovš Grega 
Published: November 2023

AbstractResting-state functional connectivity (FC) has received considerable attention in the study of brain-behavior associations. However, the low generalizability of brain-behavior studies is a common challenge due to the limited sample-to-feature ratio. In this study, we aimed to improve the generalizability of brain-behavior associations in resting-state FC by focusing on diverse and stable edges, i.e., edges that show both high between-subject and low within-subject variability. We used resting-state data from 1003 participants with multiple fMRI sessions from the Human Connectome Project to group FC edges in terms of between-subject and within-subject variability. We found that resting-state FC variability was dominated by stable individual factors. Furthermore, diverse and stable edges were primarily part of heteromodal associative networks, and we showed that diverse stable regions are associated with a domain-general cognitive core. We used canonical correlation analysis (CCA) combined with feature selection and principal component analysis (PCA) to investigate the impact of edge selection on the strength and generalizability of brain-behavior associations. Surprisingly, selection based on edge stability did not significantly affect the results, but diverse edges were more informative than uniform edges in two of the three parcellations tested. Regardless, using all edges resulted in the highest strength and generalizability of canonical correlations. Our simulations suggest that under certain circumstances a combination of feature selection and PCA could improve the generalizability of the results, depending on the sample size and the information value of the features. The lack of improvement in generalizability with selection of stable edges may be due to unreliable estimation of within-subject edge variability or because within-subject edge variability is not related to the information value of the edges for brain-behavior associations. In other words, unstable edges may be equally informative as stable ones.
Artificially inserted G-quadruplex DNA secondary structures induce long-distance chromatin activation
Authors: Roy Shuvra Shekhar , Bagri Sulochana , Vinayagamurthy Soujanya , Sengupta Avik , Then Claudia Regina , Kumar Rahul , Sridharan Sriram , Chowdhury Shantanu 
Published: November 2023

AbstractAlthough the role of G-quadruplex (G4) DNA structures has been suggested in chromosomal looping this was not tested directly. Here, to test causal function, an array of G4s, or control sequence that does not form G4s, were inserted within chromatin in cells.In vivoG4 formation of the inserted G4 sequence array, and not the control sequence, was confirmed using G4-selective antibody. Compared to the control insert, we observed a remarkable increase in the number of 3D chromatin looping interactions from the inserted G4 array. This was evident within the immediate topologically associated domain (TAD) and throughout the genome. Locally, recruitment of enhancer histone marks and the transcriptional coactivator p300/Acetylated-p300 increased in the G4-array, but not in the control insertion. Resulting promoter-enhancer interactions and gene activation were clear up to 5 Mb away from the insertion site. Together, these show the causal role of G4s in enhancer function and long-range chromatin interactions. Mechanisms of 3D topology are primarily based on DNA-bound architectural proteins that induce/stabilize long-range interactions. Involvement of the underlying intrinsic DNA sequence/structure in 3D looping shown here therefore throws new light on how long-range chromosomal interactions might be induced or maintained.
Effective Natural Language Processing Algorithms for Gout Flare Early Alert from Chief Complaints
Authors: Oliveira Lucas Lopes , Jiang Xiaorui , Babu Aryalakshmi Nellippillipathil , Karajagi Poonam , Daneshkhah Alireza 
Published: November 2023

AbstractEarly identification of acute gout is crucial, enabling healthcare professionals to implement targeted interventions for rapid pain relief and preventing disease progression, ensuring improved long-term joint function. In this study, we comprehensively explored the potential of gout flare (GF) early detection based on nurse chief complaint notes in the Emergency Department (ED). Addressing the challenge of identifying GFs prospectively during an ED visit, where documentation is typically minimal, our research focuses on employing alternative Natural Language Processing (NLP) techniques to enhance the detection accuracy. We investigate GF detection algorithms using both sparse representations by traditional NLP methods and dense encodings by medical domain-specific Large Language Models (LLMs), distinguishing between generative and discriminative models. Three methods are used to alleviate the issue of severe data imbalance, including oversampling, class weights, and focal loss. Extensive empirical studies are done on the Gout Emergency Department Chief Complaint Corpora. Sparse text representations like tf-idf proved to produce strong performance, achieving higher than 0.75 F1 Score. The best deep learning models are RoBERTa-Large-PM-M3-Voc and BioGPT, with the best F1 Scores on each dataset with a 0.8 on the 2019 dataset and a 0.85 F1 Score the 2020 dataset. We concluded that although discriminative LLMs performed better for this classification task, compared to generative LLMs, a combination of using generative models as feature extractors and employing support vector machine for classification yields promising results comparable to those obtained with discriminative models.
Control limitations in the null-space of the wrist muscle system
Authors: Lee Meng-Jung , Eden Jonathan , Gurgone Sergio , Berger Denise J , Borzelli Daniele , d’Avella Andrea , Mehring Carsten , Burdet Etienne 
Published: November 2023

ABSTRACTThe redundancy present within the musculoskeletal system may offer a non-invasive source of signals for movement augmen tation, where the muscle-to-force null-space could be controlled simultaneously to the natural limbs. Here, we investigated the viability of extracting movement augmentation control signals from the muscles of the wrist complex. Our study assessed i) if controlled variation of the muscle activation patterns in the wrist joint’s null-space is possible; and ii) whether force and null-space targets could be reached simultaneously. During the null-space target reaching condition, participants used EMG-to-force null-space muscle activation to move their cursor towards a displayed target while minimising the exerted force as visualised through the cursor’s size. Initial targets were positioned to require natural co-contraction in the null-space and if participants showed a consistent ability to reach for their current target, they would rotate 5° incrementally to generate muscle activation patterns further away from their natural co-contraction. In contrast, during the concurrent target reaching condition participants were required to match a target position and size, where their cursor position was instead controlled by their exerted flexion-extension and radial-ulnar deviation, while its size was changed by their natural co-contraction magnitude. The results collected from 10 participants suggest that while there was variation in each participant’s co-contraction behaviour, most did not possess the ability to control this variation for muscle-to-force null-space reaching. In contrast, participants did show a direction and target size dependent ability to vary isometric force and co-contraction activity concurrently. Our results show the limitations of using null-space activity in joints with a low level of redundancy.
Fast and light efficient remote focusing for volumetric voltage imaging
Authors: Böhm Urs L. , Judkewitz Benjamin 
Published: November 2023

AbstractVoltage imaging holds great potential for biomedical research by enabling noninvasive recording of the electrical activity of excitable cells such as neurons or cardiomyocytes. Camera-based detection can record from hundreds of cells in parallel, but imaging entire volumes is limited by the need to focus through the sample at high speeds. Remote focusing techniques can remedy this drawback, but have so far been either too slow or light inefficient. Here, we introduce FLIPR, a new approach for remote focusing that doubles the light efficiency and enables high-speed volumetric voltage imaging at 500 volumes/s. We show the potential of our approach by combining it with lightsheet imaging in the zebrafish spinal cord to record from >100 spontaneously active neurons in parallel.