bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry
Authors: Philip Shery Susan , Janardana Ramya , Shenoy Padmanabha , Kavadichanda Chengappa , Bairwa Devender , Sircar Geetabali , Ghosh Parasar , Wakhlu Anupam , Selvam Sumithra , Khanna Dinesh , Shobha Vineeta 
Published: December 2023

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 ( n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 ( n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 ( n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 ( n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.
Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML
Authors: Bourgeois Wallace , Cutler Jevon A. , Aubrey Brandon J. , Wenge Daniela V. , Perner Florian , Martucci Cynthia , Henrich Jill A. , Klega Kelly , Nowak Radosław P. , Donovan Katherine A. , Boileau Meaghan , Wen Yanhe , Hatton Charlie , Apazidis Athina A. , Olsen Sarah Naomi , Kirmani Nadia , Pikman Yana , Pollard Jessica A. , Perry Jennifer A. , Sperling Adam S. , Ebert Benjamin L. , McGeehan Gerard M. , Crompton Brian D. , Fischer Eric S. , Armstrong Scott A. 
Published: December 2023

Abstract
Small molecules that target the menin-KMT2A protein-protein interaction (menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A or MLL1)–rearranged (KMT2A-r) and nucleophosmin-mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study, we show that mezigdomide has increased preclinical activity in vitro as a single-agent in KMT2A-r and NPM1c AML cell lines, including sensitivity in cell lines resistant to lenalidomide and iberdomide. Further, we demonstrate that mezigdomide has the greatest capacity to synergize with and induce apoptosis in combination with menin inhibitors, including in MEN1 mutant models. We show that the superior activity of mezigdomide compared with lenalidomide or iberdomide is due to its increased depth, rate, and duration of IKAROS protein degradation. Single-agent mezigdomide was efficacious in 5 patient-derived xenograft models of KMT2A-r and 1 NPM1c AML. The combination of mezigdomide with the menin inhibitor VTP-50469 increased survival and prevented and overcame MEN1 mutations that mediate resistance in patients receiving menin inhibitor monotherapy. These results support prioritization of mezigdomide for early phase clinical trials in KMT2A-r and NPM1c AML, either as a single agent or in combination with menin inhibitors.
Nucleic acid sensing promotes inflammatory monocyte migration through biased coagulation factor VIIa signaling
Authors: Zelaya Hortensia , Grunz Kristin , Nguyen T. Son , Habibi Anxhela , Witzler Claudius , Reyda Sabine , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Bosmann Markus , Weiler Hartmut , Ruf Wolfram 
Published: December 2023

Abstract
Protease activated receptors (PARs) are cleaved by coagulation proteases and thereby connect hemostasis with innate immune responses. Signaling of the tissue factor (TF) complex with factor VIIa (FVIIa) via PAR2 stimulates extracellular signal-regulated kinase (ERK) activation and cancer cell migration, but functions of cell autonomous TF-FVIIa signaling in immune cells are unknown. Here, we show that myeloid cell expression of FVII but not of FX is crucial for inflammatory cell recruitment to the alveolar space after challenge with the double-stranded viral RNA mimic polyinosinic:polycytidylic acid [Poly(I:C)]. In line with these data, genetically modified mice completely resistant to PAR2 cleavage but not FXa-resistant PAR2–mutant mice are protected from lung inflammation. Poly(I:C)-stimulated migration of monocytes/macrophages is dependent on ERK activation and mitochondrial antiviral signaling (MAVS) but independent of toll-like receptor 3 (TLR3). Monocyte/macrophage-synthesized FVIIa cleaving PAR2 is required for integrin αMβ2-dependent migration on fibrinogen but not for integrin β1-dependent migration on fibronectin. To further dissect the downstream signaling pathway, we generated PAR2S365/T368A-mutant mice deficient in β-arrestin recruitment and ERK scaffolding. This mutation reduces cytosolic, but not nuclear ERK phosphorylation by Poly(I:C) stimulation, and prevents macrophage migration on fibrinogen but not fibronectin after stimulation with Poly(I:C) or CpG-B, a single-stranded DNA TLR9 agonist. In addition, PAR2S365/T368A-mutant mice display markedly reduced immune cell recruitment to the alveolar space after Poly(I:C) challenge. These results identify TF-FVIIa-PAR2-β-arrestin–biased signaling as a driver for lung infiltration in response to viral nucleic acids and suggest potential therapeutic interventions specifically targeting TF-VIIa signaling in thrombo-inflammation.
Low-frequency inherited complement receptor variants are associated with purpura fulminans
Authors: Bendapudi Pavan K. , Nazeen Sumaiya , Ryu Justine , Söylemez Onuralp , Robbins Alissa , Rouaisnel Betty , O’Neil Jillian K. , Pokhriyal Ruchika , Yang Moua , Colling Meaghan , Pasko Bryce , Bouzinier Michael , Tomczak Lindsay , Collier Lindsay , Barrios David , Ram Sanjay , Toth-Petroczy Agnes , Krier Joel , Fieg Elizabeth , Dzik Walter H. , Hudspeth James C. , Pozdnyakova Olga , Nardi Valentina , Knight James , Maas Richard , Sunyaev Shamil , Losman Julie-Aurore 
Published: December 2023

Abstract
Extreme disease phenotypes can provide key insights into the pathophysiology of common conditions, but studying such cases is challenging due to their rarity and the limited statistical power of existing methods. Herein, we used a novel approach to pathway–based mutational burden testing, the rare variant trend test (RVTT), to investigate genetic risk factors for an extreme form of sepsis-induced coagulopathy, infectious purpura fulminans (PF). In addition to prospective patient sample collection, we electronically screened over 10.4 million medical records from 4 large hospital systems and identified historical cases of PF for which archived specimens were available to perform germline whole-exome sequencing. We found a significantly increased burden of low-frequency, putatively function-altering variants in the complement system in patients with PF compared with unselected patients with sepsis (P = .01). A multivariable logistic regression analysis found that the number of complement system variants per patient was independently associated with PF after controlling for age, sex, and disease acuity (P = .01). Functional characterization of PF-associated variants in the immunomodulatory complement receptors CR3 and CR4 revealed that they result in partial or complete loss of anti-inflammatory CR3 function and/or gain of proinflammatory CR4 function. Taken together, these findings suggest that inherited defects in CR3 and CR4 predispose to the maladaptive hyperinflammation that characterizes severe sepsis with coagulopathy.
PhyloSophos: a high-throughput scientific name mapping algorithm augmented with explicit consideration of taxonomic science, and its application on natural product (NP) occurrence database processing
Authors: Cho Min Hyung , Cho Kwang-Hwi , No Kyoung Tai 
Published: December 2023

Abstract
Background
The standardization of biological data using unique identifiers is vital for seamless data integration, comprehensive interpretation, and reproducibility of research findings, contributing to advancements in bioinformatics and systems biology. Despite being widely accepted as a universal identifier, scientific names for biological species have inherent limitations, including lack of stability, uniqueness, and convertibility, hindering their effective use as identifiers in databases, particularly in natural product (NP) occurrence databases, posing a substantial obstacle to utilizing this valuable data for large-scale research applications.

Result
To address these challenges and facilitate high-throughput analysis of biological data involving scientific names, we developed PhyloSophos, a Python package that considers the properties of scientific names and taxonomic systems to accurately map name inputs to entries within a chosen reference database. We illustrate the importance of assessing multiple taxonomic databases and considering taxonomic syntax-based pre-processing using NP occurrence databases as an example, with the ultimate goal of integrating heterogeneous information into a single, unified dataset.

Conclusions
We anticipate PhyloSophos to significantly aid in the systematic processing of poorly digitized and curated biological data, such as biodiversity information and ethnopharmacological resources, enabling full-scale bioinformatics analysis using these valuable data resources.
DL-PPI: a method on prediction of sequenced protein–protein interaction based on deep learning
Authors: Wu Jiahui , Liu Bo , Zhang Jidong , Wang Zhihan , Li Jianqiang 
Published: December 2023

Abstract
Purpose
Sequenced Protein–Protein Interaction (PPI) prediction represents a pivotal area of study in biology, playing a crucial role in elucidating the mechanistic underpinnings of diseases and facilitating the design of novel therapeutic interventions. Conventional methods for extracting features through experimental processes have proven to be both costly and exceedingly complex. In light of these challenges, the scientific community has turned to computational approaches, particularly those grounded in deep learning methodologies. Despite the progress achieved by current deep learning technologies, their effectiveness diminishes when applied to larger, unfamiliar datasets.

Results
In this study, the paper introduces a novel deep learning framework, termed DL-PPI, for predicting PPIs based on sequence data. The proposed framework comprises two key components aimed at improving the accuracy of feature extraction from individual protein sequences and capturing relationships between proteins in unfamiliar datasets. 1. Protein Node Feature Extraction Module: To enhance the accuracy of feature extraction from individual protein sequences and facilitate the understanding of relationships between proteins in unknown datasets, the paper devised a novel protein node feature extraction module utilizing the Inception method. This module efficiently captures relevant patterns and representations within protein sequences, enabling more informative feature extraction. 2. Feature-Relational Reasoning Network (FRN): In the Global Feature Extraction module of our model, the paper developed a novel FRN that leveraged Graph Neural Networks to determine interactions between pairs of input proteins. The FRN effectively captures the underlying relational information between proteins, contributing to improved PPI predictions. DL-PPI framework demonstrates state-of-the-art performance in the realm of sequence-based PPI prediction.
The forgotten variable? Does the euthanasia method and sample storage condition influence an organisms transcriptome – a gene expression analysis on multiple tissues in pigs
Authors: Chakkingal Bhaskaran B. , Meyermans R. , Gorssen W. , Maes G. E. , Buyse J. , Janssens S. , Buys N. 
Published: December 2023

AbstractBackgroundTranscriptomic studies often require collection of fresh tissues post euthanasia. The chosen euthanasia method might have the potential to induce variations in gene expressions that are unlinked with the experimental design. The present study compared the suitability of ‘nitrogen gas in foam’ (ANOXIA) in comparison to a non-barbiturate anaesthetic, T-61® (T61), for euthanizing piglets used in transcriptome research. Further, the effect of common tissue storage conditions, RNAlater™ (RL) and snap freezing in liquid nitrogen (LN2), on gene expression profiles were also analysed.ResultsOn comparison of the 3’mRNA-Seq data generated from pituitary, hypothalamus, liver and lung tissues, no significant differential expression in the protein coding genes were detected between the euthanasia methods. This implies that the nitrogen anoxia method could be a suitable alternative for euthanasia of piglets used in transcriptomic research. However, small nuclear RNAs (snRNAs) that constitute the eukaryotic spliceosomal machinery were found to be significantly higher (log2fold change ≥ 2.0, and adjusted p value ≤ 0.1) in pituitary samples collected using ANOXIA. Non-protein coding genes like snRNAs that play an important role in pre-mRNA splicing can subsequently modify gene expression. Storage in RL was found to be superior in preserving RNA compared to LN2storage, as evidenced by the significantly higher RIN values in representative samples. However, storage in RL as opposed to LN2, also influenced differential gene expression in multiple tissues, perhaps as a result of its inability to inhibit biological activity during storage. Hence such external sources of variations should be carefully considered before arriving at research conclusions.ConclusionsSource of biological variations like euthanasia method and storage condition can confound research findings. Even if we are unable to prevent the effect of these external factors, it will be useful to identify the impact of these variables on the parameter under observation and thereby prevent misinterpretation of our results.
The association between systemic inflammation markers and the prevalence of hypertension
Authors: Jin Nake , Huang Lei , Hong Jun , Zhao Xuechen , Hu Jianan , Wang Shanshan , Chen Xudong , Rong Jiacheng , Lu Yingjie 
Published: December 2023

Abstract
Background
We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension.

Methods
A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension.

Results
The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence.

Conclusion
Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.
Dementia and comorbidities in primary care: a scoping review
Authors: Bergman Howard , Borson Soo , Jessen Frank , Krolak-Salmon Pierre , Pirani Alessandro , Rasmussen Jill , Rodrigo Jesus , Taddeo Daiana 
Published: December 2023

Abstract
Background
People with dementia (PwD) are known to have more chronic conditions compared to those without dementia, which can impact the clinical presentation of dementia, complicate clinical management and reduce overall quality of life. While primary care providers (PCPs) are integral to dementia care, it is currently unclear how PCPs adapt dementia care practices to account for comorbidities. This scoping review maps recent literature that describes the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities, identifies critical knowledge gaps and proposes potential avenues for future research.

Methods
We searched for peer-reviewed literature published between 2017–2022 in MEDLINE, Cochrane Library, and Scopus using key terms related to dementia, primary care, and comorbidity. The literature was screened for relevance by title-abstract screening and subsequent full-text screening. The prioritized papers were categorized as either ‘Risk Assessment and Prevention’, ‘Screening, Detection, and Diagnosis’ or ‘Management’ and were further labelled as either ‘Tools and Technologies’, ‘Recommendations for Clinical Practice’ or ‘Programs and Initiatives’.

Results
We identified 1,058 unique records in our search and respectively excluded 800 and 230 publications during title-abstract and full-text screening. Twenty-eight articles were included in our review, where ~ 50% describe the development and testing of tools and technologies that use pre-existing conditions to assess dementia risk. Only one publication provides official dementia screening guidelines for PCPs in people with pre-existing conditions. About 30% of the articles discuss managing the care of PwD, where most were anchored around models of multidisciplinary care and mitigating potentially inappropriate prescribing.

Conclusion
To our knowledge, this is the first scoping review that examines the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities. Given our findings, we recommend that future studies: 1) further validate tools for risk assessment, timely detection and diagnosis that incorporate other health conditions; 2) provide additional guidance into how comorbidities could impact dementia care (including prescribing medication) in primary care settings; 3) incorporate comorbidities into primary care quality indicators for dementia; and 4) explore how to best incorporate dementia and comorbidities into models/frameworks of holistic, person-centred care.
The association between satisfaction with life and anxiety symptoms among Chinese elderly: a moderated mediation analysis
Authors: Lai Cynthia Y. Y. , Chen Lu Hua , Lai Frank H. Y. , Fung Ada W. T. , Ng Shamay S. M. 
Published: December 2023

Abstract
Background
Previous studies have suggested that certain personal psychological variables (e.g., life satisfaction and cognitive function) and physical variables (e.g., body mass index [BMI]) are significantly associated with individuals’ anxiety symptoms. However, relevant research on elderly is lagging and no studies have yet investigated the combined impact of these variables on anxiety. Thus, we conducted the present study to investigate the potential moderator role of BMI and the potential mediator role of cognitive function underlying the relationship between life satisfaction and anxiety symptoms in Chinese elderly based in Hong Kong.

Methods
Sixty-seven elderly aged 65 years old and above were recruited from the local elderly community centres in this pilot study. Each participant underwent a systematic evaluation using the Satisfaction with Life Scale (SWLS), Hong Kong Version of the Montreal Cognitive Assessment (HK-MoCA), and the Hamilton Anxiety Rating Scale (HAM-A) and were measured for their body weight and height. Regression analysis using the bootstrapping method was employed to test the hypothesized moderated mediation model.

Results
Our findings demonstrated the overall model accounted for 23.05% of the variance in scores of HAM-A (F (8, 57) = 2.134, p = 0.047) in Chinese elderly. There was a significant association between life satisfaction and anxiety symptoms (p = 0.031), indicating that individuals with higher life satisfaction were associated with less anxiety symptoms. Moreover, this relationship was positively moderated by BMI (b = 0.066, 95% CI [0.004, 0.128]), especially in Chinese elderly with BMI at a lower level (b = -0.571, 95% CI [-0.919, -0.224]) and an average level (b = -0.242, 95% CI [-0.460, -0.023]). No significant mediator role was detected for cognitive function (b = -0.006, 95% CI [-0.047, 0.044]) in our model.

Conclusions
Our findings suggest that increased life satisfaction can reduce anxiety symptoms among Chinese elderly as their BMI decreases (when BMI ranged between “mean - 1SD” and “mean” of the population). The significant interaction between psychological and physical factors underlying anxiety symptoms found in this study, presents a promising opportunity for translation into multi-level psychological and physical interventions for the management of anxiety in ageing patients during clinical practice.