bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scoping review of the measurement and analysis of frailty in randomised controlled trials
Authors: Sun Yanhe , Witham Miles D , Clegg Andy , Taylor Rod S , Dibben Grace , McAllister David , Hanlon Peter 
Published: November 2024

Abstract

Background
Frailty is of increasing interest in trials, either as a target of intervention, as an outcome or as a potential treatment modifier. However, frailty measurement is often highly variable. This scoping review assessed how frailty is quantified in randomised controlled trials (RCTs), in what context and for what purposes.

Methods
We searched five electronic databases for RCTs in which frailty was measured among trial participants. We extracted data on intervention type, the frailty measure used and the purpose for which frailty was assessed. We then compared these data according to reasons for frailty assessment.

Results
We identified 415 RCTs assessing frailty across a range of interventions. Frailty was used to define the target population (166 trials), as an outcome (156 trials), as an effect modifier examining interaction of frailty on treatment effect (61 trials), as a purely descriptive characteristic (42 trials) or as a prognostic marker examining the impact of frailty on future health outcome (78 trials). The trials used 28 different measures of frailty (plus 29 additional trial-specific measures). The frailty phenotype model was the most common overall (164 trials), for defining the target population (90/166 trials) and as an outcome (81/156 trials). The cumulative deficit model frailty index was also frequently used (102 trials) and was most common among trials assessing treatment effect modification (21/61 trials).

Conclusion
Frailty measurement in RCTs is highly variable. Understanding the properties of respective frailty measures and how these relate to frailty as encountered in clinical practice is a priority to ensure that trial findings can inform healthcare delivery for people living with frailty.
tcrBLOSUM: an amino acid substitution matrix for sensitive alignment of distant epitope-specific TCRs
Authors: Postovskaya Anna , Vercauteren Koen , Meysman Pieter , Laukens Kris 
Published: November 2024

Abstract
Deciphering the specificity of T-cell receptor (TCR) repertoires is crucial for monitoring adaptive immune responses and developing targeted immunotherapies and vaccines. To elucidate the specificity of previously unseen TCRs, many methods employ the BLOSUM62 matrix to find TCRs with similar amino acid (AA) sequences. However, while BLOSUM62 reflects the AA substitutions within conserved regions of proteins with similar functions, the remarkable diversity of TCRs means that both TCRs with similar and dissimilar sequences can bind the same epitope. Therefore, reliance on BLOSUM62 may bias detection towards epitope-specific TCRs with similar biochemical properties, overlooking those with more diverse AA compositions. In this study, we introduce tcrBLOSUMa and tcrBLOSUMb, specialized AA substitution matrices for CDR3 alpha and CDR3 beta TCR chains, respectively. The matrices reflect AA frequencies and variations occurring within TCRs that bind the same epitope, revealing that both CDR3 alpha and CDR3 beta display tolerance to a wide range of AA substitutions and differ noticeably from the standard BLOSUM62. By accurately aligning distant TCRs employing tcrBLOSUMb, we were able to improve clustering performance and capture a large number of epitope-specific TCRs with diverse AA compositions and physicochemical profiles overlooked by BLOSUM62. Utilizing both the general BLOSUM62 and specialized tcrBLOSUM matrices in existing computational tools will broaden the range of TCRs that can be associated with their cognate epitopes, thereby enhancing TCR repertoire analysis.
Hypometabolic mismatch with atrophy and tau pathology in mixed Alzheimer and Lewy body disease
Authors: Duong Michael Tran , Das Sandhitsu R , Khandelwal Pulkit , Lyu Xueying , Xie Long , McGrew Emily , Dehghani Nadia , McMillan Corey T , Lee Edward B , Shaw Leslie M , Yushkevich Paul A , Wolk David A , Nasrallah Ilya M 
Published: November 2024

Abstract
Polypathology is a major driver of heterogeneity in clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer Disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy Body Disease (LBD). Patients with Mixed Etiology Dementia (MED) such as AD+LBD have faster progression and potentially differential responses to targeted treatments, though the diagnosis of AD+LBD can be challenging given overlapping clinical and imaging features. Development and validation of improved in vivo biomarkers are required to study relationships between N and S and identify imaging patterns reflecting mixed AD+LBD pathologies.
We hypothesize that individual proteinopathies, such as T and S, are associated with commensurate levels of N. Thus, we assessed biomarkers of A, T, N and S with positron emission tomography (PET), magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) seeding amplification assay (SAA) data to determine molecular presentations of mixed A+S+ vs. A+S– cognitively impaired patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
We found A+S+ patients had parieto-occipital 18F-Fluorodeoxyglucose hypometabolism (a measure of N) disproportionate to the degree of regional atrophy or T burden, highlighting worse hypometabolism associated with S+ SAA. Following up on this hypometabolic mismatch with CSF metabolite and proteome analyses, we found that A+S+ patients exhibited lower CSF levels of dopamine metabolites and synaptic markers like neuronal pentraxin-2 (NPTX2), suggesting that altered neurotransmission and neuron integrity contribute to this dissociation between metabolic PET and MRI. Potential confounders exist when studying relations between N, AD and LBD pathologies, including neuroinflammation and other non-Alzheimer pathologies in MED, though our findings imply posterior hypometabolic mismatch is related more to S than vascular or TDP-43 pathology.
A+S+ patients had posterior mismatch with excessive 18F-Fluorodeoxyglucose hypometabolism relative to atrophy or T load, possibly reflecting impaired neuron integrity. Further research must disentangle the impact of multiple proteinopathies and clinicopathologic factors on hypometabolism and atrophy. Cumulatively, patients with mixed AD+LBD etiologies harbor a unique metabolic PET mismatch signature.
Telemedicine in nephrology: future perspective and solutions
Authors: Sugawara Yuka , Hirakawa Yosuke , Nangaku Masaomi 
Published: November 2024

ABSTRACT
Telemedicine is a medical practice that uses electronic information and communication technologies. It is not exclusive to face-to-face care but complements face-to-face care and other forms of medical care. It has advantages such as facilitating home therapy, reducing patient travel time and costs, and empowering patients. This makes equitable access to care feasible. Clinical studies have been conducted on telemedicine in nephrology outpatient care, inpatient consultations and hemodialysis, indicating that telemedicine can improve patient satisfaction, leading to enhanced treatment owing to increased adherence and frequency of visits. However, it has not been sufficiently used in the kidney field. The key to spreading “telenephrology” (telemedicine in nephrology) is how physical examinations and laboratory/imaging/physiological tests, currently challenging to perform without face-to-face contact, can be substituted with methods optimized for the telemedicine framework. This paper describes the current status of telemedicine and telenephrology, along with advanced methods for collecting data equivalent to laboratory, imaging and physiological tests outside of hospitals, including estimation of serum creatinine levels from saliva or tear fluid, estimation of blood hemoglobin levels by taking pictures of the eyelid conjunctiva or nails with a smartphone and ultrasound of the kidneys using motion capture technology. With an understanding of the strengths and weaknesses of current telemedicine, we should make full use of it for better treatment and patient care. However, further telenephrology research is required.
Guidelines for the management of hypertension in CKD patients: where do we stand in 2024?
Authors: Theodorakopoulou Marieta , Ortiz Alberto , Fernandez-Fernandez Beatriz , Kanbay Mehmet , Minutolo Roberto , Sarafidis Pantelis A 
Published: November 2024

ABSTRACT
Until recently, major bodies producing guidelines for the management of hypertension in patients with chronic kidney disease (CKD) disagreed in some key issues. In June 2023, the European Society of Hypertension (ESH) published the new 2023 ESH Guidelines for the management of arterial hypertension a document that was endorsed by the European Renal Association. Several novel recommendations relevant to the management of hypertension in patients with CKD appeared in these guidelines, which have been updated to reflect the latest evidence-based practices in managing hypertension in CKD patients. Most of these are in general agreement with the previous 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines—some reflect different emphasis on some topics (i.e. detailed algorithms on antihypertensive agent use) while others reflect evolution of important evidence in recent years. The aim of the present review is to summarize and comment on key points and main areas of focus in patients with CKD, as well as to compare and highlight the main differences with the 2021 KDIGO Guidelines for the management of blood pressure in CKD.
Isolated microhematuria in potential kidney donors: evaluating kidney biopsy findings with dipstick urinalysis and urine microscopy results
Authors: Hammad Ehab A , Obeid Dalia A , Broering Dieter C , Shah Yaser Z , Brockmann Jens G , Marquez Kris A , Nazmi Ahmed M , Aleid Hassan A , AlManea Hadeel M , AlAbassi Amira M , Solomon Melba A , Jacob Nancy , Ali Tariq Z 
Published: November 2024

ABSTRACT

Background
Isolated microhematuria (IMH) can signal hidden glomerular disease, necessitating detailed evaluations for potential kidney donors, including kidney biopsies. The optimal strategy for deciding on kidney biopsies remains unclear. While the British Transplant Society supports dipstick analysis, KDIGO focuses solely on urine microscopy. This study explored the correlation between kidney biopsy outcomes and results from dipstick urinalysis and urine microscopy in potential kidney donors.

Methods
This retrospective study encompassed all potential kidney donors who received kidney biopsies following a positive urine dipstick result for IMH, irrespective of whether red blood cells (RBCs) were found on urine microscopy. We performed sensitivity and specificity analyses to assess the effectiveness of microscopy and dipstick urinalysis in identifying histological abnormalities in the kidney biopsies.

Results
Approximately 49% of potential donors—133 out of 271—who had kidney biopsies due to positive dipstick tests showed negative results in urine microscopy for RBCs. In total, 168 donor candidates, or 62%, had abnormal findings in their biopsies, with nearly half of those diagnosed with immunoglobulin A nephropathy having negative urine microscopy results. Furthermore, 58% of potential donors with negative urine microscopy results—77 out of 133—also exhibited abnormal biopsy findings. The urine microscopy test displayed a sensitivity of 54.2% (95% confidence interval 46.6–61.5) and a specificity of 54.4% (95% confidence interval 44.8–63.7) for detecting abnormal biopsy results.

Conclusion
This study highlighted a significant presence of donors with IMH with underlying glomerular lesions. Using urine microscopy showed limited sensitivity and specificity in identifying abnormal histopathological results. Relying solely on urine microscopy may miss critical pathologies like IgAN in prospective kidney donors. The persistence of IMH during dipstick urinalysis calls for kidney biopsy in potential donors. These findings suggest that our results be incorporated into future global guideline formulations.
Impacts of intestinal fermentation on gastroesophageal reflux disease: can the tail wag the dog?
Authors: Quigley Eamonn M M 
Published: November 2024

Summary
Communication between the foregut and the hindgut is amply illustrated by the gastro-colonic reflex and the impact of constipation on gastric function. Less well studied are the effects of the small intestinal or colonic microbiome and its metabolites on motor and secretory activities in the esophagus and stomach. In the study, the authors posit that small intestinal bacterial overgrowth promotes gastroesophageal and laryngo-pharyngeal reflux and in support of this hypothesis report an amelioration of related symptoms with antibiotic and dietary therapies. This editorial explores this hypothesis and also proposes an alternative one: changes in gastric and esophageal function consequent upon increased bacterial fermentation, not in the small intestine, but in the colon.
Collinearity-based Assembly Correction Tool GUI: Software for collinearity-based genome assembly correction
Authors: Zhang Shengcheng , Du Hejun , Zhang Xingtan , Wang Binzhong 
Published: November 2024

Abstract
Genome assembly errors can have a profound effect on downstream analyses. Collinearity-based Assembly Correction Tool GUI is designed to rectify these errors by leveraging collinearity information between the assembled genome and a reference genome. Collinearity-based Assembly Correction Tool GUI provides a user-friendly interface for visualizing and manually correcting assembly errors. It supports various operations such as insertion, deletion, inversion, and swapping of contigs and chromosomes. The software automatically reclusters, relabels, and redraws the assembly after each modification, ensuring that users can easily track changes. Collinearity-based Assembly Correction Tool GUI is a robust tool designed to efficiently correct large-scale assembly errors in polyploid genomes, featuring advanced collinearity detection capabilities.
Learning analysis of health system resilience
Authors: Thu Kyaw Myat , Bernays Sarah , Abimbola Seye 
Published: November 2024

Abstract
The emergence of ‘resilience’ as a concept for analysing health systems—especially in low- and middle-income countries—has been trailed by debates on whether ‘resilience’ is a process or an outcome. This debate poses a methodological challenge. What ‘health system resilience’ is interpreted to mean shapes the approach taken to its analysis. To address this methodological challenge, we propose ‘learning’ as a concept versatile enough to navigate the ‘process versus outcome’ tension. Learning—defined as ‘the development of insights, knowledge, and associations between past actions, the effectiveness of those actions, and future actions’—we argue, can animate features that tend to be silenced in analyses of resilience. As with learning, the processes involved in resilience are cyclical: from absorption to adaptation, to transformation, and then to anticipation of future disruption. Learning illuminates how resilience occurs—or fails to occur—interactively and iteratively within complex systems while acknowledging the contextual, cognitive, and behavioural capabilities of individuals, teams, and organizations that contribute to a system’s emergence from or evolution given shocks/stress. Learning analysis can help to resist the pull towards framing resilience as an outcome—as resilience is commonly used to mean or suggest a state or an attribute, rather than a process that unfolds, whether the outcomes are deemed positive or not. Analysing resilience as a learning process can help health systems researchers better systematically make sense of health system responses to present and future stress/shocks. In qualitative or quantitative analyses, seeing what is to be analysed as ‘learning’ rather than the more nebulous ‘resilience’ can refocus attention on what is to be measured, explained, and how—premised on the understanding that a health system with the ability to learn is the one with the ability to be resilient, regardless of the outcome of such a process.
Overcoming doubt: developing CDoH Essentials, a practical tool to introduce the commercial determinants of health
Authors: Brook Anna , Körner Katherine , van Schalkwyk May C I , Barnes Amy , Petticrew Mark 
Published: November 2024

Abstract
Despite growing awareness of the importance of commercial determinants of health (CDoH), there has been limited development or evaluation of educational and practice-focused support for public health professionals. This article reports findings from an action–research approach bringing together people with academic and practice expertise (n = 16) to co-create workshop materials (called ‘CDoH Essentials’), test and improve them through five trial workshops and explore their effects. Five English local public health teams co-facilitated the workshops in their organizations, with participants from public health teams and their internal partners (n = 94). Quantitative and qualitative data were collected throughout and analysed to understand: (1) whether the workshops met the expectations of participants, public health and academic observers, and (2) the effects of workshop participation on (a) participants’ knowledge, understanding and critical CDoH literacy, and (b) subsequent working practices and attitudes. The co-created CDoH Essentials appeared effective in meeting expectations, improving knowledge and critical CDoH literacy and promoting action on CDoH. The proportion of participants reporting ‘little’ or ‘no’ CDoH knowledge fell significantly following the workshop (55.4% vs 2.7%). Participants’ increased understanding supported reflection on the implications of the CDoH for their roles and for wider strategy and action. After 3 months, all five settings reported greater consideration of CDoH and had initiated or planned action. CDoH Essentials could be used to galvanize more effective public health action to tackle the CDoH in England and trialled in other public health contexts.
Birational Automorphism Groups of Severi–Brauer Surfaces Over the Field of Rational Numbers
Authors: Vikulova Anastasia V 
Published: November 2024

Abstract
We prove that the only non-trivial finite subgroups of birational automorphism group of non-trivial Severi–Brauer surfaces over the field of rational numbers are $\mathbb{Z}/3\mathbb{Z}$ and $(\mathbb{Z}/3\mathbb{Z})^{2}.$ Moreover, we show that $(\mathbb{Z}/3\mathbb{Z})^{2}$ is contained in $\textrm{Bir}(V)$ for any Severi–Brauer surface $V$ over a field of characteristic different from $2$ and $3$, and $(\mathbb{Z}/3\mathbb{Z})^{3}$ is contained in $\textrm{Bir}(V)$ for any Severi–Brauer surface $V$ over a field of characteristic different from $2$ and $3$, which contains a non-trivial cube root of unity.
Predicting mortality in hospitalized influenza patients: integration of deep learning-based chest X-ray severity score (FluDeep-XR) and clinical variables
Authors: Tsai Meng-Han , Ko Sung-Chu , Huang Amy Huaishiuan , Porta Lorenzo , Ferretti Cecilia , Longhi Clarissa , Hsu Wan-Ting , Chang Yung-Han , Hsiung Jo-Ching , Su Chin-Hua , Galbiati Filippo , Lee Chien-Chang 
Published: November 2024

Abstract

Objectives
To pioneer the first artificial intelligence system integrating radiological and objective clinical data, simulating the clinical reasoning process, for the early prediction of high-risk influenza patients.

Materials and Methods
Our system was developed using a cohort from National Taiwan University Hospital in Taiwan, with external validation data from ASST Grande Ospedale Metropolitano Niguarda in Italy. Convolutional neural networks pretrained on ImageNet were regressively trained using a 5-point scale to develop the influenza chest X-ray (CXR) severity scoring model, FluDeep-XR. Early, late, and joint fusion structures, incorporating varying weights of CXR severity with clinical data, were designed to predict 30-day mortality and compared with models using only CXR or clinical data. The best-performing model was designated as FluDeep. The explainability of FluDeep-XR and FluDeep was illustrated through activation maps and SHapley Additive exPlanations (SHAP).

Results
The Xception-based model, FluDeep-XR, achieved a mean square error of 0.738 in the external validation dataset. The Random Forest-based late fusion model, FluDeep, outperformed all the other models, achieving an area under the receiver operating curve of 0.818 and a sensitivity of 0.706 in the external dataset. Activation maps highlighted clear lung fields. Shapley additive explanations identified age, C-reactive protein, hematocrit, heart rate, and respiratory rate as the top 5 important clinical features.

Discussion
The integration of medical imaging with objective clinical data outperformed single-modality models to predict 30-day mortality in influenza patients. We ensured the explainability of our models aligned with clinical knowledge and validated its applicability across foreign institutions.

Conclusion
FluDeep highlights the potential of combining radiological and clinical information in late fusion design, enhancing diagnostic accuracy and offering an explainable, and generalizable decision support system.
Exploring the role of peripheral nerves in trauma-induced heterotopic ossification
Authors: Pereira Clifford T , Adams Sean H , Lloyd K C Kent , Knotts Trina A , James Aaron W , Price Theodore J , Levi Benjamin 
Published: November 2024

Abstract
Recent studies have linked pain and the resultant nociception-induced neural inflammation (NINI) to trauma-induced heterotopic ossification (THO). It is postulated that nociception at the injury site stimulates the transient receptor potential vanilloid-1 (the transient receptor potential cation channel subfamily V member 1) receptors on sensory nerves within the injured tissues resulting in the expression of neuroinflammatory peptides, substance P (SP), and calcitonin gene-related peptide (CGRP). Additionally, BMP-2 released from fractured bones and soft tissue injury also selectively activates TRVP1 receptors, resulting in the release of SP and CGRP and causing neuroinflammation and degranulation of mast cells causing the breakdown the blood-nerve barrier (BNB), leading to release of neural crest derived progenitor cells (NCDPCs) into the injured tissue. Parallel to this process BMP-2 initiates the NCDPCs toward osteogenic differentiation. CGRP has direct osteogenic effects on osteoprogenitor cells/mesenchymal stem cells, by activating BMP-2 via canonical Wnt/β-catenin signaling and cAMP-cAMP-response element binding protein signaling. BMP-2 binds to TGF-βRI and activates TGF-β-activated kinase 1 (TAK1) leading to phosphorylation of SMAD1/5/8, which binds to the co-activator SMAD4 and translocates to the nucleus to serve as transcription factor for BMP responsive genes critical in osteogenesis such as Runx2 and others. Thus, NINI phenotypes, and specifically CGRP induction, play a crucial role in THO initiation and progression through the activation of the BMP pathway, breakdown of the BNB, leading to the escape of NCDPCs, and the osteogenic differentiation of the latter.