bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection incidence, timing and dose dependency in rheumatoid arthritis patients treated with rituximab: a retrospective cohort study
Authors: Veeken Lara D , Opdam Merel A A , Verhoef Lise M , Popa Calin , van Crevel Reinout , den Broeder Alfons A 
Published: July 2023

Abstract

Objectives
Rituximab (RTX) is a safe and effective treatment for RA. However, there are some concerns about infection risk and preliminary data suggest dose and time dependency. This study aims to determine the infection incidence in a large real-life population of RA patients using RTX, with special focus on (ultra-)low dosing and time since last infusion.

Methods
RA patients treated with 1000, 500 or 200 mg RTX per cycle between 2012 and 2021 at the Sint Maartenskliniek were included in a retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infection incidence rates, dose and time relations with RTX infusion were analysed using mixed-effects Poisson regression.

Results
Among 490 patients, we identified 819 infections in 1254 patient years. Most infections were mild and respiratory tract infections were most common. Infection incidence rates were 41, 54 and 71 per 100 patient years for doses of 200, 500 and 1000 mg. Incidence rate ratio (IRR) was significantly lower for 200 mg compared with 1000 mg (adjusted IRR 0.35, 95% CI 0.17, 0.72, P = 0.004). In patients receiving 1000 or 500 mg RTX, infections seemed to occur more frequently within the first two months after infusion compared with later on in the treatment cycle, suggesting an association with peak concentration.

Conclusion
Ultra-low dosing (200 mg) of RTX is associated with a lower risk of infections in RA. Future interventions focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may lower infection risk.
Metagenomics reveals the structure of Mastrevirus–host interaction network within an agro-ecosystem
Authors: Claverie Sohini , Hoareau Murielle , Chéhida Sélim Ben , Filloux Denis , Varsani Arvind , Roumagnac Philippe , Martin Darren P , Lett Jean-Michel , Lefeuvre Pierre 
Published: July 2023

Abstract
As highly pervasive parasites that sometimes cause disease, viruses are likely major components of all natural ecosystems. An important step towards both understanding the precise ecological roles of viruses and determining how natural communities of viral species are assembled and evolve is obtaining full descriptions of viral diversity and distributions at ecosystem scales. Here, we focused on obtaining such ‘community-scale’ data for viruses in a single genus. We chose the genus Mastrevirus (family Geminiviridae), members of which have predominantly been found infecting uncultivated grasses (family Poaceae) throughout the tropical and sub-tropical regions of the world. We sampled over 3 years, 2,884 individual Poaceae plants belonging to thirty different species within a 2-ha plot which included cultivated and uncultivated areas on the island of Reunion. Mastreviruses were found in ∼8 per cent of the samples, of which 96 per cent did not have any discernible disease symptoms. The multitude of host–virus associations that we uncovered reveals both the plant species that most commonly host mastreviruses and the mastrevirus species (such as maize streak virus and maize streak Reunion virus) that have especially large host ranges. Our findings are consistent with the hypothesis that perennial plant species capable of hosting years-long mixed mastrevirus infections likely play a disproportionately important role in the generation of inter-species and inter-strain mastrevirus recombinants.
IIIMiddle English
Authors: Ash-Irisarri Kate , Atkinson Laurie , Brazil Sarah , Calder Natalie , Finn Andrew , Greene Darragh , Lindstedt Samira , Menmuir Rebecca , Ronan Mark , Sargan J D , Strickland Seth 
Published: July 2023

Abstract
This chapter has twelve sections: 1. Early Middle English (c.1050–1350); 2. Manuscript and Technical Studies; 3. Religious Prose and Verse; 4. Secular Prose; 5. Secular Verse; 6. Piers Plowman; 7. Gower; 8. Older Scots; 9. Drama; 10. The Gawain Poet; 11. Romance: Metrical, Alliterative, Malory; 12. Hoccleve and Lydgate. Section 1 is by Samira Lindstedt; section 2 is by J.D. Sargan; section 3 is by Natalie Calder; section 4 is by Mark Ronan; sections 5, 10, and 11 are by Darragh Greene; section 6 is by Seth Strickland; section 7 is by Rebecca Menmuir; section 8 is by Kate Ash-Irisarri; section 9 is by Sarah Brazil; section 12 is by Laurie Atkinson with assistance from Rebecca Menmuir.
Genistein‐mediated thermogenesis and white‐to‐beige adipocyte differentiation involve transcriptional activation of cAMP response elements in the Ucp1 promoter
Authors: Fuentes‐Romero Rebeca , Velázquez‐Villegas Laura A. , Vasquez‐Reyes Sarai , Pérez‐Jiménez Berenice , Domínguez Velázquez Zuleima N. , Sánchez‐Tapia Mónica , Vargas‐Castillo Ariana , Tobón‐Cornejo Sandra , López‐Barradas Adriana M. , Mendoza Valentín , Torres Nimbe , López‐Casillas Fernando , Tovar Armando R. 
Published: July 2023

AbstractGenistein is an isoflavone present in soybeans and is considered a bioactive compound due to its widely reported biological activity. We have previously shown that intraperitoneal genistein administration and diet supplementation activates the thermogenic program in rats and mice subcutaneous white adipose tissue (scWAT) under multiple environmental cues, including cold exposure and high‐fat diet feeding. However, the mechanistic insights of this process were not previously unveiled. Uncoupling protein 1 (UCP1), a mitochondrial membrane polypeptide responsible for dissipating energy into heat, is considered the most relevant thermogenic marker; thus, we aimed to evaluate whether genistein regulates UCP1 transcription. Here we show that genistein administration to thermoneutral‐housed mice leads to the appearance of beige adipocyte markers, including a sharp upregulation of UCP1 expression and protein abundance in scWAT. Reporter assays showed an increase in UCP1 promoter activity after genistein stimulation, and in silico analysis revealed the presence of estrogen (ERE) and cAMP (CRE) response elements as putative candidates of genistein activation. Mutation of the CRE but not the ERE reduced genistein‐induced promoter activity by 51%. Additionally, in vitro and in vivo ChIP assays demonstrated the binding of CREB to the UCP1 promoter after acute genistein administration. Taken together, these data elucidate the mechanism of genistein‐mediated UCP1 induction and confirm its potential applications in managing metabolic disorders.
Ophthalmia Neonatorum, Helen Keller, and the Social Dimensions of Eye Disease
Authors: Harman Lynn E. , Margo Curtis E. 
Published: July 2023

Purpose:
The aim of this study was to describe how an early 20th-century American celebrity attempted to influence public perception of ophthalmic neonatorum.

Methods:
This study reviews the editorial written by Helen Keller in the 1909 Ladies’ Home Journal and related historical documents about the prevention of blindness from neonatal conjunctivitis.

Results:
Although blind, deaf, and nulliparous, Helen Keller at the age of 29 sensed that the newborn children of many American women were being denied preventative treatment for ophthalmia neonatorum. In her editorial in the Ladies’ Home Journal discussing the complications of venereal disease she urged women to become proactive in matters of personal and family health care.

Conclusions:
Helen Keller viewed blindness from ophthalmia neonatorum as a failure of the American health care system. Her solution was to impart women with enough knowledge to seek care from educated medical professionals. The observation that many women and their children were receiving substandard care reflected a fundamental problem with disparities in the delivery of perinatal health care. Her insights are as relevant today as they were in 1909.
Point-of-care Ultrasound to Assess Hemodynamic Contributors to Acute Kidney Injury in Pediatric Patients With Cerebral Malaria: A Pilot Study
Authors: Lintner Rivera Michael , Prager Ross , Gushu Montfort Bernard , June Sylvester , Phiri Tusekile , Salameh Jean-Paul , Johnson Hunter C. , Taylor Terrie , O’Brien Nicole F. 
Published: July 2023

Background:
Acute kidney injury is common in severe malaria and is independently associated with mortality. The pathogenesis of acute kidney injury (AKI) in severe malaria remains incompletely understood. Ultrasound-based tools such as point-of-care ultrasound (POCUS), ultrasound cardiac output monitors (USCOMs) and renal arterial resistive index (RRI) can be used to detect hemodynamic and renal blood flow abnormalities contributing to AKI in malaria.

Methods:
We conducted a prospective study of Malawian children with cerebral malaria to determine the feasibility of using POCUS and USCOM to characterize hemodynamic contributors to severe AKI (Kidney Disease: Improving Global Outcomes stage 2 or 3). The primary outcome was feasibility (completion rate of study procedures). We also assessed for differences in POCUS and hemodynamic variables for patients with or without severe AKI.

Results:
We enrolled 27 patients who had admission cardiac and renal ultrasounds and USCOM. Completion rates were high for cardiac (96%), renal (100%) and USCOM studies (96%). Severe AKI occurred in 13 of 27 patients (48%). No patients had ventricular dysfunction. Only 1 patient in the severe AKI group was determined to be hypovolemic (P = 0.64). No significant differences in USCOM, RRI or venous congestion parameters were detected among patients with and without severe AKI. Mortality was 11% (3/27) with the 3 deaths occurring in the severe AKI group (P = 0.056).

Conclusions:
Ultrasound-based cardiac, hemodynamic and renal blood flow measurements appear to be feasible in pediatric patients with cerebral malaria. We were unable to detect hemodynamic or renal blood flow abnormalities contributing to severe AKI in cerebral malaria. Larger studies are needed to corroborate these findings.
Center-based First-line Therapy Is a Significant Predictor for Mortality of Fournier Gangrene
Authors: Rieger Constantin , Hübers Max , Kastner Lucas , Pfister David , Holling Heinz , Heidenreich Axel 
Published: July 2023

Introduction:
Fournier gangrene is a life-threatening urological disease that requires rapid surgical intervention. Despite major improvements in medical therapy, the mortality of Fournier gangrene has not changed during the past 25 years. To potentially improve the outcome, we analyzed different medical processes for overall mortality in the treatment of Fournier gangrene.

Methods:
We performed a retrospective single-center study of 21 patients with Fournier gangrene. Patients were grouped according to initial symptoms, first medical advice, blood tests, medical history, and further clinical processes and compared using a t test, χ2 test, or Fisher exact test. A t test for heterogeneous variances was used if a Levene test showed significantly different variances, otherwise a t test for homogeneous variances was used. The log-rank test was applied for survival analysis. Logistic regression was applied to identify potential clinical predictors for mortality. Follow-up was performed until 130 days after the first surgical intervention.

Results:
There were no significant differences in the mortality rate of patients depending on the day and time of presentation in the hospital. Of the patients first consulting a urologist (either outpatient or hospital), no patient died within the first 120 days. By contrast, approximately 70% of patients who were transferred by a hospital without urologic specialization or a nonurologic outpatient clinic (P = .008) died within the first 130 days after surgery. Multivariate survival analysis showed that the type of first doctor's advice could serve as a significant factor in determining patients' mortality (P = .031), which also correlated with a significantly shorter duration of the first surgical procedure (110 vs 54 minutes, P = .019).

Conclusion:
Despite the small cohort, we were able to show a significant correlation between the initial doctor's advice, either by a urologist or nonurologist, and the patient's mortality. Considering the life-threatening potential of Fournier gangrene, professionals should develop strategies to educate nonurologists and raise awareness about this disease and its clinical presentation to optimize rapid intervention and reduce mortality.
An updated systematic review and quantitative synthesis of physical activity levels in multiple sclerosis
Authors: Jeng Brenda , DuBose Noah G. , Martin Trevor B. , Šilić Petra , Flores Victoria A. , Zheng Peixuan , Motl Robert W. 
Published: July 2023

ABSTRACT

Objective
This paper provided an updated quantitative synthesis of physical activity levels in persons with multiple sclerosis (MS) compared with controls and other clinical populations.

Design
A systematic search through PubMed, Scopus, and PsycINFO was conducted for articles published between August, 2016 and July, 2022. Articles that included a group comparison of at least one measurement of physical activity between adults with MS and controls or other clinical populations were included in the meta-analysis.

Results
Twenty-four studies met the inclusion criteria and yielded a total of 119 comparisons. There was a moderate difference in physical activity levels between persons with MS and controls (effect size [ES] = –0.56,p < 0.01), but no significant difference between persons with MS and other clinical populations (ES = 0.01,p = 0.90). The pooled ESs comparing MS with controls (Q104
= 457.9,p < 0.01) as well as with clinical populations (Q13
= 108.4,p < 0.01) were heterogeneous. Moderating variables included sex, disability status, measurement method, outcome, intensity, and application of an MS-specific cut-point.

Conclusion
Physical activity levels remain significantly lower in persons with MS compared with controls, but the magnitude of difference has become smaller over the past decade. There is a need for continued development of effective physical activity programs that can reach the greater community with MS.
Body composition and physical performance one year after COVID-19
Authors: Peball Marina , Rass Verena , Valent Dora , Beer Ronny , Schiefecker Alois Josef , Limmert Victoria , Putnina Lauma , Heim Beatrice , Ellmerer Philipp , Carbone Federico , Mahlknecht Philipp , Kofler Mario , Lindner Anna , Kindl Philipp , Sahanic Sabina , Coen Maximilian , Pizzini Alex , Pfausler Bettina , Kiechl Stefan , Sonnweber Thomas , Tancevski Ivan , Löffler-Ragg Judith , Djamshidian Atbin , Helbok Raimund , Seppi Klaus 
Published: July 2023

AbstractObjectiveLong-term consequences after coronavirus-disease (COVID-19) include physical complaints which may impair physical recovery and quality of life.DesignWe assessed body composition and physical ability in patients twelve months after COVID-19. Consecutively recruited patients recovering from mild to severe COVID-19 were assessed using bioelectrical impedance analysis, 6-minute-walk-test, additional scales for physical performance, and health-related quality of life.ResultsOverall physical recovery was good (i.e., Glasgow Outcome Scale-Extended ≥7 in 96%, Modified Rankin Scale ≤1 in 87%, Eastern Cooperative Oncology Group ≤1 in 99%). Forty-four-% of the 69 patients experienced a significant BMI-increase in the year post-COVID-19 (≥1 kg/m2) whereas skeletal-muscle-mass-index was reduced in only 12%. Patients requiring intensive-care-treatment (n = 15, 22%) during acute COVID-19 more often had a BMI-increase (p = 0.002), worse 6-minute-walk-test-performance (p = 0.044), and higher body fat mass (p = 0.030) at the one-year-follow-up when compared to patients with mild (n = 22, 32%) and moderate (n = 32, 46%) acute COVID-19. BMI-increase was also more frequent in patients who had no professional rehabilitation (p = 0.014).ConclusionAlthough patients with severe COVID-19 had increased BMI and body fat and performed worse in physical outcome measures one year after COVID-19, overall physical recovery was satisfying. Translating these findings to variants beyond the alpha-strain of SARS-CoV-2-virus needs further studies.
Longitudinal Patterns of Engagement and Clinical Outcomes: Results From a Therapist-Supported Digital Mental Health Intervention
Authors: Aschbacher Kirstin , Rivera Luisa M. , Hornstein Silvan , Nelson Benjamin W. , Forman-Hoffman Valerie L. , Peiper Nicholas C. 
Published: July 2023

ABSTRACT

Objective
Digital mental health interventions (DMHIs) are an effective treatment modality for common mental disorders like depression and anxiety; however, the role of intervention engagement as a longitudinal “dosing” factor is poorly understood in relation to clinical outcomes.

Methods
We studied 4978 participants in a 12-week therapist-supported DMHI (June 2020–December 2021), applying a longitudinal agglomerative hierarchical cluster analysis to the number of days per week of intervention engagement. The proportion of people demonstrating remission in depression and anxiety symptoms during the intervention was calculated for each cluster. Multivariable logistic regression models were fit to examine associations between the engagement clusters and symptom remission, adjusting for demographic and clinical characteristics.

Results
Based on clinical interpretability and stopping rules, four clusters were derived from the hierarchical cluster analysis (in descending order): a) sustained high engagers (45.0%), b) late disengagers (24.1%), c) early disengagers (22.5%), and d) immediate disengagers (8.4%). Bivariate and multivariate analyses supported a dose-response relationship between engagement and depression symptom remission, whereas the pattern was partially evident for anxiety symptom remission. In multivariable logistic regression models, older age groups, male participants, and Asians had increased odds of achieving depression and anxiety symptom remission, whereas higher odds of anxiety symptom remission were observed among gender-expansive individuals.

Conclusions
Segmentation based on the frequency of engagement performs well in discerning timing of intervention disengagement and a dose-response relationship with clinical outcomes. The findings among the demographic subpopulations indicate that therapist-supported DMHIs may be effective in addressing mental health problems among patients who disproportionately experience stigma and structural barriers to care. Machine learning models can enable precision care by delineating how heterogeneous patterns of engagement over time relate to clinical outcomes. This empirical identification may help clinicians personalize and optimize interventions to prevent premature disengagement.
Spousal Synchrony in Allostatic Load Among Older Couples in the Health and Retirement Study
Authors: Yu Yan-Liang , Juster Robert-Paul 
Published: July 2023

ABSTRACT

Objective
Using national data from the Health and Retirement Study, this study examined interpartner associations of allostatic load (AL) among 2338 different-sex couples (N = 4676 individuals) over a 4-year period among older American couples from a dyadic approach.

Methods
AL was indexed by immune (C-reactive protein), metabolic (high-density lipoprotein cholesterol, total cholesterol, and glycosylated hemoglobin), renal (cystatin C), cardiovascular (systolic and diastolic blood pressures, pulse rate), and anthropometric (waist and body mass index) parameters using the traditional count-based formulation. Actor-partner interdependence models were used to assess interpartner concordance in AL.

Results
Higher partners’ baseline AL was significantly associated with higher own AL both at baseline and 4 years later. In addition, partners’ baseline AL was significantly associated with own AL 4 years later only in women but not men. Lastly, we did not observe any significant moderating effect of relationship quality on interpartner AL concordance.

Conclusions
The findings suggest that older couples’ physiological responses to environmental stress are not only linked concurrently, but the associations persist after 4 years, alluding to long-term impacts of couples’ psychosocial context and physiology on each other.
BioSignal Copilot: Leveraging the power of LLMs in drafting reports for biomedical signals
Authors: Liu Chunyu , Ma Yongpei , Kothur Kavitha , Nikpour Armin , Kavehei Omid 
Published: July 2023

AbstractRecent advances in Large Language Models (LLMs) have shown great potential in various domains, particularly in processing text-based data. However, their applicability to biomedical time-series signals (e.g. electrograms) remains largely unexplored due to the lack of a signal-to-text (sequence) engine to harness the power of LLMs. The application of biosignals has been growing due to the improvements in the reliability, noise and performance of front-end sensing, and back-end signal processing, despite lowering the number of sensing components (e.g. electrodes) needed for effective and long-term use (e.g. in wearable or implantable devices). One of the most reliable techniques used in clinical settings is producing a technical/clinical report on the quality and features of collected data and using that alongside a set of auxiliary or complementary data (e.g. imaging, blood tests, medical records).This work addresses the missing puzzle in implementing conversational artificial intelligence (AI), a reliable, technical and clinically relevant signal-to-text (Sig2Txt) engine. While medical foundation models can be expected, reports of Sig2Txt engine in large scale can be utilised in years to come to develop foundational models for a unified purpose. In this work, we propose a system (SignalGPT or BioSignal Copilot) that reduces medical signals to a freestyle or formatted clinical, technical report close to a brief clinical report capturing key features and characterisation of input signal. In its ideal form, this system provides the tool necessary to produce the technical input sequence necessary for LLMs as a step toward using AI in the medical and clinical domains as an assistant to clinicians and patients. To the best of our knowledge, this is the first system for bioSig2Txt generation, and the idea can be used in other domains as well to produce technical reports to harness the power of LLMs. This method also improves the interpretability and tracking (history) of information into and out of the AI models. We did implement this aspect through a buffer in our system.As a preliminary step, we verify the feasibility of the BioSignal Copilot (SignalGPT) using a clinical ECG dataset to demonstrate the advantages of the proposed system. In this feasibility study, we used prompts and fine-tuning to prevent fluctuations in response. The combination of biosignal processing and natural language processing offers a promising solution that improves the interpretability of the results obtained from AI, which also leverages the rapid growth of LLMs.