bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Short Nicholas J. , Jabbour Elias , Jain Nitin , Senapati Jayastu , Nasr Lewis , Haddad Fadi G. , Li Zhenhua , Hsiao Yu-Chih , Yang Jun J. , Pemmaraju Naveen , Ohanian Maro , Wierda William G. , Montalban-Bravo Guillermo , Borthakur Gautam , Han Lina , Xiao Lianchun , Huang Xuelin , Abramova Regina , Zhao Min , Garris Rebecca , Konopleva Marina , Ravandi Farhad , Kantarjian Hagop 
Published: January 2024

Abstract
Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of prior therapies was 2 (range, 1-6). Thirteen patients (59%) had undergone prior allogeneic stem cell transplant (allo-SCT), and 7 of 18 patients (39%) with B-cell ALL had previously received both inotuzumab ozogamicin and blinatumomab. The recommended phase 2 dose of venetoclax in the combination regimen was 400 mg daily. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 57% (CR, 43%; CRi, 14%), and 45% of responders achieved measurable residual disease negativity by multiparameter flow cytometry. Four patients proceeded to allo-SCT. The median duration of response was 6.3 months. The median overall survival was 7.1 months, and the 1-year overall survival rate was 29%. The most common grade ≥3 nonhematologic adverse events were infection in 17 patients (77%) and febrile neutropenia in 4 patients (18%). Overall, the combination of mini-hyper-CVD plus venetoclax was active in heavily pretreated relapsed/refractory ALL. Further development of venetoclax-based combinations in ALL is warranted. This trial is registered at www.clinicaltrials.gov as #NCT03808610.
Endotypic traits of supine position and supine-predominant obstructive sleep apnoea in Asian patients
Authors: Cheng Wan-Ju , Finnsson Eysteinn , Ágústsson Jón S. , Sands Scott A. , Hang Liang-Wen 
Published: January 2024

BackgroundOver half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions.MethodsWe prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea–hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA.ResultsIn our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (β= −3.46 %eupnoea, 95% CI −5.93– −1.00 %eupnoea) and reduced compensation (β= −6.79 %eupnoea, 95% CI −10.60– −2.99 %eupnoea). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (−11.98versus−6.28 %eupnoea).ConclusionsSupine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA.
Clinical efficacy and satisfaction of a digital wheeze detector in a multicentre randomised controlled trial: the WheezeScan study
Authors: Do Yen Hoang , van Aalderen Wim , Dellbrügger Ellen , Grenzbach Claude , Grigg Jonathan , Grittner Ulrike , Haarman Eric , Hernandez Toro Camilo José , Karadag Bulent , Roßberg Siri , Weichert Tina-Maria , Whitehouse Abigail , Pizzulli Antonio , Matricardi Paolo Maria , Dramburg Stephanie 
Published: January 2024

IntroductionWheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting.MethodsA multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4–84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2).ResultsA total of 167 children, with a mean±sdage of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI −2.3–9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful.ConclusionIn the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.
Genome-wide association study between copy number variation and feeding behavior, feed efficiency, and growth traits in Nellore cattle
Authors: Benfica Lorena F. , Brito Luiz F. , do Bem Ricardo D. , Mulim Henrique A. , Glessner Joseph , Braga Larissa G. , Gloria Leonardo S. , Cyrillo Joslaine N. S. G. , Bonilha Sarah F. M. , Mercadante Maria E. Z. 
Published: January 2024

Abstract
Background
Feeding costs represent the largest expenditures in beef production. Therefore, the animal efficiency in converting feed in high-quality protein for human consumption plays a major role in the environmental impact of the beef industry and in the beef producers’ profitability. In this context, breeding animals for improved feed efficiency through genomic selection has been considered as a strategic practice in modern breeding programs around the world. Copy number variation (CNV) is a less-studied source of genetic variation that can contribute to phenotypic variability in complex traits. In this context, this study aimed to: (1) identify CNV and CNV regions (CNVRs) in the genome of Nellore cattle (Bos taurus indicus); (2) assess potential associations between the identified CNVR and weaning weight (W210), body weight measured at the time of selection (WSel), average daily gain (ADG), dry matter intake (DMI), residual feed intake (RFI), time spent at the feed bunk (TF), and frequency of visits to the feed bunk (FF); and, (3) perform functional enrichment analyses of the significant CNVR identified for each of the traits evaluated.

Results
A total of 3,161 CNVs and 561 CNVRs ranging from 4,973 bp to 3,215,394 bp were identified. The CNVRs covered up to 99,221,894 bp (3.99%) of the Nellore autosomal genome. Seventeen CNVR were significantly associated with dry matter intake and feeding frequency (number of daily visits to the feed bunk). The functional annotation of the associated CNVRs revealed important candidate genes related to metabolism that may be associated with the phenotypic expression of the evaluated traits. Furthermore, Gene Ontology (GO) analyses revealed 19 enrichment processes associated with FF.

Conclusions
A total of 3,161 CNVs and 561 CNVRs were identified and characterized in a Nellore cattle population. Various CNVRs were significantly associated with DMI and FF, indicating that CNVs play an important role in key biological pathways and in the phenotypic expression of feeding behavior and growth traits in Nellore cattle.
An insight into tissue culture-induced variation origin shared between anther culture-derived triticale regenerants
Authors: Orłowska Renata , Zimny Janusz , Zebrowski Jacek , Androsiuk Piotr , Bednarek Piotr T. 
Published: January 2024

Abstract
Background
The development of the plant in vitro techniques has brought about the variation identified in regenerants known as somaclonal or tissue culture-induced variation (TCIV). S-adenosyl-L-methionine (SAM), glutathione (GSH), low methylated pectins (LMP), and Cu(II) ions may be implicated in green plant regeneration efficiency (GPRE) and TCIV, according to studies in barley (Hordeum vulgare L.) and partially in triticale (× Triticosecale spp. Wittmack ex A. Camus 1927). Using structural equation models (SEM), these metabolites have been connected to the metabolic pathways (Krebs and Yang cycles, glycolysis, transsulfuration), but not for triticale. Using metabolomic and (epi)genetic data, the study sought to develop a triticale regeneration efficiency statistical model. The culture’s induction medium was supplemented with various quantities of Cu(II) and Ag(I) ions for regeneration. The period of plant regeneration has also changed. The donor plant, anther-derived regenerants, and metAFLP were utilized to analyze TCIV concerning DNA in symmetric (CG, CHG) and asymmetric (CHH) sequence contexts. Attenuated Total Reflectance–Fourier Transfer Infrared (ATR-FTIR) spectroscopy was used to gather the metabolomic information on LMP, SAM, and GSH. To frame the data, a structural equation model was employed.

Results
According to metAFLP analysis, the average sequence change in the CHH context was 8.65%, and 0.58% was de novo methylation. Absorbances of FTIR spectra in regions specific for LMP, SAM, and GSH were used as variables values introduced to the SEM model. The average number of green regenerants per 100 plated anthers was 2.55.

Conclusions
The amounts of pectin demethylation, SAM, de novo methylation, and GSH are connected in the model to explain GPRE. By altering the concentration of Cu(II) ions in the medium, which influences the amount of pectin, triticale’s GPRE can be increased.
Putative causal relations among gut flora, serums metabolites and arrhythmia: a Mendelian randomization study
Authors: Li Kaiyuan , Liu Peng , Liu Miao , Ye Jun , Zhu Li 
Published: January 2024

Abstract
Background
The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias.

Methods
Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis.

Results
Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia.

Conclusion
This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.
Multimorbidity clusters in adults 50 years or older with and without a history of cancer: National Health Interview Survey, 2018
Authors: Plasencia Gabriela , Gray Simone C. , Hall Ingrid J. , Smith Judith Lee 
Published: January 2024

Abstract
Background
Multimorbidity is increasing among adults in the United States. Yet limited research has examined multimorbidity clusters in persons aged 50 years and older with and without a history of cancer. An increased understanding of multimorbidity clusters may improve the cancer survivorship experience for survivors with multimorbidity.

Methods
We identified 7580 adults aged 50 years and older with 2 or more diseases—including 811 adults with a history of primary breast, colorectal, cervical, prostate, or lung cancer—from the 2018 National Health Interview Survey. Exploratory factor analysis identified clusters of multimorbidity among cancer survivors and individuals without a history of cancer (controls). Frequency tables and chi-square tests were performed to determine overall differences in sociodemographic characteristics, health-related characteristics, and multimorbidity between groups.

Results
Cancer survivors reported a higher prevalence of having 4 or more diseases compared to controls (57% and 38%, respectively). Our analysis identified 6 clusters for cancer survivors and 4 clusters for controls. Three clusters (pulmonary, cardiac, and liver) included the same diseases for cancer survivors and controls.

Conclusions
Diseases clustered differently across adults ≥ 50 years of age with and without a history of cancer. Findings from this study may be used to inform clinical care, increase the development and dissemination of multilevel public health interventions, escalate system improvements, and initiate innovative policy reform.
Clinical characteristics of patients hospitalized for COVID-19: comparison between different age groups
Authors: Fabiani Ginevra , Cogozzo Carolina , De Paris Anna , Di Maria Valentina , Lagomarsini Alessia , Masotti Olimpia , Matteini Simona , Paolucci Elisa , Pelagatti Lorenzo , Pepe Francesco , Villanti Maurizio , Todde Francesca , Pini Riccardo , Innocenti Francesca 
Published: January 2024

Abstract
Background
To test whether known prognosticators of COVID-19 maintained their stratification ability across age groups.

Methods
We performed a retrospective study. We included all patients (n = 2225), who presented to the Emergency Department of the Careggi University Hospital for COVID-19 in the period February 2020—May 2021, and were admitted to the hospital. The following parameters were analyzed as dichotomized: 1) SpO2/FiO2 ≤ or > 214; 2) creatinine < or ≥ 1.1 mg/dL; 3) Lactic dehydrogenase (LDH) < or ≥ 250 U/mL; 4) C Reactive Protein (CRP) < or ≥ 60 mg/100 mL. We divided the study population in four subgroups, based on the quartiles of distribution of age (G1 18–57 years, G2 57–71 years, G3 72–81 years, G4 > 82). The primary end-point was in-hospital mortality.

Results
By the univariate analysis, the aforementioned dichotomized variables demonstrated a significant association with in-hospital mortality in all subgroups. We introduced them in a multivariate model: in G1 SpO2/FiO2 ≤ 214 (Relative Risk, RR 15.66; 95%CI 3.98–61,74), in G2 creatinine ≥ 1.1 mg/L (RR 2.87, 95%CI 1.30–6.32) and LDH ≥ 250 UI/L (RR 8.71, 95%CI 1,15–65,70), in G3 creatinine ≥ 1.1 mg/L (RR 1.98, 95%CI 1,17–3.36) and CRP ≥ 60 ng/L (RR 2.14, 95%CI 1.23–3.71), in G4 SpO2/FiO2 ≤ 214 (RR 5.15, 95%CI 2.35–11.29), creatinine ≥ 1.1 mg/L (RR 1.75, 95%CI 1.09–2.80) and CRP ≥ 60 ng/L (RR 1.82, 95%CI 1.11–2.98) were independently associated with an increased in-hospital mortality.

Conclusions
A mild to moderate respiratory failure showed an independent association with an increased mortality rate only in youngest and oldest patients, while kidney disease maintained a prognostic role regardless of age.
Diagnostic accuracy of BASIC-Q for detection of cognitive impairment in a primary care setting – a cross-validation study
Authors: Oxbøll Anne-Britt , Jørgensen Kasper , Nielsen T. Rune , Christiansen Sofie D. , Nielsen Ann , Waldorff Frans B. , Waldemar Gunhild 
Published: January 2024

Abstract
Objectives
This study aims to evaluate the diagnostic accuracy and reliability of a new, brief questionnaire, ‘Brief Assessment of Impaired Cognition– Questionnaire’ (BASIC-Q) for detection of cognitive impairment, primarily developed for use in primary care. BASIC-Q has three components: Self-report, Informant report, and Orientation. Self-report and Orientation are completed by the individual and Informant report is answered by a close relative.

Methods
We included 275 participants ≥ 70 years, without a prior diagnosis of dementia, and with a close relative who agreed to participate as an informant. Participants were included prospectively in 14 general practices in urban and rural Denmark using a convenience sampling method. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the informant-completed Functional Activities Questionnaire (FAQ) and reported memory concern were used as a reference standard for the classification of the participants’ cognitive function.

Results
BASIC-Q demonstrated a fair to good diagnostic accuracy to differentiate between people with cognitive impairment and normal cognition with an area under the ROC curve (AUC) of 0.84 (95% CI 0.79–0.89) and a sensitivity and specificity of 0.80 (95% CI 0.72–0.87) and 0.71 (95% CI 0.63–0.78). A prorated BASIC-Q score derived from BASIC-Q without Informant report had significantly lower classification accuracy than the full BASIC-Q. The test-retest reliability of BASIC-Q was good with an intraclass correlation coefficient of 0.84.

Conclusion
BASIC-Q is a brief, easy-to-use questionnaire for identification of cognitive impairment in older adults. It demonstrated fair to good classification accuracy in a general practice setting and can be a useful case-finding tool when suspecting dementia in primary health care.
Impairments of functional exercise capacity, muscle strength, balance and kinesiophobia in patients with chronic kidney disease: a cross-sectional study
Authors: Katayıfçı Nihan , Hüzmeli İrem , İriş Döndü , Turgut Faruk Hilmi 
Published: January 2024

AbstractBackgroundMuscle weakness, balance, and functional capacity are affected in patients with chronic kidney disease (CKD) in dialysis. However, studies about kinesiophobia, peripheral and respiratory muscle strength, balance, exercise capacity, fatigue, and physical activity level in patients with CKD 3–4 are limited. The study aimed to compare the functional exercise capacity, peripheral and respiratory muscle strength, pulmonary function, balance, kinesiophobia, physical activity, fatigue, and dyspnea between patients with CKD 3–4 and controls.MethodsThis cross-sectional study included 43 patients and 45 controls. Functional exercise capacity [6-Minute Walking Test (6MWT)], peripheral and respiratory muscle strength, pulmonary function, dyspnea, fatigue, physical activity, balance [Berg Balance Scale (BBS)], and kinesiophobia were evaluated.ResultsDemographic characteristics were similar in patients [53(50–57) y, 26 M/17F] and controls [51(4.506-55) y, 33 M/12F] (p > 0.05). The 6MWT, respiratory and peripheral muscle strength, pulmonary function, physical activity, and BBS were significantly lower, and the level of dyspnea and kinesiophobia were higher in patients compared with controls (p < 0.05).ConclusionsPatients had impaired functional exercise capacity, upper and lower extremity muscle strength, respiratory muscle strength, pulmonary function, and balance, increased perception of dyspnea and kinesiophobia, and reduced physical activity level compared with controls. Patients should be directed to cardiopulmonary rehabilitation programs.
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report
Authors: Fukuda Natsuki , Kanai Daisuke , Hoshino Kaoru , Fukuda Yuriko , Morita Ryutaro , Ishikawa Yuki , Kanaoka Tomohiko , Toya Yoshiyuki , Kirino Yohei , Wakui Hiromichi , Tamura Kouichi 
Published: January 2024

Abstract
Background
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme1 (UBA1) gene and characterised by an overlap between autoinflammatory and haematologic disorders.

Case presentation
We reported a case of a 67-year-Japanese man receiving peritoneal dialysis (PD) who had recurrent aseptic peritonitis caused by the VEXAS syndrome. He presented with unexplained fevers, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed high serum C-reactive protein concentration and increased cell count in PD effluent. He was treated with antibiotics for PD-related peritonitis, but this was unsuccessful. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images demonstrated intense FDG uptake in his left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and he was treated with oral prednisolone (PSL) 15 mg daily with good response. However, he was unable to taper the dose to less than 10 mg daily because his symptoms flared up. Since Tocilizumab was initiated, he could taper PSL dose to 2 mg daily. Sanger sequencing of his peripheral blood sample showed a mutation of the UBA1 gene (c.122 T > C; p.Met41Thr). We made a final diagnosis of VEXAS syndrome. He suffered from flare of VEXAS syndrome at PSL of 1 mg daily with his cloudy PD effluent. PSL dose of 11 mg daily relieved the symptom within a few days.

Conclusions
It is crucial to recognise aseptic peritonitis as one of the symptoms of VEXAS syndrome and pay attention to the systemic findings in the patients.