bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing and testing community-based tuberculosis (TB) screening intervention to increase TB referral, case detection and knowledge among sexual minority people in urban Bangladesh: a mixed-method study protocol
Authors: Sarwar Golam , Reza Masud , Khan Mohammad Niaz Morshed , Gourab Gorkey , Rahman Mahbubur , Rana A K M Masud , Khan Shaan Muberra , Irfan Samira Dishti , Ahmed Shahriar , Banu Rupali Sisir , Banu Sayera , Khan Sharful Islam 
Published: September 2020

IntroductionAlthough Bangladesh is a country of generalised tuberculosis (TB) epidemic, the HIV prevalence is low among general populations, and 3.9% among key populations. Despite the high possibility of HIV–TB coinfection, scientifically tested approaches for increasing TB case detection among sexual minority people are yet to be developed and implemented in Bangladesh. Such approaches could foster service delivery linkages between communities and the government health system. Findings of this experimental research are likely to provide new insights for programme managers and policy planners for adopting a similar approach in order to enhance TB referral, thus ultimately increasing TB case detections and reducing the likelihood of TB-related mortalities and morbidities, irrespective of HIV status.Methods and analysisThis operational research will follow a quasi-experimental design, applying both qualitative and quantitative methods, in two drop-in centres in three phases. Phase 1 will encompass baseline data collection and development of a community-based TB screening approach. In phase 2, the newly developed intervention will be implemented, followed by end-line data collection in phase 3. Qualitative data collection will be continued throughout the first and second phases. The baseline and end-line data will be compared both in the intervention and comparison areas to measure the impact of the intervention.Ethics and disseminationEthical approval was obtained from the Institutional Review Board of International Centre for Diarrhoeal Disease Research, Bangladesh. The findings will be disseminated through diverse scientific forums including peer-reviewed journals, presentation at conferences and among the policy-makers for policy implication. The study started in January 2019 and will continue until June 2020.
Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study
Authors: Kartas Anastasios , Doundoulakis Ioannis , Ntiloudi Despoina , Koutsakis Athanasios , Kosmidis Diamantis , Rampidis Georgios , Apostolopoulou Sotiria , Frogoudaki Alexandra , Tzifa Afrodite , Avramidis Dimosthenis , Ntzoyvara Olga , Liori Sotiria , Mousiama Tereza , Mouratoglou Sophia Anastasia , Karvounis Haralambos , Giannakoulas George 
Published: September 2020

IntroductionThe risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA.Methods and analysisPReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a ‘real-world’ setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria.Ethics and disseminationThe study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals.Trial registration numberNCT03854149; Pre-results.
Sociodemographic and lifestyle predictors of incident hospital admissions with multimorbidity in a general population, 1999–2019: the EPIC-Norfolk cohort
Authors: Luben Robert , Hayat Shabina , Wareham Nicholas , Pharoah Paul P , Khaw Kay-Tee 
Published: September 2020

BackgroundThe ageing population and prevalence of long-term disorders with multimorbidity are a major health challenge worldwide. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospital admissions with multimorbidity. We aimed to explore the independent associations for a range of demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity.MethodsWe examined incident hospital admissions with multimorbidity in 25 014 men and women aged 40–79 in a British prospective population-based study recruited in 1993–1997 and followed up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥3, were investigated using multivariable logistic regression models for the 10-year period 1999–2009 and repeated with independent measurements in a second 10-year period 2009–2019.ResultsBetween 1999 and 2009, 18 179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidities were observed in 6% and 12% of participants, respectively. Age per 10-year increase (OR 2.19, 95% CI 2.06 to 2.33) and male sex (OR 1.32, 95% CI 1.19 to 1.47) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking (OR 1.86, 95% CI 1.60 to 2.15), body mass index >30 kg/m² (OR 1.48, 95% CI 1.30 to 1.70) and physical inactivity (OR 1.16, 95% CI 1.04 to 1.29) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase (OR 0.86, 95% CI 0.81 to 0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period in 2009–2019.ConclusionAge, male sex and potentially modifiable lifestyle behaviours including smoking, body mass index, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.
Two chair test: a substitute of 6 min walk test appear cardiopulmonary reserve specific
Authors: Bhattacharyya Parthasarathi , Saha Dipanjan , Paul Mintu , Ganguly Dhiman , Mukherjee Biswarup , Roy Chowdhury Sushmita , RoyChoudhury Sourav , Agarwal Pawan , Halder Indranil , Ghosh Roy Debanu , Ray Shuvanan 
Published: September 2020

BackgroundA simple and efficient exercise test possible in a small space is welcome to supplement 6 min walk test (6MWT) that demands a 100 feet corridor to perform.MethodsThe proposed two chair test (2CT) makes a person to sit and move five times between two chairs placed face to face at 5 feet apart and note the changes in pulse-rate (PR) and arterial oxygen saturation (SpO2) at every 10 s for 2 min after that. Comparison of the post-exercise measurements (PR and SpO2) with a repeat performance in same patients was done for reproducibility and doing the same after 6MWT and 2CT in another set of patients was meant for for acceptability. The statistical analysis was made on moment to moment change, mean maximal difference and mean cumulative difference for the measurements using p value, z-score, r value and principal component analysis (PCA).FindingsA total of 40 and 60 volunteers were included for testing reproducibility and acceptability. On both the sets, the difference in most of comparisons between the measured variable (PR and SpO2) showed the p values remaining insignificant (>0.05), and z-score being <1 SD of the corresponding other and the correlation coefficients (r) remaining excellent (>0.9). Furthermore, the PCA shows complete overlapping. The post-exercise changes did not corelate the walking distance in 6MWT.InterpretationThe proposed 2CT demands small space and appears reproducible and comparable with 6MWT in terms of its post-exercise impact on PR and SpO2. This novel test also appears more of cardiopulmonary reserve specific.
Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion
Authors: Mercer Rachel Mary , Varatharajah Rebecca , Shepherd Gillian , Lu Qiang , Castro-Añón Olalla , McCracken David J , Dudina Alexandra , Addala Dinesh , Tsikrika Stamatoula , George Vineeth , Banka Radhika , Asciak Rachelle , Hassan Maged , Hallifax Robert , Bedawi Eihab O , Shute Janis Kay , Rahman Najib M 
Published: September 2020

IntroductionCurrent guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a ‘real world’ population.MethodsA retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration.ResultsA diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ21df=26.27, p<0.001) and insufficient samples (χ21df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ21df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures.ConclusionsAn initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered.
Development and validation of a machine learning-based prediction model for near-term in-hospital mortality among patients with COVID-19
Authors: Parchure Prathamesh , Joshi Himanshu , Dharmarajan Kavita , Freeman Robert , Reich David L , Mazumdar Madhu , Timsina Prem , Kia Arash 
Published: September 2020

ObjectivesTo develop and validate a model for prediction of near-term in-hospital mortality among patients with COVID-19 by application of a machine learning (ML) algorithm on time-series inpatient data from electronic health records.MethodsA cohort comprised of 567 patients with COVID-19 at a large acute care healthcare system between 10 February 2020 and 7 April 2020 observed until either death or discharge. Random forest (RF) model was developed on randomly drawn 70% of the cohort (training set) and its performance was evaluated on the rest of 30% (the test set). The outcome variable was in-hospital mortality within 20–84 hours from the time of prediction. Input features included patients’ vital signs, laboratory data and ECG results.ResultsPatients had a median age of 60.2 years (IQR 26.2 years); 54.1% were men. In-hospital mortality rate was 17.0% and overall median time to death was 6.5 days (range 1.3–23.0 days). In the test set, the RF classifier yielded a sensitivity of 87.8% (95% CI: 78.2% to 94.3%), specificity of 60.6% (95% CI: 55.2% to 65.8%), accuracy of 65.5% (95% CI: 60.7% to 70.0%), area under the receiver operating characteristic curve of 85.5% (95% CI: 80.8% to 90.2%) and area under the precision recall curve of 64.4% (95% CI: 53.5% to 75.3%).ConclusionsOur ML-based approach can be used to analyse electronic health record data and reliably predict near-term mortality prediction. Using such a model in hospitals could help improve care, thereby better aligning clinical decisions with prognosis in critically ill patients with COVID-19.
Inside minds, beneath diseases: social cognition in amyotrophic lateral sclerosis-frontotemporal spectrum disorder
Authors: Lillo Patricia , Caramelli Paulo , Musa Gada , Parrao Teresa , Hughes Ricardo , Aragon Andres , Valenzuela Daniel , Cea Gabriel , Aranguiz Rafael , Guimarães Henrique Cerqueira , Rousseff Laura , Gambogi Leandro Boson , Mariano Luciano Inácio , Teixeira Antônio Lúcio , Slachevsky Andrea , de Souza Leonardo Cruz 
Published: September 2020

Objective
To compare social cognition performance between patients with amyotrophic lateral sclerosis (ALS) and those patients with behavioural variant frontotemporal dementia (bvFTD).

Methods

We included 21 participants with ALS, 20 with bvFTD and 21 healthy controls who underwent a comprehensive cognitive battery, including the short version of the Social Cognition and Emotional Assessment (Mini-SEA), which comprises the
faux pas
test and Facial Emotion Recognition Test (FERT); Mini-Mental State Examination; Frontal Assessment Battery; lexical fluency (F-A-S), category fluency (animals/minute), digit span (direct and backwards) tests and the Hayling test. A post hoc analysis was conducted with the patients with ALS divided into two subgroups: patients without cognitive impairment (ALScn; n=13) and patients with cognitive impairment (ALSci; n=8).

Results

No significant difference was noted between participant groups in terms of the age, sex and education. ALS-total group and patients with bvFTD had similar disease durations. Patients with ALSci performed poorly when compared with controls with regard to the FERT (p<0.001), the
faux pas
(p<0.004) and the Mini-SEA (p<0.002) total scores. Moreover, patients with bvFTD performed poorly in comparison with controls in executive and social cognition tests. The performance of patients with ALSci was similar to that of patients with bvFTD, while the performance of patients with ALScn was similar to that of controls.

Discussion
Our findings support a cognitive continuum between ALS and bvFTD and shed light on the cognitive heterogeneity of ALS, expanding its possible neuropsychological profiles.
Electromagnetic response to high-frequency gravitational waves having additional polarization states: distinguishing and probing tensor-mode, vector-mode and scalar-mode gravitons
Authors: Li Fang-Yu , Wen Hao , Fang Zhen-Yun , Li Di , Zhang Tong-Jie 
Published: September 2020

AbstractGravitational waves (GWs) from extra dimensions, very early universe, and some high-energy astrophysical processes might have at most six polarization states: tensor- and nontensor-mode gravitons. The peak regions or partial peak regions (of the amplitudes or energy densities) of some of such GWs are just distributed in the GHz or higher frequency band, which would be an optimal frequency band for the electromagnetic (EM) response to such high-frequency GWs (HFGWs). In this paper we investigate the EM response to the HFGWs, and for the first time we obtain the concrete form of analytic solutions of the perturbative EM fields caused by all six possible polarizations of the HFGWs in the background stable EM fields and in the proposed three dimensional synchro-resonance system (3DSR system), respectively. It is found that all such six polarizations may in principle show separability and detectability. Moreover, the detection frequency band ($$\sim 10^{8}$$

∼

10
8

to $$10^{12}$$

10
12

Hz or higher) of the signal photon fluxes by the 3DSR system and the observation frequency range ($$\sim 7\times 10^{7}$$

∼
7
×

10
7

to $$3\times 10^{9}$$

3
×

10
9

Hz) of the signals by the FAST (Five-hundred-meter Aperture Spherical Telescope, China) have a certain overlapping property, and thus their coincidence experiments in the future for observations will have high complementarity.
FAM46C and FNDC3A Are Multiple Myeloma Tumor Suppressors That Act in Concert to Impair Clearing of Protein Aggregates and Autophagy
Authors: Manfrini Nicola , Mancino Marilena , Miluzio Annarita , Oliveto Stefania , Balestra Matteo , Calamita Piera , Alfieri Roberta , Rossi Riccardo L. , Sassoè-Pognetto Marco , Salio Chiara , Cuomo Alessandro , Bonaldi Tiziana , Manfredi Marcello , Marengo Emilio , Ranzato Elia , Martinotti Simona , Cittaro Davide , Tonon Giovanni , Biffo Stefano 
Published: September 2020

Abstract

Multiple myeloma is a plasma cell neoplasm characterized by the production of unfolded immunoglobulins, which cause endoplasmic reticulum (ER) stress and sensitivity to proteasome inhibition. The genomic landscape of multiple myeloma is characterized by the loss of several genes rarely mutated in other cancers that may underline specific weaknesses of multiple myeloma cells. One of these is FAM46C that is lost in more than 10% of patients with multiple myeloma. We show here that FAM46C is part of a new complex containing the ER-associated protein FNDC3A, which regulates trafficking and secretion and, by impairing autophagy, exacerbates proteostatic stress. Reconstitution of FAM46C in multiple myeloma cells that had lost it induced apoptosis and ER stress. Apoptosis was preceded by an increase of intracellular aggregates, which was not linked to increased translation of IgG mRNA, but rather to impairment of autophagy. Biochemical analysis showed that FAM46C requires interaction with ER bound protein FNDC3A to reside in the cytoplasmic side of the ER. FNDC3A was lost in some multiple myeloma cell lines. Importantly, depletion of FNDC3A increased the fitness of FAM46C-expressing cells and expression of FNDC3A in cells that had lost it recapitulated the effects of FAM46C, inducing aggregates and apoptosis. FAM46C and FNDC3A formed a complex that modulates secretion routes, increasing lysosome exocytosis. The cellular landscape generated by FAM46C/FNDC3A expression predicted sensitivity to sphingosine kinase inhibition. These results suggest that multiple myeloma cells remodel their trafficking machinery to cope with ER stress.

Significance:
This study identifies a new multiple myeloma–specific tumor suppressor complex that regulates autophagy and unconventional secretion, highlighting the sensitivity of multiple myeloma cells to the accumulation of protein aggregates.
FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Chang Elaine , Weinstock Chana , Zhang Lijun , Charlab Rosane , Dorff Sarah E. , Gong Yutao , Hsu Vicky , Li Fang , Ricks Tiffany K. , Song Pengfei , Tang Shenghui , Waldron Peter E. , Yu Jingyu , Zahalka Eias , Goldberg Kirsten B. , Pazdur Richard , Theoret Marc R. , Ibrahim Amna , Beaver Julia A. 
Published: September 2020

Abstract
On December 18, 2019, the FDA granted accelerated approval to enfortumab vedotin-ejfv (PADCEV; Astellas and Seattle Genetics) for treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a programmed cell death protein 1 or programmed death ligand 1 inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Substantial evidence of effectiveness for this application is obtained from Cohort 1 of the single-arm, multicenter Study EV-201. Patients received enfortumab vedotin (EV) 1.25 mg/kg (up to a maximum dose of 125 mg) intravenously on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Confirmed objective response rate in the 125-patient efficacy population determined by blinded independent central review was 44% [95% confidence interval (CI), 35.1–53.2], with complete responses in 12%. Median response duration was 7.6 months (95% CI, 6.3–not estimable). Grade 3–4 adverse reactions occurred in 73% of patients. Hyperglycemia, peripheral neuropathy, ocular disorders, skin reactions, infusion site extravasations, and embryo-fetal toxicity are labeled as warnings and precautions for EV. The article summarizes the data and the FDA thought process supporting accelerated approval of EV. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Cardiac Abnormalities Seen in Pediatric Patients During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: An International Experience
Authors: Clark Bradley C. , Sanchez‐de-Toledo Joan , Bautista‐Rodriguez Carles , Choueiter Nadine , Lara Diego , Kang Hechaan , Mohsin Shazia , Fraisse Alain , Cesar Sergi , Shaikh Abdul Sattar , Escobar‐Diaz Maria C. , Hsu Daphne T. , Randanne Paula C. , Aslam Nadeem , Kleinmahon Jake , Lamour Jacqueline M. , Johnson Jonathan N. , Sarquella‐Brugada Georgia , Chowdhury Devyani 
Published: September 2020

Background
During the severe acute respiratory syndrome Coronavirus 2 pandemic, there has been an increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi‐system inflammatory syndrome during the severe acute respiratory syndrome Coronavirus 2 pandemic.

Methods and Results
We reviewed data on previously healthy pediatric patients (≤18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain, and Pakistan with multi‐system inflammatory syndrome in children and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings, and initial therapies. A total of 55 patients presented with multi‐system inflammatory syndrome in children. Thirty‐five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion, and 11 (20%) with coronary abnormalities. Twenty‐seven (49%) required intensive care unit admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), D‐dimer, and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular block, transient atrioventricular block, and ventricular tachycardia.

Conclusions
To our knowledge, we describe the first international cohort of pediatric patients with multi‐system inflammatory syndrome in children during the severe acute respiratory syndrome Coronavirus 2 pandemic with a range of cardiac manifestations. This article brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow‐up.