bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-shifting for refugee mental health and psychosocial support: A scoping review of services in humanitarian settings through the lens of RE-AIM
Authors: Cohen Flora , Yaeger Lauren 
Published: March 2021

Background: Decades of war, famines, natural disasters, and political upheaval have led to the largest number of displaced persons in human history. The refugee experience is fraught with obstacles from preflight to resettlement, leading to high rates of mental distress including post-traumatic stress disorder, depression, and anxiety. However, there is a paucity of mental health services for refugees in transit. To meet the needs of this vulnerable population, researchers are experimenting with teaching lay community members basic tools for the delivery of mental health and psychosocial support services (MHPSS). However, there are research gaps about the use of implementation science to inform the delivery of applicable interventions, especially within low resource settings, and even less in the humanitarian context. Methods: This review utilizes an implementation science framework (RE-AIM) to assess the reach, effectiveness, adoption, implementation, and maintenance of these interventions. Studies included varying interventions and modes of delivery within refugee camp and urban settings. A comprehensive search strategy led to the inclusion and analysis of 11 unique studies. Results: While current research documents adaptation strategies, feasibility, and fidelity checks through routine monitoring, there is still a dearth of evidence regarding capacity building of lay providers in humanitarian settings. Barriers to this data collection include a lack of homogeneity in outcomes across studies, and a lack of comprehensive adaptation strategies which account for culture norms in the implementation of interventions. Furthermore, current funding prioritizes short-term solutions for individuals who meet criteria for mental illnesses and therefore leaves gaps in sustainability, and more inclusive programming for psychosocial services for individuals who do not meet threshold criteria. Conclusion: Findings contribute to the literature about task-shifting for MHPSS in humanitarian contexts, especially illuminating gaps in knowledge about the lay counselor experiences of these interventions. Plain language summary: There is a growing number of refugees forced to make homes in temporary camps or urban centers as they await resettlement, a process that can last decades. These refugees are at risk of serious mental health outcomes due to ongoing stress and trauma. One strategy commonly used in global mental health is the training of lay providers to deliver basic mental health and psychosocial programming to communities. While this tactic is currently being tested in refugee settings, there is limited evidence about the implementation of this strategy. The following scoping review aims to assess the implementation of task-shifting interventions within refugee settings, through the use of a robust implementation science framework.
Gene therapy for hemophilia B using CB 2679d-GT: a novel factor IX variant with higher potency than factor IX Padua
Authors: Nair Nisha , De Wolf Dries , Nguyen Phuong Anh , Pham Quang Hong , Samara-Kuko Ermira , Landau Jeff , Blouse Grant E. , Chuah Marinee K. , VandenDriessche Thierry 
Published: March 2021

Abstract
Sustained expression of therapeutic factor IX (FIX) levels has been achieved after adeno-associated viral (AAV) vector-based gene therapy in patients with hemophilia B. Nevertheless, patients are still at risk of vector dose-limiting toxicity, particularly liver inflammation, justifying the need for more efficient vectors and a lower dosing regimen. A novel increased potency FIX (designated as CB 2679d-GT), containing 3 amino acid substitutions (R318Y, R338E, T343R), significantly outperformed the R338L-Padua variant after gene therapy. CB 2679d-GT demonstrated a statistically significant approximately threefold improvement in clotting activity when compared with R338L-Padua after AAV-based gene therapy in hemophilic mice. Moreover, CB 2679d-GT gene therapy showed significantly reduced bleeding time (approximately fivefold to eightfold) and total blood loss volume (approximately fourfold) compared with mice treated with the R338L-Padua, thus achieving more rapid and robust hemostatic correction. FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua whereas immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT, highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV-directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant.
Plasminogen: an enigmatic zymogen
Authors: Keragala Charithani B. , Medcalf Robert L. 
Published: March 2021

AbstractPlasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for &gt;40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis.
MARCKS affects cell motility and response to BTK inhibitors in CLL
Authors: Beckmann Laura , Berg Valeska , Dickhut Clarissa , Sun Clare , Merkel Olaf , Bloehdorn Johannes , Robrecht Sandra , Seifert Marc , da Palma Guerreiro Alexandra , Claasen Julia , Loroch Stefan , Oliverio Matteo , Underbayev Chingiz , Vaughn Lauren , Thomalla Daniel , Hülsemann Malte F. , Tausch Eugen , Fischer Kirsten , Fink Anna Maria , Eichhorst Barbara , Sickmann Albert , Wendtner Clemens M. , Stilgenbauer Stephan , Hallek Michael , Wiestner Adrian , Zahedi René P. , Frenzel Lukas P. 
Published: March 2021

Abstract
Bruton tyrosine kinase (BTK) inhibitors are highly active drugs for the treatment of chronic lymphocytic leukemia (CLL). To understand the response to BTK inhibitors on a molecular level, we performed (phospho)proteomic analyses under ibrutinib treatment. We identified 3466 proteins and 9184 phosphopeptides (representing 2854 proteins) in CLL cells exhibiting a physiological ratio of phosphorylated serines (pS), threonines (pT), and tyrosines (pY) (pS:pT:pY). Expression of 83 proteins differed between unmutated immunoglobulin heavy-chain variable region (IGHV) CLL (UM-CLL) and mutated IGHV CLL (M-CLL). Strikingly, UM-CLL cells showed higher basal phosphorylation levels than M-CLL samples. Effects of ibrutinib on protein phosphorylation levels were stronger in UM-CLL, especially on phosphorylated tyrosines. The differentially regulated phosphopeptides and proteins clustered in pathways regulating cell migration, motility, cytoskeleton composition, and survival. One protein, myristoylated alanine-rich C-kinase substrate (MARCKS), showed striking differences in expression and phosphorylation level in UM-CLL vs M-CLL. MARCKS sequesters phosphatidylinositol-4,5-bisphosphate, thereby affecting central signaling pathways and clustering of the B-cell receptor (BCR). Genetically induced loss of MARCKS significantly increased AKT signaling and migratory capacity. CD40L stimulation increased expression of MARCKS. BCR stimulation induced phosphorylation of MARCKS, which was reduced by BTK inhibitors. In line with our in vitro findings, low MARCKS expression is associated with significantly higher treatment-induced leukocytosis and more pronounced decrease of nodal disease in patients with CLL treated with acalabrutinib.
A rapid genotyping panel for detection of primary central nervous system lymphoma
Authors: Gupta Mihir , Burns Evan J. , Georgantas Nicholas Z. , Thierauf Julia , Nayyar Naema , Gordon Amanda , Jones SooAe S. , Pisapia Michelle , Sun Ying , Burns Ryan P. , Velarde Jose , Jordan Justin T. , Frigault Matthew J. , Nahed Brian V. , Jones Pamela S. , Barker Fred G. , Curry William T. , Gupta Rajiv , Batchelor Tracy T. , Romero Javier M. , Brastianos Priscilla K. , Marble Hetal D. , Martinez-Lage Maria , Tateishi Kensuke , Lennerz Jochen K. , Dietrich Jorg , Cahill Daniel P. , Carter Bob S. , Shankar Ganesh M. 
Published: March 2021

Abstract
Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.
The risk of community-acquired pneumonia in children using gastric acid suppressants
Authors: van der Sande Linda J.T.M. , Jöbsis Quirijn , Bannier Michiel A.G.E. , van de Garde Ewoudt M.W. , Coremans Jan J.M. , de Vries Frank , Dompeling Edward , Driessen Johanna H.M. 
Published: March 2021

BackgroundWith the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)).MethodsWe performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children.ResultsCurrent use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90–2.22) and 1.80 (95% CI 1.67–1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months.ConclusionThe use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.
Blood eosinophil counts and the development of obstructive lung disease: the Kangbuk Samsung Health Study
Authors: Park Hye Yun , Chang Yoosoo , Kang Danbee , Hong Yun Soo , Zhao Di , Ahn Jiin , Shin Sun Hye , Singh Dave , Guallar Eliseo , Cho Juhee , Ryu Seungho 
Published: March 2021

AimThe impact of blood eosinophil counts on the development of chronic obstructive lung disease (COPD) is unknown. We investigated whether a higher blood eosinophil count was associated with the risk of developing obstructive lung disease (OLD) in a large cohort of men and women free from lung disease at baseline.MethodsThis was a cohort study of 359 456 Korean adults without a history of asthma and without OLD at baseline who participated in health screening examinations including spirometry. OLD was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and FEV1<80% predicted.ResultsAfter a median (interquartile range) follow-up of 5.6 (2.9–9.2) years, 5008 participants developed incident OLD (incidence rate 2.1 (95% CI 2.1–2.2) per 1000 person-years). In the fully adjusted model, the hazard ratios for incident OLD comparing eosinophil counts of 100– <200, 200– <300, 300– <500 and ≥500versus<100 cells·μL−1were 1.07 (95% CI 1.00–1.15), 1.30 (95% CI 1.20–1.42), 1.46 (95% CI 1.33–1.60) and 1.72 (95% CI 1.51–1.95), respectively (ptrend<0.001). These associations were consistent in clinically relevant subgroups, including never-, ex- and current smokers.ConclusionIn this large longitudinal cohort study, blood eosinophil counts were positively associated with the risk of developing of OLD. Our findings indicate a potential role of the eosinophil count as an independent risk factor for developing COPD.
Referral criteria to palliative care for patients with respiratory disease: a systematic review
Authors: Philip Jennifer , Collins Anna , Smallwood Natasha , Chang Yuchieh Kathryn , Mo Li , Yang Ian A. , Corte Tamera , McDonald Christine F. , Hui David 
Published: March 2021

AimsAdvanced nonmalignant respiratory diseases are associated with significant patient morbidity, yet access to palliative care occurs late, if at all. Our aim was to examine referral criteria for palliative care among patients with advanced nonmalignant respiratory disease, with a view to developing a standardised set of referral criteria.MethodsWe performed a systematic review of all studies reporting on referral criteria to palliative care in advanced nonmalignant respiratory disease, with a focus on chronic obstructive pulmonary disease and interstitial lung disease. The systematic review was conducted and reported according to the PRISMA guidelines, and was undertaken using electronic databases (Ovid, MEDLINE, Ovid Embase and PubMed).ResultsSearches yielded 2052 unique titles, which were screened for eligibility and resulted in 62 studies addressing referral criteria to palliative care in advanced nonmalignant respiratory disease. Of 18 categories put forward for referral to palliative care, the most commonly discussed factors were hospital use (69% of papers), indicators of poor respiratory status (47%), physical and emotional symptoms (37%), functional decline (29%), need for advanced respiratory therapies (27%), and disease progression (26%).ConclusionClinicians consider referral to specialist palliative care for a wide range of disease- and needs-based criteria. Our findings highlight the need to standardise palliative care access by developing consensus referral criteria for patients with advanced nonmalignant respiratory illnesses.
The differing physiology of nitrogen and tracer gas multiple-breath washout techniques
Authors: Sandhu Dominic , Ritchie Grant A.D. , Robbins Peter A. 
Published: March 2021

BackgroundMultiple-breath washout techniques are increasingly used to assess lung function. The principal statistic obtained is the lung clearance index (LCI), but values obtained for LCI using the nitrogen (N2)-washout technique are higher than those obtained using an exogenous tracer gas such as sulfur hexafluoride. This study explored whether the pure oxygen (O2) used for the N2washout could underlie these higher values.MethodsA model of a homogenous, reciprocally ventilated acinus was constructed. Perfusion was kept constant, and ventilation adjusted by varying the swept volume during the breathing cycle. The blood supplying the acinus had a standard mixed-venous composition. Carbon dioxide and O2exchange between the blood and acinar gas proceeded to equilibrium. The model was initialised with either air or air plus tracer gas as the inspirate. Washouts were conducted with pure O2for the N2washout or with air for the tracer gas washout.ResultsAt normal ventilation/perfusion (V′/Q′) ratios, the rate of washout of N2and exogenous tracer gas was almost indistinguishable. At lowV′/Q′, the N2washout lagged the tracer gas washout. At very lowV′/Q′, N2became trapped in the acinus. Under lowV′/Q′ conditions, breathing pure O2introduced a marked asymmetry between the inspiratory and expiratory gas flow rates that was not present when breathing air.DiscussionThe use of pure O2to washout N2increases O2uptake in lowV′/Q′ units. This generates a background gas flow into the acinus that opposes flow out of the acinus during expiration, and so delays the washout of N2.
WASP: a versatile, web-accessible single cell RNA-Seq processing platform
Authors: Hoek Andreas , Maibach Katharina , Özmen Ebru , Vazquez-Armendariz Ana Ivonne , Mengel Jan Philipp , Hain Torsten , Herold Susanne , Goesmann Alexander 
Published: March 2021

AbstractBackgroundThe technology of single cell RNA sequencing (scRNA-seq) has gained massively in popularity as it allows unprecedented insights into cellular heterogeneity as well as identification and characterization of (sub-)cellular populations. Furthermore, scRNA-seq is almost ubiquitously applicable in medical and biological research. However, these new opportunities are accompanied by additional challenges for researchers regarding data analysis, as advanced technical expertise is required in using bioinformatic software.ResultsHere we present WASP, a software for the processing of Drop-Seq-based scRNA-Seq data. Our software facilitates the initial processing of raw reads generated with the ddSEQ or 10x protocol and generates demultiplexed gene expression matrices including quality metrics. The processing pipeline is realized as a Snakemake workflow, while an R Shiny application is provided for interactive result visualization. WASP supports comprehensive analysis of gene expression matrices, including detection of differentially expressed genes, clustering of cellular populations and interactive graphical visualization of the results. The R Shiny application can be used with gene expression matrices generated by the WASP pipeline, as well as with externally provided data from other sources.ConclusionsWith WASP we provide an intuitive and easy-to-use tool to process and explore scRNA-seq data. To the best of our knowledge, it is currently the only freely available software package that combines pre- and post-processing of ddSEQ- and 10x-based data. Due to its modular design, it is possible to use any gene expression matrix with WASP’s post-processing R Shiny application. To simplify usage, WASP is provided as a Docker container. Alternatively, pre-processing can be accomplished via Conda, and a standalone version for Windows is available for post-processing, requiring only a web browser.
Sex differences in the association between latent class of lifestyle and disability among older adults in China
Authors: Shi Zaixing , Lin Jianlin , Xiao Jian , Fang Ya 
Published: March 2021

AbstractBackgroundA healthy lifestyle may prevent disability for older adults. But research to date is limited to a single lifestyle behavior and ignore sex difference in the lifestyle-disability association. This study aimed at identifying sex-specific latent classes of lifestyle and their relationship with disability among older Chinese adults.MethodsData were obtained from adults aged 65 years or above in the 2018 Chinese Longitudinal Healthy Longevity Survey, a nationally representative sample of older adults in China. We used latent class analysis to categorize participants into subgroups based on three dimensions of lifestyle factors: health behaviors, psychological wellbeing, and social engagement. Disability was assessed by the activities of daily living (ADL). Multivariable logistic regression was used to evaluate the associations between the latent lifestyle classes and disability.ResultsA total of 15,771 older adults were included in this analysis, of whom 56% were women and 66% aged 80 years or above. We identified four latent lifestyle classes among older women: “Health Promoting” (28%), “Isolated and Health Harming” (34%), “Restless and Dismal” (21%), and “Restless” (17%). A different set of four lifestyle classes were identified in older men: “Health Promoting” (21%), “Isolated and Health Harming” (26%), “Restless and Dismal” (20%), and “Discordant” (33%). Compared with the “Health Promoting” class, the “Isolated and Health Harming” class (OR = 1.88, 95% CI: 1.46–2.43) and the “Restless and Dismal” class (OR = 1.67, 95% CI: 1.27–2.20) had higher risk of disability in women. The “Discordant” class had lower risk of disability in men (OR = 0.52, 95% CI: 0.37–0.72).ConclusionsOur analyses revealed different lifestyle patterns for older women and men in China. Sex differences in the associations between lifestyle and disability need to be considered when formulating interventions to prevent disability.