bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study
Authors: Su Jun-Wei , Weng Cheng-Di , Lin Xiao-Cheng , Fang Mei-Mei , Xiao Xiao , Zhang Yi-Chen , Zhang Xu-Chao , Su Jian , Xu Chong-Rui , Yan Hong-Hong , Chen Hua-Jun , Wu Yi-Long , Yang Jin-Ji 
Published: February 2024

Background: Mesenchymal–epithelial transition ( MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.
Cerebrospinal fluid shunting for the management of cryptococcal meningitis: a scoping review
Authors: Cornejo-Venegas Gonzalo , Carreras Xosse , Salcedo Andrea S. , Soriano-Moreno David R. , Salinas Jorge L. , Alave Jorge 
Published: February 2024

Objective: This scoping review aimed to describe studies that evaluate the management of cryptococcal meningitis (CM) using cerebrospinal fluid (CSF) shunts, types of shunts used, and clinically relevant patient outcomes. Methods: We searched in the following databases: PubMed, Web of Science/Core collection, Embase, the Cochrane Library, and clinicaltrials.gov on 1 April 2022. We included two-arm and one-arm cohort studies that evaluated clinically relevant patient outcomes. Case reports were used to describe the type of CSF shunts used and the rationale behind its selection. The selection and extraction processes were independently performed by two authors. Results: This study included 20 cohort studies and 26 case reports. Only seven cohort studies compared two groups. Ventriculoperitoneal shunt was the most commonly used type of shunt (82.1%). The main indications for placing a shunt were persistently high opening pressure (57.1%) and persisting neurological symptoms or deterioration (54.3%). Cohort studies suggest that patients with shunt showed improvement in some outcomes such as neurological symptoms and hospital stay length. The most common shunt complications were post-operative fever (1–35.6%) and shunt obstruction (7–16%). Conclusion: CSF shunts may improve some clinically relevant outcomes in patients with CM, but the evidence is very uncertain.
Design requirements of upper extremity supports for daily use in Duchenne muscular dystrophy with severe muscle weakness
Authors: Filius Suzanne J , Harlaar Jaap , Alberts Lonneke , Houwen-van Opstal Saskia , van der Kooij Herman , Janssen Mariska MHP 
Published: February 2024

Background People with Duchenne muscular dystrophy (DMD) cope with progressive muscular weakness and consequential upper extremity function loss. They benefit from arm supports, or arm exoskeletons, to assist arm function. Especially for severe muscle weakness (DMD ≥ Brooke Scale 4), the design of such arm support is challenging. This study aims to structurally develop functional and technical design requirements of arm supports for people with DMD Brooke Scale 4. Methods An overview of clinical characteristics and a classification of clinically meaningful activities were derived from data from the Dutch Dystrophinopathy Database and available literature. Based on these, functional and technical design requirements of arm supports were developed and matched to the achievable needs of the user. Results First, the clinical characteristics of the target population, such as strength, range of motion, and functional ability, are given. Next, clinically relevant activities of daily living are translated to functional requirements categorised in a ‘must,’ ‘should,’ and ‘could’ category. Last, the technical requirements to realise these functional goals are presented. Conclusions The recommendations following from the functional user needs, technical requirements, and safety considerations can be used to make the development of assistive arm supports for people with DMD Brooke Scale 4 more user-centred.
Knowledge and Behavior of Primary Care Physicians Regarding Utilization of Standardized Tools in Screening and Assessment of Anxiety, Depression, and Mood Disorders at a Large Integrated Health System
Authors: Waheed Abdul , Afridi Asif Khan , Rana Masooma , Arif Mobeena , Barrera Trajan , Patel Feroza , Khan Muhammad Nausherwan , Azhar Erum 
Published: February 2024

Introduction: Standardized screening, objective evaluation, and management of behavioral health conditions are major challenges in primary care. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Mood Disorder Questionnaire (MDQ) provide standardized screening and symptom management tools for generalized anxiety disorder (GAD), major depressive disorder (MDD), and Mood Disorders (MD), respectively. This study explores family physicians’ knowledge, attitudes, and practices regarding the utilization of GAD-7, PHQ-9, and MDQ in outpatient primary care offices. Methods: The study method was a cross-sectional electronic and paper survey utilizing a self-administered questionnaire that assessed primary care physicians’ demographics, knowledge, attitudes, and practices in rural and urban outpatient clinical settings regarding GAD-7, PHQ-9, and MDQ. Statistical software SAS 9.4 was used for descriptive and Chi-Square statistics. Results: Out of 320 total participants,145 responded (45.3%). Responding family physicians demonstrated a high level of familiarity with the GAD-7 (97.9%), PHQ-9 (97.9%), and MDQ (81.3%) assessment tools. However, the reported utilization rates were relatively lower than knowledge, with 62.7%, 73.1%, and 31.9% extremely likely or likely to utilize the GAD-7, PHQ-9, and MDQ as screening and monitoring tools, respectively. Less than a quarter of the total respondents use the objective score for the future management of GAD, with significantly more residents utilizing the score for GAD-7 compared to attendings ( P < .05). There was no statistical significance difference between residents and attendings for the objective evaluation of Major Depressive Disorder ( P = .26) and Mood Disorders ( P = .05). Conclusions: Despite being knowledgeable of the utility of GAD-7, PHQ-9, and MDQ, the primary care physicians in a large integrated health system in Central Pennsylvania and Northern Maryland report inconsistent utilization in their practice. Further studies are needed to determine the underlying factors contributing to the suboptimal usage of these screening tools and ways to increase it.
Hip and Pelvis Movement Patterns in Patients With Femoroacetabular Impingement Syndrome Differ From Controls and Change After Hip Arthroscopy During a Step-Down Pivot-Turn Task
Authors: Alter Thomas D. , Wichman Daniel M. , Fenn Thomas W. , Knapik Derrick M. , Espinoza Orias Alejandro , Nho Shane J. , Malloy Philip 
Published: February 2024

Background: Alterations in hip kinematics during functional tasks occur in positions that cause anterior impingement in patients with femoroacetabular impingement (FAI) syndrome. However, tasks that do not promote motions of symptomatic hip impingement remain understudied. Purpose: To compare movement patterns of the hip and pelvis during a step-down pivot-turn task between patients with FAI and controls as well as in patients with FAI before and after hip arthroscopy. Study Design: Controlled laboratory study. Methods: Three-dimensional motion capture was acquired in 32 patients with FAI and 27 controls during a step-down pivot-turn task. An FAI subsample (n = 14) completed testing 9.2 ± 2.0 months (mean ± SD; range, 5.8-13.1 months) after hip arthroscopy. Statistical parametric mapping analysis was used to analyze hip and pelvis time series waveforms (1) between the FAI and control groups, (2) in the FAI group before versus after hip arthroscopy, and (3) in the FAI group after hip arthroscopy versus the control group. Continuous parametric variables were analyzed by paired t test and nonparametric variables by chi-square test. Results: There were no significant differences in demographics between the FAI and control groups. Before hip arthroscopy, patients with FAI demonstrated reduced hip flexion ( P = .041) and external rotation ( P = .027), as well as decreased anterior pelvic tilt ( P = .049) and forward rotation ( P = .043), when compared with controls. After hip arthroscopy, patients demonstrated greater hip flexion ( P < .001) and external rotation of the operative hip ( P < .001), in addition to increased anterior pelvic tilt ( P≤ .036) and pelvic rise ( P≤ .049), as compared with preoperative values. Postoperatively, the FAI group demonstrated greater hip flexion ( P≤ .047) and lower forward pelvic rotation ( P = .003) as compared with the control group. Conclusion: Movement pattern differences between the FAI and control groups during the nonimpingement-related step-down pivot-turn task were characterized by differences in the sagittal and transverse planes of the hip and pelvis. After hip arthroscopy, patients exhibited greater hip flexion and external rotation and increased pelvic anterior tilt and pelvic rise as compared with presurgery. When compared with controls, patients with FAI demonstrated greater hip flexion and lower pelvic forward rotation postoperatively. Clinical Relevance: These findings indicate that hip and pelvis biomechanics are altered even during tasks that do not reproduce the anterior impingement position.
Childhood and adolescence physical activity and multimorbidity later in life: A systematic review
Authors: Souilla Luc , Larsen Anders C. , Juhl Carsten B. , Skou Søren T. , Bricca Alessio 
Published: February 2024

Background No systematic summary exists on childhood physical activity and later-life multimorbidity risks. We primarily investigated the association of physical activity in childhood and adolescence and the development of multimorbidity in adulthood. Secondarily, we examined whether physical activity level differ in children and adolescents with and without multimorbidity and whether there is a cross-sectional association between physical activity and multimorbidity. Methods Following Cochrane Handbook guidelines and adhering to PRISMA recommendations, we included cross-sectional, case-control and longitudinal studies that investigated the association between physical activity in children and adolescents and development of multimorbidity. Results were summarized narratively and we assessed the certainty of the evidence using the GRADE approach. The protocol was registered in PROSPERO, CRD42023407063. Results Of 9064 studies identified, 11 were included in 13 papers. Longitudinals studies suggested that being physically active in childhood and adolescence was associated with a lower risk of multimorbidity in adulthood. Three out of five studies reported lower physical activity level in children and adolescents with multimorbidity compared to those without, and two did not find a between-group difference. Cross-sectional evidence on the association between multimorbidity and lower physical activity was uncertain. Overall, the evidence certainty for all outcomes was considered low due to the indirectness and inconsistency in findings. Conclusions Childhood and adolescence physical activity appeared to be linked with a reduced risk of later-life multimorbidity but the certainty of the evidence is low. These results support the promotion of physical activity during childhood and adolescence.
Mental Health Distress Is Associated With Higher Pain Interference in Patients With Opioid Use Disorder Stabilized on Buprenorphine or Methadone
Authors: Leyde Sarah , Price Cynthia J. , Colgan Dana D. , Pike Kenneth C. , Tsui Judith I. , Merrill Joseph O. 
Published: February 2024

Background: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone. Methods: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference. Results: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions. Conclusions: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed.
Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency
Authors: Del Carpio-Cano Fabiola , Mao Guangfen , Goldfinger Lawrence E. , Wurtzel Jeremy , Guan Liying , Alam Mohammad Afaque , Lee Kiwon , Poncz Mortimer , Rao A. Koneti 
Published: February 2024

Abstract
Platelet α-granules have numerous proteins, some synthesized by megakaryocytes (MK) and others not synthesized but incorporated by endocytosis, an incompletely understood process in platelets/MK. Germ line RUNX1 haplodeficiency, referred to as familial platelet defect with predisposition to myeloid malignancies (FPDMMs), is associated with thrombocytopenia, platelet dysfunction, and granule deficiencies. In previous studies, we found that platelet albumin, fibrinogen, and immunoglobulin G (IgG) were decreased in a patient with FPDMM. We now show that platelet endocytosis of fluorescent-labeled albumin, fibrinogen, and IgG is decreased in the patient and his daughter with FPDMM. In megakaryocytic human erythroleukemia (HEL) cells, small interfering RNA RUNX1 knockdown (KD) increased uptake of these proteins over 24 hours compared with control cells, with increases in caveolin-1 and flotillin-1 (2 independent regulators of clathrin-independent endocytosis), LAMP2 (a lysosomal marker), RAB11 (a marker of recycling endosomes), and IFITM3. Caveolin-1 downregulation in RUNX1-deficient HEL cells abrogated the increased uptake of albumin, but not fibrinogen. Albumin, but not fibrinogen, partially colocalized with caveolin-1. RUNX1 KD resulted in increased colocalization of albumin with flotillin and fibrinogen with RAB11, suggesting altered trafficking of both proteins. The increased uptake of albumin and fibrinogen, as well as levels of caveolin-1, flotillin-1, LAMP2, and IFITM3, were recapitulated by short hairpin RNA RUNX1 KD in CD34+-derived MK. To our knowledge, these studies provide first evidence that platelet endocytosis of albumin and fibrinogen is impaired in some patients with RUNX1-haplodeficiency and suggest that megakaryocytes have enhanced endocytosis with defective trafficking, leading to loss of these proteins by distinct mechanisms. This study provides new insights into mechanisms governing endocytosis and α-granule deficiencies in RUNX1-haplodeficiency.
Allogeneic hematopoietic cell transplantation for adult metachromatic leukodystrophy: a case series
Authors: Riedel Andreas , Faul Christoph , Reuss Kristina , Schröder Jan C. , Lang Peter J. , Lengerke Claudia , Weissert Nadine , Hengel Holger , Gröschel Samuel , Schoels Ludger , Bethge Wolfgang A. 
Published: February 2024

Abstract
Metachromatic leukodystrophy (MLD) is a rare genetic disorder caused by pathogenic variants of the ARSA gene, leading to a deficiency of the arylsulfatase A enzyme (ARSA) and consecutive accumulation of galactosylceramide-3-0-sulfate in the nervous system. The condition leads to severe neurological deficits and subsequently results in profound intellectual and motoric disability. Especially, the adult form of MLD, which occurs in individuals aged &gt;16 years, poses significant challenges for treating physicians because of the rarity of cases, limited therapeutic options, and different allogeneic hematopoietic cell transplantation (allo-HCT) protocols worldwide. Here, we report the results of allo-HCT treatment in 4 patients with a confirmed adult MLD diagnosis. Bone marrow or mobilized peripheral progenitor cells were infused after a reduced intensity conditioning regime consisting of fludarabine and treosulfan. In 3 patients, allo-HCT was followed by an infusion of mesenchymal cells to further consolidate ARSA production. We observed a good tolerability and an increase in ARSA levels up to normal range values in all patients. A full donor chimerism was detected in 3 patients within the first 12 months. In a 1-year follow-up, patients with complete donor chimerism showed a neurological stable condition. Only 1 patient with an increasing autologous chimerism showed neurological deterioration and a decline in ARSA levels in the first year. In summary, allo-HCT offers a therapeutic option for reconstituting ARSA enzyme levels in adult patients with MLD, with tolerable side effects.
Differential expression of mast cells in the small airways and alveolar septa of current smokers and patients with small airway disease and COPD
Authors: Eapen Mathew Suji , Lu Wenying , Dey Surajit , Chia Collin , Hardikar Ashutosh , Hassan Md Imtaiyaz , Bhattarai Prem , Gaikwad Archana Vijay , Das Shatarupa , Hansbro Philip M. , Singhera Gurpreet Kaur , Hackett Tillie-Louise , Sohal Sukhwinder Singh 
Published: February 2024

BackgroundCOPD patients suffer from dysregulated and suppressed immune functionality, determined by their loss of degranulating capacity. Here we provide crucial information on the presence of degranulated mast cells (MCs) in COPD airways and demonstrate their relationship to lung physiology and airway remodelling.MethodsSmall airway lung resections from non-smoking controls (NC), normal lung function smokers (NLFS), small airway disease (SAD), and mild-to-moderate COPD current smokers (COPD-CS) and ex-smokers (COPD-ES) were dual immuno-stained with MC tryptase and degranulation marker lysosome-associated membrane protein (LAMP)-1. Total MCs, degranulating MCs and non-MCs were enumerated in small airway epithelium and subepithelium, and in alveolar septa.ResultsIn the small airway wall subepithelial areas, COPD-CS and COPD-ES patients had significantly lower MCs than the NC group (p<0.05), although the numbers were considerably higher in the small airway epithelium (p<0.01). Degranulating non-MCs were higher in SAD (p<0.05) than in COPD in the small airway subepithelium. In contrast, there were significant increases in total MCs (degranulated and non-degranulated) and degranulated non-MCs in the alveolar septum of COPD patients compared with the NC group (p<001). The lower numbers of MCs in the subepithelium correlated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC (FEF25–75%), higher smoking rates in COPD patients, and increased small airway wall thickness and extracellular matrix. The increase in MCs in the alveolar septum negatively correlated with FEF25–75%.ConclusionsThis study is the first to assess the differential pattern of MC, degranulating MC and non-MC populations in the small airways and alveoli of COPD patients. The spatial positioning of the MCs within the airways showed variable correlations with lung function.
Measuring accuracy of International Classification of Diseases codes in identification of patients with non-cystic fibrosis bronchiectasis
Authors: Green O'Neil , Liautaud Sybille , Knee Alexander , Modahl Lucy 
Published: February 2024

IntroductionNon-cystic fibrosis bronchiectasis is a disease which is increasing in incidence and prevalence worldwide. The incidence of the disease is frequently estimated using databases that rely on International Classification of Diseases, ninth and tenth revisions, clinical modification (ICD-9-CM/ICD-10-CM) discharge diagnoses. Code accuracy has proved to be a major issue for other diagnoses using ICD codes. This study aims to investigate the accuracy of the ICD codes for the diagnosis of non-cystic fibrosis bronchiectasis.MethodsThis is a retrospective diagnostic accuracy study which compares the radiologist's diagnosis of bronchiectasis with the ICD code reflection of that diagnosis at discharge.ResultsSensitivities were 34% (same for both ICD-9-CM and ICD-10-CM windows) and specificities ranged from 69% for the ICD-9-CM window to 81% for ICD-10-CM window.ConclusionWe observed that ICD codes are an insufficient method to identify patients with a radiologist diagnosis of bronchiectasis.