bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational patterns and their correlation to CHIP-related mutations and age in hematological malignancies
Authors: Stengel Anna , Baer Constance , Walter Wencke , Meggendorfer Manja , Kern Wolfgang , Haferlach Torsten , Haferlach Claudia 
Published: September 2021

Abstract
Acquired somatic mutations are crucial for the development of most cancers. We performed a comprehensive comparative analysis of the mutational landscapes and their correlation with CHIP-related (clonal hematopoiesis of indeterminate potential) mutations and patient age of 122 genes in 3096 cases of 28 different hematological malignancies. Differences were observed regarding (1) the median number of mutations (highest, median n = 4; lowest, n = 0); (2) specificity of certain mutations (high frequencies in atypical chronic myeloid leukemia [aCML; ASXL1, 86%], follicular lymphoma [FL; KMT2D, 87%; CREBBP, 73%], hairy cell lymphoma [BRAF, 100%], lymphoplasmacytic lymphoma [MYD88, 98%; CXCR4, 51%], myeloproliferative neoplasm [MPN; AK2, 68%]); (3) distribution of mutations (broad distribution within/across the myeloid/lymphoid lineage for TET2, ASXL1, DNMT3A, TP53, BCOR, and ETV6); (4) correlation of mutations with patient’s age (correlated with older age across entities: TET2, DNMT3A, ASXL1, TP53, EZH2, BCOR, GATA2, and IDH2; younger age: KIT, POT1, RAD21, U2AF2, and WT1); (5) correlation of mutation number per patient with age. Moreover, we observed high frequencies of mutations in RUNX1, SRSF2, IDH2, NRAS, and EZH2 in cases comprising at least 1 DTA (DNMT3A, TET2, ASXL1) mutation, whereas in cases without DTA mutations, TP53, KRAS, WT1, and SF3B1 were more frequent across entities, suggesting differences in pathophysiology. These results give further insight into the complex genetic landscape and the role of DTA mutations in hematological neoplasms and define mutation-driven entities (myelodysplastic syndrome/MPN overlap; secondary acute myeloid) in comparison with entities defined by chromosomal fusions (chronic myeloid leukemia; myeloid/lymphoid neoplasm with eosinophilia).
Waterpipe smoking and subsequent cigarette and e-cigarette use: a cohort study
Authors: Hanewinkel Reiner , Morgenstern Matthis , Sargent James D. , Goecke Michaela , Isensee Barbara 
Published: September 2021

AimWe tested the hypothesis that waterpipe smoking increases the likelihood to try conventional and electronic cigarettes.MethodsIn 2017 and 2018, 2752 German adolescents (mean age: 14.9 years), who had never tried conventional cigarettes or e-cigarettes, took part in a longitudinal survey with a 6-month observational period. Multiple regression analyses tested the association between waterpipe use at baseline and first experimentation with e-cigarettes at follow-up. The models adjusted for risk-taking propensity (sensation seeking and experimentation with alcohol and marijuana), age, sex, migration background, type of school and peer substance use.ResultsSome 381 adolescents (12.5% of the survey population) reported waterpipe smoking at baseline. The overall initiation rate during the 6 months was 4.9% (n=134) for conventional cigarettes and 10.5% (n=288) for e-cigarettes. Prior waterpipe smoking significantly predicted cigarette use (adjusted relative risk (ARR)=1.81, 95% CI 1.19–2.76), as well as e-cigarette use (ARR=3.29, 95% CI 2.53–4.28). In addition, a significant interaction between waterpipe use and sensation seeking was found (ARR=0.56, 95% CI 0.33–0.95), with waterpipe use being more predictive of later e-cigarette initiation for lower sensation-seeking individuals.DiscussionWaterpipe use predicted both later cigarette and e-cigarette use independent of all other assessed risk factors, indicating that waterpipe use might be a risk factor on its own. The results suggest that the association was stronger for adolescents with a lower risk-taking propensity, which brings this group into focus for prevention efforts. However, further research is needed to understand whether these associations are causal.
Prediction of COPD by the single-breath nitrogen test and various respiratory symptoms
Authors: Olofson Jan , Bake Björn , Bergman Bengt , Vanfleteren Lowie E.G.W. , Svärdsudd Kurt 
Published: September 2021

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD,i.e.incident COPD events, in relation to the presence of various respiratory symptoms.A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model.The N2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20–2.22; p<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of ∼70% and ∼90% for a very steep N2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively.The alveolar N2-slope should be considered in the critical need for further research on early diagnosis of COPD.
Diagnostic value of biomarkers for paediatric urinary tract infections in primary care: systematic review and meta-analysis
Authors: Boon Hanne A. , Struyf Thomas , Bullens Dominique , Van den Bruel Ann , Verbakel Jan Y. 
Published: September 2021

Abstract
Background
Accurate diagnosis of urinary tract infection is essential as children left untreated may suffer permanent renal injury.

Aim
To compare the diagnostic values of biomarkers or clinical prediction rules for urinary tract infections in children presenting to ambulatory care.

Design and setting
Systematic review and meta-analysis of ambulatory care studies.

Methods
Medline, Embase, WOS, CINAHL, Cochrane library, HTA and DARE were searched until 21 May 2021. We included diagnostic studies on urine or blood biomarkers for cystitis or pyelonephritis in children below 18 years of age. We calculated sensitivity, specificity and likelihood ratios. Data were pooled using a bivariate random effects model and a Hierarchical Summary Receiver Operating Characteristic analysis.

Results
Seventy-five moderate to high quality studies were included in this review and 54 articles in the meta-analyses. The area under the receiver-operating-characteristics curve to diagnose cystitis was 0.75 (95%CI 0.62 to 0.83, n = 9) for C-reactive protein, 0.71 (95% CI 0.62 to 0.80, n = 4) for procalcitonin, 0.93 (95% CI 0.91 to 0.96, n = 22) for the dipstick test (nitrite or leukocyte esterase ≥trace), 0.94 (95% CI 0.58 to 0.98, n = 9) for urine white blood cells and 0.98 (95% CI 0.92 to 0.99, n = 12) for Gram-stained bacteria. For pyelonephritis, C-reactive protein < 20 mg/l had LR- of 0.10 (95%CI 0.04–0.30) to 0.22 (95%CI 0.09–0.54) in children with signs suggestive of urinary tract infection.

Conclusions
Clinical prediction rules including the dipstick test biomarkers can support family physicians while awaiting urine culture results. CRP and PCT have low accuracy for cystitis, but might be useful for pyelonephritis.
The yield of tuberculosis contact investigation in low- and middle-income settings: a systematic review and meta-analysis
Authors: Velleca Mariana , Malekinejad Mohsen , Miller Cecily , Abascal Miguel Lucia , Reeves Hailey , Hopewell Philip , Fair Elizabeth 
Published: September 2021

Abstract
Background
Contact investigation, the systematic evaluation of individuals in close contact with an infectious tuberculosis (TB) patient, is a key active case-finding strategy for global TB control. Better estimates of the yield of contact investigation can guide strategies to reduce the number of underreported and underdiagnosed TB cases, approximately three million cases per year globally. A systematic review (Prospero ID # CRD42019133380) and meta-analysis was conducted to update and enhance the estimates of the yield of TB contact investigation in low- and middle-income countries (LMIC). Pubmed, Web of Science, Embase and the WHO Global Index Medicus were searched for peer-reviewed studies (published between January 2006–April 2019); studies reporting the number of active TB or latent tuberculosis infection (LTBI) found through contact investigation were included. Pooled data were meta-analyzed using a random effects model and risk of bias was assessed.

Results
Of 1,644 unique citations obtained from database searches, 110 studies met eligibility criteria for descriptive data synthesis and 95 for meta-analysis. The pooled yields of contact investigation activities for different outcomes were: secondary cases of all active TB (defined as those bacteriologically confirmed or clinically diagnosed) 2.87% (2.61–3.14, I2 97.79%), bacteriologically confirmed active TB 2.04% (1.77–2.31, I2 98.06%), and LTBI 43.83% (38.11–49.55, I2 99.36%). Yields are interpreted as the percent of contacts screened who are diagnosed with active TB as a result of TB contact investigation activities. Pooled estimates were substantially heterogenous (I2 ≥ 75%).

Conclusions
This study provides methodologically rigorous and up-to-date estimates for the yield of TB contact investigation activities in low- and middle-income countries (LMIC). While the data are heterogenous, these findings can inform strategic and programmatic planning for scale up of TB contact investigation activities.
Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students
Authors: Kamenshchikova Alena , Wolffs Petra F. G. , Hoebe Christian J. P. A. , Penders John , Park Hyun Y. , Kambale Mateus S. , Horstman Klasien 
Published: September 2021

Abstract
Background
Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of ‘stool and stories’ that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR.

Methods
A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis.

Results
The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling.

Conclusion
The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the ‘stool and stories’ approach is important for a transdisciplinary basis of AMR stewardship.
Nomogram predicting the risk of three-year chronic kidney disease adverse outcomes among East Asian patients with CKD
Authors: Ye Huizhen , Chen Youyuan , Ye Peiyi , Zhang Yu , Liu Xiaoyi , Xiao Guanqing , Zhang Zhe , Kong Yaozhong , Liang Gehao 
Published: September 2021

Abstract
Background
Chronic kidney disease (CKD) is a common health challenge. There are some risk models predicting CKD adverse outcomes, but seldom focus on the Mongoloid population in East Asian. So, we developed a simple but intuitive nomogram model to predict 3-year CKD adverse outcomes for East Asian patients with CKD.

Methods
The development and internal validation of prediction models used data from the CKD-ROUTE study in Japan, while the external validation set used data collected at the First People’s Hospital of Foshan in southern China from January 2013 to December 2018. Models were developed using the cox proportional hazards model and nomogram with SPSS and R software. Finally, the model discrimination, calibration and clinical value were tested by R software.

Results
The development and internal validation data-sets included 797 patients (191 with progression [23.96%]) and 341 patients (89 with progression [26.10%]), respectively, while 297 patients (108 with progression [36.36%]) were included in the external validation data set. The nomogram model was developed with age, eGFR, haemoglobin, blood albumin and dipstick proteinuria to predict three-year adverse-outcome-free probability. The C-statistics of this nomogram were 0.90(95% CI, 0.89–0.92) for the development data set, 0.91(95% CI, 0.89–0.94) for the internal validation data set and 0.83(95% CI, 0.78–0.88) for the external validation data-set. The calibration and decision curve analyses were good in this model.

Conclusion
This visualized predictive nomogram model could accurately predict CKD three-year adverse outcomes for East Asian patients with CKD, providing an easy-to-use and widely applicable tool for clinical practitioners.
Association between social capital and depression among critically ill patients: evidence from a cross-sectional study in rural Shandong, China
Authors: Zhang Yaru , Li Jiajia , Fang Feng , Fu Wenhao 
Published: September 2021

Abstract
Background
With an increasing number of critically ill patients, attention should be paid to both their physical health and mental health. The objective of this study is to examine the links between depression and social capital among critically ill patients.

Methods
Data for 1043 patients with critical illnesses was collected with a stratified cluster random sampling method in rural Shandong, China. Depression symptoms were measured using a short form version of the Center for Epidemiologic Studies Depression Scale (CESD-10) and the total scores of them were dichotomized. We associated structural social capital with social networks, social participation, and social support. Cognitive social capital includes the degree of availability of social trust and reciprocity. Binary logistic regression was used to explore whether social capital was significantly associated with depression among patients with critical illnesses.

Results
We found that 68.5% of the critically ill patients in our sample population had depression. CESD-10 scores were negatively correlated with social capital, including occupations of their frequent contacts, social trust in relatives and friends, distance to the nearest medical institution and medical assistance convenience from non-spouse. In addition, low economic status, and low self-rated health were more significantly correlated with depression in critically ill patients.

Conclusions
Our findings suggest that more attention should be paid to the mental health of critically ill patients and more formal society, community and government support form given, particularly in rural China.
Validation of the Persian version of the Positive Mental Health Scale
Authors: Naghavi Azam , Teismann Tobias , Asgari Zahra , Eizadifard Razieh , Brailovskaia Julia 
Published: September 2021

Abstract
Background
Positive mental health (PMH) is a factor of far-reaching salutogenetic importance. The present study aimed at validating the Persian version of the Positive Mental Health Scale (PMH-Scale).

Methods
Reliability and validity of the Persian version of the PMH-Scale were established in an Iranian student sample (N = 573). Internal consistency, convergent and discriminant validity were investigated, and exploratory factor analysis was conducted. Furthermore, it was assessed how PMH scores moderate the association between depressive symptoms and suicide ideation/behavior.

Results
The Persian version of the PMH-Scale was shown to have a unidimensional structure with excellent internal consistency, as well as good convergent and divergent validity. PMH differentiated between participants with higher vs. lower suicide risk. Furthermore, PMH proved to moderate the association between depressive symptoms and suicide ideation/behavior.

Conclusions
The results suggest that the PMH-Scale is a brief, reliable, and valid measure of subjective and psychological well-being that can be used in Iranian student samples and research settings.
Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial
Authors: Wluka Anita E. , Urquhart Donna M. , Teichtahl Andrew J. , Hussain Sultana Monira , Forbes Andrew , Arnold Carolyn , Wang Yuanyuan , Cicuttini Flavia M. 
Published: September 2021

Abstract
Background
Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo.

Methods/design
One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done.

Discussion
This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record.

Trial registration
Australian New Zealand Clinical Trials Registry prior to recruitment commencing (ACTRN12615000301561, March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.
The epidemiology and etiology of adhesive capsulitis in the U.S. Medicare population
Authors: Sarasua Sara M. , Floyd Sarah , Bridges William C. , Pill Stephan G. 
Published: September 2021

Abstract
Background
Adhesive capsulitis (AC) of the shoulder, also known as frozen shoulder, causes substantial pain and disability. In cases of secondary AC, the inflammation and fibrosis of the synovial joint can be triggered by trauma or surgery to the joint followed by extended immobility. However, for primary AC the inciting trigger is unknown. The burden of the disorder among the elderly is also unknown leading to this age group being left out of therapeutic research studies, potentially receiving delayed diagnoses, and unknown financial costs to the Medicare system. The purpose of this analysis was to describe the epidemiology of AC in individuals over the age of 65, an age group little studied for this disorder. The second purpose was to investigate whether specific medications, co-morbidities, infections, and traumas are risk factors or triggers for primary AC in this population.

Methods
We used Medicare claims data from 2010–2012 to investigate the prevalence of AC and assess comorbid risk factors and seasonality. Selected medications, distal trauma, and classes of infections as potential inflammatory triggers for primary AC were investigated using a case–control study design with patients with rotator cuff tears as the comparison group. Medications were identified from National Drug codes and translated to World Health Organization ATC codes for analysis. Health conditions were identified using ICD9-CM codes.

Results
We found a one-year prevalence rate of AC of approximately 0.35% among adults aged 65 years and older which translates to approximately 142,000 older adults in the United States having frozen shoulder syndrome. Diabetes and Parkinson’s disease were significantly associated with the diagnosis of AC in the elderly. Cases were somewhat more common from August through December, although a clear seasonal trend was not observed. Medications, traumas, and infections were similar for cases and controls.

Conclusions
This investigation identified the burden of AC in the US elderly population and applied case–control methodology to identify triggers for its onset in this population. Efforts to reduce chronic health conditions such as diabetes may reduce seemingly unrelated conditions such as AC. The inciting trigger for this idiopathic condition remains elusive.