bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspirin for primary prevention of cardiovascular disease: a meta-analysis with a particular focus on subgroups
Authors: Gelbenegger Georg , Postula Marek , Pecen Ladislav , Halvorsen Sigrun , Lesiak Maciej , Schoergenhofer Christian , Jilma Bernd , Hengstenberg Christian , Siller-Matula Jolanta M. 
Published: November 2019

Abstract

Background
The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups.

Methods
Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed.

Results
Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93–1.02; RR 0.99; 95% CI, 0.90–1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86–0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77–0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82–0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30–1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, − 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80–0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82–0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83–0.95), with a non-significant effect in females.

Conclusions
Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups.

Systematic review registration
PROSPERO CRD42019118474.
A 3-circular RNA signature as a noninvasive biomarker for diagnosis of colorectal cancer
Authors: Ye Dao-xiong , Wang Si-si , Huang Ying , Chi Pan 
Published: November 2019

Abstract

Background
Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed.

Methods
CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs.

Results
Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis.

Conclusion
In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.
Does the inflammatory potential of diet affect disease activity in patients with inflammatory bowel disease?
Authors: Mirmiran Parvin , Moslehi Nazanin , Morshedzadeh Nava , Shivappa Nitin , Hébert James R. , Farsi Farnaz , Daryani Naser Ebrahimi 
Published: November 2019

Abstract

Background
Diet is an important modulator of inflammation, which is associated with inflammatory bowel disease (IBD). In this study, we examined whether the inflammatory properties of diets are associated with disease activity in patients with IBD.

Methods
A cross-sectional study was conducted on 143 IBD patients, including 32 patients with Crohn’s disease (CD) and 111 patients with ulcerative colitis (UC). Dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The inflammatory potential of the diet was assessed by calculating the two scores of Dietary Inflammatory Index (DII®), and the Empirical Dietary Inflammatory Pattern (EDIP), and CD and UC disease activity were determined by the Crohn’s disease activity index (CDAI) and the Mayo score, respectively. Associations of the inflammatory indices as median and as tertiles with disease activity were analyzed using logistic regression in a univariate model and after adjusting for total energy intake (continuous), type of disease (CD and UC) and drug consumption (no drugs, single drug, and multiple drugs).

Results
Sixty-four IBD patients (44.8%) in this study had active disease.The DII® score and the EDIP did not differ significantly between active and inactive patients (− 1.45 ± 1.04 vs.− 1.20 ± 1.24; 0.56 ± 0.22 vs. 0.53 ± 0.28, respectively). After adjusting for energy intake, drug use, and IBD type, the odds (95%CIs) of active disease among patients in tertile 3 compared to those in tertile 1 were 0.84 (0.32–2.17) for DII and 1.50 (0.61–3.72) for EDIP; neither of which were statistically significantly different from the rates in tertile 1.

Conclusions
Although point estimates were in the expected direction of increased risk, the inflammatory potential of diet, assessed using DII or EDIP, was not associated with severity of disease in IBD patients. Whether diet-related inflammation affects disease activity in patients with IBD deserves further investigations.
Overcoming a travel burden to high-volume centers for treatment of retroperitoneal sarcomas is associated with improved survival
Authors: Schmitz Robin , Adam Mohamed A. , Blazer Dan G. 
Published: November 2019

Abstract

Background
Guidelines recommend treatment of retroperitoneal sarcomas (RPS) at high-volume centers. However, high-volume centers may not be accessible locally. This national study compared outcomes of RPS resection between local low-volume centers and more distant high-volume centers.

Methods
Patients treated for RPS were identified from the National Cancer Database (1998–2012). Travel distance and annual hospital volume were divided into quartiles. Two groups were identified: (1) short travel to low-volume hospitals (ST/LV), (2) long travel to high-volume hospitals (LT/HV). Outcomes were adjusted for clinical, tumor, and treatment characteristics.

Results
Two thousand five hundred ninety-nine patients met the inclusion criteria. The LT/HV cohort was younger and more often white (p < 0.01). The LT/HV group had more comorbidities, higher tumor grade, and more often radical resections and radiotherapy (all p < 0.05). The ST/LV group underwent significantly more R2 resections (4.4% vs. 2.6%, p = 0.003). Thirty-day mortality was significantly lower in the LT/HV group (1.2% vs. 2.8%, p = 0.0026). Five-year survival was better among the LT/HV group (63% vs. 53%, p < 0.0001). After adjustment, the LT/HV group had a 27% improvement in overall survival (HR 0.73, p = 0.0009).

Conclusions
This national study suggests that traveling to high-volume centers for the treatment of RPS confers a significant short-term and long-term survival advantage, supporting centralized care for RPS.
Detecting compensatory movements of stroke survivors using pressure distribution data and machine learning algorithms
Authors: Cai Siqi , Li Guofeng , Zhang Xiaoya , Huang Shuangyuan , Zheng Haiqing , Ma Ke , Xie Longhan 
Published: November 2019

Abstract

Background
Compensatory movements are commonly employed by stroke survivors during seated reaching and may have negative effects on their long-term recovery. Detecting compensation is useful for coaching the patient to reduce compensatory trunk movements and improving the motor function of the paretic arm. Sensor-based and camera-based systems have been developed to detect compensatory movements, but they still have some limitations, such as causing object obstructions, requiring complex setups and raising privacy concerns. To overcome these drawbacks, this paper proposes a compensatory movement detection system based on pressure distribution data and is unobtrusive, simple and practical. Machine learning algorithms were applied to classify compensatory movements automatically. Therefore, the purpose of this study was to develop and test a pressure distribution-based system for the automatic detection of compensation movements of stroke survivors using machine learning algorithms.

Methods
Eight stroke survivors performed three types of reaching tasks (back-and-forth, side-to-side, and up-and-down reaching tasks) with both the healthy side and the affected side. The pressure distribution data were recorded, and five features were extracted for classification. The k-nearest neighbor (k-NN) and support vector machine (SVM) algorithms were applied to detect and categorize the compensatory movements. The surface electromyography (sEMG) signals of nine trunk muscles were acquired to provide a detailed description and explanation of compensatory movements.

Results
Cross-validation yielded high classification accuracies (F1-score>0.95) for both the k-NN and SVM classifiers in detecting compensation movements during all the reaching tasks. In detail, an excellent performance was achieved in discriminating between compensation and noncompensation (NC) movements, with an average F1-score of 0.993. For the multiclass classification of compensatory movement patterns, an average F1-score of 0.981 was achieved in recognizing the NC, trunk lean-forward (TLF), trunk rotation (TR) and shoulder elevation (SE) movements.

Conclusions
Good classification performance in detecting and categorizing compensatory movements validated the feasibility of the proposed pressure distribution-based system. Reliable classification accuracy achieved by the machine learning algorithms indicated the potential to monitor compensation movements automatically by using the pressure distribution-based system when stroke survivors perform seated reaching tasks.
Implementation of a behavioral medicine approach in physiotherapy: a process evaluation of facilitation methods
Authors: Fritz Johanna , Wallin Lars , Söderlund Anne , Almqvist Lena , Sandborgh Maria 
Published: November 2019

Abstract

Background
In a quasi-experimental study, facilitation was used to support implementation of the behavioral medicine approach in physiotherapy. The facilitation consisted of an individually tailored multifaceted intervention including outreach visits, peer coaching, educational materials, individual goal-setting, video feedback, self-monitoring in a diary, manager support, and information leaflets to patients. A behavioral medicine approach implies a focus on health related behavior change. Clinical behavioral change was initiated but not maintained among the participating physiotherapists. To explain these findings, a deeper understanding of the implementation process is necessary. The aim was therefore to explore the impact mechanisms in the implementation of a behavioral medicine approach in physiotherapy by examining dose, reach, and participant experiences.

Methods
An explorative mixed-methods design was used as a part of a quasi-experimental trial. Twenty four physiotherapists working in primary health care were included in the quasi-experimental trial, and all physiotherapists in the experimental group (n = 15) were included in the current study. A facilitation intervention based mainly on social cognitive theory was tested during a 6-month period. Data were collected during and after the implementation period by self-reports of time allocation regarding participation in different implementation methods, documentation of individual goals, ranking of the most important implementation methods, and semi-structured interviews. Descriptive statistical methods and inductive content analysis were used.

Results
The physiotherapists participated most frequently in the following implementation methods: outreach visits, peer coaching, educational materials, and individual goal-setting. They also considered these methods to be the most important for implementation, contributing to support for learning, practice, memory, emotions, self-management, and time management. However, time management support from the manager was lacking.

Conclusions
The findings indicate that different mechanisms govern the initiation and maintenance of clinical behavior change. The impact mechanisms for initiation of clinical behavior change refers to the use of externally initiated multiple methods, such as feedback on practice, time management, and extrinsic motivation. The lack of self-regulation capability, intrinsic motivation, and continued support after the implementation intervention period were interpreted as possible mechanisms for the failure of maintaining the behavioral change over time.
Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
Authors: Beerepoot Shanice , Nierkens Stefan , Boelens Jaap Jan , Lindemans Caroline , Bugiani Marianna , Wolf Nicole I. 
Published: November 2019

AbstractMetachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies.
The work, goals, challenges, achievements, and recommendations of orphan medicinal product organizations in India: an interview-based study
Authors: Choudhury Mohua Chakraborty , Saberwal Gayatri 
Published: November 2019

AbstractBackgroundOrphan medicinal products (OMPs) are intended for the diagnosis, prevention, management or treatment of rare diseases (RDs). Each RD affects only a small fraction of the population,and therefore, historically, industry hesitated to undertake relevant research and development (R&D). In response, the governments of many countries came up with orphan drug policies and RD policies which were hugely successful in incentivizing companies to do so. In India, in the absence of any such policy until recently, there are very few organizations involved in RD R&D.ObjectivesWe wished to understand (i) the OMP Organizations’ (OMPOs’) areas of work and the nature of their work, (ii) their goals, (iii) the challenges they faced and how they were overcoming them, (iv) their achievements, and (v) their recommendations to the government to help their R&D, their success as commercial entities (where applicable), and patients’ access to their products or services.ResultsTen of the 14 OMPOs are companies, whereas four are not-for-profit organizations. Almost all of the OMPOs are heavily into R&D. Six have already made their products or services available to patients. Four plan to out-license their products after the pre-clinical phase or phase 1 trials, eight plan to cater to patients directly and two of the OMPOs have been established only recently and thus do not yet have any product or service to offer patients. Nine OMPOs import about 90% of the components in the production process, which comprises either capital or recurrent expenditure. For most, locally manufactured alternatives are not available or are of inadequate quality. Most of the OMPOs have had productive collaborations with local or foreign academics or hospitals for R&D, animal efficacy studies, clinical trials or providing services to patients. The main challenges for the OMPOs are the lack of adequate funding, supportive government policies, and a conducive ecosystem.ConclusionsThese OMPOs are pioneers in their respective fields in India, and despite the challenges, have achieved new levels of innovation. With suitable government policies, they could scale up and provide relevant products and services to the large number of RD patients in the country whose medical needs are largely unmet.
Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3
Authors: Li Quan-Fu , Dong Yi , Yang Lu , Xie Juan-Juan , Ma Yin , Du Yi-Chu , Cheng Hao-Ling , Ni Wang , Wu Zhi-Ying 
Published: November 2019

Abstract

Background
Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3.

Methods
Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements.

Results
Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = − 0.4217, p = 0.0003) and brainstem volumes (r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat.

Conclusions
Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.
Molecular cytogenetic analysis and genetic counseling: a case report of eight 46,XX males and a literature review
Authors: Yue Fagui , Zhang Hongguo , Xi Qi , Jiang Yuting , Li Leilei , Liu Ruizhi , Wang Ruixue 
Published: November 2019

AbstractBackground46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques.Case presentationWe identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of theSRYgene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygousDAX1mutation (c.498G > A, p.R166R), which was not previously reported inSRY-negative XX males.ConclusionsWe proposed that this synonymousDAX1mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended forSRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.