bluuebunny/crossref_metadata_2025_split huggingface dataset:
A minimal clinically important difference measured by the Cambridge Pulmonary Hypertension Outcome Review for patients with idiopathic pulmonary arterial hypertension
Authors: Bunclark Katherine , Doughty Natalie , Michael Alice , Abraham Nisha , Ali Samantha , Cannon John E , Sheares Karen , Speed Nicola , Taboada Dolores , Toshner Mark , Pepke‐Zaba Joanna 
Published: February 2021

Several patient‐reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to the individual, however remain unknown. We sought to identify minimal clinically important differences in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and to validate these against objective markers of functional capacity. Minimal clinically important differences were established from a discovery cohort (n = 129) of consecutive incident cases of idiopathic pulmonary arterial hypertension with CAMPHOR scores recorded at treatment‐naïve baseline and 4–12 months following pulmonary arterial hypertension therapy. An independent validation cohort (n = 87) was used to verify minimal clinically important differences. Concurrent measures of functional capacity relative to CAMPHOR scores were collected. Minimal clinically important differences were derived using anchor‐ and distributional‐based approaches. In the discovery cohort, mean (SD) was 54.4 (16.4) years and 64% were female. Most patients (63%) were treated with sequential pulmonary arterial hypertension therapy. Baseline CAMPHOR scores were: Symptoms, 12 (7); Activity, 12 (7) and quality of life, 10 (7). Pulmonary arterial hypertension treatment resulted in significant improvements in CAMPHOR scores (p < 0.05). CAMPHOR minimal clinically important differences averaged across methods for health status improvement were: Symptoms, –4 points; Activity, –4 points and quality of life –3 points. CAMPHOR Activity score change ≥minimal clinically important difference was associated with significantly greater improvement in six‐minute walk distance, in both discovery and validation populations. In conclusion, CAMPHOR scores are responsive to pulmonary arterial hypertension treatment. Minimal clinically important differences in pulmonary hypertension‐specific scales may provide useful insights into treatment response in future clinical trials.
CoachMS, an innovative closed-loop, interdisciplinary platform to monitor and proactively treat MS symptoms: A pilot study
Authors: Block Valerie J , Gopal Arpita , Rowles William , -Yueh Chu , Gelfand Jeffrey M , Bove Riley 
Published: February 2021

Background There are numerous challenges to treating co-occurring symptoms in multiple sclerosis (MS). Objective To pilot the feasibility of a novel symptom management platform, CoachMS, to monitor MS symptoms (bladder function, ambulation, and mood: BAM) and respond to changes in real-time. Methods In this 12-week randomized controlled pilot trial, participants’ symptoms were monitored using weekly questionnaires and remote ambulatory monitoring (Fitbit Flex2®). Behavioral change principles used included shared goal setting at 2 weeks. Between weeks 2-12, the CoachMS group received targeted contact and interventions if symptoms worsened; the control group were treated through usual clinic practice. Our outcomes were feasibility (retention, adherence and acceptability; primary) and proportion of recommended treatments pursued (secondary); efficacy was explored. Results Of 21 participants enrolled, 13 (62%) completed the study; protocol adherence was excellent. CoachMS participants demonstrated greater follow-through with clinical recommendations than controls (OR 9.3, 95% CI (0.9, 97.6)). As a cohort, each BAM symptom tended to improve. Suicidality was detected in one control participant, resulting in urgent evaluation and hospitalization. Conclusions The innovative CoachMS platform was feasible and acceptable in this cohort with baseline BAM symptoms. It could represent an accessible, cost-effective tool to monitor MS symptoms in real-time; a larger trial is planned.
Trends and determinants of HIV transmission among men who inject drugs in the Pokhara Valley, Nepal: analysis of cross-sectional studies
Authors: Hogan Sam , Page Andrew , Ogbo Felix , Dixit Sameer , Rajbhandari Rajesh Man , Rawal Bir , Deuba Keshab 
Published: February 2021

Abstract
Background
HIV is a major public health issue around the world, especially in developing countries. Although the overall prevalence of HIV in Nepal is relatively low, there are specific sub-populations where the prevalence is far higher than the national average. One of these sub-groups is male people who inject drugs (male PWIDs). In order to understand the reasons for the differences in prevalence, a series of socio-demographic, behavioural and knowledge-based risk factors need to be assessed.

Methods
The study used a series of 7 cross-sectional survey datasets from Pokhara (Nepal), collected between 2003 and 2017 (N = 2235) to investigate trends in HIV prevalence among male PWIDs by socio-demographic and behavioural and knowledge-based risk factors. A series of logistic regression models were conducted to investigate the association between study factors and HIV.

Results
HIV prevalence decreased from the levels seen in 2003 (22.0%) and 2005 (21.7%), with the lowest prevalence recorded in 2015 (2.6%), however prevalence has increased in the most recent period (4.9%). A lower risk of HIV was associated with younger age (<=24 years compared to > 24 years, OR = 0.17, 95% CI = 0.10–0.31), being married (OR = 1.91, 95% CI = 1.25–3.02) and shorter duration of drug use (<=4 years compared to > 4 years, OR = 0.16, 95% CI = 0.09–0.29). A higher risk of HIV was associated with low (compared to secondary or higher) education level (OR = 2.76, 95% CI = 1.75–4.36), a lack of addiction treatment (OR = 2.59, 95% CI = 1.64–4.08), and recent use of unsterilized injection equipment (OR = 2.22, 95% CI = 1.20–4.11).

Conclusion
The prevalence of HIV in male PWIDs in Pokhara has been variable, but overall has reduced in recent years to 2.6% before increasing in 2017 to 4.9%. The main determinants which increase the risk of HIV among male PWIDs in Pokhara are low education level, a lack of treatment for drug addiction and the recent use of unsterilised equipment. Each of these indicate the need to improve addiction treatment and education programs for intra-venous drug use to aid this key population in avoiding risk-taking behaviours.
Inspiring the future generation of oncologists: a UK-wide study of medical students’ views towards oncology
Authors: Rallis Kathrine S. , Wozniak Anna Maria , Hui Sara , Nicolaides Marios , Shah Neha , Subba Beena , Papalois Apostolos , Sideris Michail 
Published: February 2021

Abstract
Background
One in 2 people born in the UK after 1960 are expected to require oncology input in their lifetime. However, only 36% of UK medical schools provide dedicated oncology placements and teaching indicating a discordance between public health impact and training. We designed a UK-wide survey to capture medical students’ views on current oncology teaching and the potential role of a national undergraduate oncology symposium as an educational, networking and motivational tool.

Methods
We undertook a national cross-sectional survey of UK medical students’ views in oncology and satisfaction with teaching using pre-designed questionnaires. We also distributed a dedicated survey (pre and post-conference) to compare medical students’ motivation towards a career in oncology after attending the national symposium. This study was prospectively approved by QMUL Ethics Committee (Reference number QMREC2348). Statistical analysis included univariate inferential tests on SPSS and GraphPad software.

Results
The national survey was completed by 166 students representing 22 UK medical schools. Students reported limited interest, knowledge and exposure to oncology, lack of confidence in skills, and teaching dissatisfaction. Oncology was perceived as a challenging specialty (mean 4.5/5 ± 0.7), yet most students estimate receiving only 1–2 weeks of dedicated oncology teaching. The national symposium generated a statically significant increase in students’ interest, knowledge, and confidence in skills surrounding oncology, improving students’ perceived ability to cope with the emotional challenges in this field.

Conclusion
Students’ views towards oncology alongside their teaching dissatisfaction underpin the need to revisit and strive to improve current undergraduate oncology curricula. Increasing medical student oncology exposure by proposing outcome-based guidelines and adopting a standardised undergraduate oncology curriculum should be the foremost priority in inspiring future oncologists to ensure excellent cancer patient care.
Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA
Authors: Paolisso Pasquale , Foà Alberto , Bergamaschi Luca , Donati Francesco , Fabrizio Michele , Chiti Chiara , Angeli Francesco , Toniolo Sebastiano , Stefanizzi Andrea , Armillotta Matteo , Rucci Paola , Iannopollo Gianmarco , Casella Gianni , Marrozzini Cinzia , Galiè Nazzareno , Pizzi Carmine 
Published: February 2021

Abstract
Background
Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA.

Methods
Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF).

Results
The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients—obs-AMI and MINOCA—NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI (p < 0.001), a larger LVEDV (p = 0.003) and a lower LVEF (p < 0.001) compared to normoglycemic ones. Conversely, MINOCA patients showed a trivial myocardial damage, irrespective of admission glucose levels.

Conclusions
Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.
Effect of different thermal stimuli on improving microcirculation in the contralateral foot
Authors: Ren Weiyan , Xu Liqiang , Zheng Xuan , Pu Fang , Li Deyu , Fan Yubo 
Published: February 2021

Abstract
Background
The lower extremities of the body often suffer from impaired microcirculation, particularly in the elderly or people with underlying conditions such as diabetes. Especially for people suffering from peripheral vascular diseases, skin lesions or wearing an external fixator in one side of limbs, direct contact treatments are not suitable for them to improve microcirculation. Heating the contralateral limb has been reported to improve blood flow in the impaired limb. However, its effect on plantar microvascular responses has not been previously investigated. Thus, the aim of this study was to explore how heating by warm bath and infrared radiation affects the circulations in the contralateral foot. Twelve healthy adults participated in this study and were randomly assigned to either placing the left foot in a warm bath or exposing it to infrared radiation for 10 min intervention every other day. The skin temperature (Temp) and skin blood flow (SBF) in the second metatarsal head of the contralateral foot were measured before and after the intervention.

Results
The results showed that both Temp (Bath: from 29.05 ± 3.56 °C to 31.03 ± 4.14 °C; Infrared: from 29.98 ± 3.86 °C to 31.07 ± 3.92 °C) and SBF (Bath: from 62.26 ± 48.12 PU to 97.76 ± 63.90 PU; Infrared: from 63.37 ± 39.88 PU to 85.27 ± 47.62 PU) in the contralateral foot were significantly increased after heating in both tests (p < 0.05). However, the contralateral SBF increased for 5 min after heating in warm bath test, but only for 1 min in infrared radiation test.

Conclusions
The results of this study show that both heating methods are the effective at increasing contralateral Temp and SBF, but the warm bath has a stronger residual thermal effect.
The cannabinoid receptor CB1 affects the proliferation and apoptosis of adenomyotic human uterine smooth muscle cells of the junctional zone: a mechanism study
Authors: Wang Sha , Li Bohan , Shen Xue , Duan Hua , Guo Zhengchen , Li Xiao , Sun Fuqing 
Published: February 2021

AbstractBackgroundThe denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis.MethodsJZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation.ResultsWe demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2.ConclusionsOur results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling.
The potential role of chemotaxis and the complement system in the formation and progression of thoracic aortic aneurysms inferred from the weighted gene coexpression network analysis
Authors: Lei Chuxiang , Yang Dan , Chen Wenlin , Kan Haoxuan , Xu Fang , Zhang Hui , Wang Wei , Ji Lei , Zheng Yuehong 
Published: February 2021

AbstractBackgroundThoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks.MethodsWe analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm.ResultsWe identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis.CX3CR1,C3, andC3AR1were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells.ConclusionChemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.
Mid-term results of bilateral synchronous total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis
Authors: Han Lei , Quan Renfu , Pei Zhenle , Cao Guoping , Hu Yungen , Liu Jingjing 
Published: February 2021

Abstract
Background
Total hip arthroplasty (THA) for bony ankylosis is technically challenging in patients with ankylosing spondylitis (AS). This study aimed to determine the mid-term results of bilateral synchronous THA for bony ankylosis in patients with AS.

Methods
Nineteen cases of bony ankylosis in patients with AS who received bilateral synchronous THA were included in this study (17 males and 2 females, mean age 49.2 years). Disease duration was 5–38 years (mean 18 years and 6 months). All patients received cementless THA. Intraoperative blood loss, visual analog scale (VAS) score, and complications were assessed. Harris hip scores evaluated the clinical effect.

Results
Patients were followed up for 62–98 months (mean 82.5 months). VAS score decreased from 7.42 ± 0.92 to 2.42 ± 0.83, Harris hip score improved from 21.8 ± 7.2 to 80.3 ± 6.5, and the flexion-extension range of the hip improved from 0 to 142.3 ± 6.2°. One patient with septum bronchiale had a fracture intraoperatively and was treated with wire strapping. One patient had a traction injury of the femoral nerve postoperatively and recovered 1 year after the operation. Loosening and subsidence were not observed in all patients. Heterotopic bone formation was noted in 3 patients. No complications such as joint dislocation, acute infection, and deep vein thrombosis were found.

Conclusion
Bilateral synchronous THA was effective for bony ankylosis of the hip in patients with AS because it improved patients’ quality of life and had satisfactory mid-term outcomes.
Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2
Authors: Li Yuan , Liu Yanping , Guo Qiang 
Published: February 2021

AbstractCartilage defects frequently occur around the knee joint yet cartilage has limited self-repair abilities. Hydrogel scaffolds have excellent potential for use in tissue engineering. Therefore, the aim of the present study was to assess the ability of silk fibroin (SF) hydrogel scaffolds incorporated with chitosan (CS) nanoparticles (NPs) to repair knee joint cartilage defects. In the present study, composite systems of CS NPs incorporated with transforming growth factor-β1 (TGF-β1; TGF-β1@CS) and SF incorporated with bone morphogenetic protein-2 (BMP-2; TGF-β1@CS/BMP-2@SF) were developed and characterized with respect to their size distribution, zeta potential, morphology, and release of TGF-β1 and BMP-2. Bone marrow stromal cells (BMSCs) were co-cultured with TGF-β1@CS/BMP-2@SF extracts to assess chondrogenesis in vitro using a cell counting kit-8 assay, which was followed by in vivo evaluations in a rabbit model of knee joint cartilage defects. The constructed TGF-β1@CS/BMP-2@SF composite system was successfully characterized and showed favorable biocompatibility. In the presence of TGF-β1@CS/BMP-2@SF extracts, BMSCs exhibited normal cell morphology and enhanced chondrogenic ability both in vitro and in vivo, as evidenced by the promotion of cell viability and the alleviation of cartilage defects. Thus, the TGF-β1@CS/BMP-2@SF hydrogel developed in the present study promoted chondrogenic ability of BMSCs both in vivo and in vitro by releasing TGF-β1 and BMP-2, thereby offering a novel therapeutic strategy for repairing articular cartilage defects in knee joints.
Development of new 9-ball test protocols for assessing expertise in cue sports
Authors: Pan Jing Wen , Komar John , Kong Pui Wah 
Published: February 2021

Abstract
Background
This study aimed to develop new test protocols for evaluating 9-ball expertise levels in cue sports players.

Methods
Thirty-one male 9-ball players at different playing levels were recruited (recreational group, n = 8; university team, n = 15; national team, n = 8). A 15-ball test was administered to indicate overall performance by counting the number of balls potted. Five skill tests (power control, cue alignment, angle, back spin, and top spin) were conducted to evaluate specific techniques by calculating error distances from pre-set targets using 2D video analysis.

Results
Intra-class correlation analyses revealed excellent intra-rater and inter-rater reliability in four out of five skill tests (ICC > 0.95). Significant between-group differences were found in 15-ball test performance (p <  0.001) and absolute error distances in the angle (p <  0.001), back spin (p = 0.006), and top spin tests (p = 0.045), with the recreational group performing worst while the national team performing best. Greater inter-trial variability was observed in recreational players than the more skilled players (p <  0.005).

Conclusions
In conclusion, the 9-ball test protocols were reliable and could successfully discriminate between different playing levels. Coaches and researchers may employ these protocols to identify errors, monitor training, and rank players.
Microbial diversity characterization of seawater in a pilot study using Oxford Nanopore Technologies long-read sequencing
Authors: Liem M. , Regensburg-Tuïnk T. , Henkel C. , Jansen H. , Spaink H. 
Published: February 2021

Abstract
Objective
Currently the majority of non-culturable microbes in sea water are yet to be discovered, Nanopore offers a solution to overcome the challenging tasks to identify the genomes and complex composition of oceanic microbiomes. In this study we evaluate the utility of Oxford Nanopore Technologies (ONT) sequencing to characterize microbial diversity in seawater from multiple locations. We compared the microbial species diversity of retrieved environmental samples from two different locations and time points.

Results
With only three ONT flow cells we were able to identify thousands of organisms, including bacteriophages, from which a large part at species level. It was possible to assemble genomes from environmental samples with Flye. In several cases this resulted in > 1 Mbp contigs and in the particular case of a Thioglobus singularis species it even produced a near complete genome. k-mer analysis reveals that a large part of the data represents species of which close relatives have not yet been deposited to the database. These results show that our approach is suitable for scalable genomic investigations such as monitoring oceanic biodiversity and provides a new platform for education in biodiversity.