bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study
Authors: El-Kadiry Abed El-Hakim , Lumbao Carlos , Salame Natasha , Rafei Moutih , Shammaa Riam 
Published: January 2022

Abstract
Background
Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP.

Methods
Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall).

Results
The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively).

Conclusions
Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections.

Graphical abstract
Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.
Two-year clinical and economic burden, risk and outcomes following application of software-assisted hexapod ring fixation systems
Authors: Reid J. Spence , Vanderkarr Mollie , Ray Bidusee , Chitnis Abhishek , Holy Chantal E. , Sparks Charisse 
Published: January 2022

Abstract
Background
Multiplanar external fixation systems that employ software-assisted deformity correction consist of rings connected by angled struts, defined as hexapod ring fixators (HRF). Costs and outcomes associated with the application of HRFs are not well documented. This study was designed to provide a nationwide baseline understanding of the clinical presentation, risks, outcomes and payer costs, and healthcare resource utilization (HCU) of patients requiring application of an HRF, from the day of, and up to 2 years, post-application.

Methods
Patients with HRF application (“index”) between 2007 and 2019 within the IBM Marketscan® Commercial Claims database were identified and categorized based on diagnosis: acquired deformity, arthropathy, congenital deformity, deep infection, nonunion, fracture, and other post-operative fracture sequelae. Demographics, comorbidities at index, complications post-index, HCU, and payments were analyzed. Payments were estimated using a generalized linear model and were adjusted for inflation to the 2020 consumer price index. Rates of deep infection and amputation were estimated up to 2 years post-index using Poisson regressions, and risk factors for each were estimated using logistic regression models.

Results
Six hundred ninety-five patients were included in our study (including 219 fractures, 168 congenital deformities, 68 deep infections, 103 acquired deformities). Comorbidities at index were significantly different across groups: less than 2% pediatrics vs 18% adults had 3 or more comorbidities, < 1% pediatric vs 29% adults had diabetes. Index payments ranged from $39,250–$75,350, with 12-months post-index payments ranging from $14,350 to $43,108. The duration of the HRF application ranged from 96 days to 174 days. Amputation was observed in patients with deep infection (8.9, 95% confidence interval (CI): 3.2–23.9%), nonunion (5.0, 95%CI: 1.6–15.4%) or fracture (2.7, 95%CI: 0.9–7.6%) at index. Complicated diabetes was the main predictor for deep infection (odds ratio (OR): 5.14, 95%CI: 2.50–10.54) and amputation (OR: 5.26, 95%CI: 1.79–15.51).

Conclusions
Findings from this longitudinal analysis demonstrate the significant heterogeneity in patients treated with HRF, and the wide range in treatment intensity, payments, and outcomes. Risks for deep infection and amputation were primarily linked to the presence of complicated diabetes at the time of HRF application, suggesting a need for careful management of comorbid chronic conditions in patients requiring HRF for orthopedic care.
Polymorphism of MMP-3 gene and imbalance expression of MMP-3 / TIMP-1 in articular cartilage are associated with an endemic osteochondropathy, Kashin- Beck disease
Authors: Shi Bohui , Guo Xiong , Iv Aili , Zhang Zengtie , Shi Xiaowei 
Published: January 2022

Abstract
Background
The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-3 (MMP-3) plays a central role in the initiation and progression of cartilage destruction, however, no study has reported on the relationship between KBD and MMP-3. The objective of this study was to explore the polymorphism of MMP-3 gene and expression of MMP-3 / TIMP-1(Tissue inhibitors of matrixmetalloproteinases-1) in the pathogenesis of KBD.

Methods
Single nucleotide polymorphism (SNP) genotyping was conducted in 274 KBD cases and 248 healthy controls for eight SNPs in MMP-3 using the Sequenom MassARRAY system. Additionally, the expression of MMP-3、TIMP-1 in different layers of the articular cartilage was analyzed by immunohistochemistry for 22 KBD patients, 15 osteoarthritis (OA) patients and 21 controls.

Results
The results showed that six SNPs (rs520540、rs591058、rs679620、rs602128、rs639752 and rs678815) in MMP-3 were associated with the increased risk of KBD, however, after Bonferroni correction, only the SNP rs679620 in the recessive model remained significant difference (OR = 2.31, 95%CI = 1.29–4.14, P = 0.0039), homozygous for “T” allele have a risk for KBD than “C” allele carriers. Moreover, the percentages of cells expressing MMP-3 in articular cartilage were significantly higher in the KBD and OA groups than in the controls (t = 5.37 and 4.19, P<0.01). While the KBD and OA groups had lower levels of TIMP-1 positive staining compared with the controls (t = 5.23and 5.06, P<0.01). And there was no significant different between KBD and OA for the levels of MMP-3 and TIMP-1 positive staining (t = 0.05and 0.28, P>0.05).

Conclusions
MMP-3 is associated with the susceptibility of KBD, and the imbalance expression of MMPs / TIMPs leading to cartilage degradation may play an important role in cartilage degradation and osteoarthritis formation in OA and KBD.
Complexities of interprofessional identity formation in dental hygienists: an exploratory case study
Authors: Imafuku Rintaro , Nagatani Yukiko , Yamada Saeko 
Published: January 2022

Abstract
Background
In a super-aging society, medical-dental collaboration is increasingly vital for comprehensive patient care. Particularly in dysphagia rehabilitation and perioperative oral functional management, dental hygienists’ active involvement is pivotal to interprofessional collaborative practice. Despite this societal expectation, dental hygienists’ experiences and perceptions of interprofessional collaboration have not been explored. This study aims to investigate dental hygienists’ interprofessional identity formation and perceptions of interprofessional collaboration. Specifically, it was explored from the perspectives of dental hygiene students and hospital dental hygienists.

Methods
This study is underpinned by Wenger’s social theory of learning, which focuses on identity as a component in the process of learning in communities. Semi-structured interviews were conducted with 11 dental hygiene students in their final year at a technical college and five dental hygienists engaging in interprofessional care at a university hospital in Japan. The narrative data were analysed using an inductive approach to thematic analysis to extract themes regarding the identification of self in interprofessional teams.

Results
Dental hygiene students found several barriers to the collaboration, including power relation and conceptual hierarchy, limited understanding of other professional roles, and differences in language and jargon. They viewed themselves as inferior in the interprofessional team. This resulted from their limited knowledge about general health and less responsibility for problems directly related to patient life and death. However, they could ultimately perceive the negative experiences positively as challenges for the future through reflection on learning in clinical placements. Contrarily, dental hygienists did not have such negative perceptions as the students did. Rather, they focused on fulfilling their roles as dental professionals in the interprofessional team. Their identities were formed through actively involving, coordinating their activity, and creating new images of the world and self in inter-professional communities of practice.

Conclusions
Interprofessional identity is relational as well as experiential, which is developed in complex and socially dynamic processes across intra- and inter-professional communities of practice. Engagement, imagination, and alignment are essential aspects of their interprofessional identities, which inform conceptual foundations of interprofessional education and collaborative practice in health care.
Mannheimia haemolytica serovars associated with respiratory disease in cattle in Great Britain
Authors: Mason Colin , Errington Jane , Foster Geoffrey , Thacker Jennifer , Grace Oliver , Baxter-Smith Katharine 
Published: January 2022

Abstract
Background
Mannheimia haemolytica is commonly associated with respiratory disease in cattle worldwide as a cause of fibrinous pneumonia, bronchopneumonia and pleuritis. M. haemolytica is further subdivided into 12 serovars, however not all are considered to be pathogenic in cattle. The study aim was to determine the most common serovars of M. haemolytica associated with respiratory disease in cattle in Great Britain, which is currently unknown and could be useful information for clinicians when considering preventative strategies.

Results
One hundred four M. haemolytica isolates isolated from bovine clinical pathology and post-mortem samples from pneumonia cases between 2016 and 2018 were tested using a multiplex PCR assay to identify M. haemolytica serovars A1, A2 and A6. 46 isolates (44.2%) typed as M. haemolytica serovar A1, 31 (29.8%) as M. haemolytica serovar A2 and 18 isolates (17.3%) as M. haemolytica serovar A6. Nine isolates (8.7%) were not A1, A2 or A6 so were considered to belong to other serovars or were not typable.

Conclusion
This study highlights the importance of M. haemolytica serovars other than A1 which may be responsible for respiratory disease in cattle and could help guide the veterinarian when making choices on preventative vaccination programmes.
A genomic mutation spectrum of collecting duct carcinoma in the Chinese population
Authors: Zhang Huaru , Lu Xiaojun , Huang Gang , Hua Meimian , Zhang Wenhui , Wang Tao , Huang Liqun , Wang Ziwei , Chen Qing , Li Jing , Yang Qing , Yang Guosheng 
Published: January 2022

AbstractBackgroundRenal collecting duct carcinoma (CDC) is a rare and lethal subtype of renal cell carcinoma (RCC). The genomic profile of the Chinese population with CDC remains unclear. In addition, clinical treatments are contradictory. In this study, we aimed to identify the genomic mutation spectrum of CDC in the Chinese population.MethodsWhole-exome sequencing was performed using the Illumina Novaseq™ 6000 platform. MuTect2 detects single-nucleotide variants (SNVs) and small scale insertions/deletions (INDELs). The identified mutations were annotated with ANNOVAR and validated by Sanger sequencing. Control-FREEC was used to detect copy number variation (CNV), and GISTIC was applied to detect frequently mutated altered regions. These data were compared with associated The Cancer Genome Atlas cohorts.ResultsTen normal-matched CDC patients were included. The mean tumour mutation burden was 1.37 Mut/Mb. Six new recurrent somatic mutated genes were identified, includingRBM14,MTUS1,GAK,DST,RNF213andXIRP2(20% and 2 of 10, respectively), and validated by Sanger sequencing. In terms of common mutated genes,SETD2was altered in both CDC and other RCC subtypes but not in bladder urothelial carcinoma (BLCA);CDKN2Awas a driver gene in both CDC (SNV: 10%, 1 of 10) and BLCA but not in other RCC subtypes. Next, 29 amplifications and 6 deletions of recurrent focal somatic CNVs were identified by GISTIC2.0, which displayed differences from kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and BLCA cohorts. Of note,CDKN2A(CNV alteration: 30%, 3 of 10) andCDKN2A-AS1were the only overlapping genes of these four cohorts. Importantly, theCDKN2Amutation in our cohort differed from previous studies in urinary carcinomas. Moreover,CDKN2A-altered cases had significantly worse overall survival than wild-type cases in both KIRC and KIRP cohorts. In addition, the most frequently altered genomic pathway of our CDC cohort was theCDKN2A-mediated p53/RB1 pathway.ConclusionsOur study offers the first genomic spectrum of the Chinese population with CDC, which differs from that of the Western population. The alteredCDKN2A-mediated p53/RB1 pathway might provide new insight into potential therapeutic targets for CDC patients.
On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial
Authors: Jiang Tao , Chen Jianhua , Xu Xingxiang , Cheng Ying , Chen Gongyan , Pan Yueyin , Fang Yong , Wang Qiming , Huang Yunchao , Yao Wenxiu , Wang Rui , Li Xingya , Zhang Wei , Zhang Yanjun , Hu Sheng , Guo Renhua , Shi Jianhua , Wang Zhiwu , Cao Peiguo , Wang Donglin , Fang Jian , Luo Hui , Geng Yi , Xing Chunyan , Lv Dongqing , Zhang Yiping , Yu Junyan , Cang Shundong , Zhang Yaxi , Zhang Jiao , Yang Zeyu , Shi Wei , Zou Jianjun , Zhou Caicun , Ren Shengxiang 
Published: January 2022

Abstract
Background
Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown.

Methods
Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values.

Results
Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy.

Conclusion
On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC.

Trial registration
ClinicalTrials.gov identifier: NCT03668496.
Fit for purpose. Co-production of complex behavioural interventions. A practical guide and exemplar of co-producing a telehealth-delivered exercise intervention for people with stroke
Authors: Ramage Emily R. , Burke Meredith , Galloway Margaret , Graham Ian D. , Janssen Heidi , Marsden Dianne L. , Patterson Amanda J. , Pollack Michael , Said Catherine M. , Lynch Elizabeth A. , English Coralie 
Published: January 2022

Abstract
Background
Careful development of interventions using principles of co-production is now recognized as an important step for clinical trial development, but practical guidance on how to do this in practice is lacking. This paper aims (1) provide practical guidance for researchers to co-produce interventions ready for clinical trial by describing the 4-stage process we followed, the challenges experienced and practical tips for researchers wanting to co-produce an intervention for a clinical trial; (2) describe, as an exemplar, the development of our intervention package.

Method
We used an Integrated Knowledge Translation (IKT) approach to co-produce a telehealth-delivered exercise program for people with stroke. The 4-stage process comprised of (1) a start-up planning phase with the co-production team. (2) Content development with knowledge user informants. (3) Design of an intervention protocol. (4) Protocol refinement.

Results and reflections
The four stages of intervention development involved an 11-member co-production team and 32 knowledge user informants. Challenges faced included balancing conflicting demands of different knowledge user informant groups, achieving shared power and collaborative decision making, and optimising knowledge user input. Components incorporated into the telehealth-delivered exercise program through working with knowledge user informants included: increased training for intervention therapists; increased options to tailor the intervention to participant’s needs and preferences; and re-naming of the program. Key practical tips include ways to minimise the power differential between researchers and consumers, and ensure adequate preparation of the co-production team.

Conclusion
Careful planning and a structured process can facilitate co-production of complex interventions ready for clinical trial.

﻿Graphical Abstract
Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system
Authors: Wen Guanmei , Yao Leyi , Hao Yali , Wang Jinheng , Liu Jinbao 
Published: January 2022

AbstractAtherosclerosis is a chronic inflammatory disease caused mainly by lipid accumulation and excessive inflammatory immune response. Although the lipid-lowering and cardioprotective properties of bilirubin, as well as the negative relationship between bilirubin and atherosclerosis, were well documented, it is not yet clear whether bilirubin can attenuate atherosclerosis in vivo. In this study, we investigated the role of bilirubin in improving atherosclerosis. We found that mildly elevated bilirubin significantly reduced the risk factors of atherosclerosis, such as plasma glucose, total cholesterol, and low-density lipoprotein cholesterol, and the formation of atherosclerotic plaques, liver total cholesterol, and cholesterol ester concentration in apolipoprotein E-deficient (ApoE−/−) mice fed a western-type (high fat) diet. It was further found that bilirubin could promote the degradation of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), a rate-limiting enzyme for endogenous cholesterol synthesis. Using mass cytometry-based high dimensional single cell analysis, we observed a decrease of natural killer cells and an increase of dendritic cells and myeloid-derived suppressor cells, which all are closely associated with atherosclerosis risk factors and contribute to the improvement of atherosclerosis, in ApoE−/− mice treated with bilirubin. By in-depth analysis, modulation of multiple spleen or peripheral blood T cell clusters exhibiting either positive or negative correlations with total cholesterol or low-density lipoprotein cholesterol was detected after bilirubin treatment. In this study, we demonstrate that bilirubin serves as a negative regulator of atherosclerosis and reduces atherosclerosis by inhibiting cholesterol synthesis and modulating the immune system.
Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region
Authors: Ge Zhuowang , Yin Chengye , Li Yingze , Tian Ding , Xiang Yin , Li Qianhui , Tang Yong , Zhang Yachen 
Published: January 2022

AbstractCardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-β1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.