bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis: data from the osteoarthritis initiative
Authors: Harkey Matthew S. , Davis Julie E. , Price Lori Lyn , Ward Robert J. , MacKay James W. , Eaton Charles B. , Lo Grace H. , Barbe Mary F. , Zhang Ming , Pang Jincheng , Stout Alina C. , Lu Bing , McAlindon Timothy E. , Driban Jeffrey B. 
Published: May 2020

Abstract
Background
We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis.

Methods
We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone marrow lesion (BML) volume (four regions: medial/lateral tibia/femur), and whole knee effusion-synovitis volume on 3 T MR images with semi-automated programs. We calculated two MR-based composite scores. Cumulative damage was the sum of standardized cartilage damage. Disease activity was the sum of standardized volumes of effusion-synovitis and BMLs. We focused on annual images from 2 years before to 2 years after radiographic onset (or a matched time for those without knee osteoarthritis). To determine between group differences in the composite metrics at all time points, we used generalized linear mixed models with group (3 levels) and time (up to 5 levels). For our prognostic analysis, we used multinomial logistic regression models to determine if one-year worsening in each composite metric change associated with future accelerated knee osteoarthritis (odds ratios [OR] based on units of 1 standard deviation of change).

Results
Prior to disease onset, the accelerated KOA group had greater average disease activity compared to the typical and no KOA groups and this persisted up to 2 years after disease onset. During a pre-radiographic disease period, the odds of developing accelerated KOA were greater in people with worsening disease activity [versus typical KOA OR (95% confidence interval [CI]): 1.58 (1.08 to 2.33); versus no KOA: 2.39 (1.55 to 3.71)] or cumulative damage [versus typical KOA: 1.69 (1.14 to 2.51); versus no KOA: 2.11 (1.41 to 3.16)].

Conclusions
MR-based disease activity and cumulative damage metrics may be prognostic markers to help identify people at risk for accelerated onset and progression of knee osteoarthritis.
The human arthritic hip joint is a source of mesenchymal stromal cells (MSCs) with extensive multipotent differentiation potential
Authors: Wagenbrenner Mike , Heinz Tizian , Horas Konstantin , Jakuscheit Axel , Arnholdt Joerg , Herrmann Marietta , Rudert Maximilian , Holzapfel Boris M. , Steinert Andre F. , Weißenberger Manuel 
Published: May 2020

Abstract
Background
While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint.

Methods
MSCs were isolated and multiplied in adherent monolayer cell cultures. Osteogenesis and adipogenesis were induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ß1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes.

Results
This in vitro research showed that the isolated cells from all four donor tissues grew plastic-adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MSC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MSC-pellets, except for those from the LCF. Interestingly, all differentiated MSCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition, the examination of an exemplary selected donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis.

Conclusions
This study proved the presence of MSC-like cells in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MSCs used. Further research is necessary to fully determine the tripotent differentiation potential of cells isolated from the LCF and capsule tissue of the hip joint.
Surgical-only treatment of pancreatic and extra-pancreatic metastases from renal cell carcinoma - quality of life and survival analysis
Authors: Brozzetti Stefania , Bini Simone , De Lio Nelide , Lombardo Carlo , Boggi Ugo 
Published: May 2020

Abstract
Background
Treatment of pancreatic metastases (PM) from renal cell carcinoma (RCC) is still an issue between surgeons and oncologists, in the era of target-therapy.

Methods
Data from 26 patients undergoing resection of PM and extra-PM from RCC, with R0 intention were retrospectively analysed. No one received adjuvant chemotherapy. Patients were divided into two groups; Group A comprehends 14 patients who developed synchronous (5) or methacronous (9) extra-PM. Group B comprehends 12 patients that developed PM only.

Results
No intraoperative mortality was recorded. Complications occurred in 14 patients (53.8%), all but 2 (7.26%) were graded I and II according to Clavien-Dindo classification.
Recurrences occurred in 8 patients (30.8%), of whom, 5 (62.5%) were submitted for further resections in other sites.
Three-, five- and ten-year observed overall survival were respectively 88,5% [95%CI: 0,56 – 1,33], 76,9% [95%CI: 0,47 – 1,19] and 50% [95%CI: 0,20 – 1,03]. Disease-free survival was 65,4% [95%CI: 0,38 – 1,05], at 3 years, 57,7% [95%CI 0,323 – 0,952] at 5 years and 42,9% [95%CI 0,157 – 0,933], at 10 years. QoL analysis, through WHOQOL-BREF questionnaire, assessed at last available follow up revealed a mean score of 75,9 ± 11,6 on 100 points.

Conclusion
Despite no significant differences in survival between patients affected by Pancreatic or Extra-Pancreatic metastases, PM patients seems to show better outcome when managed surgically. mRCC patients, eligible for radical metastasectomy, tend to have long survival rates, reduced recurrence rates and good QoL.

Study registration
This paper was registered retrospectively in ClinicalTrials.gov with Identification number: NCT03670992.
Too much safety? Safeguards and equal access in the context of voluntary assisted dying legislation
Authors: McDougall Rosalind , Pratt Bridget 
Published: May 2020

AbstractBackgroundIn June 2019, the Australian state of Victoria joined the growing number of jurisdictions around the world to have legalised some form of voluntary assisted dying. A discourse of safety was prominent during the implementation of the Victorian legislation.Main textIn this paper, we analyse the ethical relationship between legislative “safeguards” and equal access. Drawing primarily on Ruger’s model of equal access to health care services, we analyse the Victorian approach to voluntary assisted dying in terms of four dimensions: horizontal equity, patient agency, high quality care, and supportive social norms. We argue that some provisions framed as safeguards in the legislation create significant barriers to equal access for eligible patients.ConclusionsWhile safety is undoubtedly ethically important, we caution against an overemphasis on safeguarding in voluntary assisted dying legislation given the implications for equal access.
Prospective monitoring of imaging guideline adherence by physicians in a surgical collaborative: comparison of statistical process control methods for detecting outlying performance
Authors:   for the Michigan Urological Surgery Improvement Collaborative (MUSIC), Inadomi Michael , Singh Karandeep , Qi Ji , Dunn Rodney , Linsell Susan , Denton Brian , Hurley Patrick , Kleer Eduardo , Montie James , Ghani Khurshid R. 
Published: May 2020

Abstract
Background
Systematic, automated methods for monitoring physician performance are necessary if outlying behavior is to be detected promptly and acted on. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we evaluated several statistical process control (SPC) methods to determine the sensitivity and ease of interpretation for assessing adherence to imaging guidelines for patients with newly diagnosed prostate cancer.

Methods
Following dissemination of imaging guidelines within the Michigan Urological Surgery Improvement Collaborative (MUSIC) for men with newly diagnosed prostate cancer, MUSIC set a target of imaging < 10% of patients for which bone scan is not indicated. We compared four SPC methods using Monte Carlo simulation: p-chart, weighted binomial CUSUM, Bernoulli cumulative sum (CUSUM), and exponentially weighted moving average (EWMA). We simulated non-indicated bone scan rates ranging from 5.9% (within target) to 11.4% (above target) for a representative MUSIC practice. Sensitivity was determined using the average run length (ARL), the time taken to signal a change. We then plotted actual non-indicated bone scan rates for a representative MUSIC practice using each SPC method to qualitatively assess graphical interpretation.

Results
EWMA had the lowest ARL and was able to detect changes significantly earlier than the other SPC methodologies (p < 0.001). The p-chart had the highest ARL and thus detected changes slowest (p < 0.001). EWMA and p-charts were easier to interpret graphically than CUSUM methods due to their ability to display historical imaging rates.

Conclusions
SPC methods can be used to provide informative and timely feedback regarding adherence to healthcare performance target rates in quality improvement collaboratives. We found the EWMA method most suited for detecting changes in imaging utilization.
Coronary heart disease and mortality following a breast cancer diagnosis
Authors: Guo Aixia , Zhang Kathleen W. , Reynolds Kristi , Foraker Randi E. 
Published: May 2020

Abstract
Background
Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

Methods
We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. The receipt of potentially cardiotoxic breast cancer treatments was indicated if the patient received anthracyclines or hormone therapies. We modeled the outcomes of post-cancer diagnosis CHD and death, respectively.

Results
Results of these approaches indicated that the joint effect of poor CVH and receipt of cardiotoxic treatments on CHD (75.9%) and death (39.5%) was significantly higher than their independent effects [poor CVH (55.9%) and cardiotoxic treatments (43.6%) for CHD, and poor CVH (29.4%) and cardiotoxic treatments (35.8%) for death].

Conclusions
Better CVH appears to be protective against the development of CHD even among women who had received potentially cardiotoxic treatments. This study determined the extent to which attainment of ideal CVH is important not only for CHD and mortality outcomes among women diagnosed with breast cancer.
Building collective power in citizen-led initiatives for health accountability in Guatemala: the role of networks
Authors: Hernández Alison , Hurtig Anna-Karin , Goicolea Isabel , San Sebastián Miguel , Jerez Fernando , Hernández-Rodríguez Francisco , Flores Walter 
Published: May 2020

Abstract
Background
Citizen-led accountability initiatives are a critical strategy for redressing the causes of health inequalities and promoting better health system governance. A growing body of evidence points to the need for putting power relations at the forefront of understanding and operationalizing citizen-led accountability, rather than technical tools and best practices. In this study, we apply a network lens to the question of how initiatives build collective power to redress health system failures affecting marginalized communities in three municipalities in Guatemala.

Methods
Network mapping and interpretive discussions were used to examine relational qualities of citizen-led initiatives’ networks and explore the resources they offer for mobilizing action and influencing health accountability. Participants in the municipal-level initiatives responded to a social network analysis questionnaire focused on their ties of communication and collaboration with other initiative participants and their interactions with authorities regarding health system problems. Discussions with participants about the maps generated enriched our view of what the ties represented and their history of collective action and also provided space for planning action to strengthen their networks.

Results
Our findings indicate that network qualities like cohesiveness and centralization reflected the initiative participants’ agency in adapting to their sociopolitical context, and participants’ social positions were a key resource in providing connection to a broad base of support for mobilizing collective action to document health service deficiencies and advocate for solutions. Their legitimacy as “representatives of the people” enabled them to engage with authorities from a bolstered position of power, and their iterative interactions with authorities further contributed to develop their advocacy capabilities and resulted in accountability gains.

Conclusions
Our study provided evidence to counter the tendency to underestimate the assets and capabilities that marginalized citizens have for building power, and affirmed the idea that best-fit, with-the-grain approaches are well-suited for highly unequal settings characterized by weak governance. Efforts to support and understand change processes in citizen-led initiatives should include focus on adaptive network building to enable contextually-embedded approaches that leverage the collective power of the users of health services and grassroots leaders on the frontlines of accountability.
HIV knowledge, risky behaviours and public health care services attendance among adolescents from the Grassroot soccer Zimbabwe programme
Authors: Mzingwane Mayibongwe Louis , Mavondo Greanious Alfred , Mantula Fennie , Mapfumo Claudinos , Gwatiringa Calleta , Moyo Bhekimpilo , Dube Primrose , Chaibva Cynthia Nombulelo 
Published: May 2020

Abstract
Background
Interventions aimed at improving accessing of health care services, including HIV testing, remain a priority in global HIV eradication efforts. Grassroot Soccer Zimbabwe (GRSZ) is an adolescent health organisation that uses the popularity of soccer to promote healthy behaviours. We assessed HIV knowledge levels, risky behaviours and attitudes in school going adolescents and young adults who attended GRSZ programmes and determined if HIV knowledge levels were associated with increased levels of accessing of health care services by youths.

Methods
This was a cross-sectional study carried out on 450 participants aged 13–30 years who attended at least one of the three programmes offered by GRSZ. Self-administered and self-reporting questionnaires were used to collect information on participants’ demographics, knowledge on HIV and reproductive health, sources of information, access to HIV and reproductive health services and attitudes and risky behaviours.

Results
A total of 392 (87.1%) responses were received. High HIV and reproductive health knowledge levels were recorded (77.7%) on our scale with females recording higher levels (81.1%) than males (71.1%). The majority of participants (72%) indicated willingness to abstain from risky behaviours such as use of drugs and attending youth sex parties. However about 33.3% of the participants who had sexual intercourse reported having condomless sex. There was marginal association between high HIV and reproductive health knowledge levels and accessing health care services in the past 24 months (p = 0.045).

Conclusions
HIV and reproductive health knowledge levels were relatively high among adolescents and were associated with accessing health care services in the past 24 months. There however are some gaps associated with engaging in risky sexual behaviours such as condomless sex which could be addressed by using these findings to assist organizations working with adolescents, educators and policy makers in developing programmes that address adolescent sexual behaviours.
Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy
Authors: Wang Shengwei , Cui Hao , Ji Keshan , Song Changpeng , Ren Changwei , Guo Hongchang , Zhu Changsheng , Wang Shuiyun , Lai Yongqiang 
Published: May 2020

Abstract
Background
Type 2 diabetes mellitus is common in cardiovascular disease. It is associated with adverse clinical outcomes for patients who had undergone coronary artery bypass and valve operations. The aim of this study was to evaluate the impact of type 2 diabetes mellitus on the midterm outcomes of patients with hypertrophic cardiomyopathy who underwent septal myectomy.

Methods
We retrospectively analyzed the data of 67 hypertrophic cardiomyopathy patients with type 2 diabetes mellitus who underwent septal myectomy from two medical centers in China from 2011 to 2018. A propensity score–matched cohort of 134 patients without type 2 diabetes mellitus was also analyzed.

Results
During a median follow-up of 28.0 (interquartile range: 13.0–3.0) months, 9 patients died. The cause of death of all of these patients was cardiovascular, particularly sudden cardiac death in 3 patients. Patients with type 2 diabetes mellitus had a higher rate of sudden cardiac death (4.5% vs. 0.0%, p = 0.04). The Kaplan–Meier survival analysis revealed that the rates of predicted 3-year survival free from cardiovascular death (98.1% vs. 95.1%, p = 0.14) were similar between the two groups. However, the rates of predicted 3-year survival free from sudden cardiac death (100% vs. 96.7%, p = 0.01) were significantly higher in hypertrophic cardiomyopathy patients without type 2 diabetes mellitus than in those with type 2 diabetes mellitus. Furthermore, after adjustment for age and sex, only N-terminal pro-brain natriuretic peptide (hazards ratio: 1.002, 95% confidence interval: 1.000–1.005, p = 0.02) and glomerular filtration rate ≤ 80 ml/min (hazards ratio: 3.23, 95% confidence interval: 1.34–7.24, p = 0.047) were independent risk factors for hypertrophic cardiomyopathy patients with type 2 diabetes mellitus.

Conclusions
Hypertrophic cardiomyopathy patients with and without type 2 diabetes mellitus have similar 3-year cardiovascular mortality after septal myectomy. However, type 2 diabetes mellitus is associated with higher sudden cardiac death rate in these patients. In addition, N-terminal pro-brain natriuretic peptide and glomerular filtration rate ≤ 80 ml/min were independent risk factors among hypertrophic cardiomyopathy patients with type 2 diabetes mellitus.
Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum
Authors: Ansbro Megan R. , Jacob Christopher G. , Amato Roberto , Kekre Mihir , Amaratunga Chanaki , Sreng Sokunthea , Suon Seila , Miotto Olivo , Fairhurst Rick M. , Wellems Thomas E. , Kwiatkowski Dominic P. 
Published: May 2020

Abstract
Background
Long regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of Plasmodium falciparum malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified single nucleotide polymorphisms as well as copy number variations in the plasmepsin 2 and plasmepsin 3 genes, which encode haemoglobin-degrading proteases that associate with clinical and in vitro piperaquine resistance.

Results
To accurately and quickly determine the presence of copy number variations in the plasmepsin 2/3 genes in field isolates, this study developed a quantitative PCR assay using TaqMan probes. Copy number estimates were validated using a separate SYBR green-based quantitative PCR assay as well as a novel PCR-based breakpoint assay to detect the hybrid gene product. Field samples from 2012 to 2015 across three sites in Cambodia were tested using DNA extracted from dried blood spots and whole blood to monitor the extent of plasmepsin 2/3 gene amplifications, as well as amplifications in the multidrug resistance transporter 1 gene (pfmdr1), a marker of mefloquine resistance. This study found high concordance across all methods of copy number detection. For samples derived from dried blood spots, a success rate greater than 80% was found in each assay, with more recent samples performing better. Evidence of extensive plasmepsin 2/3 copy number amplifications was observed in Pursat (94%, 2015) (Western Cambodia) and Preah Vihear (87%, 2014) (Northern Cambodia), and lower levels in Ratanakiri (16%, 2014) (Eastern Cambodia). A shift was observed from two copies of plasmepsin 2 in Pursat in 2013 to three copies in 2014–2015 (25% to 64%). Pfmdr1 amplifications were absent in all samples from Preah Vihear and Ratanakiri in 2014 and absent in Pursat in 2015.

Conclusions
The multiplex TaqMan assay is a robust tool for monitoring both plasmepsin 2/3 and pfmdr1 copy number variations in field isolates, and the SYBR-green and breakpoint assays are useful for monitoring plasmepsin 2/3 amplifications. This study shows increasing levels of plasmepsin 2 copy numbers across Cambodia from 2012 to 2015 and a complete reversion of multicopy pfmdr1 parasites to single copy parasites in all study locations.