bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the continuity and coordination of ambulatory care through feedback and facilitated dialogue—a study protocol for a cluster-randomised trial to evaluate the ACD study (Accountable Care in Germany)
Authors: Sundmacher Leonie , Flemming Ronja , Leve Verena , Geiger Isabel , Franke Sebastian , Czihal Thomas , Krause Clemens , Wiese Birgitt , Meyer Frank , Brittner Matthias , Pollmanns Johannes , Martin Johannes , Brandenburg Paul , Schultz Annemarie , Brua Emmanuelle , Schneider Udo , Dortmann Olga , Rupprecht Christoph , Wilm Stefan , Schüttig Wiebke 
Published: September 2021

Abstract
Background
Patients in Germany are free to seek care from any office-based physician and can always ask for multiple opinions on a diagnosis or treatment. The high density of physicians and the freedom to choose among them without referrals have led to a need for better coordination between the multiple health professionals treating any given patient. The objectives of this study are to (1) identify informal networks of physicians who treat the same patient population, (2) provide these physicians with feedback on their network and patients, using routine data and (3) give the physicians the opportunity to meet one another in facilitated network meetings.

Methods
The Accountable Care Deutschland (ACD) study is a prospective, non-blinded, cluster-randomised trial comprising a process and economic evaluation of informal networks among 12,525 GPs and office-based specialists and their 1.9 million patients. The units of allocation are the informal networks, which will be randomised either to the intervention (feedback and facilitated meetings) or control group (usual care). The informal networks will be generated by identifying connections between office-based physicians using complete datasets from the Regional Associations of Statutory Health Insurance (SHI) Physicians in Hamburg, Schleswig Holstein, North Rhine and Westphalia Lip, as well as data from three large statutory health insurers in Germany. The physicians will (a) receive feedback on selected indicators of their own treatment activity and that of the colleagues in their network and (b) will be invited to voluntary, facilitated network meetings by their Regional Association of SHI physicians. The primary outcome will be ambulatory-care-sensitive hospitalisations at baseline, at the end of the 2-year intervention period, and at six months and at 12 months after the end of the intervention period. Data will be analysed using the intention-to-treat principle. A pilot study preceded the ACD study.

Discussion
Cochrane reviews show that feedback can improve everyday medical practice by shedding light on previously unknown relationships. Providing physicians with information on how they are connected with their colleagues and what the outcomes are of care delivered within their informal networks can help them make these improvements, as well as strengthen their awareness of possible discontinuities in the care they provide.

Trial registration
German Clinical Trials Register DRKS00020884. Registered on 25 March 2020—retrospectively registered.
Vaccine trials during a pandemic: potential approaches to ethical dilemmas
Authors: Alqahtani Manaf , Mallah Saad I. , Stevenson Nigel , Doherty Sally 
Published: September 2021

AbstractEver since the emergence of the coronavirus disease 2019 (COVID-19), global public health infrastructures and systems, along with community-wide collaboration and service, have risen to an unprecedented challenge. Vaccine development was immediately propelled to the centre of all our scientific, public health and community efforts. Despite the development of SARS-CoV-2 vaccines arguably being the greatest and most palpable achievements of the past 12 months, they have also been one of the most contentious and debated issues during the pandemic. However, what uniquely differentiates vaccine development is its intimate relationship with the community it seeks to serve; both in its clinical trial testing as an efficacious and safe prophylactic, and its post-developmental ‘roll-out’ success, as an effective public health tool. These relationships have birthed a myriad of complexities, from community-based mistrust, to academically contended ethical dilemmas. Indeed, the accelerated advances in the COVID-19 vaccine race have further exacerbated this phenomenon, bringing with it new ethical dilemmas that need to be examined to ensure the continued clinical success of these therapeutics and a renewed societal trust in clinical medicine.In this paper, we discuss two major ethical dilemmas: (1) the equipoise of continuing new vaccine trials in the advent of successful candidates and (2) the maleficence of blinded placebo arms. Accordingly, we discuss six different potential approaches to these ethical dilemmas: (1) continuing with placebo-controlled trials, (2) transitioning from placebo-controlled to open-label, (3) unblinding at-risk priority groups only, (4) transitioning to a blinded stepped-wedge cross-over design, (5) progressing to a blinded active-controlled stepped-wedge cross-over trial, and (6) conducting randomised stepped-wedge community trials. We also propose a decision-making algorithm for relevant stakeholders in advanced stages of vaccine trials.It is important to remember that the emergent nature of the COVID-19 situation does not justify a compromise on core ethical values. In fact, the discourse surrounding this topic and the decisions made will remain a potent case study and a continuously referenced example for all such future scenarios.
Presence of a cryptic Onchocerca species in black flies of northern California, USA
Authors: Kulpa Matthew , Nelson Kimberly J. , Morales Alana M. , Ryan Bonnie M. , Koschik Michelle L. , Scott Jamesina J. , Verocai Guilherme G. 
Published: September 2021

AbstractBackgroundBlack flies (Diptera: Simuliidae) serve as arthropod vectors for various species ofOnchocerca(Nematoda: Onchocercidae) that may be associated with disease in humans, domestic animals, and wildlife. The emergence of zoonoticOnchocerca lupiin North America and reports of cervid-associated zoonotic onchocerciasis byOnchocerca jakutensishighlight the need for increased entomological surveillance. In addition, there is mounting evidence thatOnchocercadiversity in North America is far greater than previously thought, currently regarded asOnchocerca cervipedisspecies complex. This study reports new geographic records and black fly vector associations of an uncharacterizedOnchocercaspecies.MethodsTo better understand the biodiversity and geographic distribution ofOnchocerca, 485 female black flies (2015: 150, 2016: 335) were collected using CO2-baited traps from February to October 2015–2016 in Lake County, northern California, USA. Individual flies were morphologically identified and pooled (≤ 10 individuals) by species, collection date, and trap location. Black fly pools were processed for DNA extraction, and subsequent PCR and sequencing targeting of the NADH dehydrogenase subunit 5 gene of filarioids.ResultsAmong the pools of black flies, there were 158 individuals ofSimulium tescorum(2015: 57, 2016: 101), 302 individuals ofSimulium vittatum(sensu lato[s.l.]) (2015: 82, 2016: 220), 16 individuals ofSimulium clarum“black” phenotype (2015: 5, 2016: 11), and 13 individuals ofS. clarum“orange” phenotype (2015: 6, 2016: 7). PCR analysis revealed the percentage of filarioid-positive pools were 7.50% (n = 3) forS. tescorum, 3.75% (n = 3) forS. vittatum(s.l., likelyS. tribulatum), 7.69% (n = 1) forS. clarum“black” phenotype, and no positives forS. clarum“orange” phenotype. Genetic distance and phylogenetic analyses suggest that the northern CaliforniaOnchocercaisolates belong to the same species reported in black flies from southern California (average pairwise comparison: 0.32%), and seem closely related toOnchocercaisolates of white-tailed deer from upstate New York (average pairwise comparison: 2.31%).ConclusionA crypticOnchocercaspecies was found in Lake County, California, and may be a part of a larger, continentally distributed species complex rather than a single described species of North America. In addition, there are at least three putative vectors of black flies (S. clarum,S. tescorum,S. vittatum) associated with this crypticOnchocercaspecies. A comprehensive reassessment of North AmericanOnchocercabiodiversity, host, and geographic range is necessary.Graphical abstract
Advances in GLP-1 treatment: focus on oral semaglutide
Authors: Eliaschewitz Freddy G. , Canani Luis Henrique 
Published: September 2021

Abstract
Background
There is currently a large arsenal of antidiabetic drugs available to treat type 2 diabetes (T2D). However, this is a serious chronic disease that affects millions of adults worldwide and is responsible for severe complications, comorbidities, and low quality of life when uncontrolled due mainly to delays in initiating treatment or inadequate therapy. This review article aims to clarify the therapeutic role of the oral formulation of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide in treating typical T2D patients. The discussion focused on metabolic, glycemic, and weight alteration effects and the safety of the therapy with this drug.

Main text
Therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) promotes strategic changes in the pathophysiological pathway of T2D and improves the secretion of glucagon and insulin, which results in a reduction in blood glucose levels and the promotion of weight loss. Until recently, the only route for semaglutide administration was parenteral. However, an oral formulation of GLP-1 RA was recently developed and approved by the Brazilian Health Regulatory Agency (ANVISA) and the Food and Drug Administration (FDA) based on the Peptide Innovation for Early Diabetes Treatment (PIONEER) program results. A sequence of 10 clinical studies compared oral semaglutide with placebo or active standard-of-care medications (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8 mg) in different T2D populations.

Conclusions
Oral semaglutide effectively reduces glycated hemoglobin (HbA1c) levels and body weight in a broad spectrum of patients with T2D and shows cardiovascular safety. Oral semaglutide broadens therapy options and facilitates the adoption of earlier GLP-1 RA treatment once T2D patients present low rates of treatment discontinuation. The main adverse events reported were related to the gastrointestinal tract, common to GLP-1 RA class drugs.
Serum albumin was negatively associated with diabetic peripheral neuropathy in Chinese population: a cross-sectional study
Authors: Yan Pijun , Tang Qian , Wu Yuru , Wan Qin , Zhang Zhihong , Xu Yong , Zhu Jianhua , Miao Ying 
Published: September 2021

Abstract
Background
Previous studies that explored the relationship of serum albumin with diabetic peripheral neuropathy (DPN) have indicated inconsistent results. Thus, the present study aimed to evaluated the association between serum albumin and DPN, defined as vibration perception threshold (VPT) values ≥ 25 V and/or inability to feel the monofilament, in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods
1465 T2DM patients aged ≥ 16 years, who completed the measurement of serum albumin and DPN screening between 2012 and 2015, were included in the cross-sectional study. Correlation and multivariate logistic regression analysis models were used to evaluate the possible relationship between serum albumin and DPN.

Results
Patients with higher quartiles of serum albumin had significantly lower VPT values and prevalence of DPN compared with those with lower quartiles (P for trend < 0.01), and there was an inverse relationship between serum albumin and VPT values and prevalence of DPN (all P < 0.01). Multivariate logistic regression analysis demonstrated that the risk of DPN was progressively decreased across serum albumin quartiles (P for trend < 0.01), and participants in the highest quartile of serum albumin were at a significantly decreased risk of DPN compared to those in the lowest quartile (odds rate: 0.311, 95% confidence intervals 0.134–0.724, P < 0.01). ROC analysis revealed that the optimal cutoff point of serum albumin for the prevalence of DPN was 39.95 g/L in patients with T2DM, with a sensitivity of 65.88% and a specificity of 66.7%.

Conclusions
Decreased levels of serum albumin might be correlated with increased risk of DPN in Chinese patients with T2DM. Future longitudinal studies with large samples are warranted to confirm our findings, and elucidate putative mechanisms for the association.
Adequacy of setting standards for kick impact in the Taekwondo electronic scoring system: comparison of a reference group model based on empirical data
Authors: Choi Chang-Hwan , Oh Hyeri , Jeon Minsoo 
Published: September 2021

Abstract
Background
In Taekwondo competitions, the rule is that points are scored when the impact of the kick reaches a predetermined threshold of strength. This study aimed to explore the adequacy of the protector and scoring system (PSS) designed to determine taekwondo body scoring based on a reference group model (RGM). Specifically, the kicking impact of the PSS was calculated using data from 188 matches fought during of 2018 Jakarta Asian Games. The RGM was designed based on empirical data by classifying the victory and defeat groups by gender and weight class, and the scoring method was set according to these criteria.

Result
The result of this study are as follows. First, there was no difference in the average impact of kicks of taekwondo players by weight class. Second, result of setting up the kick scoring impact standards of taekwondo PSS by classifying the winning and non-winning groups, the kick scoring impact set by the WT was found to be high in all weight classes except 58 kg. Lastly, result of comparing the settings of impact to score according to weight classes, the kick scoring impact standard set by the WT was higher in heavyweight (men's: under 80 kg, + 80 kg, women's: under 67 kg, over 67 kg) than in the lightweight (men's: under 58 kg, under 63 kg, under 68 kg, women's: under 49 kg, under 53 kg, under 57 kg).

Conclusion
The kick scoring impact set by the WT was found to be high in all weight classes except for the under 58 kg class defining kick scoring impact based on the standards of WT-certified PSS by classifying the matches into winning and non-winning groups. Finally, as a result of comparing the scoring impact settings according to weight class, the kick scoring impact standard set by the WT was higher for the heavier weight classes than for the lighter weight classes.
Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome
Authors: Berg Elizabeth L. , Petkova Stela P. , Born Heather A. , Adhikari Anna , Anderson Anne E. , Silverman Jill L. 
Published: September 2021

AbstractBackgroundAngelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both theUbe3amaternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems.MethodsWe used both theUbe3amaternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes.ResultsAcute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition.LimitationsThe generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy.ConclusionsDespite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.
Isolated pancreatic injury in an adolescent treated with Roux-en-Y pancreatojejunostomy: a case report and review of the literature
Authors: Naiem Mohamed Eltayeb Abdelrahman , Arabi Nassir Alhaboob 
Published: September 2021

Abstract
Background
Pancreatic injury presented as isolated injury in the pediatric population is exceptionally rare, with a conveyed incidence of less than 2% of all abdominal trauma injuries cases and a very controversial management approach for grade III injuries.

Case presentation
A 16-year-old adolescent Sudanese boy was referred to our emergency department with a 5-day history of upper and left hypochondrial pain after blunt abdominal trauma to the epigastric region with a solid object. Grade III pancreatic body trauma with major duct involvement can be successfully treated operatively. The boy was discharged home on day 10 with regular oral intake and diet. A follow-up for 6 months continued by phone, and it was uneventful with no further complications.

Conclusions
Roux-en-Y pancreatojejunostomy reconstruction can be a safe and valuable surgical option when the surgical approach is considered for grade III pancreatic injury.
The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits
Authors: Guzman Roberto Alfonso , Maruyama Masahiro , Moeinzadeh Seyedsina , Lui Elaine , Zhang Ning , Storaci Hunter W. , Tam Kaysie , Huang Elijah Ejun , Utsunomiya Takeshi , Rhee Claire , Gao Qi , Yao Zhenyu , Yang Yunzhi Peter , Goodman Stuart B. 
Published: September 2021

AbstractBackgroundApproximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH.MethodsIn vitro studies:Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.ResultsIn vitro studies:PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo:The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups.ConclusionThe use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.
Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality
Authors: Laucyte-Cibulskiene Agne , Ward Liam J. , Ebert Thomas , Tosti Giulia , Tucci Claudia , Hernandez Leah , Kautzky-Willer Alexandra , Herrero Maria-Trinidad , Norris Colleen M. , Pilote Louise , Söderberg Magnus , Brismar Torkel B. , Ripsweden Jonaz , Stenvinkel Peter , Raparelli Valeria , Kublickiene Karolina ,   The GOING-FWD Consortium
Published: September 2021

Abstract
Background
Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality.

Methods
ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality.

Results
Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02).

Conclusions
In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.