bluuebunny/crossref_metadata_2025_split huggingface dataset:
End-stage knee osteoarthritis with and without sarcopenia and the effect of knee arthroplasty – a prospective cohort study
Authors: Ho Kevin Ki-Wai , Lau Lawrence Chun-Man , Chau Wai-Wang , Poon Queena , Chung Kwong-Yin , Wong Ronald Man-Yeung 
Published: January 2021

Abstract
Background
Sarcopenia often accompanies osteoarthritis (OA), which is managed by total knee arthroplasty (TKA) in the late stage. Recent studies have suggested a higher risk of post-operative complications after TKA in sarcopenic OA subjects, but whether TKA can benefit them similar to non-sarcopenic subjects remains unexplored. This study aimed to examine the dynamic, mutual impact of sarcopenia and TKA in a one-year post-operative period.

Methods
This prospective cohort study was conducted between 2015 to 2018 at our hospital. Patients with end-stage OA of the knee waiting for TKA were recruited into the study. Primary outcome measures were change in muscle strength, mass and function. Secondary outcome measures were quality of life (QOL) measurements for pain, psychological and physical health.

Results
Fifty-eight patients were recruited, of which 79.3% were female and 32.8% already had sarcopenia at baseline. The average age of sarcopenic subjects and non-sarcopenic subjects was comparable (67.89 ± 7.07 vs. 67.92 ± 6.85; p = 0.99), but sarcopenic subjects had a lower body mass index (BMI) (25.64 ± 2.64 vs. 28.57 ± 4.04; p = 0.01). There was a statistically significant improvement in walking speed (10.24 ± 5.35 vs. 7.69 ± 2.68, p < 0.01) and muscle strength in both sarcopenic and non-sarcopenic patients after TKA. This was accompanied by an improvement trend in muscle mass in all subjects. There was no change in handgrip power before and after TKA and subsequent follow-up (19.31 ± 5.92 vs. 18.98 ± 6.37 vs. 19.36 ± 7.66; p = 0.97). QOL measured before, after and at follow-up with WOMAC (total: 42.27 ± 15.98 vs. 20.65 ± 15.24 vs. 16.65 ± 18.13) and SF12v2 (PCS: 33.06 ± 8.55 vs. 38.96 ± 8.01 vs. 40.67 ± 7.93) revealed progressive significant improvement (both comparisons p ≤ 0.01). Further analysis with the IPAQ also found increased engagement of high-intensity activities.

Conclusions
This study showed that sarcopenia among patients with end-stage OA of the knee is not uncommon, but both sarcopenic and non-sarcopenic OA patients achieved significant clinical and functional improvement after TKA. Further studies with a larger sample size and different ethnicities could help ascertain a beneficial role of TKA in sarcopenic OA subjects.

Trial registration
Registry: ClinicalTrials.gov, Registration number: NCT03579329. Date of registration: 6 July 2018. Retrospectively registered.
Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?
Authors: Onoe Tamehito , Hara Satoshi , Yamada Kazunori , Zoshima Takeshi , Mizushima Ichiro , Ito Kiyoaki , Mori Takayasu , Daimon Shoichiro , Muramoto Hiroaki , Shimizu Maki , Iguchi Akira , Kuma Akihiro , Ubara Yoshifumi , Mitobe Michihiro , Tsuruta Hiroaki , Kishimoto Nao , Imura Junko , Konoshita Tadashi , Kawano Mitsuhiro 
Published: January 2021

Abstract
Background
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients.

Methods
Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed.

Results
Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected.

Conclusions
Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.
Identification of a novel GRIN2D variant in a neonate with intractable epileptic encephalopathy-a case report
Authors: Jiao Jiancheng , Li Li , Sun Min , Fang Junchen , Meng Lingzhi , Zhang Yudong , Jia Chao , Ma Li 
Published: January 2021

Abstract
Background
N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. The functional NMDA receptors are heterotetramers consisting mainly of two GluN1 and two GluN2 subunits. GluN2 is encoded by the GRIN2D gene. A few case series have shown that GRIN2D variants are linked to developmental and epileptic encephalopathy. In this article, we report a novel GRIN2D variant, namely c.2021C > A (p.T674K) in a neonate with intractable epileptic encephalopathy.

Case presentation
A 12-day-old boy who had stiffness of the lower and upper extremities since birth was transferred from a local hospital to our department. On admission, the patient presented with head tilting backwards, staring, apnea and hypertonia of limbs. Video electroencephalogram showed continuous, generalized or multi-focal spike-wave and spike-and-slow wave discharges and hypsarrhythmia. A treatment regimen composed of phenobarbital, midazolam, levetiracetam and clonazepam was administered, which however led to only partial control of the seizure. Whole-exome sequencing identified c.2021C > A (p.T674K) in GRIN2D in the patient while such a mutation was not detected in the parents. The patient was hospitalized for 1 month and died of sudden cardio-respiratory arrest 2 weeks after discharge.

Conclusions
A novel variant of GRIN2D was identified in a neonate with epileptic encephalopathy. Epilepsy associated with this GRIN2D mutation is refractory to conventional anti-epileptic medications.
Thickness of subcutaneous fat is a risk factor for incisional surgical site infection in acute appendicitis surgery: a prospective study
Authors: Thapa Bikas , Sutanto Edward , Bhandari Raju 
Published: January 2021

AbstractBackgroundIncisional surgical site infection (SSI) is a significant source of postoperative morbidity resulting in increased length of stay and cost. In this study, our aim was to evaluate the association between thickness of subcutaneous fat (TSF) and incisional SSI among patients undergoing open appendectomy in low-resource settings.Methods90 patients with acute uncomplicated appendicitis who underwent emergency open appendectomy from December 2017 to August 2018 were included in this prospective study. TSF was measured preoperatively using ultrasound. TSF and other possible predictors of incisional SSI, including body mass index and other clinical characteristics, were assessed by univariate and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis evaluated the predictive value of TSF and the optimum cut-off value for TSF was determined using the Youden index.ResultsThe prevalence of incisional SSI was 13.3% (12/90). TSF was independently associated with incisional SSI (P < 0.001). Additionally, history of smoking (P = 0.048) was also associated with incisional SSI. A model of incisional SSI using a cut-off of 23.0 mm for TSF was moderately accurate (area under curve 0.83, confidence interval 0.70–0.97; sensitivity 83.3%; specificity 76.9%).ConclusionsThe study demonstrated that TSF, as evaluated by ultrasound, is a predictor in the development of incisional SSI in patients with acute appendicitis undergoing open appendectomy. These findings suggest that ultrasound is useful both for the evaluation of TSF and the prediction of incisional SSI risk factor in low-resource settings.
Short and long-term impact of four sets of actions on acute ischemic stroke management in Rhône County, a population based before-and-after prospective study
Authors: Schott A. M. , Termoz A. , Viprey M. , Tazarourte K. , Vecchia C. Della , Bravant E. , Perreton N. , Nighoghossian N. , Cakmak S. , Meyran S. , Ducreux B. , Pidoux C. , Bony T. , Douplat M. , Potinet V. , Sigal A. , Xue Y. , Derex L. , Haesebaert J. 
Published: January 2021

Abstract
Background
Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County.

Methods
The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006–7 and 2015–16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term.

Results
Between 2015–16 and 2006–7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p < 0.0001), calls to emergency call-center from 40 to 68% (p < 0.0001), first admission in stroke unit from 8 to 30% (p < 0.0001), and MRI within 24 h from 18 to 42% (p < 0.0001). Onset-to-reperfusion time significantly decreased from 3h16mn [2 h54-4 h05] to 2h35mn [2 h05-3 h19] (p < 0.0001), mainly related to a decrease in delay from admission to imaging. A significant decrease of disability was observed, as patients with mild disability (mRS [0–2]) at 12 months increased from 48 to 61% (p < 0.0001). Pre-hospital times, however, did not change significantly.

Conclusions
We observed significant improvement in access to reperfusion therapy, mainly through a strong decrease of in-hospital management times, and in 12-month disability after the implementation of four sets of actions between 2006 and 2016 in the Rhône County. Reducing pre-hospital times remains a challenge.
Outreach-based clinical pharmacist prescribing input into the healthcare of people experiencing homelessness: a qualitative investigation
Authors: Johnsen Sarah , Cuthill Fiona , Blenkinsopp Janice 
Published: January 2021

AbstractBackgroundSeverely and multiply disadvantaged members of the homeless population are disproportionately vulnerable to exceptionally high levels of multi-morbidity and premature death. Given widespread calls for the development of interventions that might improve the uptake and effectiveness of healthcare for this population, this study investigated patient and other stakeholder perspectives regarding an outreach service, delivered by prescribing pharmacists in collaboration with a local voluntary sector provider, within homelessness services and on the street in Glasgow (UK).MethodsThe qualitative study involved semi-structured face-to-face interviews with 40 purposively sampled individuals with current or recent experience of homelessness (32 of whom had direct experience of the service and 8 of whom did not), all (n = 4) staff involved in frontline delivery of the service, and 10 representatives of stakeholder agencies working in partnership with the service and/or with the same client group. Pseudonymised verbatim interview transcriptions were analysed systematically via thematic and framework analysis.ResultsThe service was effective at case finding and engaging with patients who were reluctant to utilise or physically unable to access existing (mainstream or specialist ‘homeless’) healthcare provision. It helped patients overcome many of the barriers that homeless people commonly face when attempting to access healthcare, enabled immediate diagnosis and prescription of medication, and catalysed and capitalised on windows of opportunity when patients were motivated to address healthcare needs. A number of improvements in health outcomes, including but not limited to medication adherence, were also reported.ConclusionsA proactive, informal, flexible, holistic and person-centred outreach service delivered within homelessness service settings and on the street can act as a valuable bridge to both primary and secondary healthcare for people experiencing homelessness who would otherwise ‘fall through the gaps’ of provision. Prescribing pharmacist input coupled with third sector involvement into healthcare for this vulnerable population allows for the prompt treatment of and/or prescription for a range of conditions, and offers substantial potential for improving health-related outcomes.
Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy
Authors: Wang Lin , Cai Yin , Jian Liguo , Cheung Chi Wai , Zhang Liangqing , Xia Zhengyuan 
Published: January 2021

AbstractThe prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium–glucose co-transporter 2 inhibitor) in treating DCM.
History of lower-limb complications and risk of cancer death in people with type 2 diabetes
Authors: Mohammedi Kamel , Harrap Stephen , Mancia Giuseppe , Marre Michel , Poulter Neil , Chalmers John , Woodward Mark 
Published: January 2021

Abstract
Background
Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes.

Methods
We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models.

Results
Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers.

Conclusions
PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.
RETRACTED ARTICLE: Histone methyltransferase SUV39H2 regulates LSD1-dependent CDH1 expression and promotes epithelial mesenchymal transition of osteosarcoma
Authors: Miao Yingying , Liu Guifeng , Liu Lin 
Published: January 2021

Abstract
Objective
Osteosarcoma (OS) is a malignant tumor characterized by the direct production of bone or osteoid tissues by proliferating tumor cells. Suppressor of variegation 3–9 homolog 2 (SUV39H2) is implicated in the occurrence of OS. Therefore, we designed this study to investigate effects of SUV39H2 in OS meditated by the lysine specific demethylase-1/E-cadherin (LSD1/CDH1) axis.

Methods
Clinical OS tissues and paracancerous tissues were collected for analysis of SUV39H2, LSD1 and CDH1 expression, and Kaplan–Meier survival analysis was applied to test the relationship between SUV39H2 expression and overall survival. Loss- and gain-of-function assays were conducted to determine the roles of SUV39H2, LSD1 and CDH1 in OS epithelial mesenchymal transition (EMT) and migration in OS cells, with quantitation of relevant proteins by immunofluorescence. We confirmed the effects of modulating the SUV39H2/CDH1 axis in a mouse OS tumor model.

Results
SUV39H2 and LSD1 were highly expressed, while CDH1 was downregulated in OS tissues and cells. SUV39H2 expression correlated inversely with overall survival of patients with OS. SUV39H2 positively regulated LSD1 expression, while LSD1 negatively regulated CDH1 expression. SUV39H2 or LSD1 overexpression, or CDH1 silencing promoted migration and EMT, as indicated by reduced E-cadherin and dramatically upregulated Vimentin and N-cadherin of OS cells. SUV39H2 expedited the progression of OS, which was reversed by CDH1 repression in the setting of OS in vitro and in vivo.

Conclusions
Collectively, our results demonstrate highly expressed SUV39H2 in OS elevates the expression of LSD1 to downregulate CDH1 expression, thereby aggravating OS, providing a potential therapeutic target for treatment of OS.
Caloric restriction in female reproduction: is it beneficial or detrimental?
Authors: Sun Jiayi , Shen Xin , Liu Hui , Lu Siying , Peng Jing , Kuang Haibin 
Published: January 2021

AbstractCaloric restriction (CR), an energy-restricted intervention with undernutrition instead of malnutrition, is widely known to prolong lifespan and protect against the age-related deteriorations. Recently it is found that CR significantly affects female reproduction via hypothalamic (corticotropin releasing hormone, neuropeptide Y, agouti-related peptide) and peripheral (leptin, ghrelin, insulin, insulin-like growth factor) mediators, which can regulate the energy homeostasis. Although CR reduces the fertility in female mammals, it exerts positive effects like preserving reproductive capacity. In this review, we aim to discuss the comprehensive effects of CR on the central hypothalamus-pituitary-gonad axis and peripheral ovary and uterus. In addition, we emphasize the influence of CR during pregnancy and highlight the relationship between CR and reproductive-associated diseases. Fully understanding and analyzing the effects of CR on the female reproduction could provide better strategies for the management and prevention of female reproductive dysfunctions.