bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of insulin receptor in the proximal tubule and fasting augment albumin excretion
Authors: Kumari Manju , Sharma Rajni , Pandey Gaurav , Ecelbarger Carolyn M. , Mishra Prabhaker , Tiwari Swasti 
Published: January 2019

AbstractThe contribution of proximal tubules (PT) to albumin uptake is now well recognized, however, its regulation is understudied area. There are reports suggesting that insulin resistance is associated with the development of albuminuria in nondiabetic individuals. We have previously reported reduced insulin receptor (IR) expression in renal‐tubular‐epithelial cells, including PT in various models of insulin resistance. However, the effect of a physiological fall in insulin levels and the role for IR in PT in tubular albumin uptake is not clear. To address these gaps in our understanding, we estimated urine excretion and renal uptake of albumin in fasted and fed C57Bl/6 mice injected with fluorescein isothiocyanate (FITC)‐albumin (5 µg/mL/kg body weight, intraperitoneal,
n = 6 per group). In addition, we compared spot urine analysis from 33 clinically healthy humans after overnight fasting (when insulin levels are lower than in the fed state) and then at 2 hours after 75 g oral glucose challenge (postprandial). Fasted mice had attenuated renal uptake of FITC‐albumin and higher excretion in urine, relative to fed mice (
P = 0.04). Moreover, a significant drop in urine albumin‐to‐creatinine ratio (ACR) and urine albumin concentration (UAC) was observed in the postprandial state in these subjects (
P = 0.001 and
P = 0.017, for ACR and UAC, respectively). The drop was negatively associated with postprandial blood glucose levels (ρ = −0.36,
P = 0.03 for ΔUAC and ρ = −0.34,
P = 0.05 for ΔACR). To test the role of IR in PT, we analyzed 24‐hour urine albumin excretion in male mice with targeted deletion of IR from PT (insulin receptor knockout [IRKO]) and their wild‐type (WT) littermates (
n = 7 per group). IRKO mice had significantly higher 24‐hour urine albumin excretion relative to WT. Moreover, kidneys from KO mice revealed reduced expression of megalin and cubulin proteins in the PT relative to the WT. We also demonstrated insulin (100 nM) induced albumin internalization in human proximal tubule cells (hPT) and this effect of insulin was attenuated in hydroxy‐2‐naphthalenylmethylphosphonic acid (100 µM), a tyrosine kinase inhibitor, pretreated hPT. Our findings revealed albumin excretion was attenuated by glucose administration to fasting individuals implying a regulatory role for insulin in PT albumin reabsorption. Thus albuminuria associated with insulin resistance/diabetes may relate not only to glomerular dysfunction but also to impairment in insulin‐mediated reabsorption.
Troubling stereotypes: South African elite disability athletes and the paradox of (self‐)representation
Authors: Bantjes Jason , Swartz Leslie , Botha Jeanine 
Published: January 2019

AbstractDespite the increasing prominence of competitive disability sport, the literature on the experiences of disabled athletes, particularly in low‐ and middle‐ income countries, is sparse. We aimed to describe the participation experiences of a group of athletes in competitive disability sport in South Africa, as well as exploring the ways they talk about issues of identity and self‐representation in the context of elite disability sport. Data were collected via in‐depth, semistructured interviews with a purposefully sampled group of 22 athletes competing at a national level. Interviews were analyzed using thematic analysis. Participants reported that disability sport is personally transformative and that sport allows them to experience their bodies as capable and to feel a sense of pride. Participant narratives reinforced supercrip discourses and both reproduced stereotypes and challenged them. Participants experienced pride and social inclusion by reproducing aspects of supercrip discourse. The findings imply that participating in competitive disability sport can reinforce stereotypes about disability by strengthening supercrip discourses while simultaneously providing a context for internal personal transformation and private political struggles.
A dynamic reversible RNA N6‐methyladenosine modification: current status and perspectives
Authors: Bi Zhen , Liu Youhua , Zhao Yuanling , Yao Yongxi , Wu Ruifan , Liu Qing , Wang Yizhen , Wang Xinxia 
Published: January 2019

AbstractN6‐methyladenosine (m6A), as the most abundant RNA epigenetic modifications, has been shown to play critical roles in various biological functions. Research about enzymes that can catalyze and remove m6A have revealed its comprehensive roles in messenger RNA (mRNA) metabolism and other physiological processes. The “readers” including YTH domain‐containing proteins, hnRNPC, hnRNPG, hnRNPA2B1, IGF2BP1, IGF2BP2, and IGF2BP3, which can affect the fates of mRNA in an m6A‐dependent manner. In this review, we focus on recent advances in the research of the m6A modifications, especially about the latest functions of its writers, erasers, readers in RNA metabolism, cancer, and lipid metabolism. In the end, we provide insights into the underlying molecular mechanisms of m6A modifications.
Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions
Authors: Zhu Jing , Yin Tailang , Xu Yong , Lu Xiao‐Jie 
Published: January 2019

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.
Region‐resolved proteomics profiling of monkey heart
Authors: Hu Hao‐Liang , Kang Yu , Zeng Yong , Zhang Ming , Liao Qiong , Rong Ming‐Qiang , Zhang Qin , Lai Ren 
Published: January 2019

AbstractNonhuman primates (NHPs) play an indispensable role in biomedical research because of their similarities in genetics, physiological, and neurological function to humans. Proteomics profiling of monkey heart could reveal significant cardiac biomarkers and help us to gain a better understanding of the pathogenesis of heart disease. However, the proteomic study of monkey heart is relatively lacking. Here, we performed the proteomics profiling of the normal monkey heart by measuring three major anatomical regions (vessels, valves, and chambers) based on iTRAQ‐coupled LC‐MS/MS analysis. Over 3,200 proteins were identified and quantified from three heart tissue samples. Furthermore, multiple bioinformatics analyses such as gene ontology analysis, protein–protein interaction analysis, and gene‐diseases association were used to investigate biological network of those proteins from each area. More than 60 genes in three heart regions are implicated with heart diseases such as hypertrophic cardiomyopathy, heart failure, and myocardial infarction. These genes associated with heart disease are mainly enriched in citrate cycle, amino acid degradation, and glycolysis pathway. At the anatomical level, the revelation of molecular characteristics of the healthy monkey heart would be an important starting point to investigate heart disease. As a unique resource, this study can serve as a reference map for future in‐depth research on cardiac disease‐related NHP model and novel biomarkers of cardiac injury.
Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions
Authors: Malekshahabi Talieh , Khoshdel Rad Niloofar , Serra Andreas L. , Moghadasali Reza 
Published: January 2019

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a monogenic inherited renal cystic disease that occurs in different races worldwide. It is characterized by the development of a multitude of renal cysts, which leads to massive enlargement of the kidney and often to renal failure in adulthood. ADPKD is caused by a mutation in PKD1 or
PKD2 genes encoding the proteins polycystin‐1 and polycystin‐2, respectively. Recent studies showed that cyst formation and growth result from deregulation of multiple cellular pathways like proliferation, apoptosis, metabolic processes, cell polarity, and immune defense. In ADPKD, intracellular cyclic adenosine monophosphate (cAMP) promotes cyst enlargement by stimulating cell proliferation and transepithelial fluid secretion. Several interventions affecting many of these defective signaling pathways have been effective in animal models and some are currently being tested in clinical trials. Moreover, the stem cell therapy can improve nephropathies and according to studies were done in this field, can be considered as a hopeful therapeutic approach in future for PKD. This study provides an in‐depth review of the relevant molecular pathways associated with the pathogenesis of ADPKD and their implications in development of potential therapeutic strategies.
Potential biomarkers to detect traumatic brain injury by the profiling of salivary extracellular vesicles
Authors: Cheng Yan , Pereira Mandy , Raukar Neha , Reagan John L. , Queseneberry Mathew , Goldberg Laura , Borgovan Theodor , LaFrance W Curt , Dooner Mark , Deregibus Maria , Camussi Giovanni , Ramratnam Bharat , Quesenberry Peter 
Published: January 2019

AbstractTraumatic brain injury (TBI) is a common cause of death and acquired disability in adults and children. Identifying biomarkers for mild TBI (mTBI) that can predict functional impairments on neuropsychiatric and neurocognitive testing after head trauma is yet to be firmly established. Extracellular vesicles (EVs) are known to traffic from the brain to the oral cavity and can be detected in saliva. We hypothesize the genetic profile of salivary EVs in patients who have suffered head trauma will differ from normal healthy controls, thus constituting a unique expression signature for mTBI. We enrolled a total of 54 subjects including for saliva sampling, 23 controls with no history of head traumas, 16 patients enrolled from an outpatient concussion clinic, and 15 patients from the emergency department who had sustained a head trauma within 24 hr. We performed real‐time PCR of the salivary EVs of the 54 subjects profiling 96 genes from the TaqMan Human Alzheimer's disease array. Real‐time PCR analysis revealed 57 (15 genes, p < 0.05) upregulated genes in emergency department patients and 56 (14 genes,
p < 0.05) upregulated genes in concussion clinic patients when compared with controls. Three genes were upregulated in both the emergency department patients and concussion clinic patients: CDC2, CSNK1A1, and CTSD (
p < 0.05). Our results demonstrate that salivary EVs gene expression can serve as a viable source of biomarkers for mTBI. This study shows multiple Alzheimer's disease genes present after an mTBI.
Extracellular CIRP (eCIRP) and inflammation
Authors: Aziz Monowar , Brenner Max , Wang Ping 
Published: January 2019

Abstract
Cold-inducible RNA-binding protein (CIRP) was discovered 2 decades ago while studying the mechanism of cold stress adaptation in mammals. Since then, the role of intracellular CIRP (iCIRP) as a stress-response protein has been extensively studied. Recently, extracellular CIRP (eCIRP) was discovered to also have an important role, acting as a damage-associated molecular pattern, raising critical implications for the pathobiology of inflammatory diseases. During hemorrhagic shock and sepsis, inflammation triggers the translocation of CIRP from the nucleus to the cytosol and its release to the extracellular space. eCIRP then induces inflammatory responses in macrophages, neutrophils, lymphocytes, and dendritic cells. eCIRP also induces endoplasmic reticulum stress and pyroptosis in endothelial cells by activating the NF-κB and inflammasome pathways, and necroptosis in macrophages via mitochondrial DNA damage. eCIRP works through the TLR4-MD2 receptors. Studies with CIRP−/− mice reveal protection against inflammation, implicating eCIRP to be a novel drug target. Anti-CIRP Ab or CIRP-derived small peptide may have effective therapeutic potentials in sepsis, acute lung injury, and organ ischemia/reperfusion injuries. The current review focuses on the pathobiology of eCIRP by emphasizing on signal transduction machineries, leading to discovering novel therapeutic interventions targeting eCIRP in various inflammatory diseases.
Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle‐induced implant loosening: Evidence from a rat model
Authors: Hu Bin , Wu Haobo , Shi Zhongli , Ying Zhimin , Zhao Xiang , Lin Tiao , Hong Jianqiao , Wang Yangxin , Yang Yute , Cai Xunzi , Yan Shigui 
Published: January 2019

ABSTRACTParticle‐induced implant loosening is a major challenge to long‐term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early‐stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri‐implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri‐implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri‐implant osteolysis. Implant fixation and peri‐implant bone mass were evaluated using biomechanical testing, micro‐CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push‐out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri‐implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri‐implant osteolysis, resulting in improved implant fixation and increased peri‐implant bone volume. Clinical significance: The innovative application of sequential treatment in peri‐implant osteolysis could be used clinically to improve the prognosis of patients with early‐stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489–1497, 2019.
Impact of intramural and extramural vascular invasion on stage II‐III colon cancer outcomes
Authors: Leijssen Lieve G. J. , Dinaux Anne M. , Amri Ramzi , Taylor Martin S. , Deshpande Vikram , Bordeianou Liliana G. , Kunitake Hiroko , Berger David L. 
Published: January 2019

Background and ObjectivesVascular invasion, in particular extramural venous invasion (EMVI), is a pathologic characteristic that has been extensively studied in rectal cancer but rarely in colon cancer. This study aims to evaluate its prognostic role in stage II‐III colon cancer.MethodsAll stage II‐III colon cancer patients who underwent surgery between 2004 and 2015 were reviewed. We compared patients without invasion, with intramural invasion only (IMVI), EMVI only, and both IMVI/EMVI (n = 923).ResultsEMVI was associated with other high‐risk features, including T4, N+ disease, lymphatic, and perineural invasion (P < 0.001). EMVI+ patients had higher rates of locoregional and distant recurrence and subsequently disease‐specific mortality (stage‐II, odds ratio [OR] 3.64; P = 0.001; stage‐III OR, 1.94; P = 0.009), whereas outcomes were comparable between IMVI and no vascular invasion (OR, 1.21; P = 0.764; OR, 1.28, P = 0.607, respectively). The adjusted HRs for EMVI+ patients on disease‐free survival, and disease‐specific survival were 2.07 (
P < 0.001) and 1.67 (
P = 0.027), respectively. Moreover, EMVI+ stage‐II patients fared worse than EMVI– stage‐III patients, even after adjusting for adjuvant chemotherapy.ConclusionEMVI is a strong predictor for worse oncologic outcomes in stage II‐III colon cancer patients, whereas IMVI is not. It is also associated with worse outcomes compared in patients with higher stage disease who are EMVI negative.
Long‐term follow‐up of RET Y791F carriers in Denmark 1994‐2017: A National Cohort Study
Authors: Høxbroe Michaelsen Sanne , Ornstrup Marie Juul , Poulsen Morten Møller , Bennedbæk Finn Noe , Gaustadnes Mette , Rossing Maria , Darling Peter , Vestergaard Peter , Mathiesen Jes Sloth 
Published: January 2019

Background and ObjectivesRecently, a comprehensive study presented evidence that a long‐disputed REarranged during Transfection (RET) variant, RET Y791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RET Y791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long‐term follow‐up.MethodsA national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RET Y791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow‐up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease).ResultsIn total, twenty RET Y791F‐carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years.ConclusionsOur national cohort study of all Danish RET Y791F carriers substantiates the claim that the RET Y791F variant is nonpathogenic.
Patients with in‐transit melanoma metastases have comparable survival outcomes following isolated limb infusion or intralesional PV‐10—A propensity score matched, single center study
Authors: Read Tavis , Fayers Warren , Thomas Janine , Wagels Michael , Barbour Andrew , Mark Smithers B. 
Published: January 2019

Background and ObjectiveIsolated limb infusion (ILI) and intralesional PV‐10 are well described locoregional therapies for in‐transit melanoma. The objective of this study was to assess the effect of these treatments on survival outcomes within a cohort matched for key characteristics.MethodsPatients were treated using ILI or intralesional PV‐10 at a single institution and the data prospectively recorded. Propensity score matching was performed using key covariates within a logistic regression model. The primary outcome was the melanoma‐specific survival.ResultsSeventy‐two patients nonrandomized were successfully matched. Both treatments produced similar best overall responses. The median melanoma‐specific survival (MSS) was 74.4 months from ILI and 36.4 months from PV‐10 treatments (P = 0.164). Within the ILI subgroup, the 12‐, 24‐, 36‐ and 60‐month MSS rates were 85.3%, 75.3%, 60.1%, and 60.1%, respectively. From the time of PV‐10 the corresponding 12‐, 24‐, 36‐, and 60‐month MSS rates were 82.6%, 70.0%, 53.9%, and 35.9%. On multivariate analysis, there was a significant difference in survival comparing completely with noncomplete responders (
P = 0.031).ConclusionsThese findings demonstrate that ILI and PV‐10 treatments for in‐transit disease produce comparable long‐term survival. Both therapies have reproducible response rates and predominantly localized and tolerable side‐effects.
The current practice of open neck mass biopsy in the diagnosis of head and neck cancer: A retrospective cohort study
Authors: Akkina Sarah R. , Kim Roderick Y. , Stucken Chaz L. , Pynnonen Melissa A. , Bradford Carol R. 
Published: January 2019

ObjectiveTo characterize current use of open neck mass biopsy for diagnosis of squamous cell carcinoma in patients presenting with a neck mass.MethodsUsing the University of Michigan Specialized Program of Research Excellence in Head and Neck Cancer patient database (2008–2014), we reviewed patients’ referral documentation to identify those who received open neck mass biopsies as part of their squamous cell carcinoma diagnosis. We compared subsequent treatment between patients who did and did not receive an open neck mass biopsy.ResultsOf 940 patients, 50 patients had received open neck mass biopsy leading to squamous cell carcinoma diagnosis. Only 19 of 50 patients (38%) had undergone fine‐needle aspiration prior to open neck mass biopsy. There were no statistically significant differences in treatment or outcomes between patients who did and those who did not receive open neck mass biopsy.ConclusionOptimal care for patients who present with a neck mass is fine‐needle aspiration. Unfortunately, these data show that many patients undergo open neck mass biopsy for diagnosis, often without prior fine‐needle aspirate. Compared to fine‐needle aspiration, open biopsy incurs additional risks of general anesthesia and greater surgical risks. While our data did not find statistically significant differences between treatment offered and outcomes, this small study was not expected to demonstrate a difference in outcomes. Further work is needed to promote the utility of fine‐needle aspiration for diagnosis of neck mass and to discourage use of open neck mass biopsy as a primary diagnostic intervention.Level of Evidence2c (Outcomes Research)
Oxidative Epigallocatechin Gallate Coating on Polymeric Substrates for Bone Tissue Regeneration
Authors: Madhurakkat Perikamana Sajeesh Kumar , Lee Sang Min , Lee Jinkyu , Ahmad Taufiq , Lee Min Suk , Yang Hee Seok , Shin Heungsoo 
Published: January 2019

AbstractPlant derived flavonoids have not been well explored in tissue engineering applications due to difficulties in efficient formulations with biomaterials for controlled presentation. Here, the authors report that surface coating of epigallocatechin gallate (EGCG) on polymeric substrates including poly (L‐lactic acid) (PLLA) nanofibers can be performed via oxidative polymerization of EGCG in the presence of cations, enabling regulation of biological functions of multiple cell types implicated in bone regeneration. EGCG coating on the PLLA nanofiber promotes osteogenic differentiation of adipose‐derived stem cells (ADSCs) and is potent to suppress adipogenesis of ADSCs while significantly reduces osteoclastic maturation of murine macrophages. Moreover, EGCG coating serves as a protective layer for ADSCs against oxidative stress caused by hydrogen peroxide. Finally, the in vivo implantation of EGCG‐coated nanofibers into a mouse calvarial defect model significantly promotes the bone regeneration (61.52 ± 28.10%) as compared to defect (17.48 ± 11.07%). Collectively, the results suggest that EGCG coating is a simple bioinspired surface modification of polymeric biomaterials and importantly can thus serve as a promising interface for tuning activities of multiple cell types associated with bone fracture healing.