bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced oxygenation but not fibrosis defined by functional magnetic resonance imaging predicts the long-term progression of chronic kidney disease
Authors: Sugiyama Kei , Inoue Tsutomu , Kozawa Eito , Ishikawa Masahiro , Shimada Akira , Kobayashi Naoki , Tanaka Junji , Okada Hirokazu 
Published: September 2018

Abstract

Background
Although chronic hypoxia and fibrosis may be a key to the progression of chronic kidney disease (CKD), a noninvasive means of measuring these variables is not yet available. Here, using blood oxygen level–dependent (BOLD) and diffusion-weighted (DW) magnetic resonance imaging (MRI), we assessed changes in renal tissue oxygenation and fibrosis, respectively, and evaluated their correlation with prognosis for renal function.

Methods
The study was conducted under a single-center, longitudinal, retrospective observational design. We examined the prognostic significance of T2* values of BOLD-MRI and apparent diffusion coefficient (ADC) values on DW-MRI and other clinical parameters. The rate of decline in estimated glomerular filtration rate (eGFR) was calculated by linear regression analysis using changes in eGFR during the observation period.

Results
A total of 91 patients were enrolled, with a mean age of 55.8 ± 15.6 years. Among patients, 51 (56.0%) were males and 38 (41.8%) had diabetes mellitus. The mean eGFR was 49.2 ± 28.9 mL/min/1.73 m2 and the mean observation period was 5.13 years. ADC values of DW-MRI but not T2* values of BOLD-MRI were well correlated with eGFR at the initial time point. The mean annual rate of decline in eGFR during the 5-year observation period was −1.92 ± 3.00 mL/min/1.73 m2. On multiple linear regression analysis, the rate of decline in eGFR was significantly correlated with eGFR at the start point, period average amount of proteinuria and T2* values, but not with ADC values (t = 2.980, P = 0.004).

Conclusions
Reduced oxygenation as determined by low T2* values on BOLD-MRI is a clinically useful marker of CKD progression.
Drug discovery in China: challenges and opportunities
Authors: Wang Ling 
Published: September 2018

Abstract
Human history is also a chronicle of battling against diseases. Thanks to the rapid advancement of life science and biotechnologies such as gene editing and deep sequencing, recent decades have seen more and more untreatable illnesses on the verge of being conquered. However, an efficient drug-innovation system involves multiple driving forces—policy stimulation and commercial interests play important roles, besides advances in science and technology. Therefore, establishing the synergism among various driving forces is essential for new drug discovery and development. As the most populous country in the world, China has the largest population of a broad spectrum of diseases, offering a unique environment for research and development in biomedicine and disease therapies. Although most pharmaceutical companies in China have been focused on making generic drugs in the past, some efforts in developing first-in-class drugs are paying off, especially in the small-molecule drugs. What are the emerging trends in drug discovery? What does Artificial Intelligence (AI) bring to drug development and medical treatments? In the future, how will China take advantage of abundant resources and proactive policies to accelerate drug development? Recently, NSR organized a forum focusing on these issues, with the attendance of five distinguished domestic pharmaceutical scientists.

Ke Ding Professor in the College of Pharmacy, Jinan University, Jinan, China

Shengyong Yang Professor in the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

Zhen Yang Professor in the Department of Chemistry, Peking University, Beijing, China

Ao Zhang Professor in the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Demin Zhou Professor in the School of Pharmaceutical Sciences, Peking University, Beijing, China

Mu-ming Poo (Chair) Director of the Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Executive Editor-in-Chief of NSR, Shanghai, China
The Theory of Gendered Prejudice
Authors: Sidanius Jim , Hudson Sa-kiera T. J. , Davis Gregory K. , Bergh Robin 
Published: September 2018

Abstract
Over the last twenty-five years or so, there has been a growing awareness among race and gender scholars that a fully adequate analysis of these two forms of societal oppression cannot be done in isolation from one another. That is, an understanding of racism and sexism is fundamentally incomplete without an appreciation of how race and gender intersect and interact with one another in the creation and maintenance of group-based hierarchy and oppression. This chapter argues that while intersectionalist and critical race theorists have qualitatively (and occasionally quantitatively) drawn attention to the fact that the racial and gender dimensions of oppression are both interactively implicated in the maintenance of group-based inequality, a fully satisfactory empirical analysis of the dynamics of racism and sexism has yet to be achieved. Using the theoretical frameworks of evolutionary psychology and social dominance theory (SDT), this chapter offers an alternative understanding of the intersectional entanglement of racism and sexism. This chapter introduces the theory of gendered prejudice, a derivative of SDT, and posits that a satisfactory account of racism, or what social dominance theorists generalize as “arbitrary-set” oppression, is a deeply gendered phenomenon.
Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India
Authors: Sharma-Oates Archana , Shaaban Abeer M , Tomlinson Ian , Wynne Luke , Cazier Jean-Baptiste , Sundar Sudha 
Published: September 2018

Abstract
Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is rising. Major differences in the clinical presentation of breast and ovarian cancers exist between India and the United Kingdom. For example, Indian patients with breast cancer typically present a decade earlier than in the UK. Reasons for this could be multifactorial, including differences in underlying biology, environmental risks, and other systematic factors including access to screening. One possible explanation lies in variable incidence or penetrance of germline mutations in genes such as BRCA1 and BRCA2. We performed a methodical database and literature review to investigate the prevalence and spectrum of high-risk cancer susceptibility genes in Indian patients with breast and ovarian cancers. We identified 148 articles, but most studies were small, with inconsistent inclusion criteria and based on heterogeneous technologies, so that mutation frequency could not be reliably ascertained. Data were also often lacking on penetrance, histopathology, and survival outcomes. After filtering out unsuitable studies, only 13 remained, comprising 1028 patients. Large-scale research studies are urgently needed to determine mutation prevalence, spectra, and clinico-pathological features, and hence derive guidelines for screening, treatment, and prevention specific to the Indian population.
Perioperative Management of Buprenorphine: Solving the Conundrum
Authors: Quaye Aurora Naa-Afoley , Zhang Yi 
Published: September 2018

Abstract

Objective
There is no consensus on the optimal perioperative management of patients on buprenorphine (BUP) for opioid use disorder (OUD). This article will review the available literature on BUP and the analgesic efficacy of BUP combined with full mu-opioid agonists and discuss the conflicting management strategies in the context of acute pain and our institution’s protocol for the periprocedural management of BUP.

Methods
We searched published data on BUP periprocedural management from inception through March 2018 without language restrictions. Study selection included publications reporting outcomes on perioperative pain management in OUD patients maintained on BUP.

Results
Our search resulted in four case reports supporting periprocedural discontinuation of BUP and two case series, one secondary observational study, one prospective matched cohort study, and four retrospective cohort studies supporting periprocedural continuation of BUP. No clinical trials were identified.

Conclusions
Maintaining BUP perioperatively does not lead to worsened clinical outcomes. Patients can receive adequate pain control from mu-opioid agonists while maintained on BUP. Based upon available evidence, we recommend continuing BUP at a reduced dose when indicated to avoid withdrawal symptoms and to facilitate the analgesic efficacy of mu-opioid agonists administered in combination for acute postoperative pain.
Basic Knowledge of Contraception and Emergency Contraception is Low Among Recent Medical School Graduates
Authors: Miller Michael , Marengo Antoinette 
Published: September 2018

PURPOSE:
To evaluate the knowledge of recent medical school graduates regarding contraception and emergency contraception

BACKGROUND:
The Association of Professors of Gynecology and Obstetrics (APGO) medical student educational objectives includes contraception and emergency contraception among expected competencies, but little information exists on whether these objectives are being met.

METHODS:
A 28-question survey of basic contraception knowledge was created, including questions about LARC methods (12 questions), Tier 2 methods (10 questions) and emergency contraception (4 questions). Two consecutive intern classes were evaluated during hospital orientation.

RESULTS:
157 interns completed the survey, representing 73 medical schools. The overall correct score was 51.8%. Subscores were 56.7% for LARC methods, 62% for tier 2 methods, and 22.2% for emergency contraception. Men scored lower than women overall, 50% vs. 60.4%, P<.001, and on all subscores. Men were also less comfortable with contraceptive knowledge than women, 5.8 vs. 6.7 on a 10-point Likert scale, P=.006. Osteopathic physicians scored lower than allopathic physicians on overall score, 49.6% vs. 54.6%, P=.04, and emergency contraception, 12.5% vs. 25%, P=.01, but not on LARC, tier 2 methods or self-reported comfort. Those with high self-reported comfort levels scored higher on overall score, LARC and tier 2 methods, but not on emergency contraception. There was no difference in overall score when evaluated by amount of training received during medical school.

DISCUSSION:
Despite ubiquitous prescribing, medical school graduates have only rudimentary knowledge of contraception, particularly emergency contraception. Individual medical schools should evaluate their programs to determine how to improve knowledge of these important topics.
Influences of COMT rs4680 and OPRM1 rs1799971 Polymorphisms on Chronic Postsurgical Pain, Acute Pain, and Analgesic Consumption After Elective Cesarean Delivery
Authors: Wang Lizhong , Wei Changna , Xiao Fe , Chang Xiangyang , Zhang Yinfa 
Published: September 2018

Objectives:
The main objectives of this study were to assess the effects of cathechol-O-methyl-transferase (COMT) rs4680 and μ-opioid receptor rs1799971 polymorphisms alone or genotype combinations on chronic postsurgical pain (CPSP), acute pain, and analgesic consumption after elective cesarean delivery in a Chinese cohort.

Materials and Methods:
Two hundred sixty-six patients undergoing elective cesarean delivery with a Pfannenstiel incision under spinal anesthesia were enrolled in this prospective, observational study. All patients were screened for rs4680 and rs1799971 using a peripheral venous blood sample of DNA. Postoperative pain relief was provided by IV patient-controlled analgesia with sufentanyl and tramadol for 48 hours postoperatively. Postoperative pain scores and analgesic consumption were assessed, and CPSP was evaluated 3 months after surgery in all patients.

Results:
Twenty-nine patients (29/266; 10.9%) developed CPSP at 3 months after surgery. The risk factors for CPSP included previous cesarean delivery and higher analgesic consumptions at 24 hours and 48 hours postoperatively (P=0.032, 0.015, and 0.008, reapectively). No associations were found between CPSP and a single rs4680 and rs1799971 polymorphism, or their combinations (P>0.05). In contrast, patients with rs1799971 GG required higher patient-controlled analgesics at 24 hours and 48 hours postoperatively compared with those with other genotypes (GG>AG>AA). However, no significant effects of interactions between the 2 single nucleotide polymorphisms on analgesic consumption were observed.

Discussion:
Our results indicate that cathechol-O-methyl-transferase rs4860 and μ-opioid receptor rs1799971 may not contribute to CPSP development after cesarean delivery. The genotype of rs1799971 affects postcesarean analgesic requirement, while the rs4680 do not. Additional larger studies are needed to confirm these findings.
Impact of Synchronous Telemedicine Models on Clinical Outcomes in Pediatric Acute Care Settings: A Systematic Review*
Authors: Nadar Mahmoud , Jouvet Philippe , Tucci Marisa , Toledano Baruch , Sicotte Claude 
Published: September 2018

Objectives:
To evaluate the impact of synchronous telemedicine models on the clinical outcomes in pediatric acute care settings.

Data Sources:
Citations from EBM Reviews, MEDLINE, EMBASE, Global Health, PubMed, and CINAHL.

Study Selection:
We identified studies that evaluated the impact of synchronous telemedicine on clinical outcomes between January 2000 and April 2018. All studies involving acutely ill children in PICUs, pediatric cardiac ICUs, neonatal ICUs, and pediatric emergency departments were included. Publication inclusion criteria were study design, participants characteristics, technology type, interventions, settings, outcome measures, and languages.

Data Extraction:
Two authors independently screened each article for inclusion and extracted information, including telecommunication method, intervention characteristics, sample characteristics and size, outcomes, and settings.

Data Synthesis:
Out of the 789 studies initially identified, 24 were included. The six main outcomes of interest published were quality of care, hospital and standardized mortality rate, transfer rate, complications and illness severity, change in medical management, and length of stay. The use of synchronous telemedicine results improved quality of care and resulted in a decrease in the transfer rate (31–87.5%) (four studies), a shorter length of stay (8.2 vs 15.1 d) (six studies), a change or reinforcement of the medical care plan, a reduction in complications and illness severity, and a low hospital and standardized mortality rate. Overall, the quality of the included studies was weak.

Conclusions:
Despite the broad recommendations found for using telemedicine in pediatric acute care settings, high-quality evidence of its impacts is still lacking. Further robust studies are needed to better determine the clinical effectiveness and the associated impacts of telemedicine in pediatric acute care settings.
Microvascular Hepatic Artery Anastomosis in Pediatric Living Donor Liver Transplantation: 73 Consecutive Cases Performed by a Single Surgeon
Authors: Zuo Kevin J. , Draginov Arman , Panossian Andre , Fecteau Annie , Borschel Gregory H. , Ho Emily S. , Zuker Ronald M. 
Published: September 2018

Background:
Living donor liver transplantation is an important strategy of procuring segmental liver allografts for pediatric patients with liver failure, as suitably sized whole donor organs are scarce. The early pediatric living donor liver transplantation experience was associated with high rates of hepatic artery thrombosis, graft loss, and mortality. Collaboration with microsurgeons for hepatic artery anastomosis in pediatric living donor liver transplantation has decreased rates of arterial complications; however, reported outcomes are limited.

Methods:
A 14-year retrospective review was undertaken of children at the authors’ institution who underwent living donor liver transplantation with hepatic artery anastomosis performed by a single microsurgeon using an operating microscope. Data were collected on demographics, cause of liver failure, graft donor, vessel caliber, vessel anastomosis, arterial complications, and long-term follow-up.

Results:
Seventy-three children with end-stage liver failure underwent living donor liver transplantation with microvascular hepatic artery anastomosis. The commonest cause for liver failure was biliary atresia (63 percent). A total of 83 end-to-end hepatic artery anastomoses were completed using an operating microscope. Hepatic artery complications occurred in five patients, consisting of three cases of kinked anastomoses that were revised without complications and two cases of hepatic artery thrombosis (3 percent), of which one resulted in graft loss and patient death. Patient survival was 94 percent at 1 year and 90 percent at 5 years.

Conclusions:
Microvascular hepatic artery anastomosis in pediatric patients undergoing living donor liver transplantation is associated with a low hepatic artery complication rate and excellent long-term liver graft function. Collaboration between microsurgeons and transplant surgeons can significantly reduce technical complications and improve patient outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Theory of cytoskeletal reorganization during crosslinker-mediated mitotic spindle assembly
Authors: Lamson A. R. , Edelmaier C. J. , Glaser M. A. , Betterton M. D. 
Published: September 2018

AbstractCells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, during which micro-tubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, crosslinking, and motor-protein activity. Remarkably, using passive crosslinkers, fission yeast can assemble a bipolar spindle in the absence of motor proteins. We develop a torque-balance model that describes this reorganization due to dynamic microtubule bundles, spindle-pole bodies, the nuclear envelope, and passive crosslinkers to predict spindle-assembly dynamics. We compare these results to those obtained with kinetic Monte Carlo-Brownian dynamics simulations, which include crosslinker-binding kinetics and other stochastic effects. Our results show that rapid crosslinker reorganization to microtubule overlaps facilitates crosslinker-driven spindle assembly, a testable prediction for future experiments. Combining these two modeling techniques, we illustrate a general method for studying cytoskeletal network reorganization.
Gpr63is a novel modifier of microcephaly inTtc21bmouse mutants
Authors: Snedeker J. , Gibbons WJ , Prows D.R. , Stottmann R.W. 
Published: September 2018

ABSTRACTThe primary cilium is a critical signaling center for proper embryonic development. Previous studies have demonstrated that mice lackingTtc21bhave impaired retrograde trafficking within the cilium and multiple organogenesis phenotypes, including microcephaly. Interestingly, the severity of the microcephaly inTtc21baln/alnhomozygous null mutants is considerably affected by the genetic background.Ttc21baln/alnmutants on an FVB/NJ background develop a forebrain significantly smaller than mutants on a C57BL/6J background. We performed a Quantitative Trait Locus (QTL) analysis to identify potential genetic modifiers and identified two regions linked to differential forebrain size:modifier of alien QTL1 (Moaq1)on chromosome 4 at 27.8 Mb andMoaq2on chromosome 6 at 93.6 Mb. These QTLs were validated by constructing congenic strains. Further analysis ofMoaq1identified a brain specific orphan G-protein coupled receptor (GPCR),Gpr63, as a candidate gene. We identified a SNP between the FVB and B6 strains inGpr63, which creates a missense mutation predicted to be deleterious in the FVB protein. We first demonstrated thatGpr63can localize to the cilium and then used CRISPR-Cas9 genome editing to create FVB congenic mice with the B6 sequence ofGpr63and a deletion allele leading to a truncation of the GPR63 C-terminal tail. These alleles genetically interact withTtc21baln/aln, validatingGpr63as a forebrain modifier ofTtc21band strongly supportingGpr63as the variant causal gene (i.e., the quantitative trait gene, QTG) forMoaq1.
Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions
Authors: Lin Yanxian , McCarty James , Rauch Jennifer N. , Delaney Kris T. , Kosik Kenneth S. , Fredrickson Glenn H. , Shea Joan-Emma , Han Songi 
Published: September 2018

AbstractThe conditions that lead to the liquid-liquid phase separation (LLPS) of the tau protein, a microtubule associated protein whose pathological aggregation has been implicated in neurodegenerative disorders, are not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding its LLPS. Using a combination of EPR, turbidity measurements, and microscopy, we show that tau and RNA form complex coacervates with lower critical solution temperature (LCST) behavior. The coacervates are reversible, and the biopolymers can be driven to the supernatant phase or coacervate phase by varying the experimental conditions (temperature, salt concentration, tau:RNA charge ratio, total polymer concentration and osmotic stress). Furthermore, the coacervates can be driven to a fibrillar state through the addition of heparin. The equilibrium phase diagram of the tau/RNA complex coacervate system can be described by a Flory-Huggins model, augmented by an approximate Voorn Overbeek electrostatic term (FH-VO), after fitting the experimental data to an empirical Flory interaction parameter divided into an entropic and enthalpic term. However, a more advanced model in which tau and RNA are treated as discrete bead-spring chains with a temperature-dependent excluded volume interaction and electrostatic interactions between charged residues, investigated through field theoretic simulations (FTS), provided direct and unique insight into the thermodynamic driving forces of tau/RNA complexation. FTS corroborated the experimental finding that the complex coacervation of tau and RNA is has an entropy-driven contribution, with a transition temperature around the physiological temperature of 37 °C and salt concentrations around 100-150 mM. Together, experiment and simulation show that LLPS of tau can occur under physiological cellular conditions, but has a narrow equilibrium window over experimentally tunable parameters including temperature, salt and tau concentrations. Guided by our phase diagram, we show that tau can be driven towards LLPS underlivecell coculturing conditions with rationally chosen experimental parameters.
Non‐invasive three‐dimensional power Doppler imaging for the assessment of acute cerebral blood flow alteration in a mouse model of subarachnoid haemorrhage
Authors: Yamamoto Shuzo , Mutoh Tatsushi , Sasaki Kazumasu , Mutoh Tomoko , Tatewaki Yasuko , Taki Yasuyuki 
Published: September 2018

SummaryWe aimed to evaluate the feasibility of a non‐invasive method of cerebral blood flow (CBF) measurement using high‐frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3‐dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r2 = 0.52, P < 0.0001) and normalized CBF changes (r2 = 0.74 P < 0.0001). These data suggest that the 3D power Doppler analysis may have the potential for reflecting real‐time CBF changes during the acute phase of experimental SAH, which may be applicable to preclinical studies on early brain injury.