bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Paraventricular Melatonin Receptor 2 Mediates Melatonin-Conferred Cardioprotection Against Myocardial Ischemia/Reperfusion Injury
Authors: Zhang Chao , Yang Jin-Bao , Quan Wei , Feng Ying-Da , Feng Jian-Yu , Cheng Liu-Siyuan , Li Xiao-Qiang , Zhang Hui-Nan , Chen Wen-Sheng 
Published: May 2020

Abstract:
Previous studies have shown that melatonin (Mel) can effectively ameliorate myocardial ischemia/reperfusion (MI/R) injury, but the mechanism is yet to be fully elucidated. Mel receptors are expressed in the paraventricular nucleus (PVN), which is also involved in regulating cardiac sympathetic nerve activity. The aim of this study was to examine whether Mel receptors in the PVN are involved in the protective effects of Mel against MI/R injury. The results of quantitative polymerase chain reaction, western blot, and immunofluorescence assays indicated that Mel receptor 2 (MT2) expression in the PVN was upregulated after MI/R. Intraperitoneal administration of Mel significantly improved post-MI/R cardiac function and reduced the infarct size, whereas shRNA silencing of MT2 in the PVN partially blocked this effect. Intraperitoneal administration of Mel reduced sympathetic nerve overexcitation caused by MI/R, whereas shRNA silencing of MT2 in the PVN partially diminished this effect. Furthermore, enzyme-linked immunosorbent assay and western blot results indicated that intraperitoneal administration of Mel lowered the levels of inflammatory cytokines in the PVN after MI/R injury, whereas the application of sh-MT2 in the PVN reduced this effect of Mel. Mel significantly reduced the levels of NF-κB after astrocyte oxygen and glucose deprivation/reoxygenation injury, and this effect was offset when MT2 was silenced. The above experimental results suggest that MT2 in the PVN partially mediated the protective effects of Mel against MI/R injury, and its underlying mechanisms may be related to postactivation amelioration of PVN inflammation and reduction of cardiac sympathetic nerve overexcitation.
HLA-B*58:01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia
Authors: Low Dyoi E , Nurul-Aain Ahmad Fauzi , Tan Wooi Chiang , Tang Jyh Jong , Bakhtiar Mohammed Faizal , Murad Shahnaz , Chang Choong Chor , Too Chun Lai , Tang Min Moon 
Published: May 2020

Objective
The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.

Methods
We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).

Results
HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6–164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9–470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5–169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3–1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8–619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6–442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.

Conclusion
Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN
Cost-effectiveness analysis of pretreatment screening for NUDT15 defective alleles
Authors: Zarca Kevin , Chansavang Albain , Loriot Marie-Anne , Durand-Zaleski Isabelle , Pallet Nicolas 
Published: May 2020

Background
Nucleotide triphosphate diphosphatase (NUDT15) genetic testing in addition to thiopurine methyl transferase (TPMT) is recommended to reduce the incidence of adverse severe myelotoxicity episodes induced by thiopurines.

Objective
We assessed the cost-effectiveness ratio of combined screening for TMPT and NUDT15 defective alleles by genotyping or next-generation sequencing (NGS) using TPMT genotyping as the reference. Because of the genetic differences in thiopurine toxicity, we tested the screening strategies on individuals of Caucasian and Asian descent.

Methods
A decision tree compared conventional TPMT genotyping with combined TPMT/NUDT15 genotyping or NGS using a Monte-Carlo microsimulation model of patients with inflammatory bowel disease. The main outcome was the incremental cost-effectiveness ratios (ICER) with effectiveness being one averted severe myelotoxicity requiring hospitalization.

Results
The mean estimated cost of the TPMT genotyping for one year is twice in Asian compared with Caucasian patients (980 euro/patient versus 488 euro/patient), and the effectiveness of TPMT genotyping in Caucasian avoided 43 severe myelosuppressions per 10 000 patients over a year compared with 3.6 per 10 000 patients in Asian. Combined TPMT/NUDT15 genotyping compared with TPMT genotyping had an ICER of 7 491 281 euro per severe myelotoxicity averted in Caucasian, compared to 619 euro in Asian. The ICER of the NGS-based screening strategy is disproportionally high compared with genotyping, irrespective of ethnic descent.

Conclusion
With a low cost-effectiveness threshold, combined screening for NUDT15 and TPMT defective alleles is cost-effective compared to TMPT screening alone in patients of Asian descent, but is unrealistic from a cost-effectiveness point of view in Caucasians.
ASSOCIATION OF SERUM VASOGENIC AND PROINFLAMMATORY FACTORS WITH CLINICAL RESPONSE TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR FOR DIABETIC MACULAR EDEMA
Authors: Brito Pedro S. , Costa Jorge V. , Barbosa-Matos Catarina , Costa Sandra M. , Correia-Pinto Jorge , Silva Rufino M. 
Published: May 2020

Purpose:
To study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti–vascular endothelial growth factor injections for diabetic macular edema (DME).

Methods:
Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change < 10%, a CST change >20%, and a CST <330 µm, achieving an improvement ≥2 lines of visual acuity, achieving visual acuity ≥20/40.

Results:
A significant improvement in CST and visual acuity was seen from third month onwards. Twenty-eight (48.1%) cases were classified as “early responders,” 24 (35.8%) as “late responders”, and 15 (22.4%) as “poor responders.” Serum vascular endothelial growth factor–A levels were significantly lower in “poor responders” (P = 0.006). C-reactive protein (hsCRP) was associated with a limited anatomic response (<10% CST change) (P = 0.002, OR = 1.845, cutoff value of hsCRP = 1.84 mg/L). hsCRP was also negatively associated with obtaining a final CST <330 µm (P = 0.04, r2 = 0.112, OR = 0.643). Baseline visual acuity was significantly associated with 12th month visual acuity (P < 0.001, r2 = 0.602) and also with an improvement ≥2 visual acuity lines (P = 0.009, OR = 20.54).

Conclusion:
Increased high-sensitivity C-reactive protein was associated with limited anatomic response to anti–vascular endothelial growth factor treatment and persistent DME. Poor responders had significantly lower values of serum vascular endothelial growth factor–A, suggesting an alternative pathogenic pathway for persisting DME.
A Prospective Analysis of iStent Inject Microstent Implantation: Surgical Outcomes, Endothelial Cell Density, and Device Position at 12 Months
Authors: Gillmann Kevin , Mansouri Kaweh , Ambresin Aude , Bravetti Giorgio E. , Mermoud André 
Published: May 2020

Precis:
The surgical outcome of iStent inject devices is associated with device protrusion within the anterior chamber. Schlemm canal (SC) dilatation has a prognostic value. iStent inject devices do not move within the first year after implantation.

Introduction:
The iStent inject is a device designed to be implanted ab-interno through the trabecular meshwork. The present study follows up on our preliminary report, using successive in vivo anterior segment optical coherence tomography (AS-OCT) imaging to analyze the associations between stent positioning, iridocorneal angle structures, and surgical outcomes.

Methods:
In total, 54 eyes of 42 patients (73.3±7.4 y) with cataract and mild-to-moderate open-angle glaucoma were examined in this prospective study. All patients underwent implantation of 2 iStent inject devices combined with phacoemulsification. Patients were followed up over a 12-month period. AS-OCT was performed after 3 and 12 months. Thirty unoperated fellow eyes served as control eyes.

Results:
Intraocular pressure (IOP) decreased from 16.5±4.2 mm Hg at baseline to 15.1±3.7 mm Hg at 12 months (−8.7%; P=0.004), while medications decreased from 1.8±1.0 to 0.5±0.9 (−72.2%; P<0.001). Unmedicated IOP≤18 mm Hg was achieved in 58.8% of operated eyes. No sight-threatening complications were reported. On AS-OCT, 44.9% of devices were buried within the trabeculum. Device position was unchanged between scans. Regression analysis elicited significant predictors: SC dilatation effect [risk ratio (RR)=0.230; P=0.003], greatest SC diameter (RR=0.991; P=0.049), extrusion of the most anterior device (RR=0.993; P=0.012), gonioscopically visible devices (RR=0.406; P=0.040), baseline treatments (RR=2.214; P=0.001), and baseline IOP (RR=0.184; P=0.006). Endothelial cell density decreased by 14.6% at 12 months (P<0.001).

Conclusions:
This study demonstrates the IOP-lowering and medication-lowering potential of iStent inject surgery in primary open-angle and pseudoexfoliative glaucoma. It confirms that surgical outcomes are positively associated with device protrusion within the anterior chamber, and suggests SC dilatation effect as a favorable prognostic indicator. It shows that stents are stable in time, highlighting the importance of the initial implantation location.
Endogenous Vancomycin-Resistant Enterococcus gallinarum Endophthalmitis in Hematologic Malignancy
Authors: Shahin Alexander V. , Elkhayat Adam I. , Greene John N. 
Published: May 2020

Abstract
Patients with hematologic malignancy are immunocompromised either due to the underlying disease or from chemotherapy, resulting in an increased risk for opportunistic infections. Neutropenic patients with vancomycin-resistant Enterococci colonization are at risk of bacteremia with rare endogenous dissemination, which can result in hematogenous spread to the eye. We describe a patient with a hematologic malignancy with treatment-related neutropenia who developed endogenous vancomycin-resistant Enterococcus gallinarum endophthalmitis along with a review of the literature related to this case.
Thromboelastography as a tool for monitoring blood coagulation dysfunction after adequate fluid resuscitation can predict poor outcomes in patients with septic shock
Authors: Zhao Hui , Cai Xiujun , Liu Ning , Zhang Zhongheng 
Published: May 2020

Background:
Coagulation abnormalities are universal in patients with septic shock and likely play a key role in multiple organ dysfunction syndrome. Early diagnosis and management of sepsis-induced coagulopathy can influence the outcome. Thromboelastography (TEG) can effectively distinguish hypercoagulability and hypocoagulability in patients with septic shock. TEG may be a useful tool to objectively evaluate the degree and risk of sepsis.

Methods:
A total of 76 adult patients with septic shock were enrolled and divided into four groups: patients with hypotension requiring vasopressor and serum lactate level >2 mmol/L (group A), patients with hypotension requiring vasopressor and serum lactate level ≤2 mmol/L (group B), patients with mean arterial pressure ≥65 mmHg and serum lactate level >2 mmol/L (group C), and patients with mean arterial pressure ≥65 mmHg and serum lactate level ≤2 mmol/L (group D) after adequate fluid resuscitation. TEG values were obtained at the emergency room and after 6 hours of adequate fluid resuscitation. Data on fibrinogen (FIB) levels, international normalized ratio (INR), activated partial thromboplastin time (aPTT), blood gas, platelet count, and d-dimers were also collected.

Results:
The length of stay in the intensive care unit was 9.11 ± 5.36 days. Mortality rate was 6.58%. The values of reaction time, kinetics time, maximum amplitude, alpha angle, aPTT, INR, serum creatinine, FIB, and sepsis-related organ failure assessment (SOFA) score showed a significant differences. The results of the routine coagulation tests, blood gas volume, platelet count, procalcitonin level, d-dimer level, white blood cell count, creatinine level, disseminated intravascular coagulation score, SOFA score, and TEG values after adequate fluid resuscitation were significantly different between groups A and B, groups A and C, groups A and D, groups B and D, and groups C and D.

Conclusion:
TEG is helpful in predicting the severity of sepsis and outcome of patients.
Self-management Needs of Adults With Congenital Heart Disease
Authors: Hays Laura H. , McSweeney Jean C. , Mitchell Anita , Bricker Christina , Green Angela , Landes Reid D. 
Published: May 2020

Background
Adults with congenital heart disease (CHD) are an emerging adult heart disease subset, now outnumbering the pediatric population with CHD.

Objective
We aimed to gain understanding and knowledge of what adults with CHD perceive as important for self-management and describe these needs across demographic factors, developmental characteristics, lesion severity, and quality of life.

Methods
We used a descriptive mixed-methods online survey merging 4 instruments: Adult CHD Self-management Experience Questionnaire; Adult CHD Demographic Questionnaire; Adaptive Behavior Assessment System, Third Edition; and Stanford Quality of Life Visual Numeric. Participants with CHD 18 to 30 years of age with initial defect repair before 12 months of age were recruited through support from the Adult Congenital Heart Association, clinic adult CHD support groups, and newspaper advertising. Thematic analysis for short-answer questions, descriptive analysis for demographic data and the visual numeric, and intrument-specific scoring assistant software for the Adaptive Behavior Assessment System were used.

Results
We received 22 responses from 13 women and 9 men. These individuals represented 15 different heart defect diagnoses, mostly of moderate or complex lesion severity. Most had postsecondary education and were employed. Four prominent themes emerged related to self-management: desire for connectivity—psychological support; a plan for the future—education about health and life expectations; coping needs—skills for mental stress; and access to care—navigation of healthcare systems.

Conclusions
Future longitudinal research and replication studies with larger samples are needed. Educational materials and targeted interventions that promote self-management benefit the aging adult with CHD population.
Special Article: Translational Science Update. Pharmacological Implications of Emerging Schizophrenia Genetics
Authors: Birnbaum Rebecca , Weinberger Daniel R. 
Published: May 2020

Abstract
Recent schizophrenia genome-wide association studies (GWAS) have identified genomic variants of common and rare frequency, significantly associated with schizophrenia. While numerous functional genomics efforts are ongoing to elucidate the biological effects of schizophrenia risk variants, a consideration of their therapeutic implications is timely and imperative, for patients as well as for an iterative effect on elucidating the underlying biology and pathophysiology of illness. The current article reviews efforts to translate emerging schizophrenia genomics into novel approaches to target discovery and therapeutic intervention. Though the path from ‘genetic risk to therapy’ is far from straightforward, there are provocative early possibilities that harbor the promise of treatment based on causation rather than phenomenology, as well as ‘precision psychiatry,’ a basis for stratifying patients to enable more precise and effective, personalized therapy.
Correlates to Increased Risk of Sexual Assault and Sexual Harassment Among LGBT+ University Students
Authors: Tilley Donna Scott , Kolodetsky Ann , Cottrell Damon , Tilton Abigail 
Published: May 2020

ABSTRACT

Background
Although the rates of sexual assault in general are alarming, students who identify as lesbian, gay, bisexual, transgender, queer, asexual, or pansexual, hereafter referred to as LGBT+, are even more likely to experience sexual assault.

Aim
The aim of this study was to examine the correlates to sexual assault and other forms of sexual misconduct of LGBT+ college students.

Methods
The Administrator Researcher Campus Climate Collaborative campus climate survey was administered at 10 universities, and a final sample size of 6,973 student surveys were analyzed. All continuous and categorical data were compared by sexual orientation using linear mixed models and logistic generalized linear mixed models.

Results
In this study, we learned that LGBT+ students are more likely than their heterosexual peers to have friends who approve of risky sexual behavior, which is correlated with sexual victimization; understand that absence of physical resistance does not confer consent; engage in bystander intervention; and anticipate supportive responses from peers. LGBT+ students are less likely than their heterosexual peers to feel an overall sense of well-being, perceive that the campus climate regarding sexual misconduct was positive, and feel that the campus was safe. There were no differences between LGBT+ students and heterosexual students regarding most elements of consent, perpetration of any sexual misconduct (stalking, sexual harassment, sexual assault), or stalking victimization.

Discussion
Interventions to reduce campus sexual assault must be tailored to fit the students. Lack of clarity around consent and bystander intervention education are the mainstay of campus sexual assault prevention efforts.
Effect of the implementation of a new guideline for minor head injury on computed tomography-ratio and hospitalizations in the Netherlands
Authors: van den Brand Crispijn L. , Perotti Joeri R. , van der Linden M. Christien , Tolido Tanya , Jellema Korné 
Published: May 2020

Objective
A new nationwide guideline for minor head injury was introduced in the Netherlands in 2010. The effect on computed tomography (CT) ratio and hospital admission ratio after introduction of the guideline is unknown. The aim was to reduce these numbers as part of cost-effective health care. Therefore, we assessed the effect on these variables after introduction of the guideline.

Methods
We used an interrupted time-series study design. Data selection was done 3 years before (2007–2009) and several years after (2012, 2014, 2015) introduction of the guideline.

Results
Data collection was performed for 3880 patients. Introduction of the new guideline was associated with an increase in CT ratio from 24.6% before to 55% after introduction (P < 0.001). This increase is the result of both the new guideline and a secular trend. Besides this, hospital admissions increased from 14.7 to 23.4% (P < 0.001) during the study period. This increase was less clearly associated with the new guideline. After introduction of the guideline there was no significant difference in (intra)cranial traumatic findings (2.6% vs. 3.4%; P = 0.13) and neurosurgical interventions (0.1% vs. 0.2%; P = 0.50).

Conclusion
Between 2007 and 2015, a marked increase in CT ratio and hospital admissions has been observed. The increase in CT ratio seems to be caused both by the new guideline and by a secular trend to perform more CT scans. Adaptations to the guideline should be considered to improve patient care and cost-effectiveness in patients with minor head injury.
Clinical Utility of Histological and Radiological Evaluations of Tumor Necrosis for Predicting Prognosis in Pancreatic Cancer
Authors: Kudo Masashi , Kobayashi Tatsushi , Gotohda Naoto , Konishi Masaru , Takahashi Shinichiro , Kobayashi Shin , Sugimoto Motokazu , Okubo Satoshi , Martin John , Cabral Horacio , Ishii Genichiro , Kojima Motohiro 
Published: May 2020

Objectives
Tumor necrosis is often found in pancreatic ductal adenocarcinoma (PDAC). Objective histological assessment and adequate radiological detection of necrosis could be used as biomarkers for therapeutic decision. However, standardized clinical utility of necrosis remains unknown. Here, we aimed to determine the prognostic potential of histological and radiological evaluations of necrosis.

Methods
We investigated histological necrosis in 221 patients, who underwent surgery for PDAC, and classified its size as small (≤5 mm) or large (>5 mm). We also evaluated poorly enhanced areas on preoperative computed tomography to assess their ability for predicting histological necrosis and postoperative prognosis.

Results
Tumor necrosis was found in 115 patients (52%) and was related to tumor area, lymph node metastasis, and lymphovascular invasion. Size of necrosis was significantly associated with tumor area, perimeter of necrosis, circularity of necrosis, number of ruptured cancer glands, and presence of collagen bundle (P < 0.05 for all). Both presence of necrosis and their size were strongly correlated to postoperative prognosis. Patients with poorly enhanced areas showed worse prognosis (P < 0.01).

Conclusions
Our findings underline the capacity of histological and radiological assessment of tumor necrosis for prognosis prediction in PDAC.