bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Protective Roles of PPARα Activation in Triptolide-Induced Liver Injury
Authors: Hu Dan-Dan , Zhao Qi , Cheng Yan , Xiao Xue-Rong , Huang Jian-Feng , Qu Yan , Li Xian , Tang Ying-Mei , Bao Wei-Min , Yang Jin-Hui , Jiang Tao , Hu Jia-Peng , Gonzalez Frank J , Li Fei 
Published: June 2019

Abstract
Triptolide (TP), one of the main active ingredients in Tripterygium wilfordii Hook F, is clinically used to treat immune diseases but is known to cause liver injury. The aim of this study was to investigate the biomarkers for TP-induced hepatotoxicity in mice and to determine potential mechanisms of its liver injury. LC/MS-based metabolomics was used to determine the metabolites that were changed in TP-induced liver injury. The accumulation of long-chain acylcarnitines in serum indicated that TP exposure disrupted endogenous peroxisome proliferator-activated receptor α (PPARα) signaling. Triptolide-induced liver injury could be alleviated by treatment of mice with the PPARα agonist fenofibrate, whereas the PPARα antagonist GW6471 increased hepatotoxicity. Furthermore, fenofibrate did not protect Ppara−/− mice from TP-induced liver injury, suggesting an essential role for the PPARα in the protective effect of fenofibrate. Elevated long-chain acylcarnitines may protect TP-induced liver injury through activation of the NOTCH-NRF2 pathway as revealed in primary mouse hepatocytes and in vivo. In agreement with these observations in mice, the increase in long-chain acylcarnitines was observed in the serum of patients with cholestatic liver injury compared with healthy volunteers. These data demonstrated the role of PPARα and long-chain acylcarnitines in TP-induced hepatotoxicity, and suggested that modulation of PPARα may protect against drug-induced liver injury.
Gestational and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Downregulates Junctional Proteins, Thyroid Hormone Receptor α1 Expression, and the Proliferation-Apoptosis Balance in Mammary Glands Post Puberty
Authors: Gouesse Rita-Josiane , Lavoie Mélanie , Dianati Elham , Wade Mike G , Hales Barbara F , Robaire Bernard , Plante Isabelle 
Published: June 2019

AbstractMammary gland development requires hormonal regulation during puberty, pregnancy, and lactation. Brominated flame retardants (BFRs) are endocrine disruptors; they are added to consumer products to satisfy flammability standards. Previously, we showed that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts proteins of the adherens junctions in rat dam mammary glands at weaning. Here, we hypothesize that perinatal exposure to the same BFR mixture also disrupts junctional proteins and signaling pathways controlling mammary gland development in pups. Dams were exposed through diet to a BFR mixture based on the substances in house dust; doses of the mixture used were 0, 0.06, 20, or 60 mg/kg/day. Dams were exposed continuously beginning prior to mating until pups’ weaning; female offspring were euthanized on postnatal day (PND) 21, 46, and 208. The lowest dose of BFRs significantly downregulated adherens junction proteins, E-cadherin, and β-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha 1 protein at PND 46. No effects were observed on estrogen or progesterone receptors. The low dose also resulted in a decrease in cleaved caspase-3, a downward trend in PARP levels, proteins involved in apoptosis, and an upward trend in proliferating cell nuclear antigen, a marker of proliferation. No effects were observed on ductal elongation or on the numbers of terminal end buds. Together, our results indicate that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts cell-cell interactions, thyroid hormone homeostasis and the proliferation-apoptosis balance at PND 46, a critical stage for mammary gland development.
Pattern of antibiotic prescribing and factors associated with it in eight village clinics in rural Shandong Province, China: a descriptive study
Authors: Yin Jia , Dyar Oliver James , Yang Peng , Yang Ding , Marrone Gaetano , Sun Mingli , Sun Chengyun , Sun Qiang , Lundborg Cecilia Stålsby 
Published: June 2019

Abstract

Background
This study describes the patterns of antibiotic prescribing in eight village clinics in rural China and evaluates factors associated with antibiotic prescribing using quantitative and qualitative methods.

Methods
From January 2015 to July 2017, 60 prescriptions were collected monthly from selected village clinics in Shandong, China. Village clinic doctors completed a questionnaire regarding their knowledge of antibiotic prescribing. Semi-structured interviews were conducted with 15 village doctors and 1 deputy director from the township hospital.

Results
Of the 14 526 prescriptions collected, 5851 (40.3%) contained at least one antibiotic, among which 18.4% had two or more antibiotics and 24.3% had parenteral antibiotics. The antibiotic prescribing rate (β=−0.007 [95% confidence interval −0.009 to −0.004]) showed a declining trend (1.7% per month). Higher antibiotic prescribing rates were observed for patients <45 y of age and those diagnosed with upper respiratory tract infections and among village doctors who had less working experience and a lower level of knowledge on antibiotic prescribing. Qualitative analyses suggested that antibiotic prescribing was influenced by the patients’ symptoms, patients’ requests, policies restraining the overuse of antibiotics, subsidies for referral and routine village doctor training.

Conclusions
Antibiotic prescribing has declined in the included village clinics, which may be due to the policy of reducing antibiotic overuse in primary health care centres in China.
Assessing species boundaries in the open sea: an integrative taxonomic approach to the pteropod genus Diacavolinia
Authors: Burridge Alice K , Van Der Hulst Remy , Goetze Erica , Peijnenburg Katja T C A 
Published: June 2019

AbstractTo track changes in pelagic biodiversity in response to climate change, it is essential to accurately define species boundaries. Shelled pteropods are a group of holoplanktonic gastropods that have been proposed as bio-indicators because of their vulnerability to ocean acidification. A particularly suitable, yet challenging group for integrative taxonomy is the pteropod genus Diacavolinia, which has a circumglobal distribution and is the most species-rich pteropod genus, with 24 described species. We assessed species boundaries in this genus, with inferences based on geometric morphometric analyses of shell-shape variation, genetic (cytochrome c oxidase subunit I, 28S rDNA sequences) and geographic data. We found support for a total of 13 species worldwide, with observations of 706 museum and 263 freshly collected specimens across a global collection of material, including holo‐ and paratype specimens for 14 species. In the Atlantic Ocean, two species are well supported, in contrast to the eight currently described, and in the Indo‐Pacific we found a maximum of 11 species, partially merging 13 of the described species. Distributions of these revised species are congruent with well-known biogeographic provinces. Combining varied datasets in an integrative framework may be suitable for many diverse taxa and is an important first step to predicting species-specific responses to global change.
PREVALENCE AND TIME TRENDS OF MYOPIA IN CHILDREN AND ADOLESCENTS IN CHINA
Authors: Dong Li , Kang Yi Kun , Li Yang , Wei Wen Bin , Jonas Jost B. 
Published: June 2019

Purpose:
To estimate prevalence, associated factors, and time trends of myopia in Chinese children and adolescents.

Methods:
We searched PubMed, EMBASE, and Web of Science for studies examining the prevalence of myopia in children and adolescents aged 3 years to 19 years in China before October 2018. We pooled the prevalence and associated factors for myopia and estimated time trends.

Results:
In 22 eligible studies including 192,569 individuals, the pooled prevalence (95% confidence interval [CI]) of myopia and high myopia in the study period from 1998 to 2016 was 37.7% (95% CI: 23.5–52.0%) and 3.1% (95% CI: 1.2–5.0%), respectively, with higher odds for girls than boys (myopia: odds ratio: 1.29; 95% CI: 1.14–1.46; P < 0.001; high myopia: odds ratio: 1.37; 95% CI: 1.05–1.78; P = 0.02) and with higher prevalences for urban areas than rural regions (myopia: 48.8% [95% CI: 32.3–65.3] vs. 31.9% [95% CI: 20.4–43.3; P < 0.001]). The pooled prevalence of myopia and high myopia increased from 4.7% (95% CI: 2.5–6.9) and 0.2% (95% CI: 0.0–0.5), respectively, in <7-years-olds to 56.2% (95% CI: 29.8–82.5) and 15.1% (95% CI: 6.4–23.8), respectively, in 16- to 18-year-olds. Myopic refractive error increased with older age (P < 0.001), female gender (P < 0.001), and study year (P = 0.003). Studies performed after 2013 showed a prevalence of myopia and high myopia in the 16- to 18-year-olds of 84.8% (95% CI: 84.4–85.2%) and 19.3% (95% CI: 18.6–20.2%), respectively. Assuming a further linear relationship with the study year, myopia prevalence in 2050 among children and adolescents aged 3 years to 19 years would be estimated to be about 84%.

Conclusion:
The marked rise in high myopia prevalence among adolescents in China may be of importance for high myopia as risk factor for irreversible vision loss in Chinese adults in the future.
INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUES AND OUTER RETINAL LAYER STRUCTURES
Authors: Faria Mun Yueh , Proença Helena , Ferreira Nuno G. , Sousa David Cordeiro , Neto Eliana , Marques-Neves Carlos 
Published: June 2019

Purpose:
To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery.

Methods:
Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole.

Results:
Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (>400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients.

Conclusion:
Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.
Electron Microscopic Evidence of Photoreceptor Outer-segments in the Trabecular Meshwork in a Case of Schwartz-Matsuo Syndrome
Authors: Clark Antony , Alkhotani Alaa , Yucel Yeni H. , Sylvester Carly , Kertes Peter J. , Birt Catherine M. 
Published: June 2019

Purpose:
To describe a case of photoreceptor outer segment glaucoma (Schwartz-Matsuo syndrome) with electron microscopic evidence of photoreceptor outer segments in the trabecular meshwork (TM).

Design:
This is a clinicopathologic case report.

Participant:
A 48-year-old Filipino man.

Methods:
Specimens of aqueous humor and TM in a clinical case of Schwartz-Matsuo syndrome were examined by electron microscopy.

Main Outcome Measures:
Electron photomicroscopy.

Results:
Electron microscopy showed evidence of retinal photoreceptor outer-segments in both an aqueous humor and a TM specimen.

Conclusion:
Schwartz-Matsuo syndrome is associated with the presence of photoreceptor outer segments in the TM.
Predictive Factors Associated With In-Hospital Mortality for Patients Across the Sepsis Spectrum
Authors: Baccaglini Lorena , Araz Ozgur M. , Naveed Zaeema , Whitsitt Ben , Beachy Micah , Winterboer Tammy , Haynatzki Gleb , Ash Michael 
Published: June 2019

Introduction
Sepsis poses a large burden for hospitals across the world owing to its high resource utilization and poor patient outcomes. This project aimed to assess and quantify the importance of sepsis-specific predictors for in-hospital mortality. Several studies have identified comorbidities and clinical laboratory variables associated with mortality among the severe sepsis population, but few have combined the 2 in making a model specific for all sepsis patients.

Methods
We used clinical and laboratory variables seen at the time of first lactic acid measurement and patient characteristics upon admission to develop a logistic regression model to predict mortality in a sepsis population at 2 area hospitals in Omaha, Nebraska.

Results
Overall, sepsis-related mortality was 12.9%. Advanced age, a higher number of comorbidities, and leucopenia were positively associated with mortality, whereas preexisting diabetes was negatively associated with mortality. Each 1 mmol/L difference in lactic acid levels was positively associated with 1.38 times higher adjusted odds (95% confidence interval, 1.30–1.48) of mortality after adjustment for other covariates. For every 1% decrease in hematocrit, the adjusted odds of mortality were 1.04 times higher (95% confidence interval, 1.02–1.06).

Conclusions
We identified a number of sepsis mortality predictors. The negative association between preexisting diabetes mellitus and sepsis mortality requires further investigation.
Microbiological Spectrum of Infection-Related Febrile Episodes in Adult Patients With Hematologic Malignancies
Authors: Miradi Mahdi , Sheybani Fereshte , Sarvghad Mohammad Reza , Allahyari Abolghasem , Arian Mahnaz , Nooghabi Mehdi Jabbari 
Published: June 2019

Background
In recent years, antimicrobial resistance and the limited number of new antimicrobials under development have profoundly complicated treatment options especially in patients with hematologic malignancies that are treated with sequential courses of antimicrobial therapy. These issues emphasize on the importance of surveillance studies to monitor antimicrobial resistance and implement the antimicrobial stewardship strategies in health care centers.

Methods
The study was a prospective cohort with the aim of evaluating the microbiological spectrum of infection-related febrile episodes in adult patients with hematologic malignancies who admitted in a 1000-bed teaching hospital affiliated to Mashhad University of Medical Sciences, Iran.

Results
One hundred eight infection-related febrile episodes were identified in 108 individuals with hematologic malignancies of whom 18.5% had bacteremia. The most commonly isolated pathogens were coagulase-negative staphylococci (40%), followed by Escherichia coli (25%), and Klebsiella spp (10%), respectively. Carbapenems and glycopeptides were prescribed in the empirical regimen of 96.4% and 61.2% of patients. Although more than 67% of them needed to be deescalated at the second key time of antimicrobial therapy, it was performed only in 9%.

Conclusions
Our study highlighted the high rates of prescription of broad-spectrum antimicrobials in the empirical regimen of patients and a poor adherence to appropriate deescalation strategies after the second key time point of antimicrobial therapy among physicians in charge of patients with hematologic malignancies. It also emphasizes the importance of developing infrastructure for implementation and adherence to antimicrobial stewardship strategies in hematologic malignancy wards in developing countries such as Iran.
Sepsis, Helicoid Bacteremia, and Pneumatosis Intestinalis
Authors: Lacy Mark D. , Fisher Mark A. 
Published: June 2019

Abstract
Spirochetal or helical configurations are unusual among human pathogens. The number of organisms that will grow in standard blood culture media and stain well with Gram stain is even less common. This is a fatal case of sepsis with pneumatosis intestinalis due to the anaerobic spiral-formed pathogen Anaerobiospirillum succiniciproducens. It is followed by a brief discussion of organisms to consider when the laboratory calls to report “a spirochete is growing in the blood culture” along with a caveat in choosing antimicrobial therapy when A. succiniciproducens is a possibility.
Human pathogens configured as helixes or spirals are comprised by a limited number of genera. Furthermore, most of the pathogens reported in the clinical literature will not stain with Gram stain. This is a case of one such pathogen, which may be included in the differential diagnosis of the prudent infectious disease specialist when told by the microbiology laboratory, “we see spirochetes on the gram stain of the blood culture.”
Preseason Vestibular Ocular Motor Screening in Children and Adolescents
Authors: Iverson Grant L. , Cook Nathan E. , Howell David R. , Collings Laurel J. , Kusch Cody , Sun Jonathan , Virji-Babul Naznin , Panenka William J. 
Published: June 2019

Objectives:
The primary purpose of this study was to examine vestibular/ocular motor screening (VOMS) test performance in a sample of healthy youth ice hockey players. A particular focus was to investigate the potential effects of age and pre-existing health conditions, including concussion history, attention-deficit/hyperactivity disorder (ADHD), learning disability (LD), headaches/migraines, and depression/anxiety on preseason baseline VOMS performance, including the near point of convergence (NPC) distance.

Design:
Cross-sectional cohort.

Setting:
Outpatient physiotherapy clinic.

Participants:
Three hundred eighty-seven male youth hockey players, with an average age of 11.9 years (SD = 2.2, range = 8-17), completed the VOMS and responded to self- or parent-reported demographic and medical history questionnaires during preseason baseline assessments.

Independent Variables Assessed:
Age, sex, and mental and physical health history including ADHD, headaches, depression, anxiety, migraine, and LD.

Outcome Measure:
Vestibular/ocular motor screening.

Results:
The large majority of boys scored within normal limits on the VOMS, ie, they reported no symptom provocation of more than 2 points on any VOMS subset (89%) and had a normal NPC distance, ie, <5 cm (78%). The individual VOMS subtests had low abnormality rates, and demographic and pre-existing health conditions, such as age, headache or migraine history, previous neurodevelopmental conditions, or mental health problems, were not associated with clinically meaningful symptom provocation during the VOMS.

Conclusions:
There was a low rate of abnormal findings for the individual VOMS subtests, with the exception of NPC distance, among male youth hockey players during preseason assessment.
Understanding Gunshot Residue Evidence and Its Role in Forensic Science
Authors: Vachon Crystina R. , Martinez Michael V. 
Published: June 2019

AbstractGunshot residue, or GSR, can be a valuable tool in forensic science, but its importance depends greatly on how it is utilized during an investigation and applied in criminal courts. This comprehensive review defines what constitutes GSR resulting from a discharged firearm. Sampling methods and analytical testing instrumentation will be discussed along with data interpretation and limitations of analysis.
Development of a Genomic DNA Reference Material Panel for Thalassemia Genetic Testing
Authors: Yin Zhen-Zhen , Qu Shou-Fang , Huang Chuan-Feng , Chen Fang , Li Jian-Biao , Chen Shi-Ping , Zheng Yu , Zhang Xi , Yang Xue-Xi , Xie Long-Xu , Wei Ji-Tao , Wei Feng-Xiang , Guo Jian , Huang Jie 
Published: June 2019

AbstractThalassemia is one of the most common autosomal recessive inherited diseases worldwide, and it is also highly prevalent and variable in Southern China. Various types of genetic testing technologies have been developed for diagnosis and screening of thalassemia. Characterized genomic DNA reference materials are necessary for assay development, validation, proficiency testing and quality assurance. However, there is no publicly available reference materials for thalassemia genetic testing as yet. To address the need for these materials, the National Institutes for Food and Drug Control and the China National Gene Bank established 31 new cell lines with 2 wild genotypes and 29 distinct genotypes of thalassemia which account for approximately 90% thalassemia carriers in China. The genomic DNA of 31 cell lines were characterized by four clinical genetic testing laboratories using different genetic testing methods and technology platforms. The genotyping results were concordant among four laboratories. In addition, the results of stability test demonstrated that the genotypes of these DNA samples were not influenced by preanalytical conditions such as long-term exposure to high temperature(37□) environment and repeated freeze-thawing. In conclusion, we developed the first national panel of 31 genomic DNA reference materials which are renewable and publicly available for the quality assurance of various genetic testing methods and will facilitate research and development in thalassemia genetic testing.
Regression from pathological hypertrophy is sexually dimorphic and stimulus-specific
Authors: Muehleman Deanna , Swearingen Alison R. , Leinwand Leslie A. 
Published: June 2019

AbstractAimsPathological cardiac hypertrophy is the result of increased cardiomyocyte size, leading to thickening of the left ventricular walls and a decrease in the left ventricular chamber. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, while it persists in others. Here, we investigate mechanisms leading to regression of pathological cardiac hypertrophy in two mouse models, in addition to defining the sex differences associated with hypertrophy and regression.Methods and ResultsTwo pathological hypertrophic stimuli were used in male and female mice (Isoproterenol or Angiotensin II). The stimulus was removed after 7 days of treatment, then the left ventricle was studied at intervals up to 7 days following the removal of the stimulus. Following Isoproterenol removal, male hearts returned to baseline sizes in 4 days while it took 7 days for female hearts to regress. After Angiotensin II removal, the left ventricular masses of males and females did not regress. ERK1/2 was activated in response to both Isoproterenol and Angiotensin II in males, then decreased back to baseline one day after stimulus removal. Expression of ECM genes was greater in response to Angiotensin II and remained elevated longer after Angiotensin II removal, compared to Isoproterenol. Further, collagen content may be playing a role in the irreversible state of Angiotensin II induced hypertrophy as hydroxyproline content was increased following the removal of Angiotensin II in both males and females.ConclusionsRegression of pathological cardiac hypertrophy is possible in some people and in some mouse models; however, the ability for the heart to regress is dependent on the stimulus and biological sex. Further, molecular changes including cellular signaling, protein degradation pathways and the formation of a fibrotic network may contribute to the ability to reverse pathological cardiac hypertrophy and are stimulus- and sex-dependent.Translational PerspectivePathological cardiac hypertrophy is a major risk factor for mortality. If cardiac hypertrophy persists for an extended time, there can be many maladaptive changes to the myocardium. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, but not in others. While cardiac hypertrophy has been studied extensively, very little is understood about regression of cardiac hypertrophy. It is important that we have a better understanding of mechanisms leading to regression and why this process might not be reversible in some individuals.