bluuebunny/crossref_metadata_2025 huggingface dataset:
Homelessness and Hepatitis A—San Diego County, 2016–2018
Authors: Peak Corey M , Stous Sarah S , Healy Jessica M , Hofmeister Megan G , Lin Yulin , Ramachandran Sumathi , Foster Monique A , Kao Annie , McDonald Eric C
Published: August 2019

Background

Hepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016–2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease.

Methods

We tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines.

Results

Among 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH had 3.3 (95% confidence interval [CI], 1.5–7.9) times higher odds of HAV infection, 2.5 (95% CI, 1.7–3.9) times higher odds of hospitalization, and 3.9 (95% CI, 1.1–16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination.

Conclusions

PEH were at higher risk of infection with HAV and of severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.
Depression and family arguments: disentangling reciprocal effects for women and men
Authors: Wong Jessie J , Frost Nickolas D , Timko Christine , Heinz Adrienne J , Cronkite Ruth
Published: August 2019

Background

Depression is a debilitating condition that affects the individual and the family.

Objective

This study sought to identify potential reciprocal influences between family arguments and depressive symptoms among clinically depressed patients over a 23-year span.

Methods

The present study employed a longitudinal, observational design with 424 depressed patients. Separate cross-lagged path models examined longitudinal associations for women and men over 23 years while adjusting for age, income, and marital and parental status.

Results

Among depressed men, more severe baseline depressive symptoms predicted more family arguments 10 years later. Among depressed women, more severe baseline depressive symptoms predicted fewer family arguments 1 year later, while more severe depressive symptoms at 10-year follow-up predicted more family arguments at 23-year follow-up. More family arguments predicted more severe depressive symptoms among women and men, with some variation in the time intervals of these associations.

Conclusion

These findings suggest that while depressive symptoms may temporarily diminish family arguments among women, such symptoms were associated with more family arguments over longer time intervals. Moreover, family arguments put depressed men and women at risk for more severe depressive symptoms. These results support the use of screening for family arguments and interventions to help depressed individuals develop skills to manage interpersonal conflict.
Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy
Authors: Pelorosso Cristiana , Watrin Françoise , Conti Valerio , Buhler Emmanuelle , Gelot Antoinette , Yang Xiaoxu , Mei Davide , McEvoy-Venneri Jennifer , Manent Jean-Bernard , Cetica Valentina , Ball Laurel L , Buccoliero Anna Maria , Vinck Antonin , Barba Carmen , Gleeson Joseph G , Guerrini Renzo , Represa Alfonso
Published: August 2019

Single germline or somatic activating mutations of mammalian target of rapamycin (mTOR) pathway genes are emerging as a major cause of type II focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC). A double-hit mechanism, based on a primary germline mutation in one allele and a secondary somatic hit affecting the other allele of the same gene in a small number of cells, has been documented in some patients with TSC or FCD. In a patient with HME, severe intellectual disability, intractable seizures and hypochromic skin patches, we identified the ribosomal protein S6 (RPS6) p.R232H variant, present as somatic mosaicism at ~15.1% in dysplastic brain tissue and ~11% in blood, and the MTOR p.S2215F variant, detected as ~8.8% mosaicism in brain tissue, but not in blood. Overexpressing the two variants independently in animal models, we demonstrated that MTOR p.S2215F caused neuronal migration delay and cytomegaly, while RPS6 p.R232H prompted increased cell proliferation. Double mutants exhibited a more severe phenotype, with increased proliferation and migration defects at embryonic stage and, at postnatal stage, cytomegalic cells exhibiting eccentric nuclei and binucleation, which are typical features of balloon cells. These findings suggest a synergistic effect of the two variants. This study indicates that, in addition to single activating mutations and double-hit inactivating mutations in mTOR pathway genes, severe forms of cortical dysplasia can also result from activating mutations affecting different genes in this pathway. RPS6 is a potential novel disease-related gene.
Review of Mathematical Models of Vaccination for Preventing Congenital Cytomegalovirus Infection
Authors: Lanzieri Tatiana M , Gastañaduy Paul A , Gambhir Manoj , Plotkin Stanley A
Published: August 2019

Background

Several cytomegalovirus (CMV) vaccine candidates are under development. To reduce the burden of congenital CMV infection, potential strategies under consideration include vaccination of adult women, adolescent girls, and/or young children (both sexes).

Methods

We reviewed 5 studies that used infectious disease modeling to assess the potential impact of vaccination for preventing congenital CMV infection. All models assumed CMV vaccination would prevent primary infection and 2 models also assumed prevention of reinfections and reactivations.

Results

Despite differences in structure, assumptions, and population data, infant vaccination (both sexes) was the optimal strategy in all models, but in 1 model vaccinating seronegative women at 19–21 years of age was also optimal (for duration of vaccine protection ≥8 years). In 3 models, infant vaccination increased average age at primary infection as a result of decreased secondary transmission (herd immunity) combined with waning vaccine-induced immunity. This effect could increase the risk of congenital CMV infections in populations where primary CMV infection occurs early in childhood but could be minimized by administering a second dose of vaccine during adolescence.

Conclusions

Understanding vaccine efficacy and duration of immunity, and how these might vary depending on CMV serostatus and age at vaccination, will be key to defining CMV vaccination strategies.
Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on the Fitness of Contemporary Influenza A(H1N1)pdm09 and A(H3N2) Strains
Authors: Checkmahomed Liva , M’hamdi Zeineb , Carbonneau Julie , Venable Marie-Christine , Baz Mariana , Abed Yacine , Boivin Guy
Published: August 2019

Background

Baloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence.

Methods

Influenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR.

Results

I38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50%:50% mixture evolved to 70%:30% (WT/mutant) for A(H1N1) and 88%:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments.

Conclusion

The fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.
Mapping Aedes aegypti (Diptera: Culicidae) and Aedes albopictus Vector Mosquito Distribution in Brownsville, TX
Authors: Myer Mark H , Fizer Chelsea M , Mcpherson Kenneth R , Neale Anne C , Pilant Andrew N , Rodriguez Arturo , Whung Pai-Yei , Johnston John M
Published: August 2019

Aedes mosquitoes are vectors of several emerging diseases and are spreading worldwide. We investigated the spatiotemporal dynamics of Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) mosquito trap captures in Brownsville, TX, using high-resolution land cover, socioeconomic, and meteorological data. We modeled mosquito trap counts using a Bayesian hierarchical mixed-effects model with spatially correlated residuals. The models indicated an inverse relationship between temperature and mosquito trap counts for both species, which may be due to the hot and arid climate of southern Texas. The temporal trend in mosquito populations indicated Ae. aegypti populations peaking in the late spring and Ae. albopictus reaching a maximum in winter. Our results indicated that seasonal weather variation, vegetation height, human population, and land cover determine which of the two Aedes species will predominate.
Toronto Workshop on Late Recurrence in Estrogen Receptor–Positive Breast Cancer: Part 1: Late Recurrence: Current Understanding, Clinical Considerations
Authors: Dowling Ryan J O , Kalinsky Kevin , Hayes Daniel F , Bidard Francois-Clement , Cescon David W , Chandarlapaty Sarat , Deasy Joseph O , Dowsett Mitch , Gray Robert J , Henry N Lynn , Meric-Bernstam Funda , Perlmutter Jane , Sledge George W , Bratman Scott V , Carey Lisa A , Chang Martin C , DeMichele Angela , Ennis Marguerite , Jerzak Katarzyna J , Korde Larissa A , Lohmann Ana Elisa , Mamounas Eleftherios P , Parulekar Wendy R , Regan Meredith M , Schramek Daniel , Stambolic Vuk , Thorat Mangesh A , Whelan Timothy J , Wolff Antonio C , Woodgett Jim R , Sparano Joseph A , Goodwin Pamela J
Published: August 2019

Disease recurrence (locoregional, distant) exerts a significant clinical impact on the survival of estrogen receptor–positive breast cancer patients. Many of these recurrences occur late, more than 5 years after original diagnosis, and represent a major obstacle to the effective treatment of this disease. Indeed, methods to identify patients at risk of late recurrence and therapeutic strategies designed to avert or treat these recurrences are lacking. Therefore, an international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. In this article, the major issues surrounding late recurrence are defined and current approaches that may be applicable to this challenge are discussed. Specifically, diagnostic tests with potential utility in late-recurrence prediction are described as well as a variety of patient-related factors that may influence recurrence risk. Clinical and therapeutic approaches are also reviewed, with a focus on patient surveillance and the implementation of extended endocrine therapy in the context of late-recurrence prevention. Understanding and treating late recurrence in estrogen receptor–positive breast cancer is a major unmet clinical need. A concerted effort of basic and clinical research is required to confront late recurrence and improve disease management and patient survival.
Anti-Myelin Proteolipid Protein Peptide Monoclonal Antibodies Recognize Cell Surface Proteins on Developing Neurons and Inhibit Their Differentiation
Authors: Sobel Raymond A , Eaton Mary Jane , Jaju Prajakta Dilip , Lowry Eugene , Hinojoza Julian R
Published: August 2019

Using a panel of monoclonal antibodies (mAbs) to myelin proteolipid protein (PLP) peptides, we found that in addition to CNS myelin, mAbs to external face but not cytoplasmic face epitopes immunostained neurons in immature human CNS tissues and in adult hippocampal dentate gyrus and olfactory bulbs, that is neural stem cell niches (NSCN). To explore the pathobiological significance of these observations, we assessed the mAb effects on neurodifferentiation in vitro. The mAbs to PLP 50–69 (IgG1κ and IgG2aκ), and 178–191 and 200–219 (both IgG1κ) immunostained live cell surfaces and inhibited neurite outgrowth of E18 rat hippocampal precursor cells and of PC12 cells, which do not express PLP. Proteins immunoprecipitated from PC12 cell extracts and captured by mAb-coated magnetic beads were identified by GeLC-MS/MS. Each neurite outgrowth-inhibiting mAb captured a distinct set of neurodifferentiation molecules including sequence-similar M6 proteins and other unrelated membrane and extracellular matrix proteins, for example integrins, Eph receptors, NCAM-1, and protocadherins. These molecules are expressed in adult human NSCN and are implicated in the pathogenesis of many chronic CNS disease processes. Thus, diverse anti-PLP epitope autoantibodies may inhibit neuronal precursor cell differentiation via multispecific recognition of cell surface molecules thereby potentially impeding endogenous neuroregeneration in NSCN and in vivo differentiation of exogenous neural stem cells.
A machine-learning approach for identifying the counterparts of submillimetre galaxies and applications to the GOODS-North field
Authors: Liu Ruihan Henry , Hill Ryley , Scott Douglas , Almaini Omar , An Fangxia , Gubbels Chris , Hsu Li-Ting , Lin Lihwai , Smail Ian , Stach Stuart
Published: August 2019

Identifying the counterparts of submillimetre (submm) galaxies (SMGs) in multiwavelength images is a critical step towards building accurate models of the evolution of strongly star-forming galaxies in the early Universe. However, obtaining a statistically significant sample of robust associations is very challenging due to the poor angular resolution of single-dish submm facilities. Recently, a large sample of single-dish-detected SMGs in the UKIDSS UDS field, a subset of the SCUBA-2 Cosmology Legacy Survey (S2CLS), was followed up with the Atacama Large Millimeter/submillimeter Array (ALMA), which has provided the resolution necessary for identification in optical and near-infrared images. We use this ALMA sample to develop a training set suitable for machine-learning (ML) algorithms to determine how to identify SMG counterparts in multiwavelength images, using a combination of magnitudes and other derived features. We test several ML algorithms and find that a deep neural network performs the best, accurately identifying 85 per cent of the ALMA-detected optical SMG counterparts in our cross-validation tests. When we carefully tune traditional colour-cut methods, we find that the improvement in using machine learning is modest (about 5 per cent), but importantly it comes at little additional computational cost. We apply our trained neural network to the GOODS-North field, which also has single-dish submm observations from the S2CLS and deep multiwavelength data but little high-resolution interferometric submm imaging, and we find that we are able to classify SMG counterparts for 36/67 of the single-dish submm sources. We discuss future improvements to our ML approach, including combining ML with spectral energy distribution fitting techniques and using longer wavelength data as additional features.
The Medical Review Panel in Louisiana Neurosurgery and Beyond
Authors: Kosty Jennifer , Jiang Bowen , LeFever Devon C , Brougham Jared R , White Frederick , Orrico Katie , Guthikonda Bharat ,   on behalf of the Council of State Neurosurgical Societies (CSNS)
Published: August 2019

For the past several decades, medical malpractice claims in the state of Louisiana have been screened by a pretrial medical review panel (MRP). Composed of 3 physicians and 1 attorney, these panels are a method of filtering nonmeritorious lawsuits while expediting creditable claims. Currently, 14 jurisdictions in the United States require medical liability/malpractice cases be heard by an MRP or screening panel prior to trial. In this article, we review the MRP process in Louisiana and compare it to those in other states. Data are presented for the past 10 yr of malpractice claims in Louisiana with an emphasis on the neurosurgery specialty. Finally, the benefits and challenges of pretrial screening panels are discussed.
Molecular Epidemiology of Ceftriaxone-Nonsusceptible Enterobacterales Isolates in an Academic Medical Center in the United States
Authors: Tamma Pranita D , Sharara Sima L , Pana Zoi D , Amoah Joe , Fisher Stephanie L , Tekle Tsigereda , Doi Yohei , Simner Patricia J
Published: August 2019

Background

Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum β-lactamase (ESBL)–producing organisms almost uniformly display nonsusceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone-nonsusceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales.

Methods

All consecutive Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone minimum inhibitory concentrations (MICs) of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for β-lactamase genes using a DNA microarray–based assay.

Results

Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (blaCTX-M, blaSHV, blaTEM) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or ≥4 ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15), and the most common p-ampC gene was blaCMY-2.

Conclusions

There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.
Impact of Procalcitonin Levels Combined with Active Intervention on Antimicrobial Stewardship in a Community Hospital
Authors: Newton James A , Robinson Samantha , Ling Cheryl Lim Li , Zimmer Louise , Kuper Kristi , Trivedi Kavita K
Published: August 2019

Background

Procalcitonin (PCT) guidance alone or in conjunction with antibiotic stewardship programs (ASP) has been shown to reduce antibiotic utilization and duration of therapy without adversely affecting patient outcomes.

Methods

In a community hospital, we investigated the impact of PCT with ASP recommendations on length of stay (LOS), length of antimicrobial therapy (LOT) after ASP recommendation, and total LOT over a one-year period. Adult patients with at least one PCT value and concomitant ASP recommendations were included. Patients were grouped by provider ASP compliance and further stratified by normal versus elevated PCT values. No specific PCT algorithm was utilized.

Results

A total of 857 patients were retrospectively analyzed. Physicians complied with 73.7% of ASP recommendations. There were no significant differences in LOS based on ASP compliance. Mean LOT after ASP recommendations and mean total LOT were significantly shorter (2.5 vs. 3.9 days, p<0.0001 and 5.1 vs. 6.6 days, p<0.0001, respectively) in the ASP complier group. When stratified by initial PCT levels, ASP compliers for patients with normal PCT levels had the shortest duration of therapy for all groups; among patients with elevated PCT levels, the duration of therapy was significantly shorter in the ASP compliant group (5.79 vs. 7.12 days, p<0.0111). When controlling for baseline differences in initial PCT levels, LOS was found to be marginally shorter in the ASP compliant group (p = 0.076).

Conclusions

PCT-guided ASP physician recommendations, when accepted by providers, led to reduction in antimicrobial LOT in a community hospital. This benefit was extended across patient groups irrespective of initial PCT levels.
The Effects of Ultrasound-Guided Transversus Abdominis Plane Block on Acute and Chronic Postsurgical Pain After Robotic Partial Nephrectomy: A Prospective Randomized Clinical Trial
Authors: Covotta Marco , Claroni Claudia , Costantini Manuela , Torregiani Giulia , Pelagalli Lorella , Zinilli Antonio , Forastiere Ester
Published: August 2019

Background

Use of a locoregional analgesia technique, such as the ultrasound-guided transversus abdominis plane block (TAPb), can improve postoperative pain management. We investigated the role of TAPb in robotic partial nephrectomy, a surgery burdened by severe postoperative pain.

Methods

In this prospective trial, patients with American Society of Anesthesiologists class I–III physical status undergoing robotic partial nephrectomy were randomly assigned to standard general anesthetic plus ultrasound-guided TAPb (TAP group) or sole standard general anesthetic (NO-TAP group). The primary end point was morphine consumption 24 hours after surgery. Secondary outcomes were postoperative nausea and vomiting in the first 24 hours, sensitivity, and acute and chronic pain, as measured by multiple indicators.

Results

A total of 96 patients were evaluated: 48 patients in the TAP group and 48 in the NO-TAP group. Median morphine consumption after 24 hours was higher in the NO-TAP group compared with the TAP group (14.1 ± 4.5 mg vs 10.6 ± 4.6, P < 0.008). The intensity of acute somatic pain and the presence of chronic pain at three and six months were higher in the NO-TAP group.

Conclusions

Our results show that TAPb can significantly reduce morphine consumption and somatic pain, but not visceral pain. TAPb reduced the incidence of chronic pain.
Optimization of the experimental parameters of the ligase cycling reaction
Authors: Schlichting Niels , Reinhardt Felix , Jager Sven , Schmidt Michael , Kabisch Johannes
Published: August 2019

The ligase cycling reaction (LCR) is a scarless and efficient method to assemble plasmids from fragments of DNA. This assembly method is based on the hybridization of DNA fragments with complementary oligonucleotides, so-called bridging oligos (BOs), and an experimental procedure of thermal denaturation, annealing and ligation. In this study, we explore the effect of molecular crosstalk of BOs and various experimental parameters on the LCR by utilizing a fluorescence-based screening system. The results indicate an impact of the melting temperatures of BOs on the overall success of the LCR assembly. Secondary structure inhibitors, such as dimethyl sulfoxide and betaine, are shown to negatively impact the number of correctly assembled plasmids. Adjustments of the annealing, ligation and BO-melting temperature further improved the LCR. The optimized LCR was confirmed by validation experiments. Based on these findings, a step-by-step protocol is offered within this study to ensure a routine for high efficient LCR assemblies.
Polyethlyene Glycol 200 Can Protect Rats Against Drug-Induced Kidney Toxicity Through Inhibition of the Renal Organic Anion Transporter 3
Authors: Gu Yi-Zhong , Chu Xiaoyan , Houle Robert , Vlasakova Katerina , Koeplinger Kenneth A , Bourgeois Isabelle , Palyada Kiran , Anderson Kenneth D , Brynczka Christopher , Bhatt Bhavana , Chen Feifei , Smith Roger , Amin Rupesh , Glaab Warren E , Lebron Jose , Cox Kathleen , Sistare Frank D
Published: August 2019

MK-7680, a cyclic nucleotide prodrug, caused significant kidney tubule injury in female rats when administered orally at 1000 mg/kg/day for 2 weeks using 10% Polysorbate 80 as vehicle. However, kidney injury was absent when MK-7680 was administered at the same dose regimen using 100% Polyethylene Glycol 200 (PEG 200) as the vehicle. Subsequent investigations revealed that MK-7680 triphosphate concentrations in kidney were much lower in rats treated with MK-7680 using PEG 200 compared with 10% Polysorbate 80 vehicle, whereas plasma exposures of MK-7680 prodrug were similar. In vitro studies demonstrated that PEG 200 is an inhibitor of human renal uptake transporter organic anion transporter 3 (OAT3), of which MK-7680 is a substrate. Furthermore, PEG 200 and PEG 400 were found to interfere in vitro with human renal transporters OAT3, organic cation transporter (OCT) 2, multidrug resistance-associated protein (MRP) 2 and 4, and multidrug and toxin extrusion protein (MATE) 1 and 2K, but not OAT1. These results support a conclusion that PEG 200 may prevent MK-7680-induced kidney injury by inhibiting its active uptake into proximal tubular cells by OAT3. Caution should be exercised therefore when using PEGs as vehicles for toxicity assessment for compounds that are substrates of renal transporters.
Is living donor liver transplantation justified in high model for end-stage liver disease candidates (35+)?
Authors: Au Kin P. , Chan Albert C.Y.
Published: August 2019

Purpose of review

Application of living donor liver transplantation (LDLT) in model for end-stage liver disease (MELD) 35+ patients has been regarded with skepticism. There is concern that a partial graft may not achieve favourable outcomes, and that a healthy donor is risked for a transplant which might turn out to be futile.

Recent findings

In practice, LDLT improves access to liver graft and allows timely transplantation. Long-term results from high-volume centres revealed that outcomes of LDLT in these patients have not been jeopardized by limited graft volumes. With unimpeded vascular outflow, a partial graft could provide sufficient function to overcome the stress of transplant operation. However, LDLT is a complex operation with immense technical demand. A steep learning curve is encountered before optimal outcomes could be produced. Meanwhile, donor safety remains the paramount concern. Donor should not be evaluated for futile candidates. MELD 35+ patients with refractory sepsis or cardiac event are unlikely to benefit from liver transplantation. Borderline donors, in terms of donor safety or graft quality, should not be accepted. As in recipient operation, accumulation of experience is crucial to reduce donor mortality and morbidity.

LDLT is justified for MELD 35+ in high-volume centres with vast experience. Satisfactory recipient outcomes can be produced with minimal donor morbidity.
Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry
Authors: Tennen Ruth I. , Laskey Sarah B. , Koelsch Bertram L. , McIntyre Matthew H. ,   The 23andMe Health Team, Tung Joyce Y.
Published: August 2019

Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) — are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report any Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings provide support for the growing call for broader access to BRCA genetic testing.
Comparison of student perception and exam validity, reliability and items difficulty: cross-sectional study
Authors: Rezigalla Assad Ali , Eleragi Ali Mohammed Elhassan , Elkhalifa Masoud Ishag , Mohammed Ammar M A
Published: August 2019

Introduction

Student perception of an exam is a reflection of their feelings towards the exam items, while item analysis is a statistical analysis of students’ responses to exam items. The study was formulated to compare the student’s perception of the results of item analysis.

Material and methods

Type of the study is cross-sectional. The study was conducted in the college of medicine, in the duration from January to April 2019. The study uses a structured questionnaire and standardized item analysis of students’ exam. Participants are students registered for semester two level year (2018-2019). Exclusion criteria included all students who refused to participate in the study or do not fill the questionnaire.

Result

The response rate of the questionnaire was 88.9% (40/45). Students considered the exam as easy (70.4%). The average difficulty index of the exam is acceptable. KR-20 of the exam was 0.906. A significant correlation was reported between student perceptions towards exam difficulty and standard exam difficulty.

Discussion

Student perceptions support the evidances of exam vlaitdity. Students can estimate exam difficulty.
Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease
Authors: Parks Tom , Auckland Kathryn , Lamagni Theresa L. , Mentzer Alexander , Elliott Katherine , Guy Rebecca , Cartledge Doreen , Strakova Lenka , O’Connor Daniel , Pollard Andrew J , Chapman Stephen J. , Thomas Matthew , Brodlie Malcolm , Colot Julien , D’Ortenzio Eric , Baroux Noémie , Mirabel Mariana , Gilchrist James J. , Scott J. Anthony G. , Williams Thomas N. , Knight Julian , Steer Andrew C. , Hill Adrian V. S. , Sriskandan Shiranee
Published: August 2019

We undertook a genome-wide association study of susceptibility to invasive group A streptococcal (GAS) disease combining data from distinct clinical manifestations and ancestral populations. Amongst other signals, we identified a susceptibility locus located 18kb from PAX5, an essential B-cell gene, which conferred a nearly two-fold increased risk of disease (rs1176842, odds ratio 1.8, 95% confidence intervals 1.5-2.3, P=3.2×10−7). While further studies are needed, this locus could plausibly explain some inter-individual differences in antibody-mediated immunity to GAS, perhaps providing insight into the effects of intravenous immunoglobulin in streptococcal toxic shock.
Causal mediation analysis of Subclinical Hypothyroidism in children with obesity and Non-Alcoholic Fatty Liver Disease
Authors: Nichols Presley , Pan Yue , May Benjamin , Pavlicova Martina , Mencin Ali , Thaker Vidhu V
Published: August 2019

Context

Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity and a leading cause of liver disease in children. Subclinical hypothyroidism (SH) occurs with obesity and may contribute to dysmetabolic state that predisposes to NAFLD.

Objective

To assess the relationship between SH and NAFLD in children with biopsy-proven NAFLD compared to controls.

Design and Methods

In this retrospective study of cases from a registry of children with biopsy-proven NAFLD and age-matched controls, the association of SH with NAFLD and other cardiometabolic parameters was assessed followed by causal mediation analyses under the counter-factual framework.

Results

Sixty-six cases and 4067 age-matched controls were included in the study. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (2.3 ±1.6 vs 1±1.6, p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, LDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4thquartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 44% of the effect of modified BMI-z score on NAFLD. This comprises of 16.2% (OR = 1.1, p < 0.001) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 26.5% (OR = 1.1, p = 0.01) as an autonomous effect of TSH on NAFLD regardless of the obesity.

Conclusions

The association of SH and biopsy-proven NAFLD is demonstrated in a predominately Latino population. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.
Elevated blood pressure in the emergency department – a risk factor for incident cardiovascular disease: An EHR-based cohort study
Authors: Oras P. , Häbel H. , Skoglund P. H. , Svensson P.
Published: August 2019

Objectives

In the emergency department (ED), high blood pressure (BP) is commonly observed but mostly used to evaluate patients’ health in the short-term. We aimed to study whether ED-measured BP is associated with incident atherosclerotic cardiovascular disease (ASCVD), myocardial infarction (MI), or stroke in long-term, and to estimate the number needed to screen (NNS) to prevent ASCVD.

Design

Electronic Health Records (EHR) and national register-based cohort study. The association between BP and incident ASCVD was studied with Cox-regression.

Setting

Two university hospital emergency departments in Sweden.

Data sources

BP data were obtained from EDs EHR, and outcome information was acquired through the Swedish National Patient Register for all participants.

Participants

All patients ≥18 years old who visited the EDs between 2010 to 2016, with an obtained BP (n=300,193).

Main outcome measures

Incident ASCVD, MI, and stroke during follow-up.

Results

The subjects were followed for a median of 42 months. 8,999 incident ASCVD events occurred (MI: 4,847, stroke: 6,661). Both diastolic and systolic BP (SBP) was associated with incident ASCVD, MI, and stroke with a progressively increased risk for SBP within hypertension grade 1 (HR 1.15, 95% CI 1.06 to 1.24), 2 (HR 1.35, 95% CI 1.25 to 1.47), and 3 (HR 1.63, 95% CI 1.49 to 1.77). The six-year cumulative incidence of ASCVD was 12% for patients with SBP ≥180 mmHg compared to 2% for normal levels. To prevent one ASCVD event during the median follow-up, NNS was estimated to 151, whereas NNT to 71.

Conclusions

BP in the ED is associated with incident ASCVD, MI, and stroke. High BP recordings in EDs should not be disregarded as isolated events, but an opportunity to detect and improve treatment of hypertension. ED-measured BP provides an important and under-used tool with great potential to reduce morbidity and mortality associated with hypertension.
Reclassification of Pterulaceae Corner (Basidiomycota: Agaricales) introducing the ant-associated genus Myrmecopterula gen. nov., Phaeopterula Henn. and the corticioid Radulomycetaceae fam. nov.
Authors: Leal-Dutra Caio A. , Griffith Gareth W. , Neves Maria Alice , McLaughlin David J. , McLaughlin Esther G. , Clasen Lina A. , Dentinger Bryn T. M.
Published: August 2019

Pterulaceae was formally proposed to group six coralloid and dimitic genera [Actiniceps (=Dimorphocystis), Allantula, Deflexula, Parapterulicium, Pterula and Pterulicium]. Recent molecular studies have shown that some of the characters currently used in Pterulaceae Corner do not distinguish the genera. Actiniceps and Parapterulicium have been removed and a few other resupinate genera were added to the family. However, none of these studies intended to investigate the relationship between Pterulaceae genera. In this study, we generated 278 sequences from both newly collected and fungarium samples. Phylogenetic analyses support by morphological data allowed a reclassification of Pterulaceae where we propose the introduction of Myrmecopterula gen. nov. and Radulomycetaceae fam. nov., the reintroduction of Phaeopterula, the synonymisation of Deflexula in Pterulicium and 51 new combinations. Pterula is rendered polyphyletic requiring a reclassification; thus, it is split into Pterula, Myrmecopterula gen. nov., Pterulicium and Phaeopterula. Deflexula is recovered as paraphyletic alongside several Pterula species and Pterulicium, and is sunk into the latter genus. Phaeopterula is reintroduced to accommodate species with darker basidiomes. The neotropical Myrmecopterula gen. nov. forms a distinct clade adjacent to Pterula, and most members of this clade are associated with active or inactive attine ant nests. The resupinate genera Coronicium and Merulicium are recovered in a strongly supported clade close to Pterulicium. The other resupinate genera previously included in Pterulaceae, and which form basidiomes lacking cystidia and with monomitic hyphal structure (Radulomyces, Radulotubus and Aphanobasidium), are reclassified into Radulomycetaceae fam. nov. Allantula is still an enigmatic piece in this puzzle known only from the type specimen that requires molecular investigation. A key for the genera of Pterulaceae and Radulomycetaceae fam. nov. is provided here.
In vivolineage conversion of vertebrate muscle into early endoderm-like cells
Authors: Campbell Clyde , Lancman Joseph J. , Palazon Raquel Espin , Matalonga Jonatan , He Jiaye , Graves Alyssa , Zeng Xin-Xin I. , Mishra Rashmi , Huisken Jan , Traver David , Dong P. Duc Si
Published: August 2019

The extent to which differentiated cells, while remaining in their native microenvironment, can be reprogrammed to assume a different identity will reveal fundamental insight into cellular plasticity and impact regenerative medicine. To investigatein vivocell lineage potential, we leveraged the zebrafish as a practical vertebrate platform to determine factors and mechanisms necessary to induce differentiated cells of one germ layer to adopt the lineage of another. We discovered that ectopic co-expression of Sox32 and Oct4 in several non-endoderm lineages, including skeletal muscle, can specifically trigger an early endoderm genetic program in a cell-autonomous manner. Gene expression, live imaging, and functional studies reveal that the endoderm-induced muscle cells lose muscle gene expression and morphology, while specifically gaining endoderm organogenesis markers, such as the pancreatic specification genes,hhexandptf1a, via a mechanism resembling normal development. Endoderm induction by a pluripotent defective form of Oct4, endoderm markers appearing prior to loss of muscle cell morphology, a lack of dependence on cell division, and a lack of mesoderm, ectoderm, dedifferentiation, and pluripotency gene activation, together, suggests that reprogramming is endoderm specific and occurs via direct lineage conversion. Our work demonstrates that within a vertebrate animal, stably differentiated cells can be induced to directly adopt the identity of a completely unrelated cell lineage, while remaining in a distinct microenvironment, suggesting that differentiated cellsin vivomay be more amenable to lineage conversion than previously appreciated. This discovery of possibly unlimited lineage potential of differentiated cellsin vivochallenges our understanding of cell lineage restriction and may pave the way towards a vast newin vivosupply of replacement cells for degenerative diseases such as diabetes.
Proteome-wide characterization and biomarker identification of intracranial aneurysm
Authors: Sharma Tanavi , Datta Keshava K. , Kumar Munish , Dey Gourav , Khan Aafaque Ahmad , Mangalaparthi Kiran Kumar , Saharan Poonam , Shobia C. , Aggarwal Ashish , Singla Navneet , Ghosh Sujata , Rawat Amit , Dhandapani Sivashanmugam , Salunke Pravin , Chhabra Rajesh , Singh Dalbir , Takkar Aastha , Gupta Sunil K. , Keshava Prasad T. S. , Gowda Harsha , Pandey Akhilesh , Bhagat Hemant
Published: August 2019

The scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm remains incompletely understood. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. Aberrant protein expression may drive structural alterations of vasculature found in IA. To unravel these aberrations, we performed untargeted, global, quantitative proteomic analysis of aneurysm tissue and serum from patients with IA. Samples were derived from patients of three clinical sub groups– 1) unruptured aneurysm 2) ruptured aneurysm without vasospasm 3) ruptured aneurysm who developed vasospasm. A total of 937 and 294 proteins were identified in aneurysm tissue and serum samples respectively. Several proteins that are known to maintain the structural integrity of vasculature were found to be dysregulated. ORM1, a glycoprotein, was significantly upregulated in both the aneurysm tissue and serum samples of unruptured IA patients. We employed a larger cohort of patients and validated ORM1 as a potential biomarker for screening of unruptured aneurysm using ELISA. Samples from ruptured aneurysm with vasospasm showed significant upregulation of MMP9 as compared to ruptured aneurysm without vasospasm. Using a cohort of ruptured aneurysm patients with and without vasospasm, we validated MMP9 as a potential biomarker for vasospasm. This study reveals pathophysiology underlying different clinical sub groups of IA and also suggests potential biomarkers.
xQTLImp: efficient and accurate xQTL summary statistics imputation
Authors: Wang Tao , Yin Quanwei , Liu Yongzhuang , Chen Jin , Wang Yadong , Peng Jiajie
Published: August 2019

Motivation

Quantitative trait locus (QTL) analysis of multiomic molecular traits, such as gene transcription (eQTL), DNA methylation (mQTL) and histone modification (haQTL), has been widely used to infer the effects of genomic variation on multiple levels of molecular activities. However, the power of xQTL (various types of QTLs) detection is largely limited by missing association statistics due to missing genotypes and limited effective sample size. Existing hidden Markov model (HMM)-based imputation approaches require individual-level genotypes and molecular traits, which are rarely available. No available implementation exists for the imputation of xQTL summary statistics when individual-level data are missed.

Results

We present xQTLImp, a C++ software package specifically designed for efficient imputation of xQTL summary statistics based on multivariate Gaussian approximation. Experiments on a single-cell eQTL dataset demonstrates that a considerable amount of novel significant eQTL associations can be rediscovered by xQTLImp.

Availability

Software is available at https://github.com/hitbc/xQTLimp.

Contact

ydwang@hit.edu.cn or jiajiepeng@nwpu.edu.cn

Supplementary information

Supplementary data are available at Bioinformatics online.
Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing
Authors: Radens Caleb M. , Blake Davia , Jewell Paul , Barash Yoseph , Lynch Kristen W.
Published: August 2019

Distinct T cell subtypes are typically defined by the expression of distinct gene repertoires. However, there is variability between studies regarding the markers used to define each T cell subtype. Moreover, previous analysis of gene expression in T cell subsets has largely focused on gene expression rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-Seq studies of human Th1, Th2, Th17 and/or Treg cells to identify transcriptomic features that correlate consistently with subtype. We find that known master-regulators are consistently enriched in the appropriate subtype, however, cytokines and other genes often used as markers are more variable. Importantly, we also identify previously unknown transcriptomic markers that consistently differentiate between subsets, including a few Treg-specific splicing patterns. Together this work highlights the heterogeneity in gene expression between isolates of the same subtype, but also suggests additional markers that can be used to define functional groupings.
MisMatch Negativity-study showing pre-lexical sensitivity to both primary Final Accent and secondary Initial Accent in French
Authors: te Rietmolen Noémie , El Yagoubi Radouane , Astésano Corine
Published: August 2019

In French, accentuation is not lexically distinctive and tightly intertwined with intonation. This has led to the language being described of as ‘a language without accent’ and to French listeners being alleged ‘deaf to stress’. However, if one considers Di Cristo’s model in which the metrical structure of speech plays a central role, it becomes possible to envision stress templates underlying the cognitive representation of words. This event-related potential (erp) study examined whether French listeners are sensitive to the French primary final accent (fa) and secondary initial accent (ia), and whether the accents are part of the French phonologically expected stress pattern. Two oddball studies were carried out. In the first study, in one condition, deviants were presented without (−fa) and standards with final accent (+fa), while in another condition, these positions were switched. We obtained asymmetricmmnwaveforms, such that deviants −faelicited a largermmnthan deviants +fa(which did not elicit anmmn), pointing toward a preference for stress patterns withfa. Additionally, the difference waveforms between identical stimuli in different positions within the oddball paradigms indicated −fastimuli to be disfavored whether they were the deviants or the standards. In the second study, standards were always presented with both the initial and final accent, while deviants were presented either without final accent (−fa) or without initial accent (−ia). Here, we obtainedmmns both to deviants −faand to deviants −ia, although −fadeviants elicited a more amplemmn. Nevertheless, the results show that French listeners are not deaf to the initial and final accents, pointing instead to an abstract phonological representation for both accents. In sum, the results argue against the notion of stress deafness for French and instead suggest accentuation to play a more important role in French speech comprehension than is currently acknowledged.