bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study
Authors: Modica Sara , Redi David , Gagliardini Roberta , Giombini Emanuela , Bezenchek Antonia , Di Carlo Domenico , Maggiolo Franco , Lombardi Francesca , Borghetti Alberto , Farinacci Damiano , Callegaro Annapaola , Gismondo Maria R , Colafigli Manuela , Sterrantino Gaetana , Costantini Andrea , Ferrara Sergio M , Rusconi Stefano , Zazzi Maurizio , Rossetti Barbara , De Luca Andrea , Gianotti Nicola 
Published: September 2019

AbstractBackgroundAntiretroviral drug resistance mutations remain a major cause of treatment failure.ObjectivesTo evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens.Materials and methodsWe selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of &gt;50 copies/mL.ResultsWe included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39–53), 7 years (3–16) of HIV infection, nadir CD4+ 247 cells/mm3 (105–361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3–12.5) versus 3.8% (2.1–5.5) in virologically suppressed patients and 66.7% (39.5–93.9) versus 11.2% (6.5–15.9) (P&lt;0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02–1.27, P=0.024) in viraemic patients.ConclusionsA switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.
Genetic Diversity and Demographic History of an Upper Hill Dipterocarp (Shorea platyclados): Implications for Conservation
Authors: Ng Chin-Hong , Lee Soon-Leong , Tnah Lee-Hong , Ng Kevin K S , Lee Chai-Ting , Diway Bibian , Khoo Eyen 
Published: September 2019

AbstractSoutheast Asian rainforests at upper hill elevations are increasingly vulnerable to degradation because most lowland forest areas have been converted to different land uses. As such, understanding the genetics of upper hill species is becoming more crucial for their future management and conservation. Shorea platyclados is an important, widespread upper hill dipterocarp in Malaysia. To elucidate the genetic structure of S. platyclados and ultimately provide guidelines for a conservation strategy for this species, we carried out a comprehensive study of the genetic diversity and demographic history of S. platyclados. Twenty-seven populations of S. platyclados across its range in Malaysia were genotyped at 15 polymorphic microsatellite loci and sequenced at seven noncoding chloroplast DNA (cpDNA) regions. A total of 303 alleles were derived from the microsatellite loci, and 29 haplotypes were identified based on 2892 bp of concatenated cpDNA sequences. The populations showed moderately high genetic diversity (mean HE = 0.680 for microsatellite gene diversity and HT = 0.650 for total haplotype diversity) and low genetic differentiation (FST = 0.060). Bayesian clustering divided the studied populations into two groups corresponding to western and eastern Malaysia. Bottleneck analysis did not detect any recent bottleneck events. Extended Bayesian skyline analyses showed a model of constant size for the past population history of this species. Based on our findings, priority areas for in situ and ex situ conservation and a minimum population size are recommended for the sustainable utilization of S. platyclados.
Gastrointestinal histoplasmosis mimicking peritonitis carcinomatosis: a rare case of an emergent surgical presentation of HIV de novo
Authors: Engelmann Esmee W M , Posthuma Jelle J , Scholten Lianne , Blankensteijn Louise L , Boldewijn Mireille B , Gooszen Jan A H 
Published: September 2019

Abstract
Gastrointestinal perforation due to infection, including disseminated histoplasmosis, is a rare cause of the surgical acute abdomen, especially in an apparently healthy patient. We describe a rare case of gastrointestinal histoplasmosis-induced small intestine perforation as the first manifestation of acquired immune deficiency syndrome in a healthy patient. Remarkably, the disease mimicked peritonitis carcinomatosis during explorative laparoscopy.
A Bayesian Fermi-GBM short GRB spectral catalogue
Authors: Burgess J Michael , Greiner Jochen , Bégué Damien , Berlato Franceso 
Published: September 2019

ABSTRACT
Inspired by the confirmed detection of a short gamma-ray burst (GRB) in association with a gravitational wave signal, we present the first Bayesian Fermi-Gamma-ray Burst Monitor (GBM) short GRB spectral catalogue. Both peak flux and time-resolved spectral results are presented. Data are analysed with the proper Poisson likelihood allowing us to provide statistically reliable results even for spectra with few counts. All fits are validated with posterior predictive checks. We find that nearly all spectra can be modelled with a cut-off power law. Additionally, we release the full posterior distributions and reduced data from our sample. Following our previous study, we introduce three variability classes based on the observed light-curve structure.
A diagnostic tool for the identification of supernova remnants
Authors: Kopsacheili M , Zezas A , Leonidaki I 
Published: September 2019

ABSTRACT
We present new diagnostic tools for distinguishing supernova remnants (SNRs) from H ii regions. Up to now, sources with flux ratio [S ii]/H$\rm {\alpha }$ higher than 0.4 have been considered as SNRs. Here, we present combinations of three or two line ratios as more effective tools for the separation of these two kinds of nebulae, depicting them as 3D surfaces or 2D lines. The diagnostics are based on photoionization and shock-excitation models (mappings iii) analysed with support vector machine (SVM) models for classification. The line-ratio combination that gives the most efficient diagnostic is [O i]/H$\rm {\alpha }$ – [O ii]/H$\rm {\beta }$ – [O iii]/H$\rm {\beta }$. This method gives $98.95{{\ \rm per\ cent}}$ completeness in the SNR selection and $1.20{{\ \rm per\ cent}}$ contamination. We also define the [O i]/H$\rm {\alpha }$ SNR selection criterion and measure its efficiency in comparison with other selection criteria.
Wiener filtering and pure $\mathcal {E}/\mathcal {B}$ decomposition of CMB maps with anisotropic correlated noise
Authors: Kodi Ramanah Doogesh , Lavaux Guilhem , Wandelt Benjamin D 
Published: September 2019

ABSTRACTWe present an augmented version of our dual messenger algorithm for spin field reconstruction on the sphere, while accounting for highly non-trivial and realistic noise models such as modulated correlated noise. We also describe an optimization method for the estimation of noise covariance from Monte Carlo simulations. Using simulated Planck polarized cosmic microwave background (CMB) maps as a showcase, we demonstrate the capabilities of the algorithm in reconstructing pure $\mathcal {E}$ and $\mathcal {B}$ maps, guaranteed to be free from ambiguous modes resulting from the leakage or coupling issue that plagues conventional methods of $\mathcal {E}/\mathcal {B}$ separation. Due to its high speed execution, coupled with lenient memory requirements, the algorithm can be optimized in exact global Bayesian analyses of state-of-the-art CMB data for a statistically optimal separation of pure $\mathcal {E}$ and $\mathcal {B}$ modes. Our algorithm, therefore, has a potentially key role in the data analysis of high-resolution and high-sensitivity CMB data, especially with the range of upcoming CMB experiments tailored for the detection of the elusive primordial $\mathcal {B}$-mode signal.
Extracranial arteriovenous malformations: from bedside to bench
Authors: Qiao Congzhen , Richter Gresham T , Pan Weijun , Jin Yunbo , Lin Xiaoxi 
Published: September 2019

AbstractArteriovenous malformation (AVM) is defined as a fast-flow vascular anomaly that shunts blood from arteries directly to veins. This short circuit of blood flow contributes to progressive expansion of draining veins, resulting in ischaemia, tissue deformation and in some severe cases, congestive heart failure. Various medical interventions have been employed to treat AVM, however, management of which remains a huge challenge because of its high recurrence rate and lethal complications. Thus, understanding the underlying mechanisms of AVM development and progression will help direct discovery and a potential cure. Here, we summarize current findings in the field of extracranial AVMs with the aim to provide insight into their aetiology and molecular influences, in the hope to pave the way for future treatment.
Improved detection of diffuse glioma infiltration with imaging combinations: a diagnostic accuracy study
Authors: Verburg Niels , Koopman Thomas , Yaqub Maqsood M , Hoekstra Otto S , Lammertsma Adriaan A , Barkhof Frederik , Pouwels Petra J W , Reijneveld Jaap C , Heimans Jan J , Rozemuller Annemarie J M , Bruynzeel Anne M E , Lagerwaard Frank , Vandertop William P , Boellaard Ronald , Wesseling Pieter , de Witt Hamer Philip C 
Published: September 2019

Abstract

Background
Surgical resection and irradiation of diffuse glioma are guided by standard MRI: T2/fluid attenuated inversion recovery (FLAIR)–weighted MRI for non-enhancing and T1-weighted gadolinium-enhanced (T1G) MRI for enhancing gliomas. Amino acid PET has been suggested as the new standard. Imaging combinations may improve standard MRI and amino acid PET. The aim of the study was to determine the accuracy of imaging combinations to detect glioma infiltration.

Methods
We included 20 consecutive adults with newly diagnosed non-enhancing glioma (7 diffuse astrocytomas, isocitrate dehydrogenase [IDH] mutant; 1 oligodendroglioma, IDH mutant and 1p/19q codeleted; 1 glioblastoma IDH wildtype) or enhancing glioma (glioblastoma, 9 IDH wildtype and 2 IDH mutant). Standardized preoperative imaging (T1-, T2-, FLAIR-weighted, and T1G MRI, perfusion and diffusion MRI, MR spectroscopy and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET) was co-localized with multiregion stereotactic biopsies preceding resection. Tumor presence in the biopsies was assessed by 2 neuropathologists. Diagnostic accuracy was determined using receiver operating characteristic analysis.

Results
A total of 174 biopsies were obtained (63 from 9 non-enhancing and 111 from 11 enhancing gliomas), of which 129 contained tumor (50 from non-enhancing and 79 from enhancing gliomas). In enhancing gliomas, the combination of apparent diffusion coefficient (ADC) with [18F]FET PET (area under the curve [AUC], 95% CI: 0.89, 0.79‒0.99) detected tumor better than T1G MRI (0.56, 0.39‒0.72; P &lt; 0.001) and [18F]FET PET (0.76, 0.66‒0.86; P = 0.001). In non-enhancing gliomas, no imaging combination detected tumor significantly better than standard MRI. FLAIR-weighted MRI had an AUC of 0.81 (0.65–0.98) compared with 0.69 (0.56–0.81; P = 0.019) for [18F]FET PET.

Conclusion
Combining ADC and [18F]FET PET detects glioma infiltration better than standard MRI and [18F]FET PET in enhancing gliomas, potentially enabling better guidance of local therapy.
Functional Characterization of Three Novel Genes Encoding Diacylglycerol Acyltransferase (DGAT) from Oil-Rich Tubers of Cyperus esculentus
Authors: Liu Dantong , Ji Hongying , Yang Zhenle 
Published: September 2019

AbstractCyperus esculentus is probably the only plant that is known to accumulate large amounts of oil in its tubers. However, the underlying metabolic mechanism and regulatory factors involved in oil synthesis of tubers are still largely unclear. In this study, one gene encoding type I diacylglycerol acyltransferase (DGAT) (CeDGAT1) and two genes encoding type II DGAT (CeDGAT2a and CeDGAT2b) from C. esculentus were identified and functionally analyzed. All three DGAT genes were found to be expressed in tuber, root and leaf tissues. CeDGAT1 is highly expressed in roots and leaves, whereas CeDGAT2b is dominantly expressed in tubers. Furthermore, the temporal expression pattern of CeDGAT2b is well coordinated with the oil accumulation in developing tubers. When each CeDGAT was heterologously expressed in triacylglycerol (TAG)-deficient mutant of Saccharomyces cerevisiae, Arabidopsis thaliana wild type or its TAG1 mutant with AtDGAT1 disruption, only CeDGAT2b showed the ability to restore TAG biosynthesis with lipid body formation in yeast mutant, enhance seed oil production of Arabidopsis wild type and rescue multiple seed phenotypes of TAG1 mutant. In addition, CeDGAT2b was shown to have a substrate preference for unsaturated fatty acids toward TAG synthesis. Taken together, our results indicated that CeDGAT2b from C. esculentus is an actively functional protein and is most likely the major contributor to tuber oil biosynthesis containing common fatty acids, in contrast to oil-rich seeds and fruits where DGAT1 plays a more central role than DGAT2 in oil production accumulating normal fatty acids, whereas DGAT2 is a primary regulator for oil synthesis rich in unusual fatty acids.
Global, regional and national burden of gout, 1990–2017: a systematic analysis of the Global Burden of Disease Study
Authors: Xia Yang , Wu Qijun , Wang Hanyuan , Zhang Shuang , Jiang Yuting , Gong Tingting , Xu Xin , Chang Qing , Niu Kaijun , Zhao Yuhong 
Published: September 2019

Abstract

Objectives
The burden of gout has been increasing globally. However, little is known about the global, regional and national distribution and time trend of this disease. We present a comprehensive analysis of the Global Burden of Disease Study 2017 on gout burden estimates for 195 countries or territories between 1990 and 2017.

Methods
Age-standardized prevalence and disability-adjusted life-years of gout were reported between 1990 and 2017 in 195 countries and territories, and associations between these estimates and sociodemographic index (SDI) were further explored. Total and annual percent change between 1990 and 2017 were calculated to quantify the time trends of gout burden.

Results
Age-standardized prevalence rates (95% uncertainty interval) per 100 000 persons were 790.90 (706.10–881.90) and 253.49 (225.69–284.02) in 2017 in males and females, respectively. The annual percent change in age-standardized prevalence (males, 0.22%; females, 0.38%) and disability-adjusted life-years (males, 0.21%; females, 0.38%) of gout increased every year from 1990 to 2017, globally. The highest increase was detected in high-SDI countries, especially in high-income North America. A non-linear association was observed between burden of gout and SDI, with the lowest estimates of gout burden when SDI value was about 0.6. High BMI was the leading risk factor for the burden of gout.

Conclusion
These study results suggest a globally rising trajectory of gout burden between 1990 and 2017. More effective interventions, such as detailed and intensive dietary managements and other prevention strategies for reducing obesity, should be carried out to reverse this trend, especially in females and high-SDI countries.
Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Male Reproductive Functions in Mice
Authors: Shi Mingxin , Whorton Allison E , Sekulovski Nikola , MacLean James A , Hayashi Kanako 
Published: September 2019

Abstract
This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on male reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 males. Prenatal exposure to BPA, BPE, and BPS decreased sperm counts and/or motility and disrupted the progression of germ cell development as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F3 males. Dysregulated serum levels of estradiol-17β and testosterone, as well as expression of steroidogenic enzymes in F3 adult testis were also observed. In the neonatal testis, although apoptosis and DNA damage were not affected, mRNA levels of DNA methyltransferases, histone methyltransferases, and their associated factors were increased by BP exposure. Furthermore, BP exposure induced immunoreactive expression of DNMT3A in Sertoli cells, strengthened DNMT3B, and weakened H3K9me2 and H3K9me3 in germ cells of the neonatal testis, whereas DNMT1, H3K4me3, and H3K27ac were not affected. In adult testis, stage-specific DNMT3B was altered by BP exposure, although DNMT3A, H3K9me2, and H3K9me3 expression remained stable. These results suggest that prenatal exposure to BPA, BPE, and BPS induces transgenerational effects on male reproductive functions probably due to altered epigenetic modification following disruption of DNMTs and histone marks in the neonatal and/or adult testis.
Mucinous Ovarian Carcinoma
Authors: Morice Philippe , Gouy Sebastien , Leary Alexandra 
Published: September 2019

(Abstracted from N Engl J Med 2019;380:1256–1266)
Mucinous ovarian cancer is a rare form of epithelial ovarian cancer, accounting for approximately 3% of all cases. New understanding of the biological features of this unique disease requires an update to traditional diagnostic and therapeutic protocols that have been historically based on guidelines for serous ovarian carcinoma.
Association of Domestic Responsibilities With Career Satisfaction for Physician Mothers in Procedural vs Nonprocedural Fields
Authors: Lyu Heather G. , Davids Jennifer S. , Scully Rebecca E. , Melnitchouk Nelya 
Published: September 2019

(Abstracted from JAMA Surg, doi:10.1001/jamasurg.2019.0529)
Despite equal enrollment of women in medical schools, they are underrepresented in surgical and procedural specialties. Compared with 33% of men, only 14% of women graduating medical school apply to surgical residencies.
Preventability Review of Severe Maternal Morbidity
Authors: Lawton Beverley A. , MacDonald E. Jane , Stanley James , Daniells Karen , Geller Stacie E. 
Published: September 2019

(Abstracted from Acta Obstet Gynecol Scand 2019;98(4):515–522)
Severe maternal morbidity (SMM) is defined as life-threatening complications in pregnancy, or within 42 days of the termination of the pregnancy. The rate of SMM is rising globally, and minorities have higher rates; in high-resource countries, the reported prevalence is reported as 3.8 to 13.8 per 1000 deliveries.
Monthly Sulfadoxine–Pyrimethamine Versus Dihydroartemisinin-Piperaquine for Intermittent Preventive Treatment of Malaria in Pregnancy: A Double-blind, Randomised, Controlled, Superiority Trial
Authors: Kajubi Richard , Ochieng Teddy , Kakuru Abel , Jagannathan Prasanna , Nakalembe Miriam , Ruel Theodore , Opira Bishop , Ochokoru Harriet , Ategeka John , Nayebare Patience , Clark Tamara D. , Havlir Diane V. , Kamya Moses R. , Dorsey Grant 
Published: September 2019

(Abstracted from Lancet 2019;393:1428–1439.)
In Africa, malaria in pregnancy presents a risk to 50 million women each year due to Plasmodium falciparum infection. Although women in endemic areas are typically asymptomatic when infected with malaria parasites, the infection is associated with maternal anemia and adverse birth outcomes including miscarriage, stillbirth, preterm birth, low birth weight, and infant mortality.
Population-Based Trends in Invasive Prenatal Diagnosis for Ultrasound-Based Indications: Two Decades of Change From 1994 to 2016
Authors: Lostchuck E. , Poulton A. , Halliday J. , Hui L. 
Published: September 2019

(Abstracted from Ultrasound Obstet Gynecol 2019;53:503–511)
Ultrasound examination, particularly the midtrimester morphology scan, and fetal chromosome analysis provide opportunities for specialist assessment, genetic testing, and perinatal management of pregnancies complicated by fetal anomalies. Advances such as fetal nuchal translucency measurement as part of the combined first-trimester screening (CFTS) test for trisomies 21, 13, and 18; maternal plasma cell-free (cf) DNA-based screening for common aneuploidies; and prenatal diagnosis with chromosomal microarray (CMA) analysis have helped further genetic testing of fetal anomalies.
Oral and sublingual immunotherapy for food allergy
Authors: Nowak-Wegrzyn Anna , Sato Sakura , Fiocchi Alessandro , Ebisawa Motohiro 
Published: September 2019

Purpose of review
To critically appraise the recent most relevant studies in the rapidly advancing field of food oral and sublingual immunotherapy.

Recent findings
Food allergen-specific immunotherapy via oral (OIT) and sublingual route (SLIT) increases the threshold of reactivity to peanut, cow's milk, egg, wheat, and many other foods in the majority of the treated individuals. This desensitized state is contingent upon the continued ingestion of the maintenance doses of the food. Permanent oral tolerance is achievable in a smaller subset of the treated individuals. The optimal duration of therapy has not been firmly established but is likely dependent on the phenotype (severity and persistence). Efficacy of food-OIT is superior compared with SLIT, whereas the safety of OIT is less favorable. Standardization of treatment protocols, maintenance dosing, duration of therapy, target populations and harmonization of the outcomes are top priorities at this stage.

Summary
OIT and SLIT represent two different routes of food allergen-specific immunotherapy. Although significant progress has been made in the last decade, both treatment modalities are still in the very early stages of development and further investigations are necessary to optimize the protocols and improve safety while maximizing efficacy.