bluuebunny/crossref_metadata_2025 huggingface dataset:
A practical approach to assess the hazardous exposure potential of investigational drugs
Authors: McLeod E Nicole , Fillis Cambree J , Blind Jill E
Published: March 2020

Purpose

A method to evaluate the hazardous exposure potential of investigational drugs was developed in order to comply with hazardous drug handling standards.

New nationwide standards require health-system pharmacies to recognize potential occupational risks and protect employees from any hazardous exposure. United States Pharmacopeia general chapter 800 (USP<800>) provides recommendations on handling precautions for commercial hazardous drugs. Recommendations for investigational drugs are less clear, with USP<800> suggesting more widespread protections when information is deemed insufficient to assess the risk. The investigational drug services pharmacy at a freestanding pediatric hospital developed a method to evaluate the hazardous potential of investigational drugs in order to determine the likelihood that a drug held an occupational handling risk. The goal of the project was to ensure compliance with hazardous drug handling standards and provide adequate employee protection while minimizing the financial burden on the health-system pharmacy.

Conclusion

Investigational drugs that meet any of 4 defined criteria should be subject to hazardous drug handling precautions until adequate safety data are available.
Temporal variation in maternal nest choice and its consequences for lizard embryos
Authors: Pruett Jenna E , Fargevieille Amélie , Warner Daniel A
Published: March 2020

Microhabitat choice of nest sites is an important maternal effect that influences the survival and development of embryos in oviparous species. Embryos of many species display a high degree of plasticity in response to developmental environments, which places maternal nesting behavior under strong selective pressure, particularly in temporally changing environments. Nesting behavior varies widely across taxa that exhibit diverse reproductive strategies. The brown anole (Anolis sagrei), for example, lays one egg every 7–10 days across an extended reproductive season from April to October. This aspect of their reproduction provides an opportunity to examine temporal shifts in nesting behavior and its consequences on egg survival and offspring development under seasonally changing climatic conditions. We conducted a two-part study to quantify temporal variation in maternal nesting behavior and its effect on development of A. sagrei embryos. First, we measured nest micro-environments over the nesting season. Second, we “planted” eggs across the landscape at our field site to examine the influence of nest conditions on egg survival and hatchling phenotypes. We also incubated eggs inside chambers in the field to decouple effects of nest moisture from those of other environmental variables (e.g., temperature). Females chose nest sites with higher moisture and lower temperatures relative to what was generally available across the landscape during the nesting season. In addition, eggs exposed to relatively cool temperatures had higher hatching success, and high nest moisture increased egg survival and body condition of hatchlings. Overall, we provide evidence in the field that maternal nesting behavior facilitates offspring survival.
Honest signaling of cooperative intentions
Authors: Roberts Gilbert
Published: March 2020

Trust can transform conflicting interests into cooperation. But how can individuals know when to trust others? Here, I develop the theory that reputation building may signal cooperative intent, or “trustworthiness.” I model a simple representation of this theory in which individuals 1) optionally invest in a reputation by performing costly helpful behavior (“signaling”); 2) optionally use others’ reputations when choosing a partner; and 3) optionally cooperate with that partner. In evolutionary simulations, high levels of reputation building, of choosing partners based on reputation, and of cooperation within partnerships emerged. Costly helping behavior evolved into an honest signal of trustworthiness when it was adaptive for cooperators, relative to defectors, to invest in the long-term benefits of a reputation for helping. I show using game theory that this occurs when cooperators gain larger marginal benefits from investing in signaling than do defectors. This happens without the usual costly signaling assumption that individuals are of two “types,” which differ in quality. Signaling of trustworthiness may help explain phenomena such as philanthropy, pro-sociality, collective action, punishment, and advertising in humans and may be particularly applicable to courtship in other animals.
Single-tube genotyping for small insertion/deletion mutations: simultaneous identification of wild type, mutant and heterozygous alleles
Authors: Lin Bin , Sun Jing , Fraser Iain D C
Published: March 2020

Current methods of genotyping small insertion/deletion (indel) mutations are costly, laborious, and can be unreliable. To address this, we have developed a method for small indel genotyping in a single polymerase chain reaction, with wild-type, heterozygous and mutant alleles distinguishable by band pattern in routine agarose gel electrophoresis. We demonstrate this method with multiple genes to distinguish 10 bp, 4 bp and even 1 bp deletions from the wild type. Through systematic testing of numerous primer designs, we also propose guidelines for genotyping small indel mutations. Our method provides a convenient approach to genotyping small indels derived from clustered regularly interspaced short palindromic repeats-mediated gene editing, N-ethyl-N-nitrosourea induced mutagenesis or diagnosis of naturally occurring polymorphisms/mutations.
Waning of Measured Influenza Vaccine Effectiveness Over Time: The Potential Contribution of Leaky Vaccine Effect
Authors: Tokars Jerome I , Patel Manish M , Foppa Ivo M , Reed Carrie , Fry Alicia M , Ferdinands Jill M
Published: March 2020

Background

Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6–11%/month during the 2011–2012 to 2014–2015 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees (“leaky”) rather than complete protection in a subset of vaccinees. Since it is unknown whether influenza vaccine is leaky, we simulated the 2011–2012 to 2014–2015 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE.

Methods

We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2, and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases, and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates.

Results

For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For the high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses.

Conclusions

The leaky vaccine bias could account for some, but probably not all, of the observed intraseasonal decreases in mVE. These results underscore the need for strategies to deal with intraseasonal vaccine effectiveness decline.
Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019
Authors: Zhao Juanjuan , Yuan Quan , Wang Haiyan , Liu Wei , Liao Xuejiao , Su Yingying , Wang Xin , Yuan Jing , Li Tingdong , Li Jinxiu , Qian Shen , Hong Congming , Wang Fuxiang , Liu Yingxia , Wang Zhaoqin , He Qing , Li Zhiyong , He Bin , Zhang Tianying , Fu Yang , Ge Shengxiang , Liu Lei , Zhang Jun , Xia Ningshao , Zhang Zheng
Published: March 2020

Background

The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated.

Methods

173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed.

Results

Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15–39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006).

Conclusions

Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients
Authors: Yu Fengting , Yan Liting , Wang Nan , Yang Siyuan , Wang Linghang , Tang Yunxia , Gao Guiju , Wang Sa , Ma Chengjie , Xie Ruming , Wang Fang , Tan Chianru , Zhu Lingxiang , Guo Yong , Zhang Fujie
Published: March 2020

Background

Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription–polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment.

Methods

A total of 323 samples from 76 COVID-19–confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging.

Results

In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17 429 ± 6920 copies/test) was found to be significantly higher than in throat swabs (2552 ± 1965 copies/test, P < .001) and nasal swabs (651 ± 501 copies/test, P < .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46 800 ± 17 272 vs 1252 ± 1027, P < .001) analyzed by sputum samples.

Conclusions

Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.
Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study
Authors: Li Na , Han Lefei , Peng Min , Lv Yuxia , Ouyang Yin , Liu Kui , Yue Linli , Li Qiannan , Sun Guoqiang , Chen Lin , Yang Lin
Published: March 2020

Background

The ongoing pandemic of coronavirus disease 2019 (COVID-19) has caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia.

Methods

We conducted a case-control study to compare clinical characteristics and maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia.

Results

During the period 24 January–29 February 2020, there were 16 pregnant women with confirmed COVID-19 pneumonia and 18 suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest were cesarean delivery. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest computed tomographic images of COVID-19 pneumonia. Compared to the controls, patients with COVID-19 pneumonia had lower counts of white blood cells (WBCs), neutrophils, C-reactive protein (CRP), and alanine aminotransferase on admission. Increased levels of WBCs, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. Three (18.8%) of the mothers with confirmed COVID-19 pneumonia and 3 (16.7%) with suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than in the control group. None experienced respiratory failure during their hospital stay. COVID-19 infection was not found in the newborns, and none developed severe neonatal complications.

Conclusions

Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal or cesarean delivery. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.
Impact of obesity on the evolution of outcomes in peritoneal dialysis patients
Authors: Quero Maria , Comas Jordi , Arcos Emma , Hueso Miguel , Sandoval Diego , Montero Nuria , Cruzado-Boix Pau , Cruzado Josep M , Rama Inés
Published: March 2020

Background

Some studies reveal that obesity is associated with a decrease in mortality in haemodialysis (HD) patients. However, few studies have addressed the association between body mass index (BMI) and peritoneal dialysis (PD) patients.

Methods

We performed this longitudinal, retrospective study to evaluate the impact of obesity on PD patients, using data from the Catalan Registry of Renal Patients from 2002 to 2015 (n = 1573). Obesity was defined as BMI ≥30; low weight: BMI <18.5; normal range: BMI = 18.5–24.99; and pre-obesity: BMI = 25–29.99 kg/m2. Variations in BMI were calculated during follow-up. The main outcomes evaluated were the technique and patient survival.

Results

Obesity was observed in 20% of patients starting PD. We did not find differences in sex or PD modality, with the obesity group being older (65.9% are ≥55 years versus 59% non-obese, P = 0.003) and presenting more diabetes mellitus and cardiovascular disease (CVD) (47.9% obese versus 25.1% non-obese and 41.7% versus 31.5%, respectively). We did not observe differences in haemoglobin, albumin and Kt/V in obese patients. Regarding peritonitis rate, we did not find any difference between groups, presenting more peritonitis patients on continuous ambulatory peritoneal dialysis and aged ≥65 years [sub-hazard ratio (SHR) = 1.75, P = 0.000 and SHR = 1.56, P = 0.009]. In relation to technique survival, we found higher transfer to HD in the obese group of patients in the univariate analysis, which was not confirmed in the multivariate analysis (SHR = 1.12, P = 0.4), and we did not find differences in mortality rate. In relation to being transplanted, the underweight group, elderly and patients with CVD or diabetic nephropathy presented less probability to undergo kidney transplantation (SHR = 0.65, 0.24, 0.5 and 0.54, P < 0.05). Obese patients did not present differences in survival with weight changes but in normal-weight patients, a gain of 7% of the basal weight during the first year had a protective effect on death risk (hazard ratio 0.6, P = 0.034).

Conclusions

Obese and non-obese patients starting on PD had similar outcomes.
Distribution of the Red Imported Fire Ant Solenopsis invicta (Hymenoptera: Formicidae) in Central Florida Pastures
Authors: Steele C H , King J R , Boughton E H , Jenkins D
Published: March 2020

Habitat disturbance has been found to facilitate the introduction of a wide range of species, including the red imported fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae: Myrmicinae). Despite the link between S. invicta colonization and disturbance, little is known about how different intensities or types of disturbance might impact S. invicta populations. In this study, we used S. invicta populations in cattle pastures to understand how variation in disturbance type and frequency correlates with the density of S. invicta mounds. In total, 56 plots were surveyed for mound abundance during both the wet and dry seasons on a subtropical south Florida ranch. Explanatory variables were grouped into five categories based on disturbance type: 1) historic pasture conversion; 2) modern pasture management (mowing, dragging, chopping, or aerating); 3) grazing intensity (a measure vegetation height and dung pat abundance); 4) distance to human-made and natural localized disturbance (roads, ditches, and wetlands); and 5) abiotic conditions (soil temperature, soil moisture). Overall, the average number of mounds per plot was not significantly different between seasons, but was significantly higher in intensive pastures, which are converted to nonnative forage grasses than in seminative pastures during the dry season. Time since soil disturbance (aeration and chopping of pasture) was a significant predictor of S. invicta densities in both dry and wet seasons, with an increase in time since disturbance being associated with higher mound densities. Other forms of pasture management that did not disturb the soil, such as dragging and mowing, as well as distance to localized disturbances (wetlands, roads, and ditches) were not found to have a significant correlation in either season.
Impact of the micropapillary component on the timing of recurrence in patients with resected lung adenocarcinoma
Authors: Watanabe Katsuya , Sakamaki Kentaro , Ito Hiroyuki , Yokose Tomoyuki , Yamada Kozo , Nakayama Haruhiko , Masuda Munetaka
Published: March 2020

OBJECTIVES

A micropapillary (MIP) component is reported to be associated with a poor prognosis in patients with completely resected lung adenocarcinoma. The purpose of this study was to investigate the impact of an MIP component on the timing of postoperative recurrence using hazard curves.

METHODS

A total of 1289 patients with lung adenocarcinoma who underwent complete pulmonary resection from 2008 to 2015 were studied. Hazard curves representing the changes in hazard over time were evaluated.

RESULTS

The hazard curve displayed an initial wide, high peak within 1 year after surgery in patients with an MIP component, whereas some gentle peaks around the second year were noted in patients without an MIP component. The presence of an MIP component was associated with a worse recurrence-free survival and an early recurrence in stage I patients but not in advanced-stage patients. In multivariable Cox regression, the presence of an MIP component and lymph node metastasis, pleural invasion and gender were associated with a poor prognosis.

CONCLUSIONS

Patients with an MIP component retained a high risk of early recurrence after surgery, and the risk for recurrence persisted over the long term. Even after complete resection in stage I lung adenocarcinoma patients, an MIP component remains correlated with a poor prognosis.
Long-term follow-up of abandoned transvenous defibrillator leads: a nationwide cohort study
Authors: Elgaard Anders Fyhn , Johansen Jens Brock , Nielsen Jens Cosedis , Gerdes Christian , Riahi Sam , Philbert Berit Thornvig , Haarbo Jens , Melchior Thomas Maria , Larsen Jacob Moesgaard
Published: March 2020

Aims 

Commonly, a dysfunctional defibrillator lead is abandoned and a new lead is implanted. Long-term follow-up data on abandoned leads are sparse. We aimed to investigate the incidence and reasons for extraction of abandoned defibrillator leads in a nationwide cohort and to describe extraction procedure-related complications.

Methods and results 

All abandoned transvenous defibrillator leads were identified in the Danish Pacemaker and ICD Register from 1991 to 2019. The event-free survival of abandoned defibrillator leads was studied, and medical records of patients with interventions on abandoned defibrillator leads were audited for procedure-related data. We identified 740 abandoned defibrillator leads. Meantime from implantation to abandonment was 7.2 ± 3.8 years with mean patient age at abandonment of 66.5 ± 13.7 years. During a mean follow-up after abandonment of 4.4 ± 3.1 years, 65 (8.8%) abandoned defibrillator leads were extracted. Most frequent reason for extraction was infection (pocket and systemic) in 41 (63%) patients. Procedural outcome after lead extraction was clinical success in 63 (97%) patients. Minor complications occurred in 3 (5%) patients, and major complications in 1 (2%) patient. No patient died from complication to the procedure during 30-day follow-up after extraction.

Conclusion 

More than 90% of abandoned defibrillator leads do not need to be extracted during long-term follow-up. The most common indication for extraction is infection. Abandoned defibrillator leads can be extracted with high clinical success rate and low risk of major complications at high-volume centres.
Persistence of wastewater antibiotic resistant bacteria and their genes in human fecal material
Authors: Scaccia Nazareno , Vaz-Moreira Ivone , Manaia Célia M
Published: March 2020

Domestic wastewater is a recognized source of antibiotic resistant bacteria and antibiotic resistance genes (ARB&ARGs), whose risk of transmission to humans cannot be ignored. The fitness of wastewater ARB in the complex fecal microbiota of a healthy human was investigated in feces-based microcosm assays (FMAs). FMAs were inoculated with two wastewater isolates, Escherichia coli strain A2FCC14 (MLST ST131) and Enterococcus faecium strain H1EV10 (MLST ST78), harboring the ARGs blaTEM, blaCTX, blaOXA-A and vanA, respectively. The FMAs, incubated in the presence or absence of oxygen or in the presence or absence of the antibiotics cefotaxime or vancomycin, were monitored based on cultivation, ARGs quantification and bacterial community analysis. The fecal bacterial community was dominated by members of the phyla Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia. The ARGs harbored by the wastewater isolates could be quantified after one week, in FMAs incubated under both aerobic and anaerobic conditions. These observations were not significantly different in FMAs incubated anaerobically, supplemented with sub-inhibitory concentrations of cefotaxime or vancomycin. The observation that ARGs of wastewater ARB persisted in presence of the human fecal microbiota for at least one week supports the hypothesis of a potential transmission to humans, a topic that deserves further investigation.
Binning unassembled short reads based on k-mer abundance covariance using sparse coding
Authors: Kyrgyzov Olexiy , Prost Vincent , Gazut Stéphane , Farcy Bruno , Brüls Thomas
Published: March 2020

Background

Sequence-binning techniques enable the recovery of an increasing number of genomes from complex microbial metagenomes and typically require prior metagenome assembly, incurring the computational cost and drawbacks of the latter, e.g., biases against low-abundance genomes and inability to conveniently assemble multi-terabyte datasets.

Results

We present here a scalable pre-assembly binning scheme (i.e., operating on unassembled short reads) enabling latent genome recovery by leveraging sparse dictionary learning and elastic-net regularization, and its use to recover hundreds of metagenome-assembled genomes, including very low-abundance genomes, from a joint analysis of microbiomes from the LifeLines DEEP population cohort (n = 1,135, >1010 reads).

Conclusion

We showed that sparse coding techniques can be leveraged to carry out read-level binning at large scale and that, despite lower genome reconstruction yields compared to assembly-based approaches, bin-first strategies can complement the more widely used assembly-first protocols by targeting distinct genome segregation profiles. Read enrichment levels across 6 orders of magnitude in relative abundance were observed, indicating that the method has the power to recover genomes consistently segregating at low levels.
Activation of optimally and unfavourably oriented faults in a uniform local stress field during the 2011 Prague, Oklahoma, sequence
Authors: Cochran Elizabeth S , Skoumal Robert J , McPhillips Devin , Ross Zachary E , Keranen Katie M
Published: March 2020

The orientations of faults activated relative to the local principal stress directions can provide insights into the role of pore pressure changes in induced earthquake sequences. Here, we examine the 2011 M 5.7 Prague earthquake sequence that was induced by nearby wastewater disposal. We estimate the local principal compressive stress direction near the rupture as inferred from shear wave splitting measurements at spatial resolutions as small as 750 m. We find that the dominant azimuth observed is parallel to previous estimates of the regional compressive stress with some secondary azimuths oriented subparallel to the strike of the major fault structures. From an extended catalogue, we map ten distinct fault segments activated during the sequence that exhibit a wide array of orientations. We assess whether the five near-vertical fault planes are optimally oriented to fail in the determined stress field. We find that only two of the fault planes, including the M   5.7 main shock fault, are optimally oriented. Both the M 4.8 foreshock and M   4.8 aftershock occur on fault planes that deviate 20–29° from the optimal orientation for slip. Our results confirm that induced event sequences can occur on faults not optimally oriented for failure in the local stress field. The results suggest elevated pore fluid pressures likely induced failure along several of the faults activated in the 2011 Prague sequence.
Market Power Assessment in Digital Markets – A German Perspective
Authors: Mischau Lena
Published: March 2020

Digitalisation is confronting competition law with a broad range of new challenges. Assessing the market power of businesses in digital markets has proven to be particularly difficult, and German competition law is in an on-going process of reform to address this and other related issues. This paper outlines the most important specific features of digital markets, explains how they affect the assessment of market power, and analyses the role of competition authorities and courts in decision-making.
Daily Aspirin Use Does Not Impact Clinical Outcomes in Patients With Inflammatory Bowel Disease
Authors: Patel Parita , Gao Guimin , Gulotta George , Dalal Sushila , Cohen Russell D , Sakuraba Atsushi , Rubin David T , Pekow Joel
Published: March 2020

Background

Although several studies have associated the use of nonsteroidal anti-inflammatory drugs with disease flares in patients with inflammatory bowel disease (IBD), little is known about the impact of daily aspirin use on clinical outcomes in patients with IBD.

Methods

We conducted a retrospective analysis of a prospectively collected registry of patients with IBD from May 2008 to June 2015. Patients with any disease activity with daily aspirin use were matched 1:4 to controls by age, sex, disease, disease location, and presence of cardiac comorbidity. Patients with at least 18 months of follow-up were included in the final analysis. The primary outcomes of interest were having an IBD-related hospitalization, IBD-related surgery, and requiring corticosteroids during the follow-up period.

Results

A total of 764 patients with IBD were included in the analysis, of which 174 patients were taking aspirin. There was no statistical difference in age, gender, diagnosis (Crohn’s disease vs ulcerative colitis), disease duration, Charlson Comorbidity Index, smoking status, medication usage, or baseline C-reactive protein between groups. After controlling for covariables and length of follow-up in the entire population, aspirin use was not associated with a risk of being hospitalized for an IBD-related complication (odds ratio [OR], 1.46; P = 0.10), corticosteroid use (OR, 0.99; P = 0.70), or having an IBD-related surgery (OR, 0.99; P = 0.96).

Conclusion

In this single-center analysis, aspirin use did not impact major clinical outcomes in patients with IBD. Although the effect of aspirin use on mucosal inflammation was not directly assessed in this study, these findings support the safety of daily aspirin use in this population.
The struggle for social constructivism in postsocialist Central and Eastern Europe
Authors: Havelková Barbara
Published: March 2020

This paper argues that some of the difficulties faced by gender equality in postsocialist Central and Eastern Europe (CEE) can be explained by a missing paradigmatic shift to a constructivist understanding of gender. Arguably the most explicit rejection of a constructivist gender perspective was recently served by the Bulgarian Constitutional Court’s judgment, closely analyzed in the paper, which found certain provisions of the Council of Europe Convention on preventing and combating violence against women and domestic violence (Istanbul Convention) incompatible with the Bulgarian Constitution. A constructivist analysis of gender-based violence is capable of offering a range of important contextual insights into gender-based violence, whereas those who only have biology in their analytical arsenal are more limited (for example, sexual predation is thus either an “innate” male sexual drive or a psychologically certifiable deviance). The Bulgarian Constitutional Court, as the paper shows, does not even get as far as debating the insights gender analysis offers, but rather rejects them wholesale merely because the term “gender” is used. While a constructivist, critical (feminist) understanding of gender is under attack globally, this paper shows that the assault is particularly grave in at least certain postsocialist CEE countries, where it is not a mere backlash against a reasonably well-established viewpoint, but a fierce ex ante rejection of a concept not yet understood or debated.
Ileocolic Intussusception as the Presenting Symptom of Primary Enteric Varicella-Zoster Virus Infection in a 7-Month-Old Infant
Authors: Windster Jonathan D , Ouwendijk Werner J D , Sloots Cornelius E J , Verjans Georges M G M , Verdijk Robert M
Published: March 2020

Ileocolic intussusception is the invagination of ileum into the colon. In a subset of patients, the disease is caused by mesenteric lymphadenopathy in response to (viral) infection. We present a case of an ileocolic intussusception necessitating surgery in a 7-month-old immunocompetent infant with concurrent primary wild-type varicella-zoster virus (VZV) infection, in whom chickenpox rash developed 2 days after surgery. Detailed in situ analyses of resected intestine for specific cell type markers and VZV RNA demonstrated VZV-infected lymphocytes and neurons in the gut wall and in ganglion cells of the myenteric plexus.
Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue
Authors: Hammel Jennifer H , Bellas Evangelia
Published: March 2020

Central to the development of adipose tissue (AT) engineered models is the supporting vasculature. It is a key part of AT function and long-term maintenance, but the crosstalk between adipocytes and endothelial cells is not well understood. Here, we directly co-culture the two cell types at varying ratios in a 3D Type I collagen gel. Constructs were evaluated for adipocyte maturation and function and vascular network organization. Further, these constructs were treated with forskolin, a beta-adrenergic agonist, to stimulate lipolysis and browning. Adipocytes in co-cultures were found to be less mature than an adipocyte-only control, shown by smaller lipid droplets and downregulation of key adipocyte-related genes. The most extensive vascular network formation was found in the 1:1 co-culture, supported by vascular endothelial growth factor (VEGF) upregulation. After forskolin treatment, the presence of endothelial cells was shown to upregulate PPAR coactivator 1 alpha (PGC-1α) and leptin, but not uncoupling protein 1 (UCP1), suggesting a specific crosstalk that enhances early stages of browning.
Paper, Ink, Vodun, and the Inquisition: Tracing Power, Slavery, and Witchcraft in the Early Modern Portuguese Atlantic
Authors: Fromont Cécile
Published: March 2020

In 1730, the Inquisition of Lisbon arrested José Francisco Pereira, a man raised in West Africa and enslaved in Brazil then Portugal, who had learned along his transatlantic journeys the art of making amulets known in the eighteenth century Portuguese-speaking world as bolsas de mandinga. Mixing European esoteric material into objects of Afro-Atlantic agency, bolsa-makers such as José Francisco created objects of trustworthy might that brought empowerment and security of body and mind to a diverse clientele. The bolsas, as well as similar empowered objects created in Atlantic Africa reveal the deep and mutually transformative spiritual and material connections that the slave trade engendered between Europeans and Africans in the early modern period. Common concerns produced similar answers, not least newly defined or redefined notions of witchcraft and fetish and, more broadly, conceptions about the nature of power and its multivalent entanglements with the material world.
Effectiveness and safety of an institutional aminoglycoside-based regimen as empirical treatment of patients with pyelonephritis
Authors: Elbaz Meital , Zadka Hila , Weiss-Meilik Ahuva , Ben-Ami Ronen
Published: March 2020

Objectives

To determine clinical outcomes associated with aminoglycosides versus other antimicrobial agents as empirical treatment of hospitalized patients with pyelonephritis.

Patients and methods

An institutional programme promoting aminoglycosides as empirical treatment of pyelonephritis was implemented in 2016. We reviewed the hospital records of patients with pyelonephritis from January 2017 to April 2019. The primary outcome was death within 30 days of index culture. Initial treatment with aminoglycoside-based regimens was compared with non-aminoglycoside antibiotics. Propensity score matching was performed to adjust for between-group differences in baseline covariates.

Results

The study cohort included 2026 patients, 715 treated with aminoglycosides and 1311 treated with non-aminoglycoside drugs (ceftriaxone, n = 774; piperacillin/tazobactam, n = 179; carbapenems, n = 161; and fluoroquinolones, n = 133); 589 patients (29%) had bloodstream infections. Treatment with aminoglycosides was associated with a higher likelihood of in vitro activity against clinical isolates (OR = 2.0; P < 0.001). Death at 30 days occurred in 55 (7.6%) versus 145 (11%) patients treated with aminoglycosides and non-aminoglycoside drugs, respectively (adjusted HR = 0.78; P = 0.013). Aminoglycosides were either superior or similar to comparator drugs in all patient subgroups, stratified according to age, glomerular filtration rate, bacteraemia, haemodynamic shock and infection with third-generation cephalosporin-resistant Enterobacteriaceae. The incidence of acute kidney injury was similar for aminoglycosides and comparators (2.5% versus 2.9%, respectively; P = 0.6).

Conclusions

Within the context of an institutional programme, initial empirical treatment of pyelonephritis with aminoglycosides was associated with higher rates of in vitro activity and lower overall mortality compared with non-aminoglycoside drugs, without excess nephrotoxicity.
Low-dose liposomal amphotericin B for antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell transplantation
Authors: Mendoza-Palomar Natalia , Soques Elena , Benitez-Carabante María Isabel , Gonzalez-Amores Miriam , Fernandez-Polo Aurora , Renedo Berta , Martin Maria Teresa , Soler-Palacin Pere , Diaz-de-Heredia Cristina
Published: March 2020

Background

Primary antifungal prophylaxis in paediatric allogeneic HSCT recipients is mainly based on azoles, which can have related toxicity and drug interactions. Low-dose liposomal amphotericin B (L-AmB) is an attractive intravenous alternative because of its low toxicity and lower risk of interactions.

Objectives

To evaluate the effectiveness and safety of L-AmB (1 mg/kg/day) for primary antifungal prophylaxis in pre-engraftment paediatric HSCT patients.

Patients and methods

Retrospective, observational study including all consecutive patients aged ≤18 years who underwent HSCT and received antifungal prophylaxis with intravenous L-AmB (1 mg/kg/day, from day −1 to 48 h before discharge) between January 2012 and December 2016.

Results

In total, 125 HSCT procedures in 118 patients were included, median age 7.2 years (IQR 4.2–11.5). Haematological malignancies were the main underlying condition (63.6%), and 109 (87.2%) were considered at high risk for invasive fungal infection (IFI). Ten patients (7.7%), all high risk, developed breakthrough IFI (three Candida spp., seven invasive mould infections) and tended to have higher overall mortality. The only statistically significant risk factor for IFI was cytomegalovirus co-infection. Adverse events, all grade I, occurred in 25 (20%), requiring L-AmB withdrawal in one case. Overall survival at 30 days was 99.2%. At study completion, one patient had died of IFI.

Conclusions

The incidence of breakthrough IFI was comparable to that of previous reports, with a very low rate of significant toxicity. Thus, prophylactic L-AmB may be a safe, effective option for antifungal prophylaxis in the pre-engraftment phase for children undergoing HSCT, even those at high risk.
Impact of dietary oxidized protein on oxidative status and performance in growing pigs
Authors: Frame Carl A , Johnson Erika , Kilburn Logan , Huff-Lonergan Elisabeth , Kerr Brian J , Serao Mariana Rossoni
Published: March 2020

Rendered products from the meat industry can provide economical quality sources of proteins to the animal and feed industry. Similar to lipids, rendered proteins are susceptible to oxidation, yet the stability of these proteins is unclear. In addition, interest in understanding how oxidative stress can impact efficiency in production animals is increasing. Recent studies show that consumption of oxidized lipids can lead to a change in the oxidative status of the animal as well as decreases in production efficiency. To date, little is known about how consumption of oxidized proteins impacts oxidative status and growth performance. The objectives of this study were to determine if feeding diets high in oxidized protein to growing pigs would: 1) impact growth performance and 2) induce oxidative stress. Thirty pigs (42 d old; initial body weight [BW] 12.49 ± 1.45 kg) were randomly assigned to one of three dietary treatments with increasing levels of oxidized protein. Spray-dried bovine plasma was used as the protein source and was either unheated upon arrival, heated at 45 °C for 4 d, or heated at 100 °C for 3 d. Diets were fed for 19 d and growth performance was measured. Blood plasma (days 0 and 18), jejunum, colon, and liver tissues (day 19) were collected to analyze for markers of oxidative stress (e.g., protein oxidation, lipid oxidation, DNA damage, and glutathione peroxidase activity). Average daily gain (ADG;P < 0.01) and average daily feed intake (ADFI;P < 0.01) had a positive linear relationship to increased protein oxidation, but there was no effect on gain to feed ratio. Furthermore, protein (P = 0.03) and fat (P < 0.01) digestibility were reduced with increased protein oxidation in the diet. Crypt depth showed a positive linear relationship with dietary protein oxidation levels (P = 0.02). A trend was observed in liver samples where pigs fed the plasma heated to 45 °C had increased lipid oxidation compared with pigs fed the plasma either unheated or heated to 100 °C (P = 0.09). DNA damage in the jejunum tended to have a linear relationship with the dietary protein oxidation level (P = 0.07). Even though results suggest dietary oxidized protein did not induce oxidative stress during short-term feeding, differences in performance, gut morphology, and digestibility are likely a result of reduced protein availability.
Germline MBD4 Mutations and Predisposition to Uveal Melanoma
Authors: Derrien Anne-Céline , Rodrigues Manuel , Eeckhoutte Alexandre , Dayot Stéphane , Houy Alexandre , Mobuchon Lenha , Gardrat Sophie , Lequin Delphine , Ballet Stelly , Pierron Gaëlle , Alsafadi Samar , Mariani Odette , El-Marjou Ahmed , Matet Alexandre , Colas Chrystelle , Cassoux Nathalie , Stern Marc-Henri
Published: March 2020

Background

Uveal melanoma (UM) arises from malignant transformation of melanocytes in the uveal tract of the eye. This rare tumor has a poor outcome with frequent chemo-resistant liver metastases. BAP1 is the only known predisposing gene for UM. UMs are generally characterized by low tumor mutation burden, but some UMs display a high level of CpG>TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1093 primary UM case patients and a series of 192 UM tumors with monosomy 3 (M3).

Methods

We performed MBD4 targeted sequencing on pooled germline (n = 1093) and tumor (n = 192) DNA samples of UM patients. MBD4 variants (n = 28) were validated by Sanger sequencing. We performed whole-exome sequencing on available tumor samples harboring MBD4 variants (n = 9). Variants of unknown pathogenicity were further functionally assessed.

Results

We identified 8 deleterious MBD4 mutations in the consecutive UM series, a 9.15-fold (95% confidence interval = 4.24-fold to 19.73-fold) increased incidence compared with the general population (Fisher exact test, P = 2.00 × 10–5, 2-sided), and 4 additional deleterious MBD4 mutations in the M3 cohort, including 3 germline and 1 somatic mutations. Tumors carrying deleterious MBD4 mutations were all associated with high tumor mutation burden and a CpG>TpG hypermutator phenotype.

Conclusions

We demonstrate that MBD4 is a new predisposing gene for UM associated with hypermutated M3 tumors. The tumor spectrum of this predisposing condition will likely expand with the addition of MBD4 to diagnostic panels. Tumors arising in such a context should be recognized because they may respond to immunotherapy.
The Deuteronomistic Endorsement of Sacrificing Errant Individuals as Reflected by the Hebrew Terms Ḥērem and Biʽēr
Authors: Tatlock Jason
Published: March 2020

Despite the efforts of some scholars, biblical denunciations of one form of human sacrifice cannot be taken as condemnations of all types. Thus, while the writers of the Deuteronomistic History clearly regarded the slaying of children at the Jerusalem Tophet adversely, they accepted the legitimacy of sacrificing religiously errant individuals like murderers and others who went against their form of Yahwism. Such an endorsement is particularly represented by the biblical Hebrew ideas of sacrificial dedication (ḥērem) and burning up/consuming contamination (biʽēr). In the wake of Judah's fall and Jerusalem's destruction, the Deuteronomists promoted human sacrifice as a means to maintain or establish the purity of the Israelite community and the land of Canaan while delineating the limits of their version of a Yahwistic group.
KNOX protein KNAT1 regulates fruitlet abscission in litchi by repressing ethylene biosynthetic genes
Authors: Zhao Minglei , Li Caiqin , Ma Xingshuai , Xia Rui , Chen Jianye , Liu Xuncheng , Ying Peiyuan , Peng Manjun , Wang Jun , Shi Chun-Lin , Li Jianguo
Published: March 2020

Abscission is triggered by multiple environmental and developmental cues, including endogenous plant hormones. KNOTTED-LIKE HOMEOBOX (KNOX) transcription factors (TFs) play an important role in controlling abscission in plants. However, the underlying molecular mechanism of KNOX TFs in abscission is largely unknown. Here, we identified LcKNAT1, a KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1)-like protein from litchi, which regulates abscission by modulating ethylene biosynthesis. LcKNAT1 is expressed in the fruit abscission zone and its expression decreases during fruitlet abscission. Furthermore, the expression of the ethylene biosynthetic genes LcACS1, LcACS7, and LcACO2 increases in the fruit abscission zone, in parallel with the emission of ethylene in fruitlets. In vitro and in vivo assays revealed that LcKNAT1 inhibits the expression of LcACS/ACO genes by directly binding to their promoters. Moreover, ectopic expression of LcKNAT1 represses flower abscission in tomatoes. Transgenic plants expressing LcKNAT1 also showed consistently decreased expression of ACS/ACO genes. Collectively, these results indicate that LcKNAT1 represses abscission via the negative regulation of ethylene biosynthesis.
Production and excitation of molecules by dissipation of two-dimensional turbulence
Authors: Lesaffre P , Todorov P , Levrier F , Valdivia V , Dzyurkevich N , Godard B , Tram L N , Gusdorf A , Lehmann A , Falgarone E
Published: March 2020

The interstellar medium (ISM) is typically a hostile environment: cold, dilute and irradiated. Nevertheless, it appears very fertile for molecules. The localized heating resulting from turbulence dissipation is a possible channel to produce and excite molecules. However, large-scale simulations cannot resolve the dissipative scales of the ISM. Here, we present two-dimensional small-scale simulations of decaying hydrodynamic turbulence using the chemses code, with fully resolved viscous dissipation, time-dependent heating, cooling, chemistry and excitation of a few rotational levels of H2. We show that molecules are produced and excited in the wake of strong dissipation ridges. We carefully identify shocks and we assess their statistics and contribution to the molecular yields and excitation. We find that the formation of molecules is strongly linked to increased density as a result of shock compression and to the opening of endothermic chemical routes because of higher temperatures. We identify a new channel for molecule production via H2 excitation, illustrated by CH+ yields in our simulations. Despite low temperatures and the absence of magnetic fields (favouring CH+ production through ion-neutral velocity drifts), the excitation of the first few rotational levels of H2 shrinks the energy gap to form CH+. The present study demonstrates how dissipative chemistry can be modelled by statistical collections of one-dimensional steady-state shocks. Thus, the excitation of higher J levels of H2 is likely to be a direct signature of turbulence dissipation, and an indirect probe for molecule formation. We hope these results will help to bring new tools and ideas for the interpretation of current observations of H2 rotational lines carried out using the Stratospheric Observatory for Infrared Astronomy (SOFIA), and pave the way for a better understanding of the high-resolution mapping of H2 emission by future instruments, such as theJames Webb Space Telescope and the Space Infrared Telescope for Cosmology and Astrophysics.