bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Clostridioides difficile Infection Prevention With a Pharmacy-Controlled Policy That Adds a 3-Strain Lactobacillus Probiotic Concomitantly to Antibiotic Therapy
Authors: Maziade Pierre-Jean , Ship Noam , Sniffen Jason C , Goldstein Ellie J C
Published: May 2021

When 70% of antibiotic users took a 3-strain Lactobacillus probiotic preparation the hospital-wide rate of healthcare-associated Clostridioides difficile infection improved significantly. The incidence of C. difficile infection for those taking the probiotic along with multiple antibiotics or a single high-risk antibiotic was decreased by at least half.
Histopathological Features in Colonic Biopsies at Diagnosis Predict Long-term Disease Course in Patients with Crohn’s Disease
Authors: Rezazadeh Ardabili Ashkan , Goudkade Danny , Wintjens Dion , Romberg-Camps Mariëlle , Winkens Bjorn , Pierik Marie , Grabsch Heike I , Jonkers Daisy
Published: May 2021

Background and Aims

Crohn’s disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course.

Methods

Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates.

Results

In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%).

Conclusions

In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.
‘Ticagrelor alone vs. dual antiplatelet therapy from 1 month after drug-eluting coronary stenting among patients with STEMI’: a post hoc analysis of the randomized GLOBAL LEADERS trial
Authors: Gamal Amr S , Hara Hironori , Tomaniak Mariusz , Lunardi Mattia , Gao Chao , Ono Masafumi , Kawashima Hideyuki , Jüni Peter , Vranckx Pascal , Windecker Stephan , Hamm Christian , Steg Philippe Gabriel , Onuma Yoshinobu , Serruys Patrick W
Published: May 2021

Aim

To evaluate the efficacy and safety of ticagrelor monotherapy beyond 1 month and up to 24 months vs. standard 12-month dual antiplatelet therapy (DAPT) with aspirin and ticagrelor followed by aspirin monotherapy among ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) in the GLOBAL LEADERS trial.

Methods and results

We performed a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial comparing experimental ticagrelor monotherapy (1062 patients) with standard 12-month DAPT (1030 patients). We evaluated predefined primary and secondary endpoints in both treatment arms. Rates of net adverse clinical events (NACE), patient-oriented composite endpoints (POCE), and bleeding academic research consortium (BARC)-defined bleeding Type 3 or 5 were also evaluated. At 2 years, there were no significant differences in rates of primary endpoints in patients who had STEMI [0.89 (0.61–1.31)]. There were similar rates of NACE and POCE in both experimental and reference treatment groups at 2 years post-PCI [hazard ratio (HR) 0.96 (0.77–1.20) and 0.96 (0.77–1.21), respectively]. BARC 3 or 5 bleeding events were numerically less in experimental compared to reference treatment groups at 1 year [HR 0.55 (0.27–1.13)] and 2 years [0.61 (0.32–1.16)].

Conclusion

Presentation with STEMI has not influenced the incidence of GLOBAL LEADERS defined primary endpoints. There were no significant differences in rates of NACE, POCE, and BARC bleeding between the two treatment groups up to 2 years of follow-up. Although these findings should be viewed as exploratory, they expand the evidence on potential safety of aspirin-free antiplatelet strategies after PCI in STEMI.
Trends in blood pressure, blood lipids, and smoking from 259 753 patients with hypertension in a Swedish primary care register: results from QregPV
Authors: Bager Johan-Emil , Mourtzinis Georgios , Andersson Tobias , Nåtman Jonatan , Rosengren Annika , Björck Staffan , Manhem Karin , Hjerpe Per
Published: May 2021

Aims

To describe 8-year trends in blood pressure (BP) control, blood lipid control, and smoking habits in patients with hypertension from QregPV, a primary care register in the Region of Västra Götaland, Sweden.

Methods and results

QregPV features clinical data on BP, low-density lipoprotein cholesterol (LDL-C), and smoking habits in 392 277 patients with hypertension or coronary heart disease or diabetes mellitus or any combination of the three diagnoses. Data from routine clinical practice have been automatically reported on a monthly basis to QregPV from all primary care centres in Västra Götaland (population 1.67 million) since 2010. Additional data on diagnoses, dispensed drugs and socioeconomic factors were acquired through linkage to regional and national registers. We identified 259 753 patients with hypertension, but without coronary heart disease and diabetes mellitus, in QregPV. From 2010 to 2017, the proportion of patients with BP <140/90 mmHg increased from 38.9% to 49.1%, while the proportion of patients with LDL-C <2.6 mmol/L increased from 19.7% to 21.1% and smoking decreased from 15.7% to 12.3%. However, in 2017, only 10.0% of all patients with hypertension had attained target levels of BP <140/90 mmHg, LDL-C < 2.6 mmol/L while being also non-smokers. The remaining 90.0% were still exposed to at least one uncontrolled, modifiable risk factor for cardiovascular disease.

Conclusions

These regionwide data from eight consecutive years in 259 753 patients with hypertension demonstrate a large potential for risk factor improvement. An increased use of statins and antihypertensive drugs should, in addition to lifestyle modifications, decrease the risk of cardiovascular disease in these patients.
The spontaneous mutation rate of Drosophila pseudoobscura
Authors: Krasovec Marc
Published: May 2021

The spontaneous mutation rate is a very variable trait that is subject to drift, selection and is sometimes highly plastic. Consequently, its variation between close species, or even between populations from the same species, can be very large. Here, I estimated the spontaneous mutation rate of Drosophila pseudoobscura and Drosophila persimilis crosses to explore the mutation rate variation within the Drosophila genus. All mutation rate estimations in Drosophila varied fourfold, probably explained by the sensitivity of the mutation rate to environmental and experimental conditions. Moreover, I found a very high mutation rate in the hybrid cross between D. pseudoobscura and D. persimilis, in agreement with known elevated mutation rate in hybrids. This mutation rate increase can be explained by heterozygosity and fitness decrease effects in hybrids.
Impact of Media-Based Negative and Positive Age Stereotypes on Older Individuals’ Mental Health
Authors: Levy Becca R , Chang E-Shien , Lowe Sarah R , Provolo Natalia , Slade Martin D
Published: May 2021

Objectives

During the COVID-19 pandemic, stigmatization of older persons increased in traditional and social media. It was unknown whether this negative messaging could be detrimental to the mental health of older individuals, and whether the relatively uncommon positive messaging about older individuals could benefit their mental health.

Method

To address these gaps, we designed age-stereotype interventions based on actual news stories that appeared during the pandemic, and divided them into negative and positive versions of what we term personified (i.e., individual-based) and enumerative (i.e., number-based) age-stereotype messaging. The negative versions of the 2 types of messaging reflected the age stereotype of decline, whereas the positive versions of the 2 types of messaging reflected the age stereotype of resilience.

Results

As expected, the exposure of older individuals to the negative-age-stereotype-messaging interventions led to significantly worse mental health (i.e., more anxiety and less peacefulness), compared to a neutral condition; in contrast, the positive-age-stereotype-messaging interventions led to significantly better mental health (i.e., less anxiety and more peacefulness), compared to a neutral condition. The findings were equally strong for the personified and enumerative conditions. Also as expected, the interventions, which were self-irrelevant to the younger participants, did not significantly impact their mental health.

Discussion

This is the first-known study to experimentally demonstrate that institutional ageism, and statistics that reflect stereotypes about older individuals, can impact mental health. The results demonstrate the need for media messaging aimed at empowering older individuals during the pandemic and beyond.
Characterization of the near-surface shear wave attenuation in the Groningen gas field using borehole recording
Authors: He Yicheng , Li Junlun , Tian Wen , Li Zhiwei
Published: May 2021

The Groningen gas field located in the northern Netherlands is the largest gas field in Europe. Many induced earthquakes have occurred since the gas extraction commenced in the 1960s, especially in the last two decades, which have caused concerning social and economic problems. To better quantify the seismic hazards caused by the induced earthquakes, the near surface attenuation in the Groningen area needs to be characterized from actual earthquakes. The spectral ratio method based on multiwindow analysis has proven to be a powerful tool to estimate the S-wave attenuation parameters of shallow sediments. In this study, waveforms from earthquake events recorded by the dense network of 70 boreholes, each of which is equipped with four geophones are used to estimate the S-wave attenuation parameters of shallow sediments. There are strong lateral variations in the near-surface attenuation, which is structurally similar to the S-wave model from a previous study in the same area. Besides, the calculated $Q_S^{ - 1}$ values are inversely proportional to the frequency and depth. The averaged ${\rm{\ }}Q_S^{ - 1}$ values for depths between 0–150 m and 0–200 m are close to those of the soft soil Sendai basin in Japan. The $Q_S^{ - 1}$ values from this study have been used to model a surface peak ground acceleration (PGA) map. As expected, both near surface $Q_S^{ - 1}$ values and source mechanism have a profound effect on the modelled PGA.
The Effect of Urine Collection with a Novel External Catheter Device on Common Urine Chemistry and Urinalysis Results
Authors: Rose Gary , Pyle-Eilola Amy L
Published: May 2021

Introduction

Urine collection from incontinent individuals can be challenging. Various methods have been devised to collect the sample without catheterization. Recently the PureWick external catheter was developed to draw the sample gently away from external female genitalia. While the primary purpose of the device is to prevent moisture and maintain skin integrity, the urine that is collected may be sent for laboratory analysis. We sought to validate the use of this collection method for common urine chemistry assays and urinalysis.

Methods

Twenty pools of residual urine samples were separated into “control” and “PureWick” treated samples. The control samples were maintained at room temperature while 15 mL of urine was added to the PureWick device which was connected to a vacuum line through a collection canister. The urine collected in the canister and the controls samples were all subject to urine chemistry strip, microscopic, and automated urine chemistry analysis. Results were compared between pairs of treated and control samples.

Results

No clear affect was noted on urine strip semi-quantitative or automated chemistry analysis from the PureWick collection. There was a statistically significant decrease in microscopic measurements of white blood cells and crystals in the PureWick urine samples.

Discussion

This study supports the use of the PureWick external catheter for collection of samples for most urinalysis and urine chemistry tests.
Effects of chicory polysaccharides on the growth, antioxidant activity, and disease resistance in the Chinese mitten crab Eriocheir sinensis H. Milne Edwards, 1853 (Decapoda: Brachyura: Varunidae)
Authors: Wang Qing , Guo Li Y , Zhou Guo Q , Jiang Gong C , Ding Zheng F
Published: May 2021

An eight-week study was conducted to determine requirements for chicory polysaccharides (CP) and their effects on the growth and immunity in the Chinese mitten crab Eriocheir sinensis H. Milne Edwards, 1853, followed by a challenge assay with the white spot syndrome virus (WSSV) for ten days. Crabs were separately fed with CP-free, 0.5% CP, 1% CP, and 4% CP diets. Results showed that crabs fed with 1% and 4% CP diets exhibited significant higher growth rate than that of controls (P < 0.05). The acid phosphatase (ACP), alkaline phosphatase (AKP), and peroxidase (POD) activities in the 1% CP group were clearly higher than those in the control groups (P < 0.05). The contents of glutathione (GSH) in 1% CP and 4% CP groups were significantly higher than those in the control group (P < 0.05). Malondialdehyde (MDA) contents in experimental groups, especially in the 1% CP group, decreased significantly relative to those in the control group (P < 0.05). When challenged by WSSV, the cumulative mortality was the lowest in the 4% CP group, whereas that in the control group was the highest (P < 0.05). Our study revealed that CP-supplemented diets enhanced specific growth, antioxidant activity, and anti-WSSV resistance in E. sinensis. Based on our findings, we suggest a CP diet content of 10 g kg–1 (1%).
Penetrance of Breast Cancer Susceptibility Genes From the eMERGE III Network
Authors: Fan Xiao , Wynn Julia , Shang Ning , Liu Cong , Fedotov Alexander , Hallquist Miranda L G , Buchanan Adam H , Williams Marc S , Smith Maureen E , Hoell Christin , Rasmussen-Torvik Laura J , Peterson Josh F , Wiesner Georgia L , Murad Andrea M , Jarvik Gail P , Gordon Adam S , Rosenthal Elisabeth A , Stanaway Ian B , Crosslin David R , Larson Eric B , Leppig Kathleen A , Henrikson Nora B , Williams Janet L , Li Rongling , Hebbring Scott , Weng Chunhua , Shen Yufeng , Crew Katherine D , Chung Wendy K
Published: May 2021

Background

Unbiased estimates of penetrance are challenging but critically important to make informed choices about strategies for risk management through increased surveillance and risk-reducing interventions.

Methods

We studied the penetrance and clinical outcomes of 7 breast cancer susceptibility genes (BRCA1, BRCA2, TP53, CHEK2, ATM, PALB2, and PTEN) in almost 13 458 participants unselected for personal or family history of breast cancer. We identified 242 female participants with pathogenic or likely pathogenic variants in 1 of the 7 genes for penetrance analyses, and 147 women did not previously know their genetic results.

Results

Out of the 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 17.8% to 43.8%, depending on the gene. In clinical-impact analysis, 42.3% (95% confidence interval = 31.3% to 53.3%) of women had taken actions related to their genetic results, and 2 new breast cancer cases were identified within the first 12 months after genetic results disclosure.

Conclusions

Our study provides population-based penetrance estimates for the understudied genes CHEK2, ATM, and PALB2 and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve health care through early diagnosis and preventative screening.
COVID-19 in a Subset of Hospitalized Children in Israel
Authors: Ben-Shimol Shalom , Livni Gilat , Megged Orli , Greenberg David , Danino Dana , Youngster Ilan , Shachor-Meyouhas Yael , Dabaja-Younis Halima , Scheuerman Oded , Mor Meirav , Somekh Eli , Yakub Hanna Husam , Givon-Lavi Noga , Guri Alex , Leibovitz Eugene , Alkan Yoav , Grupel Daniel , Rubinstein Uri , Steinberg Ben Zeev Zohar , Bamberger Ellen , Asher Kuperman Amir , Grisaru-Soen Galia , Tasher Diana , Gottesman Giora , Glikman Daniel , Stein Michal
Published: May 2021

Background

Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children.

Methods

An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children <18 years across Israel (~75% of Israeli hospitals).

Results

Overall, 1007 cases (439 outpatients and 568 hospitalized) identified represent 0.35% of pediatric COVID-19 nationwide (n = 291 628). Of hospitalized cases, 464 (82%), 48 (8%), and 56 (10%) had mild, moderate/severe, and PIMS disease, respectively. The mean ± SD age was 5.6 ± 6.4 years. In mild, moderate/severe, and PIMS disease, 55%, 23%, and 4% of patients were <1 year old, respectively. Obesity was reported in 1%, 4%, and 13% of patients, respectively (P < .001). The most common symptom was fever in 67%, 60%, and 100%, respectively, whereas respiratory symptoms were documented in 33%, 41%, and 38% of patients, respectively. Lymphopenia was recorded in 25%, 60%, and 86% of cases, respectively. PIMS diagnosis was mainly serology-based (in 59%). Gastrointestinal symptoms, cardiovascular involvement, rash, and conjunctivitis were noted in 82%, 61%, 57%, and 34% of PIMS episodes, respectively. Elevated C-reactive protein (100%), ferritin, troponin, D-dimer, low albumin, and thrombocytopenia were common in PIMS. Echocardiography revealed pathological findings in 33% of patients. PIMS mainstay treatment included corticosteroids (77%) and intravenous immunoglobulin (53%). No mortality was recorded.

Conclusions

At a national level, pediatric COVID-19 is mild, even in hospitalized cases, with only a third presenting with respiratory involvement. PIMS is rare, but necessitates a high index of suspicion, and with suitable treatment prognosis is favorable.
Whole-Exome Sequencing Identifies a Recurrent Small In-Frame Deletion in MYO15A Causing Autosomal Recessive Nonsyndromic Hearing Loss in 3 Iranian Pedigrees
Authors: Nasrniya Samane , Miar Paniz , Narrei Sina , Sepehrnejad Mahsa , Nilforoush Mohammad Hussein , Abtahi Hamidreza , Tabatabaiefar Mohammad Amin
Published: May 2021

Background

Hearing loss (HL) is the most prevalent and genetically heterogeneous sensory disabilities in humans throughout the world.

Methods

In this study, we used whole-exome sequencing (WES) to determine the variant causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in 3 separate Iranian consanguineous families (with 3 different ethnicities: Azeri, Persian, and Lur), followed by cosegregation analysis, computational analysis, and structural modeling using the I-TASSER (Iterative Threading ASSEmbly Refinement) server. Also, we used speech-perception tests to measure cochlear implant (CI) performance in patients.

Results

One small in-frame deletion variant (MYO15A c.8309_8311del (p.Glu2770del)), resulting in deletion of a single amino-acid residue was identified. We found it to be cosegregating with the disease in the studied families. We provide some evidence suggesting the pathogenesis of this variant in HL based on the American College of Medical Genetics (ACMG) and Genomics guidelines. Evaluation of auditory and speech performance indicated favorable outcome after cochlear implantation in our patients.

Conclusions

The findings of this study demonstrate the utility of WES in genetic diagnostics of HL.
Chemically homogeneous evolution: a rapid population synthesis approach
Authors: Riley Jeff , Mandel Ilya , Marchant Pablo , Butler Ellen , Nathaniel Kaila , Neijssel Coenraad , Shortt Spencer , Vigna-Gómez Alejandro
Published: May 2021

We explore chemically homogeneous evolution (CHE) as a formation channel for massive merging binary black holes (BBHs). We develop methods to include CHE in a rapid binary population synthesis code, Compact Object Mergers: Population Astrophysics and Statistics (compas), which combines realistic models of binary evolution with cosmological models of the star formation history of the Universe. For the first time, we simultaneously explore conventional isolated binary star evolution under the same set of assumptions. This approach allows us to constrain population properties and make simultaneous predictions about the gravitational-wave detection rates of BBH mergers for the CHE and conventional formation channels. The overall mass distribution of detectable BBHs is consistent with existing gravitational-wave observations. We find that the CHE channel may yield up to ${\sim} 70{{\ \rm per\ cent}}$ of all gravitational-wave detections of BBH mergers coming from isolated binary evolution.
Discovery of magnetic fields along stacked cosmic filaments as revealed by radio and X-ray emission
Authors: Vernstrom T , Heald G , Vazza F , Galvin T J , West J L , Locatelli N , Fornengo N , Pinetti E
Published: May 2021

Diffuse filaments connect galaxy clusters to form the cosmic web. Detecting these filaments could yield information on the magnetic field strength, cosmic ray population, and temperature of intercluster gas; yet, the faint and large-scale nature of these bridges makes direct detections very challenging. Using multiple independent all-sky radio and X-ray maps we stack pairs of luminous red galaxies as tracers for cluster pairs. For the first time, we detect an average surface brightness between the clusters from synchrotron (radio) and thermal (X-ray) emission with ≳5σ significance, on physical scales larger than observed to date (${\ge}3$ Mpc). We obtain a synchrotron spectral index of α ≃ −1.0 and estimates of the average magnetic field strength of $30\,\mathrm{ nG} \le B \le 60 $ nG, derived from both equipartition and inverse-Compton arguments, implying a 5–15 per cent degree of field regularity when compared with Faraday rotation measure estimates. While the X-ray detection is inline with predictions, the average radio signal comes out higher than predicted by cosmological simulations and dark matter annihilation and decay models. This discovery demonstrates that there are connective structures between mass concentrations that are significantly magnetized, and the presence of sufficient cosmic rays to produce detectable synchrotron radiation.
A multiline study of the filamentary infrared dark cloud G351.78–0.54
Authors: Ryabukhina O L , Zinchenko I I
Published: May 2021

We present results of a multiline study of the filamentary infrared dark cloud G351.78–0.54 in the 1.3 and 0.8 mm wavelength bands. The lines of the three isotopologues of carbon monoxide CO, N2H+, CH3CCH, and HNCO were observed. The aim was to study the general structure of the filamentary cloud, its fragmentation, and physical parameters with the emphasis on properties of dense clumps in this cloud. Several dense clumps are identified from the N2H+ (3–2) data, their masses and virial parameters are determined using the C18O (2–1) line. Temperatures of some clumps are estimated from the CH3CCH and HNCO data. Almost all clumps appear to be gravitationally unstable. The density estimates obtained from the C18O (3–2)/(2–1) and N2H+ (3–2)/(1–0) intensity ratios are in the range n ∼ (0.3–3) × 105 cm−3. The HNCO emission is detected exclusively towards the first clump which contains the luminous IR source IRAS 17233–3606, and indicates an even higher density. It is observed in the outflow, too. The velocity shift of the higher excitation HNCO lines may indicate a movement of the hot core relative to the surrounding medium. In some clumps there is a velocity shift ∼1 km s−1 between N2H+ (3–2) and CO isotopologues. The large widths of the N2H+ (3–2) line in the clumps indicate an increase of the velocity dispersion in their dense interiors, which may be related to the star formation process. The N2H+ abundance drops towards the luminous IR source.
Interpreting the spectral lags of single-pulsed gamma-ray bursts via the photosphere in the jet model
Authors: Jiang Yun-Guo , Liu Ke-Xin , Shao Lang , Li Huai-Zhen
Published: May 2021

The prompt emission of gamma-ray bursts (GRBs) is a long-standing problem. The spectral-lag phenomenon can provide us with some clues about the emission mechanism. By analogy with the spectral lag of blazars at radio frequencies, we propose using the photosphere in the jet model to interpret the spectral lag of GRBs. Assuming a canonical jet and respecting the scaling laws of both the magnetic field and the number density of radiative particles, the radius of the photosphere and the magnetic field can be predicted. Five long bursts with known redshifts are studied. The prompt emitting regions of these bursts are located at about one or several astronomical units from the jet base. Without strictly constrained parameters, the magnetic fields at the photosphere radius are not well constrained. Taking the median values, the magnetic field is distributed in the range of 104∼107 G, which has no conflicts with the constraints obtained from the synchrotron cooling time.
A randomized phase II trial of veliparib, radiotherapy, and temozolomide in patients with unmethylatedMGMTglioblastoma: the VERTU study
Authors: Sim Hao-Wen , McDonald Kerrie L , Lwin Zarnie , Barnes Elizabeth H , Rosenthal Mark , Foote Matthew C , Koh Eng-Siew , Back Michael , Wheeler Helen , Sulman Erik P , Buckland Michael E , Fisher Lauren , Leonard Robyn , Hall Merryn , Ashley David M , Yip Sonia , Simes John , Khasraw Mustafa
Published: May 2021

Background

Temozolomide offers minimal benefit in patients with glioblastoma with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status, hence, the need for novel therapies. This study evaluated whether veliparib, a brain-penetrant poly(ADP-ribose) polymerase (PARP) inhibitor, acts synergistically with radiation and temozolomide.

Methods

VERTU was a multicenter 2:1 randomized phase II trial in patients with newly diagnosed glioblastoma and MGMT-unmethylated promotor status. The experimental arm consisted of veliparib and radiotherapy, followed by adjuvant veliparib and temozolomide. The standard arm consisted of concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide. The primary objective was to extend the progression-free survival rate at six months (PFS-6m) in the experimental arm.

Results

A total of 125 participants were enrolled, with 84 in the experimental arm and 41 in the standard arm. The median age was 61 years, 70% were male, 59% had Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 87% underwent macroscopic resection. PFS-6m was 46% (95% confidence interval [CI]: 36%-57%) in the experimental arm and 31% (95% CI: 18%-46%) in the standard arm. Median overall survival was 12.7 months (95% CI: 11.4-14.5 months) in the experimental arm and 12.8 months (95% CI: 9.5-15.8 months) in the standard arm. The most common grade 3-4 adverse events were thrombocytopenia and neutropenia, with no new safety signals.

Conclusion

The veliparib-containing regimen was feasible and well tolerated. However, there was insufficient evidence of clinical benefit in this population. Further information from correlative translational work and other trials of PARP inhibitors in glioblastoma are still awaited.
Predictors of Academic Neurosurgical Career Trajectory among International Medical Graduates Training Within the United States
Authors: Khalafallah Adham M , Jimenez Adrian E , Camp Samantha , Horowitz Melanie A , Chiu Ian , Ryu David , Charewycz Natasha , Vera Lauren , Bhoopalam Myan , Feghali James , Sharma Mayur , Lubelski Daniel , Cohen Alan R , Tamargo Rafael J , Witham Timothy , Huang Judy , Brem Henry , Mukherjee Debraj
Published: May 2021

BACKGROUND

Within the literature, there has been limited research tracking the career trajectories of international medical graduates (IMGs) following residency training.

OBJECTIVE

To compare the characteristics of IMG and US medical school graduate (USMG) neurosurgeons holding academic positions in the United States and also analyze factors that influence IMG career trajectories following US-based residency training.

METHODS

We collected data on 243 IMGs and 2506 USMGs who graduated from Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgery residency programs. We assessed for significant differences between cohorts, and a logistic regression model was used for the outcome of academic career trajectory.

RESULTS

Among the 2749 neurosurgeons in our study, IMGs were more likely to pursue academic neurosurgery careers relative to USMGs (59.7% vs 51.1%; P = .011) and were also more likely to complete a research fellowship before beginning residency (odds ratio [OR] = 9.19; P < .0001). Among current US academic neurosurgeons, USMGs had significantly higher pre-residency h-indices relative to IMGs (1.23 vs 1.01; P < .0001) with no significant differences between cohorts when comparing h-indices during (USMG = 5.02, IMG = 4.80; P = .67) or after (USMG = 14.05, IMG = 13.90; P = .72) residency. Completion of a post-residency clinical fellowship was the only factor independently associated with an academic career trajectory among IMGs (OR = 1.73, P = .046).

CONCLUSION

Our study suggests that while IMGs begin their US residency training with different research backgrounds and achievements relative to USMG counterparts, they attain similar levels of academic productivity following residency. Furthermore, IMGs are more likely to pursue academic careers relative to USMGs. Our work may be useful for better understanding IMG career trajectories following US-based neurosurgery residency training.
Beyond Strong Enforcement: Understanding the Factors Related to Retailer Compliance With Tobacco 21
Authors: Roberts Megan E , Klein Elizabeth G , Ferketich Amy K , Keller-Hamilton Brittney , Berman Micah L , Chacko Michael , Jenkins Claire F , Segall Morgan H , Woodyard Kiersten C
Published: May 2021

Introduction

Tobacco 21 (T21), which sets the minimum legal sales age for tobacco to age 21, is now a national law in the United States. Although T21 is expected to help curb youth tobacco use, its impact may be dampened due to poor retailer compliance. Even within environments where enforcement is strong (ie, compliance checks are conducted with tough sanctions for violations), compliance might vary due to other factors.

Aims and Methods

Three studies were conducted in Columbus, OH, where T21 became strongly enforced in 2018. These studies examined how retailer compliance related to features of the neighborhood in which a retailer was located (Study 1), features of the retailer (Study 2), and features of the retail cashier (Study 3).

Results

Study 1 found that, after controlling for race- and age-based factors, retailers located in high (vs. low)-poverty neighborhoods had a lower likelihood of conducting identification (ID) checks. Study 2 found that ID checks were related to whether retailers displayed signage about T21, as required by the city law. Study 3 found that, among cashiers, T21 awareness (which was high) and perceptions about T21 (which were moderate) were not generally related to their retailer’s compliance; having (vs. not having) scanners for ID checks was related to a higher likelihood of compliance.

Conclusions

These studies emphasize the many, multilevel factors influencing T21 outcomes. Findings also indicate the potential for T21 to widen disparities in tobacco use, indicating the need for strategies to equitably improve T21 compliance.

Implications

T21, which sets the minimum legal sales age for all tobacco products to age 21, is now a national law in the United States. Despite optimistic projections about what T21 could achieve, the ultimate impact may be dampened when it is applied in real-world settings. Our project revealed the many, multilevel factors influencing T21 compliance. Findings also indicate the potential for T21 to widen disparities in tobacco use if gaps in compliance persist. Strategies for equitably improving T21 compliance are discussed. This article is of relevance to areas interested in implementing or improving their local T21 enforcement.
Multiple lines of evidence indicate ongoing allopatric and parapatric diversification in an Afromontane sunbird (Cinnyris reichenowi)
Authors: Cooper Jacob C , Maddox J Dylan , McKague Kellie , Bates John M
Published: May 2021

Africa’s montane ecosystems are noteworthy not only for their isolation but for their morphologically similar bird populations that inhabit geographically disparate localities. Many species possess range disjunctions in excess of 2,000 km and appear to represent populations that have been isolated since at least the last Ice Age, including the Northern Double-collared Sunbird (Cinnyris reichenowi). Recent work on other Afromontane birds has demonstrated substantial phylogeographic structure can exist in phenotypically similar populations, with cryptic species occurring parapatrically within the same mountain range. We explored genetic, morphological, and ecological diversity within C. reichenowi to assess whether cryptic regional diversification occurs across the disjunct portions of this species’ range. Within C. reichenowi, we find consistent patterns of morphological disparity that coincide with genetic diversification between xeric and wet montane populations within the Cameroon Line in the Western population, and clear genetic differentiation between Western and Eastern populations. Our research demonstrates that the geographically isolated populations of C. reichenowi represent different species, and that ecological diversification is shaping populations within Central Africa. We show here that two named populations should be recognized as members of a western species in the Northern Double-collared Sunbird complex: nominate Cinnyris preussi preussi in the Cameroon Line montane forests, and Cinnyris preussi genderuensis in the more xeric interior of Cameroon and the Central African Republic, likely occurring in adjacent Nigeria as well.
Bringing Social Context Back In
Authors: Carlsen Hjalmar Bang , ToubØl Jonas , Ralund Snorre
Published: May 2021

This article demonstrates the utility of combining individual survey data with social media content data in order to analyze how social context predicts individual behavior. The lack of valid and reliable measures of the contexts of social interaction in which individuals are embedded has remained an Achilles heel of the survey method. The reason is that the collection of direct observation of social interaction requires qualitative analysis of the context, which, hitherto, has been too costly to collect on a large scale. Instead, researchers have resorted to indirect measures such as aggregate group composition, respondent reports of social context, and institutional accounts. However, with the recent advent of social media data, contemporary social scientists now have social interaction data on an unprecedented scale. To utilize these data for quantitative analysis, researchers have to transform text prose into good measurement. We combine qualitative content analysis and supervised machine learning in order to ensure both semantic validity and accuracy in our measure of social interaction in Facebook groups. To test the substantive performance of the direct measures of social interaction, we use it to predict individual participation in refugee solidarity activism in Denmark. Additional testing indicates that the direct measure cannot easily be replaced by indirect measures of social interaction derived from group composition and institutional accounts. We also show how contexts and individual respondents can be effectively sampled using Facebook groups. Finally, the article discusses the limitations of social media data and points to alternate settings where our design is applicable.
Corona doubt and scepticism: repression and denial as psychological defence mechanisms to process distress?
Authors: Teufel Martin , Schweda Adam , Kohler Hannah , Musche Venja , Fink Madeleine , Weismüller Benjamin , Moradian Sheila , Skoda Eva-Maria , Bäuerle Alexander
Published: May 2021

After more than a year of pandemic, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) remains a relevant health care and society issue. Movements doubting the dangerousness or the existence of the virus have emerged and became a challenge to social cohesion. About 3487 individuals (434 Corona doubters and 3053 non-doubters) have participated in an online survey (predominat age group: 35–45 years). Particularly, COVID-19-related anxiety, generalized anxiety (Generalizied Anxiety Disorder Screener, GAD-7), depression (Patient Health Questionnaire, PHQ-2) and functional/adherent safety behaviour were assessed. COVID-19 doubters describe less functional safety behaviour. Fear of the virus is evident, similar to non-doubters. Generalized anxiety and depression were significantly higher in doubters. Repression and denial as psychological defence mechanisms could be the unconscious psychological strategy for coping with the distress variables. The results point out that public strategies may only be successful in managing opinions and beliefs if they address fears and worries.
Isolated IgG2 deficiency is an independent risk factor for exacerbations in bronchiectasis
Authors: Zhang Y , Clarke A , Regan K H , Campbell K , Donaldson S , Crowe J , Rossi A G , Hill A T
Published: May 2021

Background

Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known.

Aim

To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression?

Design and Methods

This is a retrospective study (2015–20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann–Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels.

Results

Serum IgG2 levels (<2.68 g/l, 2.68–3.53 g/l and 3.54–4.45 g/l); hospital admission in the preceding 2 years; bacterial colonization with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/l and 2.68–3.53 g/l), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over 1 year compared with those who were IgG2 replete (>4.45 g/l) (P = 0.003, 0.013).

Conclusion

Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression.
Obesity as a Risk Factor for Accelerated Brain Ageing in First-Episode Psychosis—A Longitudinal Study
Authors: McWhinney Sean , Kolenic Marian , Franke Katja , Fialova Marketa , Knytl Pavel , Matejka Martin , Spaniel Filip , Hajek Tomas
Published: May 2021

Background

Obesity is highly prevalent in schizophrenia, with implications for psychiatric prognosis, possibly through links between obesity and brain structure. In this longitudinal study in first episode of psychosis (FEP), we used machine learning and structural magnetic resonance imaging (MRI) to study the impact of psychotic illness and obesity on brain ageing/neuroprogression shortly after illness onset.

Methods

We acquired 2 prospective MRI scans on average 1.61 years apart in 183 FEP and 155 control individuals. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants and calculated BrainAGE by subtracting chronological from the estimated brain age.

Results

Individuals with FEP had a higher initial BrainAGE than controls (3.39 ± 6.36 vs 1.72 ± 5.56 years; β = 1.68, t(336) = 2.59, P = .01), but similar annual rates of brain ageing over time (1.28 ± 2.40 vs 1.07±1.74 estimated years/actual year; t(333) = 0.93, P = .18). Across both cohorts, greater baseline body mass index (BMI) predicted faster brain ageing (β = 0.08, t(333) = 2.59, P = .01). For each additional BMI point, the brain aged by an additional month per year. Worsening of functioning over time (Global Assessment of Functioning; β = −0.04, t(164) = −2.48, P = .01) and increases especially in negative symptoms on the Positive and Negative Syndrome Scale (β = 0.11, t(175) = 3.11, P = .002) were associated with faster brain ageing in FEP.

Conclusions

Brain alterations in psychosis are manifest already during the first episode and over time get worse in those with worsening clinical outcomes or higher baseline BMI. As baseline BMI predicted faster brain ageing, obesity may represent a modifiable risk factor in FEP that is linked with psychiatric outcomes via effects on brain structure.
Gene Flow Increases Phylogenetic Structure and Inflates Cryptic Species Estimations: A Case Study on Widespread Philippine Puddle Frogs (Occidozyga laevis)
Authors: Chan Kin Onn , Hutter Carl R , Wood Perry L , Su Yong-Chao , Brown Rafe M
Published: May 2021

In cryptic amphibian complexes, there is a growing trend to equate high levels of genetic structure with hidden cryptic species diversity. Typically, phylogenetic structure and distance-based approaches are used to demonstrate the distinctness of clades and justify the recognition of new cryptic species. However, this approach does not account for gene flow, spatial, and environmental processes that can obfuscate phylogenetic inference and bias species delimitation. As a case study, we sequenced genome-wide exons and introns to evince the processes that underlie the diversification of Philippine Puddle Frogs—a group that is widespread, phenotypically conserved, and exhibits high levels of geographically based genetic structure. We showed that widely adopted tree- and distance-based approaches inferred up to 20 species, compared to genomic analyses that inferred an optimal number of five distinct genetic groups. Using a suite of clustering, admixture, and phylogenetic network analyses, we demonstrate extensive admixture among the five groups and elucidate two specific ways in which gene flow can cause overestimations of species diversity: 1) admixed populations can be inferred as distinct lineages characterized by long branches in phylograms; and 2) admixed lineages can appear to be genetically divergent, even from their parental populations when simple measures of genetic distance are used. We demonstrate that the relationship between mitochondrial and genome-wide nuclear $p$-distances is decoupled in admixed clades, leading to erroneous estimates of genetic distances and, consequently, species diversity. Additionally, genetic distance was also biased by spatial and environmental processes. Overall, we showed that high levels of genetic diversity in Philippine Puddle Frogs predominantly comprise metapopulation lineages that arose through complex patterns of admixture, isolation-by-distance, and isolation-by-environment as opposed to species divergence. Our findings suggest that speciation may not be the major process underlying the high levels of hidden diversity observed in many taxonomic groups and that widely adopted tree- and distance-based methods overestimate species diversity in the presence of gene flow. [Cryptic species; gene flow; introgression; isolation-by-distance; isolation-by-environment; phylogenetic network; species delimitation.]
Persistence of inefficient HIV prevention interventions: a mixed-method analysis of the reasons why
Authors: McKay Virginia R , Tetteh Emmanuel K , Reid Miranda J , Ingaiza Lucy M , Combs Todd B
Published: May 2021

Growing evidence suggests that public health organizations continue to provide inefficient interventions even when better intervention options may be available. Factors informing an organization’s decision to continue providing inefficient interventions are unclear. We present an analysis of HIV service organizations to understand factors influencing organizations to continue or end interventions. Between 2017 and 2019, HIV service organizations were recruited from the Center for Disease Control and Prevention’s (CDC) website gettested.org, in the 20 metropolitan areas with the highest HIV incidence. Organizations were eligible to participate if they had provided at least one of 37 HIV prevention interventions identified as inefficient by the CDC. 877 organizations were recruited, with a response rate of 66%, (n = 578). Thirty-eight percent (n = 213) of organizations met the eligibility criteria, and 188 organizations completed the survey asking about reasons for continuing or ending interventions. Funding status (41%, n = 79) and client demand for interventions (60%, n = 116) were reported as the primary driving factors why organizations continued ineffective interventions. Scientific evidence was a rarely reported reason for ending an inefficient intervention (12%, n = 23). Qualitative responses indicated interventions were continued if clients demanded interventions they found useful or if staff perceived interventions as improving client behavior and health outcomes. Conversely, interventions were ended if client demand or retention was low, not relevant to the target population or funding ended. The decision to continue or end inefficient interventions is influenced by a number of factors—most often by funding and client interest but not scientific evidence.