bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cleft lip/palate and educational attainment: cause, consequence or correlation? A Mendelian randomization study
Authors: Dardani Christina , Howe Laurence J , Mukhopadhyay Nandita , Stergiakouli Evie , Wren Yvonne , Humphries Kerry , Davies Amy , Ho Karen , Weinberg Seth M , Marazita Mary L , Mangold Elisabeth , Ludwig Kerstin U , Relton Caroline L , Davey Smith George , Lewis Sarah J , Sandy Jonathan , Davies Neil M , Sharp Gemma C 
Published: March 2020

Abstract

Background
Previous studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment.

Methods
We performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence.

Results
There was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) −0.05, 95% confidence interval (CI) −0.12 to 0.01, P 0.13; MR estimate (βMR) −0.002, 95% CI −0.009 to 0.006, P 0.679) or intelligence (rg −0.04, 95% CI −0.13 to 0.04, P 0.34; βMR −0.009, 95% CI −0.02 to 0.002, P 0.11).

Conclusions
Common variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.
Avian Influenza Human Infections at the Human-Animal Interface
Authors: Philippon Damien A M , Wu Peng , Cowling Benjamin J , Lau Eric H Y 
Published: March 2020

Abstract

Background
Avian influenza A viruses (AIVs) are among the most concerning emerging and re-emerging pathogens because of the potential risk for causing an influenza pandemic with catastrophic impact. The recent increase in domestic animals and poultry worldwide was followed by an increase of human AIV outbreaks reported.

Methods
We reviewed the epidemiology of human infections with AIV from the literature including reports from the World Health Organization, extracting information on virus subtype, time, location, age, sex, outcome, and exposure.

Results
We described the characteristics of more than 2500 laboratory-confirmed human infections with AIVs. Human infections with H5N1 and H7N9 were more frequently reported than other subtypes. Risk of death was highest among reported cases infected with H5N1, H5N6, H7N9, and H10N8 infections. Older people and males tended to have a lower risk of infection with most AIV subtypes, except for H7N9. Visiting live poultry markets was mostly reported by H7N9, H5N6, and H10N8 cases, while exposure to sick or dead bird was mostly reported by H5N1, H7N2, H7N3, H7N4, H7N7, and H10N7 cases.

Conclusions
Understanding the profile of human cases of different AIV subtypes would guide control strategies. Continued monitoring of human infections with AIVs is essential for pandemic preparedness.
Addressing Ethical Challenges in US-Based HIV Phylogenetic Research
Authors: Dawson Liza , Benbow Nanette , Fletcher Faith E , Kassaye Seble , Killelea Amy , Latham Stephen R , Lee Lisa M , Leitner Thomas , Little Susan J , Mehta Sanjay R , Martinez Omar , Minalga Brian , Poon Art , Rennie Stuart , Sugarman Jeremy , Sweeney Patricia , Torian Lucia V , Wertheim Joel O 
Published: March 2020

AbstractIn recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.
Impact of Housing and Infrastructure on handwashing in Peru
Authors: Malika Nipher M , Barbagelatta Guisella , Penny Mary , Reynolds Kelly A , Sinclair Ryan 
Published: March 2020

Abstract

Background
The metropolitan area of Lima, Peru has a third of the nation’s population living in slum dwellings that are hypothesized to contribute to inefficient household hygienic practices. The purpose of this study was to quantitatively assess which living conditions have the greatest impact on handwashing practices.

Methods
A cross-sectional epidemiological design of participants ≥16 y of age from San Juan de Miraflores, a slum on the outskirts of Lima, Peru, was used. Poisson regression was applied to assess the impact of living conditions on handwashing practices.

Results
We could not demonstrate a relationship between living conditions (home structure, overcrowding, water, grey water disposal) and reported handwashing. The reported lack of handwashing is associated with the number of children in the home (those with children &lt;5 y of age were more likely not to report washing their hands) and length of stay in the slum in years.

Conclusions
Living conditions play an important role in one’s health, therefore improved study designs are needed to determine which strategies are likely to be the most effective in improving outcomes for slum dwellers.
Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis
Authors: Miyajima Yurina , Ealey Kafi N , Motomura Yasutaka , Mochizuki Miho , Takeno Natsuki , Yanagita Motoko , Economides Aris N , Nakayama Manabu , Koseki Haruhiko , Moro Kazuyo 
Published: March 2020

Abstract
Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.
What Ibero-American hospitals do when things go wrong? A cross-sectional international study
Authors: Mira José Joaquín , Carrillo Irene , García-Elorrio Ezequiel , Andrade-Lourenção Daniela Campos D E , Pavan-Baptista Patricia Campos , Franco-Herrera Astolfo León , Campos-Castolo Esther Mahuina , Poblete Rodrigo , Limo Juan , Siu Hugo , Sousa Paulo 
Published: March 2020

AbstractObjectiveTo know what hospital managers and safety leaders in Ibero-American countries are doing to respond effectively to the occurrence of adverse events (AEs) with serious consequences for patients.DesignCross-sectional international study.SettingPublic and private hospitals in Ibero-American countries (Argentina, Brazil, Chile, Colombia, Mexico, Peru, Portugal and Spain).ParticipantsA convenience sample of hospital managers and safety leaders from eight Ibero-American countries. A minimum of 25 managers/leaders from each country were surveyed.InterventionsA selection of 37 actions for the effective management of AEs was explored. These were related to the safety culture, existence of a crisis plan, communication and transparency processes with the patients and their families, attention to second victims and institutional communication.Main Outcome MeasureDegree of implementation of the actions studied.ResultsA total of 190 managers/leaders from 126 (66.3%) public hospitals and 64 (33.7%) private hospitals participated. Reporting systems, in-depth analysis of incidents and non-punitive approaches were the most implemented interventions, while patient information and care for second victims after an AE were the least frequent interventions.ConclusionsThe majority of these hospitals have not protocolized how to act after an AE. For this reason, it is urgent to develop and apply a strategic action plan to respond to this imperative safety challenge. This is the first study to identify areas of work and future research questions in Ibero-American countries.
Bacterial population kinetics in heteroresistant Mycobacterium tuberculosis harbouring rare resistance-conferring mutations in gyrA and rpoB imply an epistatic interaction of mutations in a pre-XDR-TB patient
Authors: Yoshida Shiomi , Iwamoto Tomotada , Arikawa Kentaro , Sekizuka Tsuyoshi , Kuroda Makoto , Inoue Yoshikazu , Mitarai Satoshi , Tsuji Taisuke , Tsuyuguchi Kazunari , Suzuki Katsuhiro 
Published: March 2020

Abstract

Objectives
Bacterial population kinetics of strains harbouring drug resistance-conferring mutations within a patient often show cryptic resistance in clinical practice. We report a case that showed emergence and dominance of Mycobacterium tuberculosis with uncommon rpoB and gyrA mutations, followed by an rpoC compensatory mutation, during treatment.

Methods
A pre-XDR-TB patient showed heteroresistance to rifampicin and levofloxacin during treatment as a result of intermittent self-cessation. WGS was applied to investigate intra-host strain composition using five pairs of isolates from sputum samples.

Results
The subclone in this study possessed rare mutations conferring resistance to rifampicin (rpoB V170F) and levofloxacin (gyrA S91P) and it rapidly outcompeted other subclones during treatment that included levofloxacin but not rifampicin (&lt;7 days). The high-probability compensatory mutation rpoC V483A also emerged and became dominant subsequent to the rpoB V170F mutation.

Conclusions
To the best of our knowledge, this is the first case showing the emergence of such a rare variant that dominated the population within a patient during treatment of TB.
Multicentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes
Authors: Arendrup Maiken Cavling , Jørgensen Karin Meinike , Guinea Jesus , Lagrou Katrien , Chryssanthou Erja , Hayette Marie-Pierre , Barchiesi Francesco , Lass-Flörl Cornelia , Hamal Petr , Dannaoui Eric , Chowdhary Anuradha , Meletiadis Joseph 
Published: March 2020

Abstract

Objectives
Terbinafine resistance is increasingly reported in Trichophyton, rendering susceptibility testing particularly important in non-responding cases. We performed a multicentre evaluation of six EUCAST-based methods.

Methods
Ten laboratories susceptibility tested terbinafine, itraconazole, voriconazole and amorolfine against a blinded panel of 38 terbinafine WT and target gene mutant isolates. E.Def 9.3.1 modifications included: medium with/without addition of chloramphenicol and cycloheximide (CC), incubation at 25°C to 28°C for 5–7 days and three MIC endpoints [visually and spectrophotometrically (90%/50% inhibition)], generating 7829 MICs. Quality control (QC) strains were Aspergillus flavus ATCC 204304 and CNM-CM1813. Eyeball, ECOFFinder (where ECOFF stands for epidemiological cut-off) and derivatization WT upper limits (WT-ULs), very major errors (VMEs; mutants with MICs ≤WT-ULs) and major errors (MEs; WT isolates with MICs &gt;WT-ULs) were determined.

Results
MICs fell within the QC ranges for ATCC 204304/CNM-CM1813 for 100%/96% (voriconazole) and 84%/84% (itraconazole), respectively. Terbinafine MICs fell within 0.25–1 mg/L for 96%/92%, suggesting high reproducibility. Across the six methods, the number of terbinafine MEs varied from 2 to 4 (2.6%–5.2%) for Trichophyton rubrum and from 0 to 2 (0%–2.0%) for Trichophyton interdigitale. Modes for WT and mutant populations were at least seven 2-fold dilutions apart in all cases. Excluding one I121M/V237I T. rubrum mutant and two mixed WT/mutant T. interdigitale specimens, the numbers of VMEs were as follows: T. rubrum: CC visual, 1/67 (1.5%); CC spectrophotometric 90% inhibition, 3/59 (5.1%); and CC spectrophotometric 50% inhibition, 1/67 (1.5%); and T. interdigitale: none. Voriconazole and amorolfine MICs were quite uniform, but trailing growth complicated determination of itraconazole visual and spectrophotometric 90% inhibition MIC.

Conclusions
Although none of the laboratories was experienced in dermatophyte testing, error rates were low. We recommend the CC spectrophotometric 50% inhibition method and provide QC ranges and WT-ULs for WT/non-WT classification.
Effectiveness of dolutegravir-based antiretroviral treatment for HIV-2 infection: retrospective observational study from Western India
Authors: Pujari Sanjay , Patel Atul , Gaikwad Sunil , Patel Ketan , Dabhade Digamber , Chitalikar Abhishek , Joshi Kedar , Bele Vivek 
Published: March 2020

Abstract

Background
Data on the use of dolutegravir for treatment of HIV-2 infection are limited.

Objectives
To assess the effectiveness of dolutegravir in people living with HIV-2 (PLHIV-2).

Methods
A retrospective chart review was performed in two clinics in Western India. PLHIV-2 initiated on dolutegravir-based regimens were included. Response to treatment in both treatment-naive (TN) and treatment-experienced (TE; substitution and not in the context of failure) was assessed by CD4 counts and HIV-2 viral load (VL) in a proportion of individuals. The primary objective was to assess immunological effectiveness (absence of a drop in absolute CD4 counts by more than 30% of baseline). Change in absolute CD4 counts was assessed by fitting a mixed-effects model.

Results
Sixty-two PLHIV-2 treated with dolutegravir were included. The immunological effectiveness rates (95% CI) were 91.9% (82.4%–96.5%), 92% (81.1%–96.8%) and 91.6% (64.6%–98.5%) amongst all, TE and TN individuals, respectively. Median change in absolute CD4 counts at 6, 12 and 18 months were +29 cells/mm3, +101 cells/mm3 and +72 cells/mm3, respectively. The virological effectiveness rates (HIV-2 VL &lt;100 copies/mL) (95% CI) for all, TE and TN individuals were 88.8% (74.6%–95%), 89.6% (73.6%–96.4%) and 85.7% (48.6%–97.4%), respectively. Three clinical events were documented: spinal tuberculosis, relapsed non-Hodgkin’s lymphoma and herpes simplex virus retinitis. One individual reported self-limiting somnolence.

Conclusions
Dolutegravir was well tolerated and associated with immunological, virological and clinical effectiveness in both TN and TE PLHIV-2 in a large cohort from Western India. Dolutegravir-based ART is an excellent option for treatment of individuals with HIV-2 infection.
Antimicrobial susceptibility of Clostridioides difficile isolated from diarrhoeal stool specimens of Canadian patients: summary of results from the Canadian Clostridioides difficile (CAN-DIFF) surveillance study from 2013 to 2017
Authors: Karlowsky James A , Adam Heather J , Baxter Melanie R , Dutka Christopher W , Nichol Kim A , Laing Nancy M , Golding George R , Zhanel George G 
Published: March 2020

Abstract

Objectives
To summarize data generated by the Canadian Clostridioides difficile (CAN-DIFF) surveillance study from 2013 to 2017.

Methods
Isolates of C. difficile (n = 2158) were cultured from toxin-positive diarrhoeal stool specimens submitted by eight hospital laboratories to a coordinating laboratory. Antimicrobial susceptibility testing was performed according to the CLSI agar dilution method (M11, 2018). Isolate ribotypes were determined using an international, standardized, high-resolution capillary gel-based electrophoresis protocol.

Results
Of the 2158 isolates of C. difficile, 2133 (98.8%) had vancomycin MICs ≤2 mg/L [i.e. were vancomycin susceptible (EUCAST breakpoint tables, v 9.0, 2019) or WT (CLSI M100, 29th edition, 2019)]. Fidaxomicin MICs were lower than those of all other agents tested (MIC90, 0.5 mg/L); however, one isolate with a fidaxomicin MIC of &gt;8 mg/L was identified. Metronidazole MICs ranged from 0.12 to 4 mg/L; all isolates were metronidazole susceptible by the CLSI breakpoint (≤8 mg/L) compared with 96.8% susceptible by the EUCAST breakpoint (≤2 mg/L). In total, 182 different ribotypes were identified from 2013 to 2017. The most common ribotypes identified were 027 (19.3% of isolates) and 106 (8.2%). Ribotype 027 isolates were frequently moxifloxacin resistant (87.3% of isolates) and MDR (48.6%), associated with vancomycin (10/25, 40.0%) and metronidazole (58/69, 84.1%) resistance and from patients aged ≥80 years. The prevalence of ribotype 027 decreased significantly (P &lt; 0.0001) from 2013 (27.5%) to 2017 (9.0%) and was replaced by increases in ribotype 106 (P = 0.0003) and multiple less common ribotypes.

Conclusions
Periodic surveillance is required to monitor clinical isolates of C. difficile for changes to in vitro susceptibility testing profiles and ribotype evolution.
Quantitative Nuclear Magnetic Resonance Spectroscopic Analysis of Two Commonly Used Gastrointestinal Tract Drugs
Authors: Elbagary Ramzia I , Fouad Marwa A , Ezzeldin Menna I 
Published: March 2020

BackgroundTwo fast and precise quantitative nuclear magnetic resonance spectroscopic methods (qNMR) were established and evaluated for the determination of ondansetron (OND) and omeprazole (OMP) in bulk drugs and their pharmaceutical dosage forms. NMR spectra were established using dimethylsulfoxide (DMSO-d6) as a solvent and phloroglucinol as the internal standard. Proton NMR signals at 3.743, 3.811, and 5.670 ppm were used for quantitative monitoring purposes corresponding to OND, OMP, and phloroglucinol, respectively. In this study, the methods linearity, accuracy, limit of quantification, limit of detection, stability, and precision were validated as per International Conference on Harmonization (ICH) guidelines. Linearity ranges were 0.3–10 mg for OND and 1–10 mg for OMP. The student t-test and F-test were used for statistical evaluation. Herein, the proposed methods are useful and can be a successful practical appliance for OND and OMP determination in drug substances and their dosage forms.
Safety, Pharmacodynamics, and Efficacy of High- Versus Low-Dose Ascorbic Acid in Severely Burned Adults
Authors: Nagel Sarah Sophie , Radu Christian Andreas , Kremer Thomas , Meess David , Horter Johannes , Ziegler Benjamin , Hirche Christoph , Schmidt Volker Juergen , Kneser Ulrich , Hundeshagen Gabriel 
Published: March 2020

AbstractIn sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns &gt;20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid–base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA.
Food as Fuel: Performance Goals Increase the Consumption of High-Calorie Foods at the Expense of Good Nutrition
Authors: Cornil Yann , Gomez Pierrick , Vasiljevic Dimitri 
Published: March 2020

Abstract
At work, at school, at the gym club, or even at home, consumers often face challenging situations in which they are motivated to perform their best. This research demonstrates that activating performance goals, whether in cognitive or physical domains, leads to an increase in the consumption of high-calorie foods at the expense of good nutrition. This effect derives from beliefs that the function of food is to provide energy for the body (food as fuel) coupled with poor nutrition literacy, leading consumers to overgeneralize the instrumental role of calories for performance. Indeed, nutrition experts choose very different foods (lower in calorie, higher in nutritional value) than lay consumers in response to performance goals. Also, performance goals no longer increase calorie intake when emphasizing the hedonic function of food (food for pleasure). Hence, while consumer research often interprets the overconsumption of pleasurable and unhealthy high-calorie foods as a consequence of hedonic goals and self-control failures, our research suggests that this overconsumption may also be explained by a maladaptive motivation to manage energy intake.