bluuebunny/crossref_metadata_2025_split huggingface dataset:
First description of antimicrobial resistance in carbapenem-susceptible Klebsiella pneumoniae after imipenem treatment, driven by outer membrane remodeling
Authors: Tian Xuebin , Wang Qiongdan , Perlaza-Jiménez Laura , Zheng Xiangkuo , Zhao Yajie , Dhanasekaran Vijay , Fang Renchi , Li Jiahui , Wang Chong , Liu Haiyang , Lithgow Trevor , Cao Jianming , Zhou Tieli 
Published: July 2020

Abstract
Background
The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a looming threat to human health. Although there are numerous studies regarding porin alteration in association with the production of ESBLs and/or AmpC β-lactamase, a systematic study on the treatment-emergence of porins alteration in antibiotic resistance does not yet exist. The aim of this study was to investigate the underlying mechanism of resistance of K. pneumoniae during carbapenem treatment.

Results
Here, we report three strains (FK-2624, FK-2723 and FK-2820) isolated from one patient before and after imipenem treatment during hospitalization. Antibiotic susceptibility testing indicated that that the first isolate, FK-2624, was susceptible to almost all tested antimicrobials, being resistant only to fosfomycin. The subsequent isolates FK-2723 and FK-2820 were multidrug resistant (MDR). After imipenem therapy, FK-2820 was found to be carbapenem-resistant. PCR and Genome Sequencing analysis indicated that oqxA, and fosA5, were identified in all three strains. In addition, FK-2624 also harbored blaSHV-187 and blaTEM-116. The blaSHV-187 and blaTEM-116 genes were not detected in FK-2723 and FK-2820. blaDHA-1, qnrB4, aac (6′)-IIc, and blaSHV-12, EreA2, CatA2, SulI, and tetD, were identified in both FK-2723 and FK-2820. Moreover, the genes blaDHA-1, qnrB4, aac (6′)-IIc were co-harbored on a plasmid. Of the virulence factors found in this study, ybtA, ICEKp6, mrkD, entB, iroN, rmpA2–6, wzi16 and capsular serotype K57 were found in the three isolates. The results of pairwise comparisons, multi-locus sequencing typing (MLST) and pulsed-field gel electrophoresis (PFGE) revealed high homology among the isolates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that isolate FK-2820 lacked OmpK36, with genome sequence data validating that there was a premature stop codon in the ompK36 gene and real-time RT-PCR suggesting high turnover of the ompK36 non-sense transcript in FK-2820, with the steady-state mRNA level 0.007 relative to the initial isolate.

Conclusion
This study in China highlight that the alteration of outer membrane porins due to the 14-day use of imipenem play a potential role in leading to clinical presentation of carbapenem-resistance. This is the first description of increased resistance developing from a carbapenem-susceptible K. pneumoniae with imipenem treatment driven by outer membrane remodeling.
Examining the relationship between maternal body size, gestational glucose tolerance status, mode of delivery and ethnicity on human milk microbiota at three months post-partum
Authors: LeMay-Nedjelski Lauren , Butcher James , Ley Sylvia H. , Asbury Michelle R. , Hanley Anthony J. , Kiss Alex , Unger Sharon , Copeland Julia K. , Wang Pauline W. , Zinman Bernard , Stintzi Alain , O’Connor Deborah L. 
Published: July 2020

Abstract
Background
Few studies have examined how maternal body mass index (BMI), mode of delivery and ethnicity affect the microbial composition of human milk and none have examined associations with maternal metabolic status. Given the high prevalence of maternal adiposity and impaired glucose metabolism, we systematically investigated the associations between these maternal factors in women ≥20 years and milk microbial composition and predicted functionality by V4-16S ribosomal RNA gene sequencing (NCT01405547; https://clinicaltrials.gov/ct2/show/NCT01405547). Demographic data, weight, height, and a 3-h oral glucose tolerance test were gathered at 30 (95% CI: 25–33) weeks gestation, and milk samples were collected at 3 months post-partum (n = 113).

Results
Multivariable linear regression analyses demonstrated no significant associations between maternal characteristics (maternal BMI [pre-pregnancy, 3 months post-partum], glucose tolerance, mode of delivery and ethnicity) and milk microbiota alpha-diversity; however, pre-pregnancy BMI was associated with human milk microbiota beta-diversity (Bray-Curtis R2 = 0.037). Women with a pre-pregnancy BMI > 30 kg/m2 (obese) had a greater incidence of Bacteroidetes (incidence rate ratio [IRR]: 3.70 [95% CI: 1.61–8.48]) and a reduced incidence of Proteobacteria (0.62 [0.43–0.90]) in their milk, compared to women with an overweight BMI (25.0–29.9 kg/m2) as assessed by multivariable Poisson regression. An increased incidence of Gemella was observed among mothers with gestational diabetes who had an overweight BMI versus healthy range BMI (5.96 [1.85–19.21]). An increased incidence of Gemella was also observed among mothers with impaired glucose tolerance with an obese BMI versus mothers with a healthy range BMI (4.04 [1.63–10.01]). An increased incidence of Brevundimonas (16.70 [5.99–46.57]) was found in the milk of women who underwent an unscheduled C-section versus vaginal delivery. Lastly, functional gene inference demonstrated that pre-pregnancy obesity was associated with an increased abundance of genes encoding for the biosynthesis of secondary metabolites pathway in milk (coefficient = 0.0024, PFDR < 0.1).

Conclusions
Human milk has a diverse microbiota of which its diversity and differential abundance appear associated with maternal BMI, glucose tolerance status, mode of delivery, and ethnicity. Further research is warranted to determine whether this variability in the milk microbiota impacts colonization of the infant gut.
Effects of awake caudal anesthesia on mean arterial blood pressure in very low birthweight infants
Authors: Fideler Frank , Walker Michael , Grasshoff Christian 
Published: July 2020

Abstract
Background
Intraoperative blood pressure is a relevant variable for postoperative outcome in infants undergoing surgical procedures. It is therefore important to know whether the type of anesthesia has an impact on intraoperative blood pressure management in very low birth weight infants. Here, we retrospectively analyzed intraoperative blood pressure in very low birthweight infants receiving either awake caudal anesthesia without sedation, or caudal block in combination with general anesthesia, both for open inguinal hernia repair.

Methods
Ethical approval was provided by the University of Tuebingen Ethical Committee on 05/29/2018 with the project number 403/2018BO2. Patient records of infants admitted by the neonatologist (median age at birth 31.1 ± 3.5 weeks, median weight at birth 1240 ± 521 g) which were scheduled for inguinal hernia repair were retrospectively evaluated for the course of mean arterial blood pressure and perioperative interventions to stabilize blood pressure. A total of 42 patients were included, 16 patients (11 boys, 5 girls) received awake caudal anesthesia, 26 patients (22 boys, 4 girls) a combination of general anesthesia and caudal block.

Results
Approximately 3% of the measured mean arterial blood pressure values in the caudal anesthesia group were below a critical margin of 35 mmHg, in contrast to 47% in the combined anesthesia group (p < 0.001). Patients in the latter group showed a significantly larger drop of mean arterial blood pressure below 35 mmHg (4.7 ± 2.7 mmHg vs. 1.9 ± 1.6 mmHg; p < 0.005) and a significantly longer time of mean arterial blood pressure below 35 mmHg (25.6 ± 26.0 min vs. 0.9 ± 2.3 min; p < 0.001), although they received more volume and vasopressor boluses for stabilization (27 ± 14.8 ml vs. 10 ± 4.1 ml; p < 0.01 and 0.15 ± 0.06 ml vs. 0 ml of cafedrine/theoadrenaline; p < 0.001).

Conclusions
The study indicates that the use of caudal block as stand alone procedure for inguinal hernia repair in very low birthweight infants might be advantageous in preventing critical blood pressure drops compared to a combination of caudal block with general anesthesia.
A graphical approach to assess the goodness-of-fit of random-effects linear models when the goal is to measure individual benefits of medical treatments in severely ill patients
Authors: Wang Zhiwen , Diaz Francisco J. 
Published: July 2020

AbstractBackgroundTwo-dimensional personalized medicine (2-PM) models are tools for measuring individual benefits of medical treatments for chronic diseases which have potential applications in personalized medicine. These models assume normality for the distribution of random effects. It is necessary to examine the appropriateness of this assumption. Here, we propose a graphical approach to assessing the goodness-of-fit of 2-PM models with continuous responses.MethodsWe propose benefit quantile-quantile (BQQ) plots which compare the empirical quantiles of individual benefits from a patient sample predicted through an empirical Bayes (EB) approach versus the quantiles of the theoretical distribution of individual benefits derived from the assumption of normality for the random effects. We examine the performance of the approach by conducting a simulation study that compared 2-PM models with non-normal distributions for the random effects versus models with comparable normal distributions. Cramer-von Mises discrepancies were used to quantify the performance of the approach. The approach was illustrated with data from a clinical trial of imipramine for patients with depression.ResultsSimulations showed that BQQ plots were able to capture deviations from the normality assumption for the random effects and did not show any asymmetric deviations from they = xline when the random effects were normally distributed. For the depression data, the points of the BQQ plot were scattered around closely to they = xline, without presenting any asymmetric deviations. This implied the adequacy of the normality assumption for the random effects and the goodness-of-fit of the 2-PM model for the imipramine data.ConclusionBQQ plots are sensitive to violations of the normality assumption for the random effects, suggesting that the approach is a useful tool for examining the goodness-of-fit of random-effects linear models when the goal is to measure individual treatment benefits.
A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial
Authors: Iwuji Collins C. , Churchill Duncan , Bremner Stephen , Perry Nicky , To Ye , Lambert Debbie , Bruce Chloe , Waters Laura , Orkin Chloe , Geretti Anna Maria 
Published: July 2020

Abstract
Background
Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC).

Methods/design
A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures.

Discussion
We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations.

Trial registration
ISRCTN 44453201, registered 19 June 2019 and EudraCT 2018–004732-30.
A pooled analysis of the LAMP assay for the detection of Neisseria meningitidis
Authors: Fan Shu-Jin , Tan Hong-Kun , Xu Yu-Cheng , Chen Yuan-Zhi , Xie Tian-Ao , Pan Zhi-Yong , Ouyang Shi , Li Qin , Li Xiao-yan , Li Zhen-Xing , Guo Xu-Guang 
Published: July 2020

Abstract
Background
Neisseria meningitidis is a major cause of bacterial meningitis, and these infections are associated with a high mortality rate. Rapid and reliable diagnosis of bacterial meningitis is critical in clinical practice. However, this disease often occurs in economically depressed areas, so an inexpensive, easy to use, and accurate technology is needed. We performed a pooled-analysis to assess the potential of the recently developed loop-mediated isothermal amplification (LAMP) assay for detection of meningococcus.

Methods
Pubmed, Embase, and Web of Science were searched to identify original studies that used the LAMP assay to detect meningococcus. After pooling of data, the sensitivity and specificity were calculated, a summary receiver operating characteristic (SROC) curve was determined, and the area under the SROC curve was computed to determine diagnostic accuracy. Publication bias was assessed using Deek’s funnel plot.

Results
We examined 14 studies within 6 publications. The LAMP assay had high sensitivity (94%) and specificity (100%) in the detection of meningococcus in all studies. The area under the SROC curve (0.980) indicated high overall accuracy of the LAMP assay. There was no evidence of publication bias.

Discussion
The LAMP assay has accuracy comparable to bacterial culture and PCR for detection of meningococcus, but is less expensive and easier to use. We suggest the adoption of the LAMP assay to detect meningococcus, especially in economically depressed areas.
Basic epidemiological parameter values from data of real-world in mega-cities: the characteristics of COVID-19 in Beijing, China
Authors: Wang Xiaoli , Pan Yang , Zhang Daitao , Chen Lijuan , Jia Lei , Li Xinyu , Yang Peng , Wang Quanyi , Macintyre C. Raina 
Published: July 2020

AbstractBackgroundWith the spread of SARS-CoV-2 worldwide, understanding the basic epidemiological parameter values of COVID-19 from real-world data in mega-cities is essential for disease prevention and control.MethodsTo investigate the epidemiological parameters in SARS-CoV-2 infected cases in Beijing, we studied all confirmed cases and close contacts in Beijing from Jan 1st to Apr 3rd 2020. The epidemiological and virological characteristics of SARS-CoV-2 were analyzed.ResultsA total of 602 cases were positive for SARS-CoV-2, including 585 confirmed patients and 17 asymptomatic infections. The imported cases were mainly from Wuhan initially and then from abroad. Among 585 confirmed case-patients, the median age was 39 years old. The mean incubation period was 6.3 days. The secondary attack rate among households was higher than social contacts (15.6 vs 4.6%). The secondary attack rate of healthcare workers (HCWs) was higher than non-HCWs’ (7.3 vs 4.2%). The basic reproduction number was 2.0, and the average serial interval was 7.6 days. No significant genetic variant was identified.ConclusionsThe transmissibility of SARS-CoV-2 was relatively high, especially among households and from HCWs, which draws specific public health attention. So far, no evidence of widespread circulation of SARS-CoV-2 in communities in Beijing was found.
Surgical outcomes of three different weakening procedures of inferior oblique muscle in the treatment of unilateral superior oblique palsy
Authors: Farid Mohamed F. , Anany Mohamed , Abdelshafy Marwa 
Published: July 2020

Abstract
Background
To compare surgical outcomes and complications of three inferior oblique weakening procedures; Inferior Oblique Myectomy (IOM), Inferior Oblique combined Resection-Anterior Transposition (IORAT) and Inferior Oblique Anterior Transposition (IOAT) in the management of unilateral Superior Oblique (SO) palsy.

Methods
Retrospective review of medical records of all patients with unilateral SO palsy who underwent one of the aforementioned IO weakening procedures at Benha University hospital was performed. Patients were excluded if surgery was bilateral or combined with other vertical muscle surgery. Primary outcome parameters were improvement of Hypertropia (HT) in primary gaze, side gazes, on alternate head turn, Inferior Oblique Overaction (IOOA), Superior Oblique Underaction (SOUA), correction of head tilt and postoperative complications.

Results
The review reveals a total of 65 patients with unilateral SO palsy; 54 congenital and 11 acquired, who met the study criteria and were classified into 3 groups; IOM group (24cases), IORAT group (19cases) and IOAT group (22cases). Compared with IOM, both IORAT and IOAT induced significant correction of HT in primary position, ipsilateral gaze, contralateral head tilt and IOOA. IORAT was significantly more effective than IOAT in correction of HT in ipsilateral gaze and contralateral head tilt while there was no statistical difference between the three groups in correction of HT in ipsilateral gaze, contralateral head tilt and SOUA. Postoperative Anti-elevation was significantly recorded following IORAT (6 cases, 31%) than IOAT (3 cases, 13%) and IOM (one cases, 4%).

Conclusions
The IORAT and IOAT were more superior to IOM in correction of IOOA and HT in the primary position and some other gaze positions. However, superiority of IORAT over the other two procedures should be weighed against its significant association with postoperative underaction of IO muscle and anti-elevation syndrome.
Cognitive performance in children and adolescents at high-risk for obsessive-compulsive disorder
Authors: Bernardes Elisa Teixeira , Saraiva Leonardo Cardoso , e Souza Marina de Marco , Hoexter Marcelo Queiroz , Chacon Priscila , Requena Guaraci , Miguel Euripedes Constantino , Shavitt Roseli Gedanke , Polanczyk Guilherme Vanoni , Cappi Carolina , Batistuzzo Marcelo Camargo 
Published: July 2020

Abstract
Background
Cognitive performance has been studied in adults with obsessive-compulsive symptoms (OCS) and in adult relatives of patients with obsessive-compulsive disorder (OCD) Meanwhile, few studies have been conducted with children under the same conditions. This study compared the neurocognitive domains previously associated with dysfunction in OCD, especially visuoconstructive ability, visuospatial memory, executive functions, and intelligence, in children and adolescents at high risk (HR) for OCD (n = 18) and non-OCD controls (NOC) (n = 31).

Methods
For the HR group, we considered the first-degree relatives of patients with OCD that present OCS, but do not meet diagnostic criteria for OCD. Psychiatric diagnosis was assessed by experienced clinicians using the Structured Clinical Interview for DSM-IV and OCS severity was measured by the Yale-Brown Obsessive-Compulsive Scale. Neurocognitive assessment was performed with a comprehensive neuropsychological battery. Performance on the cognitive domains was compared between groups using Multivariate Analysis of Variance, whereas performance on the neuropsychological variables was compared between groups using independent t-tests in a cognitive subdomain analysis.

Results
The cognitive domain analysis revealed a trend towards significance for impairments in the motor and processing speed domain (p = 0.019; F = 3.12) in the HR group. Moreover, the cognitive subdomain analysis identified a statistically significant underperformance in spatial working memory in the HR group when compared to the NOC group (p = 0.005; t = − 2.94), and a trend towards significance for impairments in non-verbal memory and visuoconstructive tasks in the HR group.

Conclusions
Our results suggest impairments in spatial working memory and motor and processing speed in a non-clinical sample of HR participants. Considering the preliminary nature of our findings, further studies investigating these neurocognitive domains as potential predictors of pediatric OCD are warranted.
Temporal cross-correlations between air pollutants and outpatient visits for respiratory and circulatory system diseases in Fuzhou, China
Authors: Jiang Yu , Chen Jiedong , Wu Chuancheng , Lin Xin , Zhou Quan , Ji Shumi , Yang Shuangfeng , Zhang Xiaoyang , Liu Baoying 
Published: July 2020

Abstract
Background
Previous studies have suggested that there is an association between air pollutants and circulatory and respiratory diseases; however, relatively few have analyzed the association between air pollutants and outpatient visits based on the mortality, hospitalization rates, etc., especially in areas with relatively good air quality. Therefore, we conducted this study to research the association between air pollutants and outpatient visits in Fuzhou, China.

Methods
We used a generalized linear Poisson model to study the association between air pollution and outpatient visits for respiratory and circulatory diseases from 2016 to 2018 in Fuzhou, China.

Results
In the single pollutant model, nitrogen dioxide (NO2) had a significant effect. For lag day 0 to lag day 5, the effect decreased with every 10 μg/L increase in NO2. The daily maximum 8-h mean ozone (O3-8h) and upper respiratory outpatient visits were positively associated during the cold period [lag2, excess risk (ER) (95% confidence interval (CI)): 1.68% (0.44–2.94%)], while O3-8h and respiratory disease were positively associated during the warm period [lag5, ER (95% CI): 1.10% (0.11–2.10%) and lag4, ER (95% CI): 1.02% (0.032–2.02%)]. Similarly, particulate matter (PM) with an average aerodynamic diameter of less than 10 μm (PM10) and lower respiratory diseases were positively associated during the warm period [lag0, ER (95% CI): 1.68% (0.44–2.94%)]. When the concentration of O3-8h was higher than 100 μg/L, there was a positive effect on circulatory [lag5, ER (95% CI): 2.83% (0.65–5.06%)], respiratory [lag5, ER (95% CI): 2.47% (0.85–4.11%)] and upper respiratory [lag5, ER (95% CI): 3.06% (1.38–4.77%)] outpatient visits. The variation in O3-8h changed slightly when we adjusted for other air pollutants, and after adjusting for O3-8h, the ERs of the other air pollutants changed slightly. After adjusting for PM with an average aerodynamic diameter of less than 2.5 μm (PM2.5), the ERs of the other air pollutants increased, and after adjusting for NO2, the ER of PM decreased.

Conclusion
Exposure to ambient NO2, O3, PM2.5 and PM10 was associated with an increase in respiratory and circulatory system-related outpatient visits in Fuzhou, China.