bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials
Authors: Fillbrunn Mirko , Signorovitch James , André Fabrice , Wang Iris , Lorenzo Ines , Ridolfi Antonia , Park Jinhee , Dua Akanksha , Rugo Hope S. 
Published: September 2022

Abstract
Background
Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC.

Methods
Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.

Results
The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I2 = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I2 = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I2 = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I2 = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).

Conclusions
Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.
Frequency of Salmonella serotypes among children in Iran: antimicrobial susceptibility, biofilm formation, and virulence genes
Authors: Rezaei Akram , Hashemi Farhad B. , Heshteli Roya Rasooly , Rahmani Maryam , Halimi Shahnaz 
Published: September 2022

Abstract
Background/significance
Salmonella gastroenteritis causes significant morbidity among pediatric patients, mainly in developing world, such as the Middle East and North Africa (MENA) region. Concurrently, data from MENA countries like Iran, regarding prevalence of Salmonella serotypes, antimicrobial susceptibility, and biofilm production is scarce.

Material & methods
Slide agglutination was used to determine the serogroup of 140 Salmonella isolates recovered from 4477 stool specimens collected from children with gastroenteritis, and isolates were serotyped by PCR assay. The antimicrobial susceptibility of isolates to five first line drugs was assessed by disk diffusion assay using CLSI guidelines. Semi-quantitative evaluation of biofilm production was done by microtiter plate assay followed by PCR detection of biofilm-associated virulence genes csgD, pefA, and bcsA for each isolate.

Results
Nearly 94% of Salmonella isolates were recovered from ≤ 5-year-old patients, and 99% of isolates were non-typhoidal. While we found extensive diversity among Salmonella isolates, serogroup D (46%) predominated, and Salmonella Enteritidis (41%) was the most common serotype that showed the highest antimicrobial susceptibility rate (> 96%). For the first time in Iran, S. Newport serotype from human specimens was isolated. Most isolates were sensitive to all test antimicrobials, but 35% of isolates were not-typed (NT) that showed the highest resistance with 48% being resistant to ≥ 1 test antimicrobial. Majority of isolates made weak (or no) biofilm, and we found a weak association between antimicrobial susceptibility, biofilm production, or virulence genes csgD, pefA, and bcsA.

Conclusions
The most effective measure that may control pediatric salmonellosis outbreaks is raising awareness of parents of preschoolers about food safety. Isolation of highly diverse Salmonella serotypes, including many commonly isolated from animals, indicates widespread contamination of the food chain. Majority of serotypes were sensitive to first-line antimicrobials, thus presently, pediatric Salmonella infections in this region may be controlled by conventional antimicrobials. However, despite the current trend, an imminent emergence of resistant Salmonella strains is foreseen, since various serotypes resistant to > 1 antimicrobial agent are typically associated with animals. Our results warrant further investigation that includes correlation analysis of clinical data regarding treatment outcomes, and serotype attributes like virulence genes.
Associations between sleep deficit and academic achievement - triangulation across time and subject domains among students and teachers in TIMSS in Norway
Authors: Vik Frøydis N. , Nilsen Trude , Øverby Nina C. 
Published: September 2022

Abstract
Background
Sufficient sleep is important to an individual’s health and well-being, but also for school achievement among adolescents. This study investigates the associations between sleepiness, sleep deficits, and school achievements among adolescents.

Methods
This trend study involved a representative sample of Norwegian adolescents based on the “Trends in International Mathematics and Science Study” (TIMSS), N = 4499 (2015) and N = 4685 (2019) and their teachers. The students were 9th graders from a Norwegian compulsory secondary school. The survey included questions on students’ sleepiness as students reported in 2019 and sleep deficits among students that limited teaching in class as their teachers reported in 2015 and 2019. Regression, triangulation, and mediation analyses were used. Mplus was used to perform the statistical analyses.

Results
The results revealed significant negative associations between sleep deficits and school achievements, adjusted for gender, socioeconomic status (SES), and minority status among Norwegian 9th graders. These results were found for both mathematics and science achievements in 2015 and 2019. Sleepiness that the students reported was negatively associated with school achievements in 2019. Trend and mediation analyses showed that sleep deficits explained 18 and 11% of the decrease in mathematics and science achievements, respectively, from 2015 to 2019.

Conclusions
Sleep deficits were associated with school achievements in mathematics and science among Norwegian 9th graders. Mediation analyses revealed that sleep deficits explained a significant part of the decline in academic achievements. Insufficient sleep may have negative public health implications and influence adolescents’ academic achievements and competences, and should therefore be discussed in both the educational and health systems.
Views of general practitioners on end-of-life care learning preferences: a systematic review
Authors: Atreya Shrikant , Datta Soumitra S. , Salins Naveen 
Published: September 2022

Abstract
Background
General practitioners (GPs) play a pivotal role in providing end-of-life care in the community. Although they value end-of-life care, they have apprehensions about providing care in view of the limitations in knowledge and skills in end-of-life care. This review aimed to explore, synthesise, and analyse the views of general practitioners on end-of-life care learning preferences.

Methods
MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, Web of Science, and Cochrane were searched for literature on the views of general practitioners on end-of-life care learning preferences from 01/01/1990 to 31/05/2021. Methodological quality was reported.

Results
Of the 10,037 articles identified, 23 were included for the review. Five themes developed from the review. The desire to provide palliative care, as well as self-actualisation needs, relevance to practice, a sense of responsibility, and a therapeutic bond, motivates general practitioners to learn end-of-life care. Some of the learning needs expressed were pain and symptom management, communication skills, and addressing caregiver needs. Experiential learning and pragmatist learning styles were preferred learning styles. They perceived the need for an amicable learning environment in which they could freely express their deficiencies. The review also identified barriers to learning, challenges at personal and professional level, feelings of disempowerment, and conflicts in care.

Conclusion
GPs’ preference for learning about end-of-life care was influenced by the value attributed to learning, context and content, as well as preference for learning styles and the availability of resources. Thus, future trainings must be in alignment with the GPs’ learning preferences.
Has vaccination alleviated the strain on hospitals due to COVID-19? A combined difference-in-difference and simulation approach
Authors: Grøsland Mari , Larsen Vilde Bergstad , Telle Kjetil , Gjefsen Hege Marie 
Published: September 2022

Abstract
Background
Serious measures, including mass vaccination, have been taken to ensure sufficient hospital capacity during the COVID-19 pandemic. Due to high hospitalization risk in the oldest age groups, most countries prioritized elderly for vaccines. The aim of this study is to broaden the understanding of how vaccination in younger age groups relieved the strain on hospitals during the pandemic.

Methods
To determine the impact of vaccination on hospitalization, we relied on individual level data on health care use and vaccination from the Norwegian Emergency Preparedness Register Beredt C19. Using a pre-post design, we estimated the increase in hospitalization days from before to after confirmed COVID-19 for individuals aged 18-64 who were fully vaccinated (N=2 419) or unvaccinated (N=55 168) with comparison groups of vaccinated (N=4 818) and unvaccinated (N= 97 126) individuals without COVID-19. To evaluate whether vaccination itself contributed to a strain in hospitals, we use a similar design to study hospitalization rates before and after vaccination by comparing individuals vaccinated with the first dose (N=67 687) to unvaccinated individuals (N=130 769). These estimates were incorporated into a simulation of hospitalization days with different vaccine scenarios to show how the estimated results might have mattered for the hospitals and their capacity.

Results
Hospitalization days increased by 0.96 percentage point each day during the first week and 1.57 percentage points during the second week after testing positive for COVID-19 for unvaccinated individuals. The corresponding increase was 0.46 and 0.32 for vaccinated individuals, i.e., a substantial difference. The increase was significantly higher for those aged 45-64 than for those aged 18-25. We find no increase in hospitalization days due to vaccination. Simulation results show that vaccination reduced hospitalization days by 25 percent, mainly driven by age 45-64.

Conclusion
Our findings indicate that vaccination of individuals aged 18-64 did alleviate pressure on hospitals. Whereas there was a substantial relieve from vaccinating the 45-64 age group, there was no such contribution from vaccinating the 18-25 age group. Our study highlights how simulation models can be useful when evaluating alternative vaccine strategies.
Activation of oxytocin receptors in mouse GABAergic amacrine cells modulates retinal dopaminergic signaling
Authors: Hu Songhui , Wang Yurong , Han Xu , Dai Min , Zhang Yongxing , Ma Yuanyuan , Weng Shijun , Xiao Lei 
Published: September 2022

Abstract
Background
Oxytocin, secreted by oxytocin neurons in the hypothalamus, is an endogenous neuropeptide involved in modulating multiple sensory information processing pathways, and its roles in the brain have been associated with prosocial, maternal, and feeding-related behaviors. Visual information is necessary for initiating these behaviors, with the retina consisting of the first stage in the visual system mediating external stimulus perception. Oxytocin has been detected in the mammalian retina; however, the expression and possible function of oxytocin receptors (OxtR) in the retina remain unknown. Here, we explore the role of oxytocin in regulating visual information processing in the retina.

Results
We observed that OxtR mRNA and protein are expressed in the mouse retina. With Oxtr-Cre transgenic mice, immunostaining, and fluorescence in situ hybridization, we found that OxtRs are mainly expressed in GABAergic amacrine cells (ACs) in both the inner nuclear layer (INL) and ganglion cell layer (GCL). Further immunoreactivity studies showed that GABAergic OxtR+ neurons are mainly cholinergic and dopaminergic neurons in the INL and are cholinergic and corticotrophin-releasing hormone neurons in the GCL. Surprisingly, a high level of Oxtr mRNAs was detected in retinal dopaminergic neurons, and exogenous oxytocin application activated dopaminergic neurons to elevate the retinal dopamine level. Relying on in vivo electroretinographic recording, we found that activating retinal OxtRs reduced the activity of bipolar cells via OxtRs and dopamine receptors.

Conclusions
These data indicate the functional expression of OxtRs in retinal GABAergic ACs, especially dopaminergic ACs, and expand the interactions between oxytocinergic and dopaminergic systems. This study suggests that visual perception, from the first stage of information processing in the retina, is modulated by hypothalamic oxytocin signaling.
The UK Coronavirus Job Retention Scheme and smoking, alcohol consumption and vaping during the COVID-19 pandemic: evidence from eight longitudinal population surveys
Authors: Green Michael J. , Maddock Jane , Di Gessa Giorgio , Wielgoszewska Bożena , Parsons Sam , Griffith Gareth J. , Croft Jazz , Stevenson Anna J. , Huggins Charlotte F. , Booth Charlotte , Wels Jacques , Silverwood Richard J. , Patalay Praveetha , Hughes Alun D. , Chaturvedi Nishi , Howe Laura D. , Fitzsimons Emla , Katikireddi Srinivasa Vittal , Ploubidis George B. 
Published: September 2022

AbstractBackgroundEmployment disruptions can impact smoking and alcohol consumption. During the COVID-19 pandemic, many countries implemented furlough schemes to prevent job loss. We examine how furlough was associated with smoking, vaping and alcohol consumption in the UK.MethodsData from 27,841 participants in eight UK adult longitudinal surveys were analysed. Participants self-reported employment status and current smoking, current vaping and alcohol consumption (>4 days/week or 5+ drinks per typical occasion) both before and during the early stages of the pandemic (April–July 2020). Risk ratios were estimated within each study using modified Poisson regression, adjusting for a range of potential confounders, including pre-pandemic behaviour. Findings were synthesised using random effects meta-analysis.ResultsCompared to stable employment and after adjustment for pre-pandemic characteristics, furlough was not associated with smoking (ARR = 1.05; 95% CI: 0.95–1.16;I2: 10%), vaping (ARR = 0.89; 95% CI: 0.74–1.08;I2: 0%) or drinking (ARR = 1.03; 95% CI: 0.94–1.13;I2: 48%). There were similar findings for no longer being employed, and stable unemployment, though this varied by sex: stable unemployment was associated with smoking for women (ARR = 1.35; 95% CI: 1.00–1.82;I2: 47%) but not men (0.84; 95% CI: 0.67–1.05;I2: 0%). No longer being employed was associated with vaping among women (ARR = 2.74; 95% CI: 1.59–4.72;I2: 0%) but not men (ARR = 1.25; 95% CI: 0.83–1.87;I2: 0%).ConclusionsWe found no clear evidence of furlough or unemployment having adverse impacts on smoking, vaping or drinking behaviours during the early stages of the COVID-19 pandemic in the UK. Differences in risk compared to those who remained employed were largely explained by pre-pandemic characteristics.
Prenatal diagnosis identifies compound heterozygous variants in RYR1 that causes ultrasound abnormalities in a fetus
Authors: Zhao Qiuling , Li Xiaoduo , Liu Li , Zhang Xu , Pan Xin , Yao Hong , Ma Yongyi , Tan Bo 
Published: September 2022

Abstract
Objective
We presented a non-consanguineous healthy Chinese couple with five pregnancies, three early miscarriages, the fetus II-2 and II-5 with similar abnormal phenotypes of fetal hydrops, scoliosis, fetal akinesia and polyhydramnios. This study aimed to uncover the molecular etiology of this family with a history of multiple adverse pregnancies.

Materials and methods
DNA extracted from the fifth fetal umbilical cord and parents’ peripheral blood were subjected to SNP-array and whole exome sequencing. The result was verified by Sanger sequencing. Functional characterization of the c.2682G > C (p.Ile860_Pro894del) variant was completed by minigene splicing assay.

Results
Trio whole-exome sequencing has identified compound heterozygous variants in RYR1 (c.2682G > C; p.Ile860_Pro894del and c.12572G > A; p.Arg4191His) in fetus II-5. The variant c.2682G > C (p.Ile860_Pro894del) comes from the father and the c.12572G > A (p.Arg4191His) comes from the mother. The c.2682G > C (p.Ile860_Pro894del) affects the splice site resulting in exon 21 skipping, therefore is classified as likely pathogenic. The c.12572G > A (p.Arg4191His) locates in the C-terminal hot spots region of the RYR1, classified as of uncertain significance.

Conclusions
We report the first prenatal case of RYR1-related disorders in Chinese population, expanding the variant spectrum of RYR1 in fetuses.
Clinical manifestations and outcomes of severe malaria in adult patients admitted to a tertiary hospital in the Gambia
Authors: Bittaye Sheikh Omar , Jagne Abubacarr , Jaiteh Lamin ES , Nadjm Behzad , Amambua-Ngwa Alfred , Sesay Abdul Karim , Singhateh Yankuba , Effa Emmanuel , Nyan Ousman , Njie Ramou 
Published: September 2022

Abstract
Background
Malaria is a major public health concern in The Gambia. There is limited data on the clinical manifestation and outcome of severe malaria in adult patients in The Gambia. The study therefore assessed the clinical manifestations and outcome of severe malaria in adult patients admitted at the Edward Francis Small Teaching Hospital.

Methods
The study retrospectively reviewed the records of all malaria patients admitted from 18th October 2020 to 2nd February 2022. Demographic data, clinical features, investigations, treatment, and outcomes were recorded.

Results
A total of 131 confirmed malaria patients were recruited into the study. The median age was 21 yrs, range (15–90) and most of them were within the youth age group (15–24yrs) 85 (64.9%). The majority of the patients were also male 88 (67.2%) with a male to female ratio of 2:1. The most common symptom at presentation was fever 119 (90.8%) and the most common sign was pallor 48 (36.6%). Seventy-six patients (58.1%) and 55 (41.9%) patients met the criteria for severe malaria and uncomplicated malaria diagnosis, respectively. The most common clinical feature amongst patients with severe malaria were impaired consciousness 34 (44.7%), severe anaemia 26 (34.2%) and acute kidney injury 20 (26.3%). Patients with severe malaria were younger with mean age of 22.9 vs. 29 yrs (p = 0.004), more likely to be referred from a lower-level health facility 62 (81.6%) vs. 34 (61.8%) (p = 0.012), to have a longer duration of admission (p = 0.024) and to die 13 (17.1%) vs. 0 (0%) (p = 0.001) as compared to patients with uncomplicated malaria. The total mortality was 13 (9.9%) and all the patients who died had severe malaria. Mortality was higher in patients with impaired consciousness 9 (26.5%) and there was a significant relationship between death and impaired consciousness 9 (69.3%) vs. 25 (21.4%) p = 0.001.

Conclusion
Severe malaria still affects young adults in an endemic area with significant mortality. This suggests the need for targeted malaria prevention, surveillance, case management and control strategies in this population group in The Gambia to help reduce morbidity and mortality of malaria.
Optic nerve head optical coherence tomography angiography findings in patients with thyroid eye disease: a case–control study
Authors: Sabermoghaddam Aliakbar , Shoeibi Nasser , Jafarzadeh Hamid , Bakhtiari Elham , Salahi Zeinab , Saeidi Rezvani Talieh , Heidarzadeh Hamid Reza , Abrishami Mojtaba 
Published: September 2022

AbstractBackgroundTo evaluate changes in the vessel density (VD) of the optic nerve head (ONH) microvasculature in thyroid eye disease (TED) using optical coherence tomography angiography (OCTA). This study aimed to applicate the OCTA as a noninvasive modality in screening TED patients to assess sub-clinical changes.MethodsIn a cross-sectional study, the control group patients were healthy individuals with no ocular abnormalities and were euthyroid. All patients with TED had clinical features of the disease. We divided them into two groups using the clinical activity score (CAS). Patients with CAS scores 0–2 were categorized as group A, and scores three or more as group B. All vessels (AV) and small vessels (SV) VD inside disc and radial peripapillary capillary network were measured using the ONH-OCTA.ResultsWe evaluated 29 patients with TED and 28 healthy controls. The mean whole image AV VD (mean ± SD: 56.33 ± 2.56,p-value = 0.17) and the mean whole image SV VD (mean ± SD: 49.94 ± 2.56,p-value = 0.16) in the TED group had no statically significant difference compared with the control group (AV mean ± SD: 57.20 ± 20.22, SV mean ± SD: 50.84 ± 2.23). We found a non-significant decrease in AV and SV radial peripapillary capillary VD in the TED group. There was a significant decrease in the mean whole image AV VD (mean ± SD: 54.83 ± 3.07,p-value = 0.005) and the mean whole image SV VD (mean ± SD: 48.60 ± 3.18,p-value = 0.013) in CAS group B compared to group A (AV mean ± SD: 57.45 ± 1.33, SV mean ± SD: 50.95 ± 1.37).ConclusionOur study showed non-significant ONH vascular alterations in patients with TED, including reduced VD of ONH in the radial peripapillary capillary. Patients with higher CAS scores had a more noticeable decrease in ONH microvasculature.
The efficacy and safety of minocycline as adjuvant therapy in refractory mycoplasma pneumonia in Chinese children: a meta-analysis
Authors: Shen Hong-Xia , Liu Chang , Lin Hui-Jun , Xu Lu-Jie , Wang Guang-Yan , Yan Mei-Xing 
Published: September 2022

Abstract
Background
To explore the efficacy and safety of minocycline as adjuvant therapy for refractory mycoplasma pneumonia in Chinese children.

Methods
PubMed, EMBASE, Cochrane Library, CNKI, Wanfang database and VIP database were systematically searched. Studies where minocycline was used as adjuvant therapy for refractory mycoplasma pneumonia in Chinese children were included. The effect of numeration data and the measurement data were represented by odds ratios (OR) and weighted mean differences (MD), respectively. Review Manager version 5.3 was used to compare the treatment efficacy, time for the cough to subside, defervescence time, hospitalisation time, adverse events and other indicators.

Results
Ten studies involving 857 patients were included in the final analysis. Compared with the conventional treatment of refractory mycoplasma pneumonia in children, the addition of minocycline as adjuvant therapy was found to improve the treatment efficacy (OR: 5.45; 95% CI: 3.46, 8.57, p < 0.001); shorten the duration of cough (MD: -3.61; 95%CI: -4.25, -2.97, p < 0.001), fever time (MD: -4.77; 95% CI: -6.30, -3.23, p < 0.001) and hospitalisation time (MD: -5.53 (95% CI: -7.19, -3.88, p < 0.001); and decrease the concentration of C-reactive protein (MD: -13.95; 95%CI: -18.61, -9.29; p < 0.001) and the erythrocyte sedimentation rate (MD: -10.88; 95% CI: -14.05, -7.72, p < 0.001). The use of minocycline did not lead to significant adverse events (OR = 0.63; 95% CI: 0.39, 1.01, p = 0.05).

Conclusion
The use of minocycline as adjuvant treatment of refractory mycoplasma pneumonia in Chinese children has good efficacy and safety and may be promoted in clinical practice.