bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pregnancy and EARly Life study (PEARL) - a longitudinal study to understand how gut microbes contribute to maintaining health during pregnancy and early life
Authors: Phillips Sarah , Watt Rachel , Atkinson Thomas , Savva George M , Hayhoe Antonietta , Hall Lindsay J ,   on behalf of the PEARL study team, Hall Lindsay J , Philips Sarah , Watt Rachel , Cameron Martin , Clarke Paul , Lartey Jon , Hayhoe Antonietta , Savva George , Atkinson Thomas , Cambell-Kelly Melissa , Harris Laura , Summerfield Hayley 
Published: August 2021

Abstract
Background
The early life period represents the first step in establishing a beneficial microbial ecosystem, which in turn affects both short and longer-term health. Changes during pregnancy influence the neonatal microbiome; through transmission of maternal microbes during childbirth, and beyond, through nutritional programming. However, in-depth exploration of longitudinal maternal-infant cohorts, with sampling of multiple body sites, complemented by clinical and nutritional metadata, and use of cutting-edge experimental systems are limited.
The PEARL study will increase our knowledge of; how microbes (including viruses/phages, bacteria, fungi and archaea) change in composition and functional capacity during pregnancy; transmission pathways from mother to infant; the impact of various factors on microbial communities across pregnancy and early life (e.g. diet), and how these microbes interact with other microbes and modulate host processes, including links to disease onset.

Methods
PEARL is a longitudinal observational prospective study of 250 pregnant women and their newborns, with stool and blood samples, questionnaires and routine clinical data collected during pregnancy, labour, birth and up to 24 months post birth.
Metagenomic sequencing of samples will be used to define microbiome profiles, and allow for genus, species and strain-level taxonomic identification and corresponding functional analysis. A subset of samples will be analysed for host (immune/metabolite) molecules to identify factors that alter the host gut environment. Culturing will be used to identify new strains of health-promoting bacteria, and potential pathogens. Various in vitro and in vivo experiments will probe underlying mechanisms governing microbe-microbe and microbe-host interactions.

Discussion
Longitudinal studies, like PEARL, are critical if we are to define biomarkers, determine mechanisms underlying microbiome profiles in health and disease, and develop new diet- and microbe-based therapies to be tested in future studies and clinical trials.

Trial registration
This study is registered in the ClinicalTrials.gov Database with ID: NCT03916874.
Should we abandon the patient-specific instrumentation ship in total knee arthroplasty? Not quite yet!
Authors: Török László , Jávor Péter , Hartmann Petra , Bánki László , Varga Endre 
Published: August 2021

AbstractPatient-specific Instrumentation (PSI) is an innovative technique aiding the precise implementation of the preoperative plan during total knee arthroplasty (TKA) by using patient-specific guides and cutting blocks. Despite of the theoretical advantages, studies have reported contradictory results, thus there is no consensus regarding the overall effectiveness of PSI. Through the critical assessment of a meta-analysis published lately, this correspondence aims to highlight the complexity of comparing the efficacy of PSI to standard instrumentation (SI). The accuracy of component alignment, patient-reported outcome measures (PROMs), surgery time, blood loss, transfusion rate, and postoperative complications are commonly used outcomes for investigating the efficacy of PSI-aided TKA. By assessing component alignment, the expertise of the surgeon(s) should be taken into consideration, since PSI may not provide benefits for expert surgeons but might improve accuracy and patient safety during the learning curve of novice surgeons. With respect to PROMs and postoperative complications, PSI may not improve short-term results; however, long-term follow up data is missing. Regarding transfusion rates, favorable trends can be observed, but further studies utilizing recent data are needed for a clear conclusion. When assessing surgery time, we suggest focusing on operating room turnover instead of procedure time.
Relationship between bone mineral density and fragility fracture risk: a case-control study in Changsha, China
Authors: Li Hong-Li , Shen Yi , Tan Li-Hua , Fu Song-bo , Dai Ru-Chun , Yuan Ling-Qing , Sheng Zhi-Feng , Xie Zhong-Jian , Wu Xian-Ping , Liao Er-Yuan , Tang Xu-Lei , Wu Xi-Yu 
Published: August 2021

Abstract
Background
Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases.

Objective
To investigate relationship between BMD and risk of fragility fracture in native China.

Methods
3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database.

Results
BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7–2.8 times (95 % CI 2.5–3.1) and 3.6–4.1 times (95 %CI 3.0–5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6–1.7 times (95 % CI 1.5–1.8) for every 1 T-score reduction in BMD.

Conclusions
Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.
An economical and highly adaptable optogenetics system for individual and population-level manipulation of Caenorhabditis elegans
Authors: Koopman M. , Janssen L. , Nollen E. A. A. 
Published: August 2021

AbstractBackgroundOptogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures. The high degree of spatial, temporal, and intensity control that can be achieved with a light stimulus, combined with cell type-specific expression of light-sensitive ion channels, enables highly specific and precise stimulation of excitable cells. Optogenetic tools have therefore revolutionized the study of neuronal circuits in a number of models, includingCaenorhabditis elegans. Despite the existence of several optogenetic systems that allow spatial and temporal photoactivation of light-sensitive actuators inC. elegans, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, modular, and adjustable optogenetics device for use on different microscopes and worm trackers, which we called the OptoArm.ResultsThe OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles, and light color. We demonstrate OptoArm’s power in a population-based multi-parameter study on the contributions of motor circuit cells to age-related motility decline. We found that individual components of the neuromuscular system display different rates of age-dependent deterioration. The functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit ageing.ConclusionWe have assembled an economical, reliable, and highly adaptable optogenetics system which can be deployed to address diverse biological questions. We provide a detailed description of the construction as well as technical and biological validation of our set-up. Importantly, use of the OptoArm is not limited toC. elegansand may benefit studies in multiple model organisms, making optogenetics more accessible to the broader research community.
Reduced risk of placental parasitemia associated with complement fixation on Plasmodium falciparum by antibodies among pregnant women
Authors: Opi D. Herbert , Boyle Michelle J. , McLean Alistair R. D. , Reiling Linda , Chan Jo-Anne , Stanisic Danielle I. , Ura Alice , Mueller Ivo , Fowkes Freya J. I. , Rogerson Stephen J. , Beeson James G. 
Published: August 2021

Abstract
Background
The pathogenesis of malaria in pregnancy (MiP) involves accumulation of P. falciparum-infected red blood cells (pRBCs) in the placenta, contributing to poor pregnancy outcomes. Parasite accumulation is primarily mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1). Magnitude of IgG to pRBCs has been associated with reduced risk of MiP in some studies, but associations have been inconsistent. Further, antibody effector mechanisms are poorly understood, and the role of antibody complement interactions is unknown.

Methods
Studying a longitudinal cohort of pregnant women (n=302) from a malaria-endemic province in Papua New Guinea (PNG), we measured the ability of antibodies to fix and activate complement using placental binding pRBCs and PfEMP1 recombinant domains. We determined antibody-mediated complement inhibition of pRBC binding to the placental receptor, chondroitin sulfate A (CSA), and associations with protection against placental parasitemia.

Results
Some women acquired antibodies that effectively promoted complement fixation on placental-binding pRBCs. Complement fixation correlated with IgG1 and IgG3 antibodies, which dominated the response. There was, however, limited evidence for membrane attack complex activity or pRBC lysis or killing. Importantly, a higher magnitude of complement fixing antibodies was prospectively associated with reduced odds of placental infection at delivery. Using genetically modified P. falciparum and recombinant PfEMP1 domains, we found that complement-fixing antibodies primarily targeted a specific variant of PfEMP1 (known as VAR2CSA). Furthermore, complement enhanced the ability of antibodies to inhibit pRBC binding to CSA, which was primarily mediated by complement C1q protein.

Conclusions
These findings provide new insights into mechanisms mediating immunity to MiP and reveal potential new strategies for developing malaria vaccines that harness antibody-complement interactions.
The severity and risk factors for mortality in immunocompromised adult patients hospitalized with influenza-related pneumonia
Authors: Chen Liang , Han Xiudi , Li YanLi , Zhang Chunxiao , Xing Xiqian 
Published: August 2021

Abstract
Objective
To explore disease severity and risk factors for 30-day mortality of adult immunocompromised (IC) patients hospitalized with influenza-related pneumonia (Flu-p).

Method
A total of 122 IC and 1191 immunocompetent patients hospitalized with Flu-p from January 2012 to December 2018 were recruited retrospectively from five teaching hospitals in China.

Results
After controlling for confounders, multivariate logistic regression analysis showed that immunosuppression was associated with increased risks for invasive ventilation [odds ratio: (OR) 2.475, 95% confidence interval (CI): 1.511–4.053, p < 0.001], admittance to the intensive care unit (OR: 3.247, 95% CI 2.064–5.106, p < 0.001), and 30-day mortality (OR: 3.206, 95% CI 1.926–5.335, p < 0.001) in patients with Flu-p. Another multivariate logistic regression model revealed that baseline lymphocyte counts (OR: 0.993, 95% CI 0.990–0.996, p < 0.001), coinfection (OR: 5.450, 95% CI 1.638–18.167, p = 0.006), early neuraminidase inhibitor therapy (OR 0.401, 95% CI 0.127–0.878, p = 0.001), and systemic corticosteroid use at admission (OR: 6.414, 95% CI 1.348–30.512, p = 0.020) were independently related to 30-day mortality in IC patients with Flu-p. Based on analysis of the receiver operating characteristic curve (ROC), the optimal cutoff for lymphocyte counts was 0.6 × 109/L [area under the ROC (AUROC) = 0.824, 95% CI 0.744—0.887], sensitivity: 97.8%, specificity: 73.7%].

Conclusions
IC conditions are associated with more severe outcomes in patients with Flu-p. The predictors for mortality that we identified may be valuable for the management of Flu-p among IC patients.
Early postpartum abnormal glucose metabolism subtype differs according to mid-trimester lipid profile in women with gestational diabetes mellitus
Authors: Lai Fenghua , Li Zeting , Yue Shufan , Pei Ling , Xiao Huangmeng , Li Zhuyu , Li Yanbing , Xiao Haipeng , Cao Xiaopei 
Published: August 2021

Abstract
Background
It is unknown whether early postpartum abnormal glucose metabolism (AGM) in women with previous gestational diabetes mellitus (GDM) is related to their mid-trimester lipid profile. The aim of this study was to characterize the mid-trimester lipid profile of women who experienced GDM and developed into different pathophysiologic subtypes of early postpartum AGM.

Methods
A retrospective cohort study of 498 women with history of GDM was conducted. A 75-g oral glucose tolerance test (OGTT) and plasma lipid measurements were performed at 24–28 weeks of gestation and 6–12 weeks of postpartum. Insulin secretion and sensitivity were estimated using early postpartum OGTT-based indices.

Results
Women in the mid-trimester dyslipidemia group had higher postpartum 30-min and 2-h plasma glucose, higher postpartum 2-h plasma insulin, higher postpartum triglyceride (TG), higher postpartum low density lipoprotein cholesterol (LDL-c) concentrations, lower postpartum 30-min insulinogenic index (IGI30), lower postpartum insulin sensitivity index (ISI), and lower postpartum disposition index than those in the normal lipid group (all P < 0.05). Abnormal mid-trimester TG and LDL-c concentrations were associated with postpartum AGM (adjusted odds ratio [OR] = 1.786, 95 % confidence interval [CI] = 1.142–2.425; and adjusted OR = 1.621, 95 % CI = 1.323–2.051, respectively; both P < 0.05). AGM women with low IGI30 and low ISI had higher mid-trimester total cholesterol and LDL-c concentrations, and AGM women with low ISI had higher mid-trimester TG concentrations than women with NGT or other subtypes of AGM (all P < 0.05).

Conclusions
GDM women with abnormal mid-trimester TG and LDL-c were predisposed to early postpartum AGM. Postpartum AGM women who experienced GDM had heterogeneous mid-trimester lipid profile when classified according to their pathophysiologic subtype.
Emergency cardiac imaging for coronavirus disease 2019 (COVID-19) in practice: a case of takotsubo stress cardiomyopathy
Authors: Belli Oriana , Ardissino Maddalena , Bottiroli Maurizio , Soriano Francesco , Blanda Calogero , Oreglia Jacopo , Mondino Michele , Moreo Antonella 
Published: August 2021

Abstract
Background
Cardiovascular complications of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2) are known to be associated with poor outcome. A small number of case series and reports have described cases of myocarditis and ischaemic events, however, knowledge on the aetiology of acute cardiac failure in SARS-CoV2 remains limited. We describe the occurrence and risk stratification imaging correlates of ‘takotsubo’ stress cardiomyopathy presenting in a patient with Coronavirus Disease 2019 (COVID-19) in the intensive care unit.

Case summary
An intubated 53-year old patient with COVID19 suffered acute haemodynamic collapse in the intensive care unit, and was thus investigated with transthoracic echocardiography (TTE), 12-lead electrocardiograms (ECG) and serial troponins and blood tests, and eventually coronary angiography due to clinical suspicion of ischaemic aetiology. Echocardiography revealed a reduced ejection fraction, with evident extensive apical akinesia spanning multiple coronary territories. Troponins and NT-proBNP were elevated, and ECG revealed ST elevation: coronary angiography was thus performed. This revealed no significant coronary stenosis. Repeat echocardiography performed within the following week revealed a substantial recovery of ejection fraction and wall motion abnormalities. Despite requirement of a prolonged ICU stay, the patient now remains clinically stable, and is on spontaneous breathing.

Conclusion
This case report presents a case of takotsubo stress cardiomyopathy occurring in a critically unwell patient with COVID19 in the intensive care setting. Stress cardiomyopathy may be an acute cardiovascular complication of COVID-19 infection. In the COVID19 critical care setting, urgent bedside echocardiography is an important tool for initial clinical assessment of patients suffering haemodynamic compromise.
Education policies to increase rural physicians in Japan: a nationwide cohort study
Authors: Matsumoto Masatoshi , Matsuyama Yasushi , Kashima Saori , Koike Soichi , Okazaki Yuji , Kotani Kazuhiko , Owaki Tetsuhiro , Ishikawa Shizukiyo , Iguchi Seitaro , Okazaki Hitoaki , Maeda Takahiro 
Published: August 2021

Abstract
Background
Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown.

Methods
A nationwide prospective cohort study of newly licensed physicians 2014–2018 (n = 2454) of the four major types of the programs—Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)—and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014–2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce.

Results
Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P < 0.001) and scholarship alone (2220; 81% < 0.001). Relative risks of working in municipalities with the least population density quintile in Jichi, quota with scholarship, scholarship alone, and quota alone in postgraduate year 5 were 4.0 (95% CI 3.7–4.4; P < 0.001), 3.1 (2.6–3.7; < 0.001), 2.5 (2.1–3.0; < 0.001), and 2.5 (1.9–3.3; < 0.001) as compared with all Japanese physicians. There was no significant difference between each program and all physicians in the proportion of those who specialized in internal medicine or general practice in postgraduate years 3 to 5

Conclusions
Japan’s education policies to produce rural physicians are effective but the degree of effectiveness varies among the programs. Policymakers and medical educators should plan their future rural workforce policies with reference to the effectiveness and variations of these programs.
Global research publications on irrational use of antimicrobials: call for more research to contain antimicrobial resistance
Authors: Sweileh Waleed M. 
Published: August 2021

Abstract
Background
Irrational use of antimicrobials is highly prevalent. It is a major driving factor for antimicrobial resistance (AMR). Research on irrational antimicrobial use is important for developing policies and regulations to combat and contain AMR. The present study aims to provide an overview of research publications on the irrational use of antimicrobials at the national and global levels.

Methods
Publications on irrational use of antimicrobials were extracted from Scopus using a wide range of relevant keywords for the study period from 1980 to 2020.

Results
In total, 656 publications on irrational use of antimicrobials were found. The bulk of publications in this field were about irrational use in humans. A limited number of publications were found on the irrational use of antimicrobials in the context of veterinary and environment. The number of publications, contributing countries, and the mean number of authors per article increased with time, most notably in the last decade. Authors from 105 different countries participated in publishing the retrieved articles with 22 (21.0%) participated in 10 or more publications. The United States led with 140 (21.6%) articles followed distantly by China (n = 49, 7.5%), India (n = 45, 6.9%), and the United Kingdom (n = 45, 6.9%). Countries in the South-East Asian region (n = 69, 10.5%) and the African region (n = 42, 6.4%) made the least contribution. The list of most frequent author keywords included “antimicrobial stewardship” and “community pharmacies”. The research themes focused on the hospital-based rational use of antimicrobials and the self-medication practices with antimicrobials in the community. In total, 420 different journals participated in publishing the retrieved documents. The Plos One journal (17, 2.6%) ranked first. The retrieved articles received an average of 15.6 citations per article and an h-index of 52. The most frequent antimicrobials encountered in the retrieved literature were penicillin, cephalosporin, and fluoroquinolones while the most frequently encountered pathogens were S. aureus and P. aeruginosa.

Conclusion
Research on the irrational use of antimicrobials is needed from all countries and regions to implement appropriate policies to contain the AMR. Research on irrational use of antimicrobials in the context of veterinary is needed.
Hepatitis C in healthcare personnel: follow-up analysis of treatments with direct-acting antiviral agents
Authors: Westermann Claudia , Wendeler Dana , Nienhaus Albert 
Published: August 2021

Abstract
Background
Hepatitis C infections (HCV) are associated with an increase in morbidity and mortality. The aim of this study is to update the results of treatment with direct-acting antiviral agents (DAAs) using a larger population of healthcare personnel (HP) and a longer observation period.

Methods
Secondary data analysis of DAA treatment administered to HP (with confirmed occupational acquired HCV infection) between 1 January 2014 and 30 December 2018, is based on statutory accident insurance data from Germany. The end points of the study were results of a monitoring carried out 12 and 24 weeks after the end of treatment (sustained virological response, SVR), as well as side effects and the assessment of reduced work ability after treatment. Multivariate logistic regression models were constructed to investigate predictors of SVR.

Results
The study population (n = 305) mainly comprised HP with a genotype 1 infection. The average age was 63 (SD 10) and 77% were female. Two thirds of the HP suffered from fibrosis or cirrhosis, and had experience of treatment. Statistically, men were significantly more likely to suffer from cirrhosis than women (60% compared to 21%, p < 0.001). The end-of-treatment response (ETR) rate was 99% and the SVR12 and SVR24 rates were 98%. Liver cirrhosis proved to be a predictor of a statistically significant reduction in success rates.

Conclusion
DAA treatment leads to high SVR. Early HCV treatment is associated with higher SVR.