bluuebunny/crossref_metadata_2025_split huggingface dataset:
AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma
Authors: Bloedjes Timon A. , de Wilde Guus , Maas Chiel , Eldering Eric , Bende Richard J. , van Noesel Carel J. M. , Pals Steven T. , Spaargaren Marcel , Guikema Jeroen E. J. 
Published: September 2020

AbstractThe phosphatidylinositide-3 kinases and the downstream mediator AKT drive survival and proliferation of multiple myeloma (MM) cells. AKT signaling is active in MM and has pleiotropic effects; however, the key molecular aspects of AKT dependency in MM are not fully clear. Among the various downstream AKT targets are the Forkhead box O (FOXO) transcription factors (TFs) and glycogen synthase kinase 3 (GSK3), which are negatively regulated by AKT signaling. Here we show that abrogation of AKT signaling in MM cells provokes cell death and cell cycle arrest, which crucially depends on both FOXO TFs and GSK3. Based on gene expression profiling, we defined a FOXO-repressed gene set that has prognostic significance in a large cohort of patients with MM, indicating that AKT-mediated gene activation is associated with inferior overall survival. We further show that AKT signaling stabilizes the antiapoptotic myeloid cell leukemia 1 (MCL1) protein by inhibiting FOXO- and GSK3-mediated MCL1 turnover. In concordance, abrogation of AKT signaling greatly sensitized MM cells for an MCL1-targeting BH3-mimetic, which is currently in clinical development. Taken together, our results indicate that AKT activity is required to restrain the tumor-suppressive functions of FOXO and GSK3, thereby stabilizing the antiapoptotic protein MCL1 in MM. These novel insights into the role of AKT in MM pathogenesis and MCL1 regulation provide opportunities to improve targeted therapy for patients with MM.
Phase 2 multiple-dose study of an FcRn inhibitor, rozanolixizumab, in patients with primary immune thrombocytopenia
Authors: Robak Tadeusz , Kaźmierczak Maciej , Jarque Isidro , Musteata Vasile , Treliński Jacek , Cooper Nichola , Kiessling Peter , Massow Ute , Woltering Franz , Snipes Rose , Ke Juan , Langdon Grant , Bussel James B. , Jolles Stephen 
Published: September 2020

AbstractPrimary immune thrombocytopenia (ITP) is a predominantly immunoglobulin G (IgG)-autoantibody-mediated disease characterized by isolated thrombocytopenia. Rozanolixizumab, a subcutaneously infused humanized monoclonal anti-neonatal Fc receptor (FcRn) antibody, reduced serum IgG in healthy volunteers. In this phase 2, multicenter, open-label study, patients with persistent/chronic primary ITP received 1 to 5 once-weekly subcutaneous infusions of rozanolixizumab (cumulative doses, 15-21 mg/kg). Primary objectives were safety and tolerability, and secondary objectives were clinical efficacy (change in platelet count) and pharmacodynamic effect (change in IgG). In all, 51 (77.3%) of 66 patients reported 1 or more adverse events (AEs), all mild-to-moderate, most commonly headaches (26 [39.4%] of 66), of which 15 were treatment related. Four patients had serious AEs, but none were treatment related. No AEs resulted in discontinuation of the study drug. No serious infections occurred. Platelet counts of ≥50 × 109/L were achieved at least once at any time after multiple infusions (5 × 4, 3 × 7, or 2 × 10 mg/kg: 35.7%, 35.7%, and 45.5% of patients, respectively) or single infusions (15 or 20 mg/kg: 66.7% and 54.5% patients, respectively). Minimum mean IgG levels and maximum mean platelet counts both occurred by day 8 in the higher (15 and 20 mg/kg) single-dose cohorts and maximum platelet count occurred by day 11 onward in the multiple-dose cohorts. No clinically meaningful changes occurred in IgA, IgM, IgE, or albumin levels. In patients with persistent/chronic primary ITP, rozanolixizumab demonstrated a favorable safety profile and rapid, substantial platelet increases concordant with substantial IgG reductions, especially with single doses. By day 8, in the 15 and 20 mg/kg single-dose cohorts, &gt;50% patients achieved clinically relevant platelet responses (≥50 × 109/L), coinciding with the lowest mean IgG levels. These data support phase 3 development of rozanolixizumab in persistent/chronic primary ITP. This trial was registered at www.clinicaltrials.gov as #NCT02718716.
Inter-scanner reproducibility of brain volumetry: influence of automated brain segmentation software
Authors: Liu Sirui , Hou Bo , Zhang Yiwei , Lin Tianye , Fan Xiaoyuan , You Hui , Feng Feng 
Published: September 2020

Abstract
Background
The inter-scanner reproducibility of brain volumetry is important in multi-site neuroimaging studies, where the reliability of automated brain segmentation (ABS) tools plays an important role. This study aimed to evaluate the influence of ABS tools on the consistency and reproducibility of the quantified brain volumetry from different scanners.

Methods
We included fifteen healthy volunteers who were scanned with 3D isotropic brain T1-weighted sequence on three different 3.0 Tesla MRI scanners (GE, Siemens and Philips). For each individual, the time span between image acquisitions on different scanners was limited to 1 h. All the T1-weighted images were processed with FreeSurfer v6.0, FSL v5.0 and AccuBrain® with default settings to obtain volumetry of brain tissues (e.g. gray matter) and substructures (e.g. basal ganglia structures) if available. Coefficient of variation (CV) was calculated to test inter-scanner variability in brain volumetry of various structures as quantified by these ABS tools.

Results
The mean inter-scanner CV values per brain structure among three MRI scanners ranged from 6.946 to 12.29% (mean, 9.577%) for FreeSurfer, 7.245 to 20.98% (mean, 12.60%) for FSL and 1.348 to 8.800% (mean value, 3.546%) for AccuBrain®. In addition, AccuBrain® and FreeSurfer achieved the lowest mean values of region-specific CV between GE and Siemens scanners (from 0.818 to 5.958% for AccuBrain®, and from 0.903 to 7.977% for FreeSurfer), while FSL-FIRST had the lowest mean values of region-specific CV between GE and Philips scanners (from 2.603 to 16.310%). AccuBrain® also had the lowest mean values of region-specific CV between Siemens and Philips scanners (from 1.138 to 6.615%).

Conclusion
There is a large discrepancy in the inter-scanner reproducibility of brain volumetry when using different processing software. Image acquisition protocols and selection of ABS tool for brain volumetry quantification have impact on the robustness of results in multi-site studies.
Complicated COVID-19 in pregnancy: a case report with severe liver and coagulation dysfunction promptly improved by delivery
Authors: Ronnje Louise , Länsberg John-Kalle , Vikhareva Olga , Hansson Stefan R. , Herbst Andreas , Zaigham Mehreen 
Published: September 2020

Abstract
Background
It has been proposed that pregnant women and their fetuses may be particularly at risk for poor outcomes due to the coronavirus (COVID-19) pandemic. From the few case series that are available in the literature, women with high risk pregnancies have been associated with higher morbidity. It has been suggested that pregnancy induced immune responses and cardio-vascular changes can exaggerate the course of the COVID-19 infection.

Case presentation
A 26-year old Somalian woman (G2P1) presented with a nine-day history of shortness of breath, dry cough, myalgia, nausea, abdominal pain and fever. A nasopharyngeal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Her condition rapidly worsened leading to severe liver and coagulation impairment. An emergency Caesarean section was performed at gestational week 32 + 6 after which the patient made a rapid recovery. Severe COVID-19 promptly improved by the termination of the pregnancy or atypical HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelet Count) exacerbated by concomitant COVID-19 infection could not be ruled out. There was no evidence of vertical transmission.

Conclusions
This case adds to the growing body of evidence which raises concerns about the possible negative maternal outcomes of COVID-19 infection during pregnancy and advocates for pregnant women to be recognized as a vulnerable group during the current pandemic.
A prospective observational study on critically ill children with diaphragmatic dysfunction: clinical outcomes and risk factors
Authors: Xue Yang , Yang Chun-Feng , Ao Yu , Qi Ji , Jia Fei-Yong 
Published: September 2020

Abstract
Background
Diaphragmatic dysfunction (DD) has a great negative impact on clinical outcomes, and it is a well-recognized complication in adult patients with critical illness. However, DD is largely unexplored in the critically ill pediatric population. The aim of this study was to identify risk factors associated with DD, and to investigate the effects of DD on clinical outcomes among critically ill children.

Methods
Diaphragmatic function was assessed by diaphragm ultrasound. According to the result of diaphragmatic ultrasound, all enrolled subjects were categorized into the DD group (n = 24) and the non-DD group (n = 46). Collection of sample characteristics in both groups include age, sex, height, weight, primary diagnosis, complications, laboratory findings, medications, ventilatory time and clinical outcomes.

Results
The incidence of DD in this PICU was 34.3%. The level of CRP at discharge (P = 0.003) in the DD group was higher than the non-DD group, and duration of elevated C-reactive protein (CRP) (P < 0.001), sedative days (P = 0.008) and ventilatory treatment time (P < 0.001) in the DD group was significantly longer than the non-DD group. Ventilatory treatment time and duration of elevated CRP were independently risk factors associated with DD. Patients in the DD group had longer PICU length of stay, higher rate of weaning or extubation failure and higher mortality.

Conclusion
DD is associated with poorer clinical outcomes in critically ill childern, which include a longer PICU length of stay, higher rate of weaning or extubation failure and a higher mortality. The ventilatory treatment time and duration of elevated CRP are main risk factors of DD in critically ill children.

Trial registration
Current Controlled Trials ChiCTR1800020196, Registered 01 Dec 2018.
Sex differences in dementia: on the potentially mediating effects of educational attainment and experiences of psychological distress
Authors: Hasselgren Caroline , Ekbrand Hans , Halleröd Björn , Mellqvist Fässberg Madeleine , Zettergren Anna , Johansson Lena , Skoog Ingmar , Dellve Lotta 
Published: September 2020

Abstract
Background
Old-age dementias are known to disproportionally affect women as well as individuals with low educational attainment. The higher lifetime risk of dementia among women is usually attributed to their longer life expectancy. However, the impact of sex, and subsequent gender inequity, is likely to be more multifaceted than this explanation implies. Not least because of historical inequities in access to education between the sexes and the gender and socio-economic gradients in risk factors such as stress, depression and social isolation. Consequently, the present study sought to test whether differences in educational attainment and experiences of general psychological distress mediate the association between female sex and dementia.

Methods
The study utilizes data obtained through the Gothenburg H70 Birth Cohort Study and the Prospective Populations Study on Women (n = 892). Data were analysed using Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) with Weighted Least Squares Means and Variance adjusted (WLSMV) estimation. General psychological distress was indicated by a latent variable and constructed from five manifest items (previous depression, stress, self-esteem, chronic loneliness and satisfaction with social situation) that were all measured at baseline.

Results
While the results could not corroborate that education directly mediates the effect of sex on dementia, level of distress was predicted by both female sex (0.607, p < .001) and education (− 0.166, p < .01) and, in turn, shown to be significantly associated with dementia (0.167, p < .05), also after controlling for confounders. When time from baseline to diagnosis was increased through sequential exclusion of dementia cases, the effect of distress on dementia was no longer significant.

Conclusion
The overall findings suggest that social (dis) advantage predicts general psychological distress, which thereby constitutes a potential, and rarely acknowledged, pathway between female sex, education, and dementia. They further underline the importance of attending to both education and distress as ‘gendered’ phenomena when considering the nature of their associations with dementia. However, the possibility of reverse causality bias must be acknowledged and the need for longitudinal studies with longer follow-up stressed.
Prevalence and risk factors associated with severe pre-eclampsia among postpartum women in Zanzibar: a cross-sectional study
Authors: Machano Mwashamba M. , Joho Angelina A. 
Published: September 2020

Abstract
Background
Severe pre-eclampsia is more dominant in low and middle-income countries. In Sub-Saharan Africa, severe pre-eclampsia remains a major public health problem contributing to high rates of maternal mortality. Few studies have investigated the relationship between severe pre-eclampsia and associated factors in East Africa. The aim of this study was to determine the prevalence and risk factors associated with severe pre-eclampsia among postpartum women in Zanzibar.

Methods
A hospital based analytical cross-sectional study design was used. Purposive sampling was utilized for the selection of hospitals. Proportionate sampling was used for selection of representatives from each hospital and participants were selected using systematic random sampling. Postpartum mothers were included in the study. The study was conducted by an interviewer who administered a questionnaire with close ended questions and chart review for data gathering. SPSS version 23 was used for data analysis and descriptive and multiple logistic regression was performed for control of confounders.

Results
This study included a total of 400 participants with a 100% response rate. Participants ranged from 17 to 45 years of age with mean age (SD) of 28.78 (±6.296). The prevalence of severe pre-eclampsia among postpartum women was 26.3% (n = 105). After adjusting for the possible confounders, factors associated with severe pre-eclampsia were; maternal age group of 15–20 years (AOR 3.839; 95% C. I 1.037–14.210), pregnancy from new partner/husband (AOR 7.561; 95% C. I 3.883–14.724), family history of high blood pressure (AOR 6.446; C. I 3.217–12.917), diabetes prior to conception (AOR 55.827; 95% C. I 5.061–615.868), having high blood pressure in a previous pregnancy (AOR 19.382; 95% C. I 4.617–81.364), paternal age above 45 (AOR 2.401; 95% C. I 1.044–5.519) and multifetal gestation (AOR 7.62; 95% CI 2.01–28.84).

Conclusion
The prevalence of severe pre-eclampsia among postpartum women in Zanzibar is high. Common risk factors in this setting include maternal age of 15–20 years, pregnancy with a new partner, family history of high blood pressure, pre-existing diabetes prior to conception, a history of high blood pressure in previous pregnancy paternal age greater than 45 and multifetal gestation.
Intimate partner violence against women and its association with pregnancy loss in Ethiopia: evidence from a national survey
Authors: Tiruye Tenaw Yimer , Chojenta Catherine , Harris Melissa L. , Holliday Elizabeth , Loxton Deborah 
Published: September 2020

AbstractBackgroundIntimate partner violence (IPV) is major public health problem that affects many dimensions of women’s health. However, the role of IPV on women’s reproductive health in general and pregnancy loss in particular, is largely unknown in Ethiopia. Therefore, this study investigated the association between IPV and pregnancy loss in Ethiopia.MethodsA retrospective analysis of nationally representative data from the 2016 Ethiopian Demographic and Health Survey (EDHS) was conducted. Married women of reproductive age (15–49 years) who participated in the domestic violence sub-study of the survey were included in the analysis. Adjusted odds ratios were estimated using multilevel logistic regression models to represent the association of IPV with outcome variable.ResultsAmong 4167 women included in the analysis, pregnancy loss had been experienced by 467 (11.2%). In total, 1504 (36.1%) participants reported having ever experienced any form of IPV, with 25.1, 11.9, and 24.1% reporting physical, sexual and emotional IPV respectively. A total of 2371 (56.9%) women had also experienced at least one act of partner controlling behaviour. After adjusting for potential confounders, a significant association was observed between IPV (a composite measure of physical, sexual and emotional abuse) and pregnancy loss (Adjusted Odds Ratio (AOR) 1.54, 95% Confidence Interval (CI): 1.12, 2.14). The odds of pregnancy loss were also higher (AOR 1.72, 95% CI: 1.06, 2.79) among women who had experienced multiple acts of partner controlling behaviours, compared with women who had not experienced partner controlling behaviours. The intra-class correlation coefficient (ICC) indicated that pregnancy loss exhibits significant between-cluster variation (p < 0.001); about 25% of the variation in pregnancy loss was attributable to differences between clusters.ConclusionIPV against women, including partner controlling behaviour, is significantly associated with pregnancy loss in Ethiopia. Therefore, there is a clear need to develop IPV prevention strategies and to incorporate IPV interventions into maternal health programs.
Catastrophic costs of tuberculosis care in a population with internal migrants in China
Authors: Lu Liping , Jiang Qi , Hong Jianjun , Jin Xiaoping , Gao Qian , Bang Heejung , DeRiemer Kathryn , Yang Chongguang 
Published: September 2020

Abstract
Background
The internal rural-to-urban migration is one of the major challenges for tuberculosis (TB) control in China. Patient costs incurred during TB diagnosis and treatment could cause access and adherence barriers, particularly among migrants. Here, we estimated the prevalence of catastrophic costs of TB patients and its associated factors in an urban population with internal migrants in China.

Methods
A cross-sectional survey was conducted to enroll culture-confirmed pulmonary TB patients in Songjiang district, Shanghai, between December 1, 2014, and December 31, 2015. Consenting participants completed a questionnaire, which collected direct and indirect costs before and after the diagnosis of TB. The catastrophic cost was defined as the annual expenses of TB care that exceeds 20% of total household disposable income. We used logistic regression to identify factors associated with catastrophic costs.

Results
Overall, 248 drug-susceptible TB patients were enrolled, 70% (174/248) of them were from migrants. Migrant patients were significantly younger compared to resident patients. The total costs were 25,824 ($3689) and 13,816 ($1974) Chinese Yuan (RMB) in average for resident and migrant patients, respectively. The direct medical cost comprised about 70% of the total costs among both migrant and resident patients. Overall, 55% (132 of 248) of patients experienced high expenses (>10% of total household income), and 22% (55 of 248) experienced defined catastrophic costs. The reimbursement for TB care only reduced the prevalence of catastrophic costs to 20% (49 of 248). Meanwhile, 52% (90 of 174) of the internal migrants had no available local health insurance. Hospitalizations, no available insurance, and older age (> 45-year-old) contributed significantly to the occurrence of catastrophic costs.

Conclusions
The catastrophic cost of TB service cannot be overlooked, despite the free policy. Migrants have difficulties benefiting from health insurance in urban cities. Interventions, including expanded medical financial assistance, are needed to secure universal TB care.
The ultrastructural damage caused by Eugenia zeyheri and Syzygium legatii acetone leaf extracts on pathogenic Escherichia coli
Authors: Famuyide Ibukun M. , Fasina Folorunso O. , Eloff Jacobus N. , McGaw Lyndy J. 
Published: September 2020

Abstract
Background
Antibiotics are commonly added to livestock feeds in sub-therapeutic doses as growth promoters and for prophylaxis against pathogenic microbes, especially those implicated in diarrhoea. While this practice has improved livestock production, it is a major cause of antimicrobial resistance in microbes affecting livestock and humans. This has led to the banning of prophylactic antibiotic use in animals in many countries. To compensate for this, alternatives have been sought from natural sources such as plants. While many studies have reported the antimicrobial activity of medicinal plants with potential for use as phytogenic/botanical feed additives, little information exists on their mode of action. This study is based on our earlier work and describes ultrastructural damage induced by acetone crude leaf extracts of Syzygium legatii and Eugenia zeyheri (Myrtaceae) active against diarrhoeagenic E. coli of swine origin using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent microscopy (FM). Gas chromatography/mass spectrometry (GC-MS) was used to investigate the chemical composition of plant extracts.

Results
The extracts damaged the internal and external anatomy of the cytoplasmic membrane and inner structure at a concentration of 0.04 mg/mL. Extracts also led to an increased influx of propidium iodide into treated bacterial cells suggesting compromised cellular integrity and cellular damage. Non-polar compounds such as α-amyrin, friedelan-3-one, lupeol, and β-sitosterol were abundant in the extracts.

Conclusions
The extracts of S. legatii and E. zeyheri caused ultrastructural damage to E. coli cells characterized by altered external and internal morphology. These observations may assist in elucidating the mode of action of the extracts.