bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pertussis outbreak in southern Ethiopia: challenges of detection, management, and response
Authors: Mitiku Aychiluhim D. , Argaw Mesele D. , Desta Binyam F. , Tsegaye Zergu T. , Atsa Afework A. , Tefera Bekele B. , Teferi Ephrem , Rogers Deirdre , Beshir Ismael A. , Alemu Asrat G. , Ayesa Desta A. , Abate Derebe T. , Sendeku Agegnehu G. , Muloiwa Rudzani 
Published: August 2020

AbstractBackgroundDespite the availability of effective vaccines, pertussis remains endemic with high fatality rates in low and middle-income countries (LMIC). This study aims to describe an outbreak of pertussis in a health district of Ethiopia. The study highlights the challenges faced by the health system in identifying pertussis cases and appropriately responding to the outbreak at the district level.MethodsA descriptive cross-sectional study was conducted using data sourced from the District Public Health Emergency and Management (PHEM) surveillance service and outbreak management field reports. Stratified attack rates and fatality rates for pertussis are described. Systemic problems leading to the outbreak are explored and narrated. A modified CDC pertussis case definition was employed with a polymerase chain reaction used to confirm cases.ResultsFrom September 2018 to January 2019, 1840 suspected, probable, and confirmed pertussis cases and six deaths were identified. Pertussis cases ranged from 1 month to 51 years in age. An outbreak occurred in 14 out of the 24 villages of Dara Malo district. The overall attack rate was 1708 per 100,000 population with a fatality rate of 3.3 per 1000 pertussis cases. The highest attack rate of 12,689/100,000 was seen in infants. Among confirmed, probable and suspected pertussis cases, only 41.1% had completed the three-dose pertussis vaccine’s primary schedule. The household survey revealed a population coverage of 73.4 and 40.8% for Pentavalent vaccine dose one and three respectively. Investigations suggested the existence of a poor cold chain management system in the study area.ConclusionsThere is an urgent need to build capacity to strengthen routine vaccination services and improve the maintenance of the vaccine cold chain. Other LMICs are urged to take lessons learned from this outbreak to strengthen their own vaccination programs and capacitate health workers to manage local outbreaks.
The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial
Authors: Tabrizi Fatemeh Pourteymour Fard , Farhangi Mahdieh Abbasalizad , Vaezi Maryam , Hemmati Salar 
Published: August 2020

AbstractBackgroundThere is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS).MethodsIn a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention.ResultsAfter the 12-week intervention, there were significant decreases in weight (− 6.97 ± 0.52 vs. -3.19 ± 0.72 kg;P < 0.001), waist circumference (− 7.78 ± 2.50 vs. -3.73 ± 1.40 cm;P < 0.001), fat mass (− 5.19 ± 0.53 vs. -1.36 ± 0.39 kg;P < 0.001), and insulin levels (− 5.40 ± 1.86 vs. -1.19 ± 0.85 μU/mL;P < 0.001) in the spinach-derived thylakoid group compared to the placebo group. Furthermore, insulin resistance markers and serum levels of testosterone decreased significantly in the thylakoid group compared to the placebo group (P < 0.05). The changes in other parameters did not show significant differences between the two groups.ConclusionsSpinach-derived thylakoid supplementation resulted in more favorable improvements in anthropometric indices and insulin sensitivity compared to the calorie restriction alone.Trial registrationThe study was approved by the Ethics Committee of Research Vice-chancellor of Tabriz University of Medical Sciences, Tabriz, Iran, and was registered in the Iranian Registry of Clinical Trials (registration ID:IRCT20140907019082N9).
Androgen levels in the fetal cord blood of children born to women with polycystic ovary syndrome: a meta-analysis
Authors: Duan Changling , Pei Tianjiao , Li Yujing , Cao Qi , Chen Hanxiao , Fu Jing 
Published: August 2020

AbstractIntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. It is reported that intrauterine exposure to hyperandrogenism may induce the development of PCOS and associated complications in later life. To analyze the intrauterine androgen levels in infants born to PCOS mothers, we evaluated the androgen levels in fetal cord blood through a meta-analysis of observational studies.Material and methodsThe following online databases were systematically searched: PubMed, EMBASE, Cochrane library databases and Web of Science up to December 2019. Human studies compared cord blood androgen levels, including testosterone (T) and androstenedione (ADION), in fetal cord blood of mothers with and without PCOS. Statistical analysis was performed in Review Manager, Version 5.3, with the inverse variance method based on a random-effects model.ResultsA total of 7 articles were scrutinized and a total of 570 samples including 268 female and 222 male infants were qualified for review. In the mass spectrograph (MS) subgroup, PCOS mothers showed no signs of increased T concentration in umbilical cord blood at birth (4 studies; hazard ratio [HR] = − 0.05; 95% confidence interval [CI] = [− 0.33,0.24]; I2 = 7%;P = 0.75; fixed-effects model). ADION level tends to be lower in daughters’ cord blood of PCOS mothers (3 studies; HR = -0.59; 95%CI = [− 1.00, − 0.19]; I2 = 0%;P = 0.004; fixed-effects model).ConclusionsFetal cord blood T level is not related to PCOS, while ADION levels tend to be lower in the cord blood of daughters born to mothers with PCOS.
Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders
Authors: Yick Leung-Wah , Tang Chi-Ho , Ma Oscar Ka-Fai , Kwan Jason Shing-Cheong , Chan Koon-Ho 
Published: August 2020

AbstractBackgroundNeuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG.MethodsPurified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA.ResultsOral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in the spinal cord.ConclusionsOur findings support that glutamate excitotoxicity and neuroinflammation play important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.
Threat, hostility and violence in childhood and later psychotic disorder: population-based case–control study
Authors: Morgan Craig , Gayer-Anderson Charlotte , Beards Stephanie , Hubbard Kathryn , Mondelli Valeria , Di Forti Marta , Murray Robin M. , Pariante Carmine , Dazzan Paola , Craig Thomas J. , Reininghaus Ulrich , Fisher Helen L. 
Published: August 2020

BackgroundA growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.AimsUsing detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.MethodCAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.ResultsWe found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.ConclusionsOur findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.
Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial
Authors: Camidge D. Ross , Kim Hye Ryun , Ahn Myung-Ju , Yang James C. H. , Han Ji-Youn , Hochmair Maximilian J. , Lee Ki Hyeong , Delmonte Angelo , García Campelo Maria Rosario , Kim Dong-Wan , Griesinger Frank , Felip Enriqueta , Califano Raffaele , Spira Alexander , Gettinger Scott N. , Tiseo Marcello , Lin Huamao M. , Gupta Neeraj , Hanley Michael J. , Ni Quanhong , Zhang Pingkuan , Popat Sanjay 
Published: August 2020

PURPOSE Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor–naive ALK-positive non–small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501 ). We report results of the second prespecified interim analysis (150 events). METHODS Patients with ALK inhibitor–naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected. RESULTS Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration–time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69). CONCLUSION Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.
Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast-Conserving Surgery in the Modern Treatment Era: A Multicenter, Randomized Controlled Trial From China
Authors: Wang Shu-Lian , Fang Hui , Hu Chen , Song Yong-Wen , Wang Wei-Hu , Jin Jing , Liu Yue-Ping , Ren Hua , Liu Juan , Li Gao-Feng , Du Xiang-Hui , Tang Yu , Jing Hao , Ma Yu-Chao , Huang Zhou , Chen Bo , Tang Yuan , Li Ning , Lu Ning-Ning , Qi Shu-Nan , Yang Yong , Sun Guang-Yi , Liu Xin-Fan , Li Ye-Xiong 
Published: August 2020

PURPOSE No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group ( P = .019). CONCLUSION CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.
The UPRosome – decoding novel biological outputs of IRE1α function
Authors: Urra Hery , Pihán Philippe , Hetz Claudio 
Published: August 2020

ABSTRACT
Different perturbations alter the function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins in its lumen, a condition termed ER stress. To restore ER proteostasis, a highly conserved pathway is engaged, known as the unfolded protein response (UPR), triggering adaptive programs or apoptosis of terminally damaged cells. IRE1α (also known as ERN1), the most conserved UPR sensor, mediates the activation of responses to determine cell fate under ER stress. The complexity of IRE1α regulation and its signaling outputs is mediated in part by the assembly of a dynamic multi-protein complex, named the UPRosome, that regulates IRE1α activity and the crosstalk with other pathways. We discuss several studies identifying components of the UPRosome that have illuminated novel functions in cell death, autophagy, DNA damage, energy metabolism and cytoskeleton dynamics. Here, we provide a theoretical analysis to assess the biological significance of the UPRosome and present the results of a systematic bioinformatics analysis of the available IRE1α interactome data sets followed by functional enrichment clustering. This in silico approach decoded that IRE1α also interacts with proteins involved in the cell cycle, transport, differentiation, response to viral infection and immune response. Thus, defining the spectrum of IRE1α-binding partners will reveal novel signaling outputs and the relevance of the pathway to human diseases.
RACK1 regulates centriole duplication through promoting the activation of polo-like kinase 1 by Aurora A
Authors: Yoshino Yuki , Kobayashi Akihiro , Qi Huicheng , Endo Shino , Fang Zhenzhou , Shindo Kazuha , Kanazawa Ryo , Chiba Natsuko 
Published: August 2020

ABSTRACT
Breast cancer gene 1 (BRCA1) contributes to the regulation of centrosome number. We previously identified receptor for activated C kinase 1 (RACK1) as a BRCA1-interacting partner. RACK1, a scaffold protein that interacts with multiple proteins through its seven WD40 domains, directly binds to BRCA1 and localizes to centrosomes. RACK1 knockdown suppresses centriole duplication, whereas RACK1 overexpression causes centriole overduplication in a subset of mammary gland-derived cells. In this study, we showed that RACK1 binds directly to polo-like kinase 1 (PLK1) and Aurora A, and promotes the Aurora A–PLK1 interaction. RACK1 knockdown decreased phosphorylated PLK1 (p-PLK1) levels and the centrosomal localization of Aurora A and p-PLK1 in S phase, whereas RACK1 overexpression increased p-PLK1 level and the centrosomal localization of Aurora A and p-PLK1 in interphase, resulting in an increase of cells with abnormal centriole disengagement. Overexpression of cancer-derived RACK1 variants failed to enhance the Aurora A–PLK1 interaction, PLK1 phosphorylation and the centrosomal localization of p-PLK1. These results suggest that RACK1 functions as a scaffold protein that promotes the activation of PLK1 by Aurora A in order to promote centriole duplication.
This article has an associated First Person interview with the first author of the paper.
Respecting an autonomous decision to refuse life-saving treatment: a case study
Authors: Moore Emma 
Published: August 2020

Background: Autonomy is a key ethical principle in healthcare, giving patients the right to be involved in their own care. Allowing patients to make decisions based on their own values and beliefs is a fundamental aspect of evidence-based practice. Professional autonomy allows paramedics to make critical decisions around patient care in an emergency, enabling them to provide life-saving treatment. A patient's autonomy can conflict with that of a paramedic, leading to complex ethical situations which can affect the way a paramedic performs their duty of care. Decision-making is a fundamental skill for paramedics and often in the prehospital setting, paramedics have to manage situations with a certain degree of risk if they are to manage patients effectively and safely, while respecting patients' legal and ethical rights. Case presentation: An ambulance crew were called to attend a 62-year-old woman with a history of chronic obstructive pulmonary disease, respiratory arrest and stage 2 respiratory failure, who had breathing difficulties. She was deemed to have capacity by the ambulance crew under the Mental Capacity Act. The patient refused to be taken to hospital for treatment against paramedic recommendation, as she wished to receive no further treatment or hospital admission and wanted to die at home. The ambulance crew referred her to her GP. Conclusions: Paramedics experience great difficulties in making decisions, as information and alternative treatment options are often limited in the prehospital setting. One major limitation to autonomy is where an autonomous patient is refusing life-saving treatment. This can create ethical dilemmas for paramedics, leaving them to feel a sense of vulnerability and anxiety around performing their duty of care. The law is clear: an autonomous patient's decision to refuse treatment, even if it may seem unwise, must be respected in accordance with the Human Rights Act 1998.
Development of V-FAST: a vision screening tool for ambulance staff
Authors: Rowe Fiona J , Dent Joseph , Allen Frank , Hepworth Lauren R , Bates Rachel 
Published: August 2020

Background: About two-thirds of stroke survivors experience visual problems and most patients who have a stroke limited to the occipital lobe will have visual impairments only. Aim: The V-FAST screening tool, which assesses visual symptoms, eye movements, visual field and visual extinction, and a training package to improve diagnostic accuracy of identifying visual impairment in hyperacute strokes were developed and evaluated. Methods: The educational package was developed through focus groups. The pilot study screened patients with suspected strokes in prehospital settings; the V-FAST tool was used with 43 of these patients. Each participant was also assessed in hospital using the National Institutes of Health Stroke Scale (NIHSS) and the score compared to V-FAST screening results to determine sensitivity and specificity. Results: The education package includes detailed instructions with video. In the pilot study, V-FAST detected visual impairment in 75.9% of FAST-positive and 80% of FAST-negative strokes. Sensitivity and specificity compared to NIHSS were 85.7% and 42.1% respectively. Conclusion: V-FAST has good sensitivity to detect vision impairment when screening for possible strokes. The added education package facilitates greater knowledge and understanding of potential visual problems caused by stroke.
Periwound skin care considerations for older adults
Authors: Holloway Samantha , Mahoney Kirsty 
Published: August 2020

Samantha Holloway and Kirsty Mahoney discuss the unique ageing effects on adult skin and how these changes can cause the skin to be more prone to damage This article discusses the effects of ageing on the skin, particularly the main structural and functional changes that occur in the epidermis and dermis that make the skin more vulnerable to damage. Specific alterations that occur with ageing include slower epidermal turnover, flattening of the epidermal-dermal junction, loss of moisture and hydration as well as reduced immunity placing the skin at increased risk of damage. The discussion will also examine common periwound complications associated with ageing including; maceration, excoriation, dry skin, hyperkeratosis, callus, contact dermatitis and eczema. Strategies to manage these problems and interventions to reduce the risk of these complications include moisturising the skin to make it more resilient, debriding keratinised and callus tissue in the periwound area, appropriate choice of dressings to manage excessive exudate, careful removal of dressings as well as treating inflammatory conditions of the periwound skin.