bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes‐induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis
Authors: Tian Yuan , Xiao Yue‐Hai , Geng Tian , Sun Chao , Gu Jiang , Tang Kai‐Fa , Liu Bei , Liu Yi‐Meng , Sun Fa 
Published: September 2020

Background informationDiabetes‐induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism.A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC‐1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC‐1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy.ResultsCLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose‐treated GC‐1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl‐2 expression, elevated Bax expression and cleavage of Caspase‐3/‐9 in GC‐1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin‐1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC‐1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU‐overexpressing GC‐1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment.ConclusionsCLU expression is suppressed during diabetes‐induced testicular damage, whereas CLU overexpression alleviates diabetes‐induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.
Retracted: First‐line pembrolizumab vs chemotherapy in metastatic non‐small‐cell lung cancer: KEYNOTE‐024 Japan subset
Authors: Satouchi Miyako , Nosaki Kaname , Takahashi Toshiaki , Nakagawa Kazuhiko , Aoe Keisuke , Kurata Takayasu , Sekine Akimasa , Horiike Atsushi , Fukuhara Tatsuro , Sugawara Shunichi , Umemura Shigeki , Saka Hideo , Okamoto Isamu , Yamamoto Nobuyuki , Sakai Hiroshi , Kishi Kazuma , Katakami Nobuyuki , Horinouchi Hidehito , Hida Toyoaki , Okamoto Hiroaki , Atagi Shinji , Ohira Tatsuo , Han Shi Rong , Noguchi Kazuo , Ebiana Victoria , Hotta Katsuyuki 
Published: September 2020

AbstractThis prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
Body composition in women with premature ovarian insufficiency using hormone therapy and the relation to cardiovascular risk markers: A case‐control study
Authors: Freitas Alberto T. A. , Donovan Giraldo Andrea E. , Pravatta Rezende Gabriela , Yela Daniela A. , Jales Rodrigo M. , Benetti‐Pinto Cristina L. 
Published: September 2020

AbstractObjectiveTo compare body composition between women with premature ovarian insufficiency (POI) using hormone therapy and controls with normal ovarian function, and to correlate body composition with cardiovascular risk markers in the POI group.Patients and designA case‐control study of 70 women with POI matched by age and body mass index with 70 controls.MeasurementsAll were submitted to whole‐body dual‐energy X‐ray absorptiometry (DXA) to analyse body composition. In the POI group, total cholesterol, HDL‐cholesterol, LDL‐cholesterol, VLDL‐cholesterol, triglycerides, glucose, insulin, transaminases and C‐reactive protein levels were measured, as well as the thickness of the carotid artery intima‐media complex.ResultsTotal mass, fat mass, lean mass (total, percentage and index) and the android/gynoid (A/G) ratio were similar in both groups; however, bone mineral content was lower (P < .001) in the POI group. Lean and fat mass indexes were 14.19 ± 1.63 and 11.04 ± 3.58, respectively, and the percentage of gynoid to android fat was higher (51.17 ± 6.71% versus 47.74 ± 9.19%; A/G ratio = 0.93 ± 0.15) in the POI group. In addition, the increase in total mass correlated positively with glucose and ALT levels and negatively with HDL‐cholesterol. Increased A/G ratio was the measurement most frequently associated with cardiovascular risk markers.ConclusionThe body composition of women with POI using hormone therapy is similar to that of women with normal ovarian function with regard to lean and fat mass content and fat distribution. In women with POI, the higher the A/G ratio, the worse the cardiovascular risk markers.
Does forest thinning reduce fire severity in Australian eucalypt forests?
Authors: Taylor Chris , Blanchard Wade , Lindenmayer David B. 
Published: September 2020

AbstractForest thinning has been proposed to reduce fire severity. However, evidence to support this strategy in Australia is scant. We completed a detailed empirical analysis of stand history data from forests burned in wildfires in 2009 in south‐eastern Australia, to address the question: Does forest thinning reduce fire severity? The answer varied depending on fire type (Crown Burn vs. Crown Burn/Crown Scorch), forest type, and stand age. For the statistical relationship for Crown Burn, there were no thinning effects in ash‐type forests. For mixed species forests, thinning reduced the probability of Crown Burn in young stands but increased it in older stands. Data for the fire severity category of Crown Burn/Crown Scorch revealed that thinning generally elevated fire severity, irrespective of stand age, forest type, or fire zone. Except for 20‐ to 40‐year‐old mixed species forest subject to Crown Burn, proposals for thinning to reduce fire severity have limited support.
Strategic advertising of online news articles as an intervention to influence wildlife product consumers
Authors: Doughty Hunter , Wright Joss , Veríssimo Diogo , Lee Janice S. H. , Oliver Kathryn , Milner‐Gulland E. J. 
Published: September 2020

AbstractChanging human behavior is essential for biodiversity conservation, but robust approaches for large scale change are needed. Concepts like repeat message exposure and social reinforcement, as well as mechanisms like online news coverage and targeted advertisements, are currently used by private and public sectors, and could prove powerful for conservation. Thus, to explore their potential in influencing wildlife consumption, we used online advertisements through Facebook, Google, and Outbrain, to promote news articles discussing the use of a Critically Endangered antelope (the Saiga tatarica) as a traditional Chinese medicine in Singapore. Our message, tailored to middle‐aged Chinese Singaporean women, framed saiga horn products as being no longer socially endorsed. Through advert performance and in‐depth analyses of Facebook user engagement, we assessed audience response. Our message pervaded Singapore's online media (e.g., our adverts were shown almost five million times; and the story ran on seven news outlets), and resulted in widespread desirable audience responses (e.g., 63% of Facebook users' engagements included identifiably positive features like calls for public action to reduce saiga horn consumption, anger at having unknowingly used a Critically Endangered species, and self‐pledges to no longer use it; only 13% of engagements included identifiably negative features). This work shows that targeted dissemination of online news articles can have promising results, and may have wide applicability to conservation.
Investigating the capabilities of information technologies to support policymaking in COVID‐19 crisis management; a systematic review and expert opinions
Authors: Mehraeen Mohammad , Dadkhah Mehdi , Mehraeen AmirReza 
Published: September 2020

AbstractBackgroundToday, numerous countries are fighting to protect themselves against the Covid‐19 crisis, while the policymakers are confounded and empty handed in dealing with this chaotic circumstance. The infection and its impacts have made it difficult to make optimal and suitable decisions. New information technologies play significant roles in such critical situations to address and relieve stress during the coronavirus crisis. This article endeavours to recognize the challenges policymakers have typically experienced during pandemic diseases, including Covid‐19, and, accordingly, new information technology capabilities to encounter with them.Material and methodsThe current study utilizes the synthesis of findings of experts’ opinions within the systematic review process as the research method to recognize the best available evidence drawn from text and opinion to offer practical guidance for policymakers.ResultsThe results illustrate that the challenges fall into two categories including; encountering the disease and reducing the results of the disease. Furthermore, Internet of things, cloud computing, machine learning and social networking play the most significant roles to address these challenges.
Microglial phagocytosis dysfunction in the dentate gyrus is related to local neuronal activity in a genetic model of epilepsy
Authors: Sierra‐Torre Virginia , Plaza‐Zabala Ainhoa , Bonifazi Paolo , Abiega Oihane , Díaz‐Aparicio Irune , Tegelberg Saara , Lehesjoki Anna‐Elina , Valero Jorge , Sierra Amanda 
Published: September 2020

AbstractObjectiveMicroglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response during neurodegeneration. Whereas it is very efficient in physiological conditions, it is impaired in mouse and human mesial temporal lobe epilepsy, and now we extend our studies to a model of progressive myoclonus epilepsy type 1 in mice lacking cystatin B (CSTB).MethodsWe used confocal imaging and stereology‐based quantification of apoptosis and phagocytosis of the hippocampus of Cstb knockout (KO) mice, an in vitro model of phagocytosis and siRNAs to acutely reduce Cstb expression, and a virtual three‐dimensional (3D) model to analyze the physical relationship between apoptosis, phagocytosis, and active hippocampal neurons.ResultsMicroglial phagocytosis was impaired in the hippocampus of Cstb KO mice at 1 month of age, when seizures arise and hippocampal atrophy begins. This impairment was not related to the lack of Cstb in microglia alone, as shown by in vitro experiments with microglial Cstb depletion. The phagocytosis impairment was also unrelated to seizures, as it was also present in Cstb KO mice at postnatal day 14, before seizures begin. Importantly, phagocytosis impairment was restricted to the granule cell layer and spared the subgranular zone, where there are no active neurons. Furthermore, apoptotic cells (both phagocytosed and not phagocytosed) in Cstb‐deficient mice were at close proximity to active cFos+ neurons, and a virtual 3D model demonstrated that the physical relationship between apoptotic cells and cFos+ neurons was specific for Cstb KO mice.SignificanceThese results suggest a complex crosstalk between apoptosis, phagocytosis, and neuronal activity, hinting that local neuronal activity could be related to phagocytosis dysfunction in Cstb KO mice. Overall, these data suggest that phagocytosis impairment is an early feature of hippocampal damage in epilepsy and opens novel therapeutic approaches for epileptic patients based on targeting microglial phagocytosis.
Everyday sexism and racism in the ivory tower: The experiences of early career researchers on the intersection of gender and ethnicity in the academic workplace
Authors: Bourabain Dounia 
Published: September 2020

AbstractThe academic workplace is often described as a place of merit and equal opportunities. However, research shows a leaky pipeline where the share of women and people of color decreases in the higher echelons of academia. Explanations are often structural, referring to the access barriers women are confronted with, such as hiring and recruitment. This research investigates what goes wrong in the early phases of a female academic's career. From an intersectional perspective, I study the experiences with everyday sexism and racism of PhD and postdoctoral researchers across disciplines. After conducting 50 in‐depth interviews, four processes are discovered: smokescreen of equality, everyday cloning, patronization, and paternalism.
Efficacy of a novel sequential treatment regimen containing bismuth forHelicobacter pylorieradication in Turkish children
Authors: Arslan Melike , Balamtekin Necati , Günal Armağan 
Published: September 2020

AbstractBackgroundEradication rates ofHelicobacter pylori(H pylori) with standard triple therapy are gradually decreasing all over the world, including in children, due to the development of strains resistant to antimicrobials. Sequential therapy can be used as an alternative method to increase eradication rates.Materials and MethodsA total of 75 patients ≥ 8 years of age withH pylorigastritis were included in the study. According to Rome IV criteria, 38 patients had functional abdominal pain and dyspepsia, and 37 patients had alarm findings suggesting organic disease. Patients were treated with a novel sequential therapy consisting of the proton pump inhibitor (PPI)‐lansoprazole (1 mg/kg/day, maximum 30 mg daily), amoxicillin (50 mg/kg/d in two doses, maximum 2 × 1000 mg) for 7 days followed by PPI‐lansoprazole (1 mg/kg/d, maximum 30 mg daily), metronidazole (20 mg/kg/day in two doses, maximum 2 x 500 mg), tetracycline (50 mg/kg/d divided into four equal doses, maximum 4 x 500 mg), and bismuth subsalicylate (262 mg QID in patients ≤ 10 years of age, 524 mg QID in patients > 10 years of age in days 8‐14). Eradication status was evaluated byH pyloristool antigen test 8 weeks after the completion of treatment.ResultsThe mean age of the patients was 15.1 ± 2.4 years and 51 (68%) were female. No patient discontinued therapy due to side effects. All patients had antral gastritis (76.0%) or pangastritis (24.0%). The peptic ulcer rate was 6.6%. Eradication therapy was given to all patients with or without peptic ulcer.H pylorieradication was achieved in 69 (92.0%) patients and symptoms improved in 61 of those eradicated.ConclusionsAs a first‐line treatment forH pylorieradication in children, administering a novel sequential therapy including bismuth for 14 days provides a high rate of eradication.
Effects of alcohol consumption on multiple hepatocarcinogenesis in patients with fatty liver disease
Authors: Ochiai Yorinari , Kawamura Yusuke , Kobayashi Masahiro , Shindoh Junichi , Kobayashi Yuta , Okubo Satoshi , Muraishi Nozomu , Kajiwara Akira , Iritani Soichi , Fujiyama Shunichiro , Hosaka Tetsuya , Saitoh Satoshi , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Ikeda Kenji , Arase Yasuji , Hashimoto Masaji , Kumada Hiromitsu 
Published: September 2020

AimThe number of patients with fatty liver disease (FLD) is increasing globally. Ethanol consumption in FLD is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the effects of alcohol consumption on the occurrence of multiple HCCs remain unclear. We explored the relationship between the daily ethanol intake and the HCC number.MethodsThis single‐center retrospective study enrolled 114 patients without viral or immune hepatitis undergoing first‐line HCC treatment who had been diagnosed with FLD by abdominal ultrasonography or a liver biopsy at the same time as or before HCC detection. We categorized patients into four groups according to the daily alcohol consumption (<20 g: non‐alcoholic fatty liver disease, n = 45; 20–39 g: low‐intermediate ethanol intake with FLD, n = 13; 40–69 g: high‐intermediate ethanol intake with FLD, n = 31; ≥70 g: alcoholic fatty liver disease, n = 25). The relationship between the daily ethanol consumption and the number of HCCs (single or multiple) was examined.ResultsThe risk of multiple HCCs was significantly higher in the high‐intermediate ethanol intake with FLD (HR 2.89, 95% CI 1.04–8.02, P = 0.042) and alcoholic fatty liver disease (HR 3.14, 95% CI 1.07–9.22, P = 0.037) groups than in the others. A multivariate analysis showed that a daily ethanol intake ≥40 g was associated with a significantly increased risk of multiple HCCs (HR 2.82, 95% CI 1.16–6.88, P = 0.023).ConclusionsOur findings suggest that a high daily ethanol intake might lead to multiple hepatocarcinogenesis in patients with FLD.
Laboratory practices for manual blood film review: Results of an IQMH patterns of practice survey
Authors: Leung Elaine , Johnston Anna , Olsen Brian , Chang Hong , Martin Tracy , Wozniak Miranda , Good David 
Published: September 2020

AbstractIntroductionExamination of a blood film is the second most common hematology test, after the complete blood count. Interpretation of a peripheral blood film by trained laboratory professionals provides valuable diagnostic information. The Institute for Quality Management in Healthcare (IQMH) Hematology Scientific Committee developed a questionnaire to gather information regarding current practices for manual blood film review and reporting from laboratories participating in IQMH Morphology proficiency testing (PT) surveys.MethodsAn online survey was distributed to 174 laboratories, 97% submitted results.ResultsOf the respondents, the majority (82%) indicated affiliation with small‐ or medium‐sized hospitals (<500 beds). 80% of respondents had core laboratory technologists performing manual blood film reviews, while only 2% utilized dedicated hematology technologists with morphology expertise. All respondents had a policy for manual blood film review by a technologist, 70% did not have blood films reviewed by a senior/charge technologist prior to review by a physician. The majority (88%) of participants included morphological findings in their critical result list; of these, 98% include malaria and 88% include the first‐time finding of blasts as critical results. 59% of participants indicated that they have a procedure in place to ensure that interpretation and confirmation of first‐time potentially significant morphological findings are available from a physician at all times.ConclusionThis survey identified significant variation in blood film review and reporting practices across participating laboratories. The IQMH Hematology Scientific Committee will develop best practice recommendations to guide and standardize practice.
Integrating Bottom‐up into Top‐down: The Role of Local Actors in Labour Market Integration of Syrian Refugees in Turkey
Authors: Siviş Selin 
Published: September 2020

AbstractAs Turkey has become one of the leading receiving countries for asylum seekers and refugees, not only new legislative initiatives regarding the legal status of Syrians, but also immigration policies have moved to the forefront of Turkey’s agenda. In parallel with recent developments, the new Regulation on Work Permits for People under Temporary Protection was enacted in 2016. Among the 3,5 million, almost half of Syrian refugees residing in Turkey are of working age population, yet the majority have been engaged in the informal labour market. We know little about how this permit to work takes effect at the local level. Drawing on structured interviews with local actors in Adana, this article shows that the absence of an integration policy drives local actors to engage in the formulation of their own integration approach, what I call “integration work”, which results in varying degrees of collaboration within the same province.
From functions to mechanisms of the prototypic complement C5 antibody BB5.1
Authors: Milling Simon 
Published: September 2020

SummaryAntibodies that bind complement components were first identified over 30 years ago. Investigations into their functions in animal models motivated clinical studies that have now generated licensed products and a strong pipeline of future therapeutics. Despite this, the mechanisms of action of one of the first effective C5‐binding antibodies, BB5.1, were not known. Here, we report a new study that reveals these mechanisms, enabling new approaches for designing C5‐binding molecules for therapeutic use.
Mealtime support for adults with intellectual disabilities: Understanding an everyday activity
Authors: Redley Marcus 
Published: September 2020

AbstractBackgroundMealtime support has a direct bearing on the diet‐related health of men and women with intellectual disabilities as well as opportunities for expressing dietary preferences.MethodSemi‐structured interviews with a sample of direct support staff providing mealtime support to adults with intellectual disabilities.ResultsWhen managing tensions between a person's dietary preferences and ensuring safe and adequate nutrition and hydration, direct support staff are sensitive to a wide range of factors. These include the following: clinical advice; service users’ rights to choose; their (in)capacity to weigh up risks; how service users communicate; the constituents of a healthy diet; and a duty to protect service users' health.ConclusionsThose responsible for setting standards and regulating the care practices need to look beyond too simple ideas of choice and safety to recognize ways in which providing support at mealtimes is a complex activity with serious consequences for people's health and well‐being.