bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged maternal separation alters neurogenesis and synaptogenesis in postnatal dentate gyrus of mice
Authors: Zhang Qianru , Liu Feng , Yan Wenyong , Wu Yongji , Wang Mengli , Wei Jingjing , Wang Shuzhong , Zhu Xiaoyan , Chai Xuejun , Zhao Shanting 
Published: August 2020

AbstractObjectivesAs a common model for adverse early experience and depression, maternal separation (MS) is always used to investigate the psychological disease. Despite extensive and strong evidence verified the depression‐like state induced by MS, little is known about the specific mechanism of MS. Therefore, the present study aimed to investigate the neurobiology mechanism of the MS‐induced depression‐like state.MethodsTo verify the depression‐like behaviors of offspring induced by MS, a series of behavioral tests were performed. Then, in vivo electroporation and three‐dimensional reconstruction, combining with immunohistochemistry and BrdU labeling, were mainly used to explore the neurogenesis and synaptogenesis in postnatal dentate gyrus.ResultsProlonged MS indeed induced the depression‐like behaviors of offspring in adulthood. Surprisingly, learning and memory were enhanced by prolonged MS. Further investigation indicated that prolonged MS inhibited the proliferation of neural stem cells, impaired the survival, and altered the fate decision of newborn cells, whereas the total length and terminal tips of dendrite, and the spine density, especially thin spine, were significantly increased in prolonged MS mice.ConclusionsOur results elucidated that prolonged MS induced the depression‐like state by impairing postnatal neurogenesis of dentate gyrus. Importantly, our results emphasized that prolonged MS increased the spine density, especially thin spine, by increasing the total length and number of terminal tips of dendrite, thereby enhancing learning and memory.
Public reasoning about voluntary assisted dying: An analysis of submissions to the Queensland Parliament, Australia
Authors: Kirchhoffer David G. , Lui Chi‐Wai 
Published: August 2020

AbstractThe use of voluntary assisted dying as an end‐of‐life option has stimulated concerns and debates over the past decades. Although public attitudes towards voluntary assisted dying (including euthanasia and physician‐assisted suicide) are well researched, there has been relatively little study of the different reasons, normative reasoning and rhetorical strategies that people invoke in supporting or contesting voluntary assisted dying in everyday life. Using a mix of computational textual mining techniques, keyword study and qualitative thematic coding to analyse public submissions to a parliamentary inquiry into voluntary assisted dying in Australia, this study critically examines the different reasons, normative reasoning and rhetorical strategies that people invoke in supporting or contesting voluntary assisted dying in everyday life. The analysis identified complex and potentially contradictory ethical principles being invoked on both sides of the debate. These findings deepen our understanding of the moral basis of public reasoning about end‐of‐life matters and will help to inform future discussions on policy and law reform. The findings underscore the importance of sound normative reasoning and the use of caution when interpreting opinion polls to inform policy.
Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer’s disease and other tauopathies
Authors: Abey Ajantha , Davies Danielle , Goldsbury Claire , Buckland Michael , Valenzuela Michael , Duncan Thomas 
Published: August 2020

AbstractSome aged community dogs acquire a degenerative syndrome termed Canine Cognitive Dysfunction (CCD) that resembles human dementia because of Alzheimer’s Disease (AD), with comparable cognitive and behavioral deficits. Dogs also have similar neuroanatomy, share our domestic environment and develop amyloid‐β plaques, making them likely a valuable ecological model of AD. However, prior investigations have demonstrated a lack of neurofibrillary tau pathology in aged dogs, an important hallmark of AD, though elevated phosphorylated tau (p‐tau) at the Serine 396 (S396) epitope has been reported in CCD. Here using enhanced immunohistochemical methods, we investigated p‐tau in six CCD brains and six controls using the AT8 antibody (later stage neurofibrillary pathology), and an antibody against S396 p‐tau (earlier stage tau dysfunction). For the first time, we systematically assessed the Papez circuit and regions associated with Braak staging and found that all CCD dogs displayed elevated S396 p‐tau labeling throughout the circuit. The limbic thalamus was particularly implicated, with a similar labeling pattern to that reported for AD neurofibrillary pathology, especially the anterior nuclei, while the hippocampus exhibited dysfunction confined to synaptic layers and efferent pathways. The cingulate and temporal lobes displayed significantly greater tauopathy than the frontal and occipital cortices, also reflective of early Braak staging patterns in AD. Immunofluorescence confirmed that S396 was accumulating within neuronal axons, somata and oligodendrocytes. We also observed AT8 labeling in one CCD brain, near the transentorhinal cortex in layer II neurons, one of the first regions to be affected in AD. Together, these data demonstrate a concordance in regional distribution of tauopathy between CCD and AD, most evident in the limbic thalamus, an important step in further validating CCD as a translational model for human AD and understanding early AD pathogenic mechanisms.
Immunogenic chemotherapy in two mouse colon cancer models
Authors: Taniura Takahito , Iida Yuichi , Kotani Hitoshi , Ishitobi Kazunari , Tajima Yoshitsugu , Harada Mamoru 
Published: August 2020

AbstractAside from the induction of cell death, some anticancer chemotherapeutic drugs can modulate antitumor immune responses. In this study, we examined the anticancer effects of 5‐fluorouracil (5‐FU) and oxaliplatin (L‐OHP), which are standard chemotherapeutic drugs for colon cancer, combined with cyclophosphamide (CP) in two mouse colon cancer models (CT26 and MC38 colon adenocarcinoma models). In the CT26 model, two injections of 5‐FU/L‐OHP and CP significantly suppressed the growth of subcutaneously established CT26 tumors compared with either 5‐FU/L‐OHP or CP, without a significant loss of body weight. The anticancer effect was weakened in nude mice. Cured mice acquired protective immunity against CT26, and CT26‐specific cytotoxic T cells (CTLs) were induced from their spleen cells. Analysis of tumor‐infiltrating immune cells revealed that 5‐FU/L‐OHP treatment with or without CP increased the proportion of CD8+ T cells at tumor sites. The 5‐FU/L‐OHP treatment decreased the proportion of granulocytic myeloid‐derived suppressor cells (MDSCs) and increased monocytic MDSCs in tumor sites, whereas the addition of CP treatment reversed these changes. In the MC38 model, although significant anticancer effects of the triple combination therapy were seen, additional treatment with anti‐PD‐1 antibody increased the number of cured mice. These mice exhibited protective immunity against MC38, and MC38‐specific CTLs were generated from their spleen cells. Together, these results indicate that the antitumor effects of the combination of 5‐FU/L‐OHP and CP mainly depend on host T cells; moreover, the therapeutic efficacy can be effectively boosted by immune checkpoint blockade.
Characterisation of a novel peptide, Brevinin‐1H, from the skin secretion of Amolops hainanensis and rational design of several analogues
Authors: Pei Xinjie , Gong Zijian , Wu Qing , Chen Xiaoling , Wang Lei , Ma Chengbang , Xi Xinping , Chen Tianbao , Shaw Chris , Zhou Mei 
Published: August 2020

AbstractAs drug‐resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin‐1H, was identified in the skin secretion of Amolops hainanensis through ‘shotgun’ cloning. It has broad‐spectrum antimicrobial activity against tested micro‐organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues—Brevinin‐1Ha and Brevinin‐1HY—were designed based on the secondary structure of the natural peptide. Brevinin‐1HY, in which tyrosine substituted Pro11, had similar activity to the natural peptide against Gram‐negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin‐1Ha, which transferred the Rana‐box from the C‐terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α‐helix structure in an AMP can increase its target micro‐organism bioactivity to some extent.
Preschoolers’ Motivation to Over‐Imitate Humans and Robots
Authors: Schleihauf Hanna , Hoehl Stefanie , Tsvetkova Neli , König Alexander , Mombaur Katja , Pauen Sabina 
Published: August 2020

From preschool age, humans tend to imitate causally irrelevant actions—they over‐imitate. This study investigated whether children over‐imitate even when they know a more efficient task solution and whether they imitate irrelevant actions equally from a human compared to a robot model. Five‐to‐six‐year‐olds (N = 107) watched either a robot or human retrieve a reward from a puzzle box. First a model demonstrated an inefficient (Trial 1), then an efficient (Trial 2), then again the inefficient strategy (Trial 3). Subsequent to each demonstration, children copied whichever strategy had been demonstrated regardless of whether the model was a human or a robot. Results indicate that over‐imitation can be socially motivated, and that humanoid robots and humans are equally likely to elicit this behavior.
ASAH1‐related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype
Authors: Mahmoud Iman G. , Elmonem Mohamed A. , Zaki Maha S. , Ramadan Areef , Al‐Menabawy Nihal M. , El‐Gamal Aya , Mansour Lobna , Issa Mahmoud Y. , Abdel‐Hamid Mohamed S. , Abdel‐Hady Sawsan , Khalifa Iman , Ibrahim Ahmed , Solyom Alexander , Rolfs Arndt , Selim Laila 
Published: August 2020

AbstractAcid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA‐PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26‐Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA‐PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon‐5‐deletion). Both total C26‐Ceramide and its trans‐ isomer showed 100% sensitivity for the detection of ASAH1‐related disorders in tested patients. A 10‐year‐old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1‐related disorders and validated the biomarker C26‐Ceramide for supporting diagnosis in symptomatic patients.
Effects of the Argentine ant venom on terrestrial amphibians
Authors: Alvarez‐Blanco Paloma , Cerdá Xim , Hefetz Abraham , Boulay Raphaël , Bertó‐Moran Alejandro , Díaz‐Paniagua Carmen , Lenoir Alain , Billen Johan , Liedtke H. Christoph , Chauhan Kamlesh R. , Bhagavathy Ganga , Angulo Elena 
Published: August 2020

AbstractInvasive species have major impacts on biodiversity and are one of the primary causes of amphibian decline and extinction. Unlike other top ant invaders that negatively affect larger fauna via chemical defensive compounds, the Argentine ant (Linepithema humile) does not have a functional sting. Nonetheless, it deploys defensive compounds against competitors and adversaries. We estimated levels of ant aggression toward 3 native terrestrial amphibians by challenging juveniles in field ant trails and in lab ant foraging arenas. We measured the composition and quantities of toxin in L. humile by analyzing pygidial glands and whole‐body contents. We examined the mechanisms of toxicity in juvenile amphibians by quantifying the toxin in amphibian tissues, searching for histological damages, and calculating toxic doses for each amphibian species. To determine the potential scope of the threat to amphibians, we used global databases to estimate the number, ranges, and conservation status of terrestrial amphibian species with ranges that overlap those of L. humile. Juvenile amphibians co‐occurring spatially and temporally with L. humile die when they encounter L. humile on an ant trail. In the lab, when a juvenile amphibian came in contact with L. humile the ants reacted quickly to spray pygidial‐gland venom onto the juveniles. Iridomyrmecin was the toxic compound in the spray. Following absorption, it accumulated in brain, kidney, and liver tissue. Toxic dose for amphibian was species dependent. Worldwide, an estimated 817 terrestrial amphibian species overlap in range with L. humile, and 6.2% of them are classified as threatened. Our findings highlight the high potential of L. humile venom to negatively affect amphibian juveniles and provide a basis for exploring the largely overlooked impacts this ant has in its wide invasive range.
Acute stress disrupts intestinal homeostasis via GDNF‐RET
Authors: Lin Lin , Feng Bingcheng , Zhou Ruchen , Liu Yi , Li Lixiang , Wang Kairuo , Yu Yanbo , Liu Chao , Long Xin , Gu Xiang , Li Bing , Wang Xiaojie , Yang Xiaoyun , Cong Yingzi , Zuo Xiuli , Li Yanqing 
Published: August 2020

AbstractObjectivesEnterochromaffin (EC) cells have been associated with functional gastrointestinal disorders such as IBS. Recently, we found that glial cell‐derived neurotrophic factor (GDNF)‐rearranged during transfection (RET) localized in EC cells in human colonic epithelia. Here, we examine the role of GDNF‐RET in the pathophysiology of diarrhoea‐predominant irritable bowel syndrome (IBS‐D).Materials and MethodsGDNF was assessed by ELISA and immunohistochemistry in biopsies from IBS‐D patients and healthy controls. Stress was induced by using a wrap‐restraint stress (WRS) procedure to serve as an acute stress‐induced IBS model. The function of GDNF‐RET axis to intestinal stem cell (ISC) homeostasis, and EC cell numbers were assessed in vivo and in vitro.ResultsGDNF‐RET was expressed in EC cells in human colon. GDNF was significantly increased in IBS‐D patients. WRS mice showed increased GDNF‐RET levels in colon. WRS induced visceral hypersensitivity by expanding of ISC and differentiation of EC cell via GDNF‐RET. Furthermore, GDNF‐treated mice recapitulated the phenotype of WRS mice. In vitro, GDNF treatment amplified Wnt signal and increased serotonin levels in colonic organoids in a dose‐dependent manner.ConclusionsWe identified GDNF‐RET was presented in colonic epithelium of patients with IBS‐D. GDNF‐RET played important roles in regulating ISC and EC cell differentiation. Our findings, thus, provide RET inhibitor as new therapeutic targets for treatment of patients with IBS‐D.
Articulating Christian doctrine in the pluralistic world of the twenty‐first century
Authors: Persaud Winston Dwarka 
Published: August 2020

AbstractThe reviewer offers an appreciative theological summary of Veli‐Matti Kärkkäinen's monumental text, Christian Theology in the Pluralistic World: A Global Introduction. Persaud calls attention to the trinitariancentre of Kärkkäinen's theological articulation, which is the basis for Kärkkäinen's openness to finding and naming commonalities and differences between biblical, creedal, confessional Christianity and each of the two other Abrahamic faiths (Judaism and Islam) and two Asiatic faiths (Hinduism and Buddhism). The reviewer calls for further engagement with the Joint Declaration on the Doctrine of Justification (31 October 1999), in relation to the pressing question of religious conversion in today's pluralistic world.
Diabetes management during cardiac surgery in the UK: A survey
Authors: Luthra S. , Salhiyyah K. , Dritsakis G. , Thorne K. I. , Dixon E. , Ohri S. , Holt R. I. G. ,   the OCTOPuS study group
Published: August 2020

AbstractAimTo determine current practice regarding the diabetes management of people undergoing cardiac surgery in the UK.MethodsWe conducted an online survey of UK cardiothoracic surgeons. All cardiothoracic surgeons listed in the Society of Cardiothoracic Surgery membership directory were invited to participate. The survey, compiled using SurveyMonkey software, comprised 15 closed and open‐ended questions about the management of people with diabetes pre‐ and peri‐operatively.ResultsSixty‐two cardiothoracic surgeons from all 33 UK cardiac centres completed the survey. Of these, 44% responded that they routinely measure HbA1c preoperatively for all patients, 19% had an HbA1c threshold above which they would not operate and 21% currently undertake a point‐of‐care HbA1c measurement during the cardiothoracic outpatient visit. A total of 74% of respondents reported that it was ‘easy’ or ‘very easy’ to obtain a diabetes team review; diabetes nurse specialists were the members of the diabetes team working most closely with cardiac surgeons. Up to a third of the surgeons did not provide physical activity recommendations prior to admission and over 80% did not have a different preoperative or surgical diabetes protocol. Inconsistency in the responses within centres suggests that differences in practice may depend on individual surgeons rather than local policy.ConclusionsThe study demonstrates there is only limited peri‐operative management of diabetes in people undergoing cardiac surgery in the UK. There is an opportunity for greater involvement of the diabetes specialist team both before and during admission for surgery to improve outcomes.(Trial registration: ISRCTN10170306)
The dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes
Authors: Wilson Jonathan M. , Nikooienejad Amir , Robins Deborah A. , Roell William C. , Riesmeyer Jeffrey S. , Haupt Axel , Duffin Kevin L. , Taskinen Marja‐Riitta , Ruotolo Giacomo 
Published: August 2020

AbstractAimTo better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein‐related biomarkers were measured post hoc in available samples from the same study.Materials and MethodsPatients were randomized to receive once‐weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A‐I, B and C‐III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated.ResultsAt 26 weeks, tirzepatide dose‐dependently decreased apoB and apoC‐III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride‐rich lipoprotein particles (TRLP), small low‐density lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC‐III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC‐III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC‐III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability.ConclusionsTirzepatide treatment dose‐dependently decreased levels of apoC‐III and apoB and the number of large TRLP and small LDLP, suggesting a net improvement in atherogenic lipoprotein profile.
Effect of once‐weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial
Authors: van der Aart‐van der Beek Annemarie B. , Clegg Lindsay E. , Penland Robert C. , Boulton David W. , Sjöström C. David , Mentz Robert J. , Holman Rury R. , Heerspink Hiddo J. L. 
Published: August 2020

AbstractThe effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP‐1RAs may confer clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once‐weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin:creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23.7%) with eGFR data available and 2828 participants (19.2%) with UACR change data available. EQW improved eGFR slope assessed via mixed model repeated measures, compared with placebo, in participants with baseline UACR >100 mg/g (0.79 mL/min/1.73 m2/year [95% confidence interval {CI} 0.24–1.34]) and UACR >200 mg/g (1.32 mL/min/1.73 m2/year [95% CI 0.57–2.06]), but not at lower UACR thresholds. EQW reduced UACR, compared with placebo, assessed via analysis of covariance, consistently across subgroups with baseline UACR >30 mg/g (28.2% reduction), baseline UACR >100 mg (22.5% reduction) and baseline UACR >200 mg (34.5% reduction). This post hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.
The effect of soy and whole milk as a means to store avulsed teeth: A histometric study
Authors: Côvre Luiza Monzoli , Caliente Eliana Aparecida , Sonoda Celso Koogi , Brandini Daniela Atili , Poi Wilson Roberto 
Published: August 2020

AbstractBackground/AimAn adequate storage medium can help preserve the viability of periodontal ligament cells, favoring the periodontal ligament repair process. The aim of this study was to evaluate the repair process following the delayed replantation of teeth stored in soy milk and whole milk.Material and MethodsThe maxillary right incisors of 27 rats were divided into three equally sized groups: Group SM (delayed replantation with storage in soy milk), whose teeth were immersed in 50 mL of soy milk for 60 minutes; Group WM (delayed replantation with whole milk), teeth were kept for 60 minutes in 50 mL of whole milk; and Group D (delayed replantation with dry storage), teeth were kept in dry conditions for the same period (negative control). Next, the teeth of the animals of all groups were replanted into their sockets. Systemic antibiotics were given to all the animals, and then, they were euthanized after 60 days. Sections were obtained and stained with hematoxylin and eosin for histomorphometric study. The presence and location of acute and chronic inflammatory processes in the epithelial insertion of the protective and insertion periodontium were evaluated, as well as the presence, extension, depth, and repair of root resorption, and the resorption and ankylosis with bone. Statistical differences between groups were analyzed using the Dunn test.ResultsGroups SM and WM showed similar patterns in the repair of the periodontal ligament following delayed replantation, in relation to the inflammatory process in the proximities of the epithelial insertion, inflammation and organization of the periodontal ligament, plus root and bone resorption. However, in group WM, more ankylosis was observed than in group SM.ConclusionThe teeth stored in soy milk and whole milk had similar periodontal repair, which shows the potential of soy milk as a storage medium before tooth replantation.