bluuebunny/crossref_metadata_2025 huggingface dataset:
Mirid feeding preference as influenced by light and temperature‐mediated changes in plant nutrient concentration in cocoa
Authors: Awudzi Godfred K. , Hadley Paul , Hatcher Paul E. , Daymond Andrew J.
Published: August 2020

Cocoa mirids are the most important insect pests of cocoa in West Africa. This study investigated the effect of environmental parameters that are modulated by overhead shade, that is, light intensity and temperature, on nutrient and phenolic concentrations in cocoa and their subsequent effect on mirid feeding. Eight‐month‐old cocoa seedlings were maintained for 50 days in two growth chambers set to day temperatures of 25 or 30°C. Each chamber had sections with different light intensities (541, 365 and 181 μmol m−2 s−1 photosynthetically active radiation [PAR]). For the field studies at Akim Tafo in Ghana, 8‐month‐old plants of three cocoa clones were subjected to shaded (PAR = 180 μmol m−2 s−1, between 11:00 a.m. and 12:00 p.m.) and unshaded (PAR = 1,767 μmol m−2 s−1, between 11:00 a.m. and 12:00 p.m.) treatments for 50 days after which nutrient measurements and mirid choice tests were carried out. No significant effect of environment was observed on the phenolic concentration of stems under controlled environment chamber conditions. However, in the field, the phenolic concentration of stems was significantly greater for unshaded compared with shaded plants (p = .04). Under controlled conditions, the leaf nitrogen concentration increased slightly with light intensity (p = .003). The same trend was seen in stems but only at 30°C. In the field, the impact of overhead shade on nitrogen varied between cocoa clones. The concentration of carbohydrates in both leaves and stems in the field was higher under unshaded conditions. When subjected to feeding tests, stems from unshaded cocoa had significantly more mirid feeding lesions (p = .003) after 24 hr exposure to mirids compared to shaded cocoa. Mirid feeding therefore appears not to be deterred by the higher phenolic levels but rather there was a preference for cocoa tissue grown under unshaded conditions. These findings highlight the need to consider the growing environment of cocoa clones when screening for varieties with resistance to mirids.
Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue
Authors: Hall Brandon M. , Gleiberman Anatoli S. , Strom Evguenia , Krasnov Peter A. , Frescas David , Vujcic Slavoljub , Leontieva Olga V. , Antoch Marina P. , Kogan Valeria , Koman Igor E. , Zhu Yi , Tchkonia Tamara , Kirkland James L. , Chernova Olga B. , Gudkov Andrei V.
Published: August 2020

Adipose tissue is recognized as a major source of systemic inflammation with age, driving age‐related tissue dysfunction and pathogenesis. Macrophages (Mφ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA‐seq analysis of ATMs from young (8‐week‐old) and healthy aged (80‐week‐old) mice. One of the genes identified, V‐set immunoglobulin‐domain‐containing 4 (VSIG4/CRIg), encodes a Mφ‐associated complement receptor and B7 family‐related immune checkpoint protein. Here, we demonstrate that Vsig4 expression is highly upregulated with age in perigonadal white adipose tissue (gWAT) in two mouse strains (inbred C57BL/6J and outbred NIH Swiss) independent of gender. The accumulation of VSIG4 was mainly attributed to a fourfold increase in the proportion of VSIG4+ ATMs (13%–52%). In a longitudinal study, VSIG4 expression in gWAT showed a strong correlation with age within a cohort of male and female mice and correlated strongly with physiological frailty index (PFI, a multi‐parameter assessment of health) in male mice. Our results indicate that VSIG4 is a novel biomarker of aged murine ATMs. VSIG4 expression was also found to be elevated in other aging tissues (e.g., thymus) and was strongly induced in tumor‐adjacent stroma in cases of spontaneous and xenograft lung cancer models. VSIG4 expression was recently associated with cancer and several inflammatory diseases with diagnostic and prognostic potential in both mice and humans. Further investigation is required to determine whether VSIG4‐positive Mφ contribute to immunosenescence and/or systemic age‐related deficits.
Validating Self‐Reported Unhealthy Alcohol Use With Phosphatidylethanol (PEth) Among Patients With HIV
Authors: Eyawo Oghenowede , Deng Yanhong , Dziura James , Justice Amy C. , McGinnis Kathleen , Tate Janet P. , Rodriguez‐Barradas Maria C. , Hansen Nathan B. , Maisto Stephen A. , Marconi Vincent C. , O’Connor Patrick G. , Bryant Kendall , Fiellin David A. , Edelman E. Jennifer
Published: August 2020

Background

We sought to compare self‐reported alcohol consumption using Timeline Followback (TLFB) to biomarker‐based evidence of significant alcohol use (phosphatidylethanol [PEth] > 20 ng/ml). Using data from patients with HIV (PWH) entering a clinical trial, we asked whether TLFB could predict PEth > 20 ng/ml and assessed the magnitude of association between TLFB and PEth level.

Methods

We defined unhealthy alcohol use as any alcohol use in the presence of liver disease, at‐risk drinking, or alcohol use disorder. Self‐reported alcohol use obtained from TLFB interview was assessed as mean number of drinks/day and number of heavy drinking days over the past 21 days. Dried blood spot samples for PEth were collected at the interview. We used logistic regression to predict PEth > 20 ng/ml and Spearman correlation to quantify the association with PEth, both as a function of TLFB.

Results

Among 282 individuals (99% men) in the analytic sample, approximately two‐thirds (69%) of individuals had PEth > 20 ng/ml. The proportion with PEth > 20 ng/ml increased with increasing levels of self‐reported alcohol use; of the 190 patients with either at‐risk drinking or alcohol use disorder based on self‐report, 82% had PEth > 20 ng/ml. Discrimination was better with number of drinks per day than heavy drinking days (AUC: 0.80 [95% CI: 0.74 to 0.85] vs. 0.74 [95% CI: 0.68 to 0.80]). The number of drinks per day and PEth were significantly and positively correlated across all levels of alcohol use (Spearman’s R ranged from 0.29 to 0.56, all p values < 0.01).

Conclusions

In this sample of PWH entering a clinical trial, mean numbers of drinks per day discriminated individuals with evidence of significant alcohol use by PEth. PEth complements self‐report to improve identification of self‐reported unhealthy alcohol use among PWH.
Political embeddedness and firms’ choices of earnings management strategies in China
Authors: Wang Zhi , Braam Geert , Reimsbach Daniel , Wang Jiaxin
Published: August 2020

We examine whether and how political embeddedness influences financial reporting quality in China by investigating how government ownership and political connections affect Chinese listed firms’ choices of earnings management strategies. The results show that state‐owned enterprises (SOEs), and in particular, central SOEs, are more likely to substitute accrual‐based earnings management strategies with costlier but less detectable real earnings management strategies than non‐SOEs. The results also indicate that politically connected enterprises (PCEs) are more likely to employ less detectable real earnings management strategies than non‐PCEs, so much so that PCEs’ total earnings management level is higher than that of non‐PCEs.
Osteology and radiology of the vertebral column in the white‐eared opossum (Didelphis albiventris)
Authors: Inamassu Letícia Rocha , Schimming Bruno Cesar , Dadalto Carmel Rezende , Mamprim Maria Jaqueline
Published: August 2020

The white‐eared opossum present a higher roadkill number in Brazil, and the vertebral column is often affected when some type of trauma occurs. Thus, this study describes the osteology and radiology of the vertebral column in white‐eared opossum to serve as a basis for support in the veterinary clinical care, since the casuistry of care of this marsupial has increased every year. Radiographs of the cervical (C), thoracic (T), lumbar (L), sacral (S) and caudal (Cd) segments of the vertebral column were taken in thirty‐five white‐eared opossums (Didelphis albiventris). Furthermore, ten opossums without evident vertebral acquired or congenital abnormalities at the radiographic study were selected for anatomical study. Osteology was correlated with the radiographic images. The use of radiographs allowed the identification of congenital and acquired vertebral changes, as well as the identification of anatomical structures, their distribution and morphology and the number of vertebrae. The vertebral formula varied in the white‐eared opossum. In 27 of 35 white‐eared opossums (77.2%) with normal vertebral morphology, three vertebral formulas were observed: C7/T13/L6/S2 (62.9%), C7/T13/L5/S2 (5.7%) and C7/T13/L7/S2 (8.6%). Most of the specimens presented 27 caudal vertebrae. The anticlinal vertebra was identified as T10 in 77.2% and T11 in 22.8% of opossums. Cervical block vertebra was observed in two animals and sacrocaudal block vertebra in one animal. The haemal arches could be seen from Cd3–Cd4 in 80% and Cd2–Cd3 in 20% of opossums. The white‐eared opossum showed a slender vertebral column with a relatively short thoracic region, a relatively long lumbar region and a highly flexible lumbosacral transition, suggesting that this animal is a fast‐running and agile opossum. Therefore, these findings may serve as a basis for further research and support the veterinary clinical care, since the casuistry of care for this marsupial has increased every year.
Logit Mixed Logit Under Asymmetry and Multimodality of WTP: A Monte Carlo Evaluation
Authors: Scarpa Riccardo , Franceschinis Cristiano , Thiene Mara
Published: August 2020

The logit‐mixed logit (LML) model advances choice modeling by generalizing previous parametric and semi‐nonparametric specifications and allowing retrieval of flexible taste distributions. Using standard operating conditions in the field, we report results from Monte Carlo experiments designed to assess the finite sample bias‐variance tradeoff for the LML using as a benchmark conventional Mixed logit models (MXL) under asymmetric and multimodal taste distributions. The LML specification always outperforms the MXL in terms of bias, but when the variance around modes is high the mean squared error (MSE) is lower than that of MXL only at sample sizes larger than usual and with some nuances. D‐error minimizing experimental design predicated on multinomial logit significantly reduces MSE, but no clear winner is found between polynomial, step, and spline functions for the multidimensional grid function. Analysis of empirical data from a choice experiment on tap water shows that multimodality emerges only if higher number of node parameters are used in the LML.
Decision‐making in home care package spending
Authors: Rowland Diane , Joyce Catherine M.
Published: August 2020

Objective

To understand the motivations and drivers of spending decisions made by home care package recipients, in the context of high levels of unspent funds.

Methods

Qualitative study using 30 semi‐structured interviews with 38 home care package clients and/or client representatives in rural and urban Victoria conducted between December 2018 and March 2019. Interview transcripts were analysed to determine themes.

Results

Spending decisions were influenced by assessment and entry experiences, knowledge and understanding of package funds, availability and acceptability of services, and attitudes to spending.

Conclusion

Clients need confidence in their individual funds and their use in order to maximise the potential benefits. Clear, consistent communication at all stages, and additional supports to build consumer capability, will enable clients to better understand packages and their application. This in turn will optimise the capacity of home care package recipients to maximise their health and well‐being.
Exploring novel systemic biomarker approaches in grass‐pollen sublingual immunotherapy using omics
Authors: Barker‐Tejeda Tomas Clive , Bazire Raphaelle , Obeso David , Mera‐Berriatua Leticia , Rosace Domenico , Vazquez‐Cortes Sonia , Ramos Tania , Rico Maria del Pilar , Chivato Tomás , Barbas Coral , Villaseñor Alma , Escribese Maria M. , Fernández‐Rivas Montserrat , Blanco Carlos , Barber Domingo
Published: August 2020

Background

Sublingual allergen‐specific immunotherapy (SLIT) intervention improves the control of grass pollen allergy by maintaining allergen tolerance after cessation. Despite its widespread use, little is known about systemic effects and kinetics associated to SLIT, as well as the influence of the patient sensitization phenotype (Mono‐ or Poly‐sensitized). In this quest, omics sciences could help to gain new insights to understand SLIT effects.

Methods

47 grass‐pollen‐allergic patients were enrolled in a double‐blind, placebo‐controlled, multicenter trial using GRAZAX® during 2 years. Immunological assays (sIgE, sIgG4, and ISAC) were carried out to 31 patients who finished the trial. Additionally, serum and PBMCs samples were analyzed by metabolomics and transcriptomics, respectively. Based on their sensitization level, 22 patients were allocated in Mono‐ or Poly‐sensitized groups, excluding patients allergic to epithelia. Individuals were compared based on their treatment (Active/Placebo) and sensitization level (Mono/Poly).

Results

Kinetics of serological changes agreed with those previously described. At two years of SLIT, there are scarce systemic changes that could be associated to improvement in systemic inflammation. Poly‐sensitized patients presented a higher inflammation at inclusion, while Mono‐sensitized patients presented a reduced activity of mast cells and phagocytes as an effect of the treatment.

Conclusions

The most relevant systemic change detected after two years of SLIT was the desensitization of effector cells, which was only detected in Mono‐sensitized patients. This change may be related to the clinical improvement, as previously reported, and, together with the other results, may explain why clinical effect is lost if SLIT is discontinued at this point.
Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort
Authors: Amazouz Hélène , de Lauzon‐Guillain Blandine , Bourgoin‐Heck Mélisande , Just Jocelyne , Beydon Nicole , Lezmi Guillaume , Rancière Fanny , Momas Isabelle
Published: August 2020

Background

As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort.

Methods

Data on breastfeeding, consumption of infant formula (regular, pre‐/probiotics, partially hydrolysed with hypoallergenic label [pHF‐HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding‐related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy.

Results

Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre‐/probiotics for Cluster 3 [17%], pHF‐HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1, FVC), higher FeNO and higher risk of sensitization at 8 years.

Conclusion

Early pHF‐HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.
Impact of short‐acting vs. standard anaesthetic agents on obstructive sleep apnoea: a randomised, controlled, triple‐blind trial
Authors: Albrecht E. , Bayon V. , Hirotsu C. , Heinzer R.
Published: August 2020

Sleep apnoea is associated with negative outcomes following general anaesthesia. Current recommendations suggest using short‐acting anaesthetic agents in preference to standard agents to reduce this risk, but there is currently no evidence to support this. This randomised controlled triple‐blind trial tested the hypothesis that a combination of short‐acting agents (desflurane‐remifentanil) would reduce the postoperative impact of general anaesthesia on sleep apnoea severity compared with standard agents (sevoflurane‐fentanyl). Sixty patients undergoing hip arthroplasty under general anaesthesia were randomised to anaesthesia with desflurane‐remifentanil or sevoflurane‐fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnoea‐hypopnoea index on the first postoperative night. Secondary outcomes were the supine apnoea‐hypopnoea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3. Pre‐operative sleep study data were similar between groups. Mean (95%CI) values for the supine apnoea‐hypopnoea index on the first postoperative night were 18.9 (12.7–25.0) and 21.4 (14.2–28.7) events.h−1, respectively, in the short‐acting and standard anaesthesia groups (p = 0.64). Corresponding values on the third postoperative night were 28.1 (15.8–40.3) and 38.0 (18.3–57.6) events.h−1 (p = 0.34). Secondary sleep‐ and pain‐related outcomes were generally similar in the two groups. In conclusion, short‐acting anaesthetic agents did not reduce the impact of general anaesthesia on sleep apnoea severity compared with standard agents. These data should prompt an update of current recommendations.
The Second Coming of Rail: The Spanish High‐Speed Rail‐Finance Complex
Authors: Buier Natalia
Published: August 2020

This article offers a critical account of Spanish high‐speed rail (HSR) through the lens of the spatial fix. I designate the integration of Spanish HSR into a European‐wide process of circulation of finance capital as the HSR‐finance complex. The analysis of the inner workings of the HSR‐finance complex reveals the way in which European finance has laid the conditions of possibility for the development of the project and offers a forewarning about the dangers of leveraging finance capital toward green infrastructure. The analysis of the Spanish HSR‐finance complex shows that the particular form of capital circulation that has made it possible has not brought about new productive combinations but has instead deepened traditional relations of economic dependency and magnified their socioenvironmental consequences.
Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long‐term outcomes
Authors: Kelaidi Charikleia , Makis Alexandros , Tzotzola Vasiliki , Antoniadi Kondylia , Petrikkos Loizos , Tsitsikas Konstantinos , Peristeri Ioulia , Kitra Vasiliki , Stefanaki Kalliopi , Polychronopoulou Sophia
Published: August 2020

Aim

To assess very long‐term outcomes of children with severe aplastic anaemia (SAA) and impact of histopathology and of different treatments over time.

Methods

We conducted a retrospective study of 57 consecutive patients with SAA during 1973‐2019. According to period, treatment consisted of androgens, immunosuppressive treatment (IST) and haematopoietic cell transplantation (HCT) in 14, 31 and 13 patients, respectively. Histopathology immune profiles were studied on bone marrow (BM).

Results

Response rate (RR) to androgens was 35%, with long‐term survivorship in 4 of 5 responders. RR and 10‐year overall survival (OS) after IST was 65% and 80%, respectively. RR was higher in girls (92% vs 43% in boys,P = .02). Mean baseline BM values of CD34 + and of B‐lymphocytes in responders vs non‐responders were 1.3% vs 0 (P = .08) and 14.1% vs 9.7% (P = .07), respectively. After IST, BM cellularity gradually increased and cytotoxic T‐lymphocytes decreased (time variationP = .003 and 0.07, respectively). Outcome did not differ between patients with IST or frontline HCT. Ten‐year OS improved over time, increasing from 35.3% to 77.1% and 77% during 1973‐1985, 1986‐2003 and 2004‐2019, respectively.

Conclusion

Histopathology may refine response prediction to IST. The course of SAA in children, a previously fatal disease, was altered in recent times.
COVID‐19‐related issues on tele‐counseling helpline in Bangladesh
Authors: Iqbal Yeshim , Jahan Rubina , Yesmin Sakila , Selim Ashique , Siddique Shaheen Nafisa
Published: August 2020

Objective

To provide a brief description of COVID‐19‐related issues presented by callers to a tele‐counseling helpline in Bangladesh.

Method

Counselors who receive calls write brief descriptions of each call. These descriptions were coded and analyzed.

Results

Eighty‐six percent of callers displayed anxiety and/or sleeplessness; these callers also displayed a range of issues including family/interpersonal problems, financial difficulties, physical health concerns, mental illness, and difficulty managing quarantine.

Conclusion

These findings indicate the mental health challenges faced in Bangladesh due to lockdown and can inform future interventions.
Cross‐cultural translation and validation of the Malay version of the Swanson, Nolan, and Pelham Parent Rating Scale of attention deficit hyperactivity disorders symptoms among Malaysian probands: A preliminary study
Authors: Jusoh Masnira , Dzulkarnain Ahmad Aidil Arafat , Rahmat Sarah , Musa Ramli , Che Azemin Mohd Zulfaezal
Published: August 2020

The aim of this study is to evaluate the psychometric properties of the Malay version of the Swanson, Nolan, and Pelham Parent Rating Scale of attention deficit hyperactivity disorders (ADHD) symptoms (M‐SNAP‐IV). For this purpose, the SNAP‐IV scale was translated into the Malay language and was pilot‐tested on 91 parents of children aged 8 to 11 years (ADHD [n = 36] and non‐ADHD children [n = 55]). The findings depicted that the M‐SNAP‐IV has excellent content validity, internal consistency, and test‐retest reliability. The M‐SNAP‐IV is a valid and reliable screening tool to detect ADHD symptoms in children and has the advantages to assess the specific presentation of ADHD.
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

Objectives

As 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.

Methods

To 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.

Results

Prolonged 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.

Conclusions

Our 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

The 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

Some 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

Aside 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

As 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

Acid 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

Invasive 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

Objectives

Enterochromaffin (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 Methods

GDNF 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.

Results

GDNF‐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.

Conclusions

We 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

The 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.
Executive function in persisting versus remitting developmental coordination disorder
Authors: Vaivre‐Douret Laurence
Published: August 2020

This commentary is on the original article by Wilson et al. on pages 1316‐1322 of this issue.
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

Aim

To determine current practice regarding the diabetes management of people undergoing cardiac surgery in the UK.

Methods

We 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.

Results

Sixty‐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.

Conclusions

The 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

Aim

To 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 Methods

Patients 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.

Results

At 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.

Conclusions

Tirzepatide 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

The 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

Background/Aim

An 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 Methods

The 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.

Results

Groups 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.

Conclusion

The 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.
Ant sampling: the importance of pitfall trap depth as a bias factor
Authors: Jiménez‐Carmona Francisco , Carpintero Soledad , Reyes‐López Joaquín Luís
Published: August 2020

When sampling with pitfall traps, possible bias factors should be considered. In this study we compare traps of two depths. The results show that, on average, deeper traps captured more ant species (Hymenoptera: Formicidae) and higher numbers of workers, and that the relative abundances of the species were different depending on the depth of the trap, regardless of the type of habitat.