bluuebunny/crossref_metadata_2025 huggingface dataset:
Ficus deltoidea ameliorates biochemical, hormonal, and histomorphometric changes in letrozole-induced polycystic ovarian syndrome rats
Authors: Haslan Muhammad Aliff , Samsulrizal Nurdiana , Hashim Nooraain , Zin Noor Syaffinaz Noor Mohamad , Shirazi Farshad H. , Goh Yong Meng
Published: November 2021

Background

Insulin resistance and hormonal imbalances are key features in the pathophysiology of polycystic ovarian syndrome (PCOS). We have previously shown thatFicus deltoideavar.deltoideaJack (Moraceae) can improve insulin sensitivity and hormonal profile in PCOS female rats. However, biological characteristics underpinning the therapeutic effects ofF. deltoideafor treating PCOS remain to be clarified. This study aims to investigate the biochemical, hormonal, and histomorphometric changes in letrozole (LTZ)-induced PCOS female rats following treatment withF. deltoidea.

Methods

PCOS was induced in rats except for normal control by administering LTZ at 1 mg/kg/day for 21 days. Methanolic extract ofF. deltoidealeaf was then orally administered to the PCOS rats at the dose of 250, 500, or 1000 mg/kg/day, respectively for 15 consecutive days. Lipid profile was measured enzymatically in serum. The circulating concentrations of reproductive hormone and antioxidant enzymes were determined by ELISA assays. Ovarian and uterus histomorphometric changes were further observed by hematoxylin and eosin (H&E) staining.

Results

The results showed that treatment withF. deltoideaat the dose of 500 and 1000 mg/kg/day reduced insulin resistance, obesity indices, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), malondialdehyde (MDA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to near-normal levels in PCOS rats. The levels of high-density lipoprotein cholesterol (HDL), estrogen, and superoxide dismutase (SOD) are also similar to those observed in normal control rats. Histomorphometric measurements confirmed thatF. deltoideaincreased the corpus luteum number and the endometrial thickness.

Conclusions

F. deltoideacan reverse PCOS symptoms in female rats by improving insulin sensitivity, antioxidant activities, hormonal imbalance, and histological changes. These findings suggest the potential use ofF. deltoideaas an adjuvant agent in the treatment program of PCOS.
Process evaluation of a cluster randomised controlled trial to improve bronchiolitis management – a PREDICT mixed-methods study
Authors: Haskell Libby , Tavender Emma J. , O’Brien Sharon , Wilson Catherine L. , Babl Franz E. , Borland Meredith L. , Schembri Rachel , Orsini Francesca , Cotterell Elizabeth , Sheridan Nicolette , Oakley Ed , Dalziel Stuart R. ,   For the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network, Australasia
Published: November 2021

Background

Bronchiolitis is the most common reason for hospitalisation in infants. All international bronchiolitis guidelines recommend supportive care, yet considerable variation in practice continues with infants receiving non-evidence based therapies. We developed six targeted, theory-informed interventions; clinical leads, stakeholder meeting, train-the-trainer, education delivery, other educational materials, and audit and feedback. A cluster randomised controlled trial (cRCT) found the interventions to be effective in reducing use of five non-evidence based therapies in infants with bronchiolitis. This process evaluation paper aims to determine whether the interventions were implemented as planned (fidelity), explore end-users’ perceptions of the interventions and evaluate cRCT outcome data with intervention fidelity data.

Methods

A pre-specified mixed-methods process evaluation was conducted alongside the cRCT, guided by frameworks for process evaluation of cRCTs and complex interventions. Quantitative data on the fidelity, dose and reach of interventions were collected from the 13 intervention hospitals during the study and analysed using descriptive statistics. Qualitative data identifying perception and acceptability of interventions were collected from 42 intervention hospital clinical leads on study completion and analysed using thematic analysis.

Results

The cRCT found targeted, theory-informed interventions improved bronchiolitis management by 14.1%. The process evaluation data found variability in how the intervention was delivered at the cluster and individual level. Total fidelity scores ranged from 55 to 98% across intervention hospitals (mean = 78%; SD = 13%). Fidelity scores were highest for use of clinical leads (mean = 98%; SD = 7%), and lowest for use of other educational materials (mean = 65%; SD = 19%) and audit and feedback (mean = 65%; SD = 20%). Clinical leads reflected positively about the interventions, with time constraints being the greatest barrier to their use.

Conclusion

Our targeted, theory-informed interventions were delivered with moderate fidelity, and were well received by clinical leads. Despite clinical leads experiencing challenges of time constraints, the level of fidelity had a positive effect on successfully de-implementing non-evidence-based care in infants with bronchiolitis. These findings will inform widespread rollout of our bronchiolitis interventions, and guide future practice change in acute care settings.

Trial registration

Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.
Validity and reliability of the Chinese version of the partners at care transitions measure
Authors: Liu La-mei , Liu Ment-ting , Sun Meng-jie , Wang Jia-nan , Lin Bei-lei , Wang Peng , Li Qiu-fang
Published: November 2021

Background

The Partners at Care Transitions Measure (PACT-M) is a measure that assesses the quality and safety of care during the transition from hospital to home from the patient’s perspective. The aim of this study was to examine the psychometric properties of the Chinese version of the PACT-M in Mainland China.

Methods

This was a cross-sectional study. A convenience sample of patients was recruited from three tertiary hospitals affiliated with Zhengzhou University, China. A total of 402 participants were interviewed before discharge, and 306 participants were interviewed one month after discharge from hospital to home using the Chinese version of the PACT-M. The statistical methods used in this study include the critical ratio value, item total correlation, test-retest, Cronbach’s alpha, confirmatory factor analysis and exploratory factor analysis.

Results

The Chinese version of the PACT-M consists of PACT-M1 and PACT-M2, both of which have two dimensions, the number of items in both parts are consistent with the original English language version. The Cronbach’s alpha values of the PACT-M1 and PACT-M2 were 0.802 and 0.741, and the test-retest reliability values were 0.885 and 0.837. The item content validity index and scale content validity index values of the PACT-M1 and PACT-M2 were all 1.0.

Conclusion

The Chinese version of the PACT-M shows acceptable validity and reliability and can be used to assess the quality and safety of transitional care from hospital to home from the patient’s perspective in mainland China.
Apparent density, trypanosome infection rates and host preference of tsetse flies in the sleeping sickness endemic focus of northwestern Uganda
Authors: Opiro Robert , Opoke Robert , Angwech Harriet , Nakafu Esther , Oloya Francis A. , Openy Geoffrey , Njahira Moses , Macharia Mercy , Echodu Richard , Malinga Geoffrey M. , Opiyo Elizabeth A.
Published: November 2021

Background

African trypanosomiasis, caused by protozoa of the genus Trypanosoma and transmitted by the tsetse fly, is a serious parasitic disease of humans and animals. Reliable data on the vector distribution, feeding preference and the trypanosome species they carry is pertinent to planning sustainable control strategies.

Methodology

We deployed 109 biconical traps in 10 villages in two districts of northwestern Uganda to obtain information on the apparent density, trypanosome infection status and blood meal sources of tsetse flies. A subset (272) of the collected samples was analyzed for detection of trypanosomes species and sub-species using a nested PCR protocol based on primers amplifying the Internal Transcribed Spacer (ITS) region of ribosomal DNA. 34 blood-engorged adult tsetse midguts were analyzed for blood meal sources by sequencing of the mitochondrial cytochrome c oxidase 1 (COI) and cytochrome b (cytb) genes.

Results

We captured a total of 622 Glossina fuscipes fuscipes tsetse flies (269 males and 353 females) in the two districts with apparent density (AD) ranging from 0.6 to 3.7 flies/trap/day (FTD). 10.7% (29/272) of the flies were infected with one or more trypanosome species. Infection rate was not significantly associated with district of origin (Generalized linear model (GLM), χ2 = 0.018, P = 0.895, df = 1, n = 272) and sex of the fly (χ2 = 1.723, P = 0.189, df = 1, n = 272). However, trypanosome infection was highly significantly associated with the fly’s age based on wing fray category (χ2 = 22.374, P < 0.001, df = 1, n = 272), being higher among the very old than the young tsetse. Nested PCR revealed several species of trypanosomes: T. vivax (6.62%), T. congolense (2.57%), T. brucei and T. simiae each at 0.73%. Blood meal analyses revealed five principal vertebrate hosts, namely, cattle (Bos taurus), humans (Homo sapiens), Nile monitor lizard (Varanus niloticus), African mud turtle (Pelusios chapini) and the African Savanna elephant (Loxodonta africana).

Conclusion

We found an infection rate of 10.8% in the tsetse sampled, with all infections attributed to trypanosome species that are causative agents for AAT. However, more verification of this finding using large-scale passive and active screening of human and tsetse samples should be done. Cattle and humans appear to be the most important tsetse hosts in the region and should be considered in the design of control interventions.
Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
Authors: Wu Jiahe , Cao Jianlei , Fan Yongzhen , Li Chenze , Hu Xiaorong
Published: November 2021

Background

Chronic chagasic cardiomyopathy (CCC) is the leading cause of heart failure in Latin America and often causes severe inflammation and fibrosis in the heart. Studies on myocardial function and its molecular mechanisms in patients with Chronic chagasic cardiomyopathy are very limited. In order to understand the development and progression of Chronic chagasic cardiomyopathy and find targets for its diagnosis and treatment, the field needs to better understand the exact molecular mechanisms involved in these processes.

Methods

The mRNA microarray datasets GSE84796 (human) and GSE24088 (mouse) were obtained from the Gene Expression Omnibus (GEO) database. Homologous genes between the two species were identified using the online database mining tool Biomart, followed by differential expression analysis, gene enrichment analysis and protein–protein interaction (PPI) network construction. Cytohubba plug-in of Cytoscape software was used to identify Hub gene, and miRNet was used to construct the corresponding miRNA–mRNA regulatory network. miRNA-related databases: miRDB, Targetscan and miRWalk were used to further evaluate miRNAs in the miRNA–mRNA network. Furthermore, Comparative Toxicogenomics Database (CTD) and L1000 Platform were used to identify hub gene-related drugs.

Results

A total of 86 homologous genes were significantly differentially expressed in the two datasets, including 73 genes with high expression and 13 genes with low expression. These differentially expressed genes were mainly enriched in the terms of innate immune response, signal transduction, protein binding, Natural killer cell mediated cytotoxicity, Tuberculosis, Chemokine signaling pathway, Chagas disease and PI3K−Akt signaling pathway. The top 10 hub genes LAPTM5, LCP1, HCLS1, CORO1A, CD48, TYROBP, RAC2, ARHGDIB, FERMT3 and NCF4 were identified from the PPI network. A total of 122 miRNAs were identified to target these hub genes and 30 of them regulated two or more hub genes at the same time. miRDB, Targetscan and miRWalk were further analyzed and screened out hsa-miR-34c-5p, hsa-miR-34a-5p and hsa-miR-16-5p as miRNAs regulating these hub genes. Finally, Progesterone, Flutamide, Nimesulide, Methotrexate and Temozolomide were identified to target these hub genes and might be targeted therapies for Chronic chagasic cardiomyopathy.

Conclusions

In this study, the potential genes associated with Chronic chagasic cardiomyopathy are identified and a miRNA–mRNA regulatory network is constructed. This study explores the molecular mechanisms of Chronic chagasic cardiomyopathy and provides important clues for finding new therapeutic targets.
Long noncoding RNA CRART16 confers 5-FU resistance in colorectal cancer cells by sponging miR-193b-5p
Authors: Wang Jingui , Zhang Xiaoqian , Zhang Junling , Chen Shangwen , Zhu Jing , Wang Xin
Published: November 2021

Background

The emergence of chemoresistance to 5-fluorouracil (5-FU)-based chemotherapy is the main cause of treatment failure in advanced and metastatic colorectal cancer (CRC) patients. Long noncoding RNAs (lncRNAs) have been reported to be involved in 5-FU resistance. Previously, we first detected that lncRNA cetuximab resistance-associated RNA transcript 16 (CRART16) could contribute to cetuximab resistance by upregulating V-Erb-B2 erythroblastic leukemia viral oncogene homologue 3 (ERBB3) expression by sponging miR-371a-5p in CRC cells. The current study aimed to explore the role of CRART16 in acquired 5-FU resistance in CRC cells and its possible mechanism.

Methods

Quantitative real-time PCR (RT-qPCR) was used to measure the expression levels of CRART16 in a 5-FU-resistant CRC cell subline (SW620/5-FU) and the parent cell line. Lentivirus transduction was performed to establish SW620 and Caco-2 cells stably overexpressing CRART16. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were applied to measure cell chemosensitivity to 5-FU. Flow cytometric and immunofluorescence staining were adopted to assess cell apoptosis induced by 5-FU. The dual-luciferase reporter assay was used to validate the direct interactions between CRART16 and miR-193b-5p and between miR-193b-5p and high-mobility group AT-hook-2 (HMGA2). The expression levels of HMGA2, apoptosis-associated proteins and p-ERK were examined by western blotting. The statistical differences within any two groups were used Student’s t test.

Results

CRART16 was upregulated in SW620/5-FU cells. Overexpression of CRART16 reduced the sensitivity of CRC cells to 5-FU by attenuating apoptosis. In addition, CRART16 promoted 5-FU resistance by suppressing the expression of miR-193b-5p. Furthermore, CRART16 modulated the expression of HMGA2 by inhibiting miR-193b-5p and activated the MAPK signaling pathway.

Conclusions

CRART16 confers 5-FU resistance in CRC cells through the CRART16/miR-193b-5p/HMGA2/MAPK pathway.
Protein-losing enteropathy caused by disseminated Mycobacterium avium complex infection in a patient receiving antiretroviral therapy: an autopsy case report
Authors: Konishi Keiji , Nakagawa Hidenori , Nakahira Akio , Okuno Takahiro , Inoue Takeshi , Shirano Michinori
Published: November 2021

Background

Disseminated Mycobacterium avium complex infection is an important indicator of acquired immunodeficiency syndrome (AIDS) in patients with advanced human immunodeficiency virus (HIV) infection. Effective antiretroviral therapy has dramatically reduced the incidence of and mortality due to HIV infection, although drug resistance and poor medication adherence continue to increase the risk of disseminated M. avium complex infection. However, gastrointestinal lesions in cases of disseminated M. avium complex infection resulting in protein-losing enteropathy have been rarely discussed. Therefore, we present a case of protein-losing enteropathy caused by disseminated M. avium complex infection in a patient undergoing antiretroviral therapy.

Case presentation

A 29-year-old man was diagnosed with AIDS 4 years ago and was admitted for a 10-month history of refractory diarrhea and fever. Despite receiving antiretroviral therapy, the viral load remained elevated due to poor medication adherence. The patient was diagnosed with disseminated M. avium complex infection and started on antimycobacterial drugs 2 years before admission. However, the infection remained uncontrolled. The previous hospitalization 1 year before admission was due to hypoalbuminemia and refractory diarrhea. Upper gastrointestinal endoscopy revealed a diagnosis of protein-losing enteropathy caused by intestinal lymphangiectasia, and treatment with intravenous antimycobacterial drugs did not resolve his intestinal lymphangiectasia. The patient inevitably died of sepsis.

Conclusions

Clinical remission is difficult to achieve in patients with AIDS and protein-losing enteropathy caused by disseminated M. avium complex infection due to limited options of parenteral antiretroviral drugs. This report highlights the importance of identifying alternative treatments (such as an injectable formulation) for patients who do not respond to antiretroviral therapy due to protein-losing enteropathy with disseminated M. avium complex infection.
Digital conversations about depression among Hispanics and non-Hispanics in the US: a big‐data, machine learning analysis identifies specific characteristics of depression narratives in Hispanics
Authors: Castilla-Puentes Ruby , Dagar Anjali , Villanueva Dinorah , Jimenez-Parrado Laura , Valleta Liliana Gil , Falcone Tatiana
Published: November 2021

Background

Digital conversations can offer unique information into the attitudes of Hispanics with depression outside of formal clinical settings and help generate useful information for medical treatment planning. Our study aimed to explore the big data from open‐source digital conversations among Hispanics with regard to depression, specifically attitudes toward depression comparing Hispanics and non-Hispanics using machine learning technology.

Methods

Advanced machine‐learning empowered methodology was used to mine and structure open‐source digital conversations of self‐identifying Hispanics and non-Hispanics who endorsed suffering from depression and engaged in conversation about their tone, topics, and attitude towards depression. The search was limited to 12 months originating from US internet protocol (IP) addresses. In this cross-sectional study, only unique posts were included in the analysis and were primarily analyzed for their tone, topic, and attitude towards depression between the two groups using descriptive statistical tools.

Results

A total of 441,000 unique conversations about depression, including 43,000 (9.8%) for Hispanics, were posted. Source analysis revealed that 48% of conversations originated from topical sites compared to 16% on social media. Several critical differences were noted between Hispanics and non-Hispanics. In a higher percentage of Hispanics, their conversations portray “negative tone” due to depression (66% vs 39% non-Hispanics), show a resigned/hopeless attitude (44% vs. 30%) and were about ‘living with’ depression (44% vs. 25%). There were important differences in the author's determined sentiments behind the conversations among Hispanics and non-Hispanics.

Conclusion

In this first of its kind big data analysis of nearly a half‐million digital conversations about depression using machine learning, we found that Hispanics engage in an online conversation about negative, resigned, and hopeless attitude towards depression more often than non-Hispanic.
Reflection on leadership behavior: potentials and limits in the implementation of stress-preventive leadership of middle management in hospitals – a qualitative evaluation of a participatory developed intervention
Authors: Tsarouha Elena , Stuber Felicitas , Seifried-Dübon Tanja , Radionova Natalia , Schnalzer Susanne , Nikendei Christoph , Genrich Melanie , Worringer Britta , Stiawa Maja , Mulfinger Nadine , Gündel Harald , Junne Florian , Rieger Monika A.
Published: November 2021

Background

Mental health and stress prevention aspects related to workplace in hospitals are gaining increasingly more attention in research. The workplace hospital is characterized by high work intensity, high emotional demands, and high levels of stress. These conditions can be a risk for the development of mental disorders. Leadership styles can hinder or foster work-related stress and influence the well-being of employees. Through leadership interventions, leaders may be encouraged to develop a stress-preventive leadership style that addresses both, the well-being of the leaders and of the subordinates. A comprehensive qualitative description of leaders’ experiences with interventions on the topic of stress-preventive leadership is yet missing in the literature. Therefore, we address leaders of middle management regarding the development of stress-preventive leadership styles through supporting interventions. The research questions are: How do leaders of middle management perceive their leadership role in terms of effectiveness in stress prevention? Which potentials and limits in the implementation of stress-preventive leadership are experienced?

Methods

The study follows a qualitative research design and content analysis. We conducted individual interviews with leaders of middle management (n = 30) of a tertiary hospital in Germany for the participatory development of an intervention. This intervention, consisting of five consecutive modules, addressed leaders of middle management in all work areas within one hospital. After participation in the intervention, the leaders were asked to reflect on and evaluate the implementation of the contents learned within focus group discussions. Overall 10 focus group discussions with leaders (n = 60) were conducted.

Results

The results demonstrate that leaders of middle management perceived potentials for a stress-preventive leadership style (e.g., reflection on leadership role and leadership behavior, awareness/mindfulness, and conveying appreciation). However, limits were also mentioned. These can be differentiated into self-referential, subordinate-related, and above all organizational barriers for the implementation of stress-preventive leadership.

Conclusions

Some of the organizational barriers can be addressed by mid-level leadership interventions (e.g., lack of peer-exchange) or possibly by adapted leadership interventions for top management (e.g., lack of stress-preventive leadership styles in top level management). Other organizational limits are working conditions (e.g., staff shortage) that can only be influenced by health policy decisions.
Improved phenotyping procedure for evaluating resistance in rice against gall midge (Orseolia oryzae, Wood-Mason)
Authors: Cheng Ling , Huang Fugang , Jiang Zhe , Lu Baiyi , Zhong Xiaohui , Qiu Yongfu
Published: November 2021

Background

The rice gall midge (RGM, Orseolia oryzae, Wood-Mason), an important stem-feeding pest worldwide, has caused serious production losses over the past decades. Rice production practices indicate that the most reliable method for managing RGM is the deployment of cultivars that incorporate host resistance. However, the conventional phenotypic screening method of rice resistance to RGM suggested by the International Rice Research Institute (IRRI) has been used for approximately 30 years, and only 12 rice varieties/lines (including controls) can be evaluated in one tray. It is not suitable for high-throughput phenotyping of rice germplasm. Moreover, a suitable method to prepare samples for molecular biological studies of rice resistance against RGM is imperative with the rapid development of modern molecular techniques.

Results

The proper density of seedlings/RGM was determined for four seeding arrangements. A high-throughput phenotyping method (HTPM) for 60 lines/varieties infested with 36 female RGM adults in one tray, as described by method 4–3 (seeded 60 lines/varieties), was developed and verified using mutant screening. Furthermore, one RGM resistance gene flanked by markers 12RM28346 and 12RM28739 on chromosome 12 was simultaneously detected using method 2–2 (seeded 30 lines/varieties in one tray) treated with 24 RGM and analyzed using conventional and simplified grading systems. Genetic analysis of the RGM resistance gene was confirmed using a method identical to that suggested by IRRI. Finally, one bucket with 24 seedlings treated with at least five female RGM adults was efficacious and could offer adequate samples for insect development observation or molecular biological studies.

Conclusion

A highly efficient and reliable procedure for evaluation of resistance in rice to RGM was developed and improved, and was verified through mutant screening, gene mapping, genetic analysis, and insect growth and development observations.
The impact of the novel coronavirus disease (COVID-19) pandemic on drug overdose-related deaths in the United States and Canada: a systematic review of observational studies and analysis of public health surveillance data
Authors: Imtiaz Sameer , Nafeh Frishta , Russell Cayley , Ali Farihah , Elton-Marshall Tara , Rehm Jürgen
Published: November 2021

Background

There are preliminary indications that the trajectory of drug overdose-related deaths in North America has been exacerbated due to the novel coronavirus disease pandemic (COVID-19). As such, the impact of COVID-19 on drug overdose-related deaths was examined through a systematic review of the literature and percentage change analyses of surveillance data.

Methods

Systematic searches in electronic databases were conducted, a topical issue brief and bibliography were reviewed, reference lists of included studies were searched and expert consultations were held to identify studies (Registration # CRD42021230223). Observational studies from the United States and Canada were eligible for inclusion if drug overdose-related deaths were assessed in quantitative or qualitative analyses onwards from at least March 2020. In addition, percentage changes comparing drug overdose-related deaths in the second annual quarter (Q2 2020 [April to June]) with the first annual quarter (Q1 2020 [January to March]) were generated using national and subnational data from public health surveillance systems and reports from jurisdictions in the United States and Canada.

Results

Nine studies were included in the systematic review, eight from the United States and one from Canada. The maximum outcome assessment period in the included studies extended until September 2020. Drug overdose-related deaths after the onset of COVID-19 were higher compared with the months leading up to the pandemic in 2020 and the comparative months in 2019. In additional percentage change analyses, drug overdose-related deaths increased by 2 to 60% in jurisdictions in the United States and by 58% in Canada when comparing Q2 2020 with Q1 2020.

Conclusions

Drug overdose-related deaths increased after the onset of COVID-19. The current situation necessitates a multi-pronged approach, encompassing expanded access to substance use disorder treatment, undisrupted access to harm reduction services, emphasis on risk reduction strategies, provision of a safe drug supply and decriminalization of drug use.
QimmeqHealth—thyroid status of Greenland sled dogs (Canis lupus familiaris borealis)
Authors: Gjaldbæk Bolette Winnerskjold , Andersen-Ranberg Emilie Ulrikka , Langebæk Rikke , Krogh Anne Kirstine Havnsøe
Published: November 2021

Background

Greenland sled dogs (GSD) are a unique, genetically isolated population of dogs living under exceptional environmental conditions. Metabolism, and thereby thyroid hormones are affected by multiple factors. Among other activity, energy balance and environmental conditions are important. A breed-specific reference interval (RI) can be useful for diagnostics of potential thyroid-related pathologies. The aim of this study was to establish RIs of the thyroid hormones thyroxin (T4), free thyroxin (fT4), and thyroid stimulating hormone (TSH) in GSD. In addition to evaluate the effect of sex, age, season, management, and body condition score (BCS) in GSD. Physical exams and cephalic venous blood sampling were performed in the period of 2018–2019 from 265 GSD managed either privately or by the Danish navy. Serum biochemical analyses, including C-reactive protein, were performed and RIs were determined for TSH, T4 and fT4 in only healthy dogs. The RIs were determined using American Society for Veterinary Clinical Pathology guidelines and the effect of varying factors were evaluated by linear regression and further tested by Mann–Whitney test.

Results

144 GSD were included in the reference group resulting in RIs: T4: 6.44–48.65 nmol/L; fT4: 3.91–18.51 pmol/L; and TSH: 0.04–0.55 ng/mL. Female GSD had significantly higher concentrations of T4 (P = 0.039) and fT4 (P = 0.015) compared to males; a positive correlation between TSH and aging was found; T4 concentrations were significantly higher (P = 0.003) during summer; and TSH concentrations were lower in GSD managed by the navy (P < 0.0001). BCS was higher (P < 0.0001) in Sirius GSD compared to civilian GSD, and BCS was positively correlated with T4 and negatively correlated with TSH.

Conclusions

Reference intervals for T4, fT4 and TSH in GSD were established. The RI for T4 and fT4 was lower compared to other breeds. In addition, sex, age, season, management and BCS demonstrated variable effects on thyroid hormones. Our results can be used as a foundation for improving management and further research of GSD.
Possible role of the gut microbiota in the pathogenesis of anorexia nervosa
Authors: Sudo Nobuyuki
Published: November 2021

Anorexia nervosa (AN), an eating disorder, is characterized by extreme weight loss and fear of weight gain. Psychosocial factors are thought to play important roles in the development and progression of AN; however, biological factors also presumably contribute to eating disorders. Recent evidence has shown that the gut microbiota plays an important role in pathogenesis of neuropsychiatric disorders including AN. In this article, we describe the possible role of the gut microbiota in the development and persistence of AN, based on the latest research works, including those of our group.
Hydroxychloroquine synergizes with the PI3K inhibitor BKM120 to exhibit antitumor efficacy independent of autophagy
Authors: Peng Xin , Zhang Shaolu , Jiao Wenhui , Zhong Zhenxing , Yang Yuqi , Claret Francois X. , Elkabets Moshe , Wang Feng , Wang Ran , Zhong Yuxu , Chen Zhe-Sheng , Kong Dexin
Published: November 2021

Background

The critical role of phosphoinositide 3-kinase (PI3K) activation in tumor cell biology has prompted massive efforts to develop PI3K inhibitors (PI3Kis) for cancer therapy. However, recent results from clinical trials have shown only a modest therapeutic efficacy of single-agent PI3Kis in solid tumors. Targeting autophagy has controversial context-dependent effects in cancer treatment. As a FDA-approved lysosomotropic agent, hydroxychloroquine (HCQ) has been well tested as an autophagy inhibitor in preclinical models. Here, we elucidated the novel mechanism of HCQ alone or in combination with PI3Ki BKM120 in the treatment of cancer.

Methods

The antitumor effects of HCQ and BKM120 on three different types of tumor cells were assessed by in vitro PrestoBlue assay, colony formation assay and in vivo zebrafish and nude mouse xenograft models. The involved molecular mechanisms were investigated by MDC staining, LC3 puncta formation assay, immunofluorescent assay, flow cytometric analysis of apoptosis and ROS, qRT-PCR, Western blot, comet assay, homologous recombination (HR) assay and immunohistochemical staining.

Results

HCQ significantly sensitized cancer cells to BKM120 in vitro and in vivo. Interestingly, the sensitization mediated by HCQ could not be phenocopied by treatment with other autophagy inhibitors (Spautin-1, 3-MA and bafilomycin A1) or knockdown of the essential autophagy genes Atg5/Atg7, suggesting that the sensitizing effect might be mediated independent of autophagy status. Mechanistically, HCQ induced ROS production and activated the transcription factor NRF2. In contrast, BKM120 prevented the elimination of ROS by inactivation of NRF2, leading to accumulation of DNA damage. In addition, HCQ activated ATM to enhance HR repair, a high-fidelity repair for DNA double-strand breaks (DSBs) in cells, while BKM120 inhibited HR repair by blocking the phosphorylation of ATM and the expression of BRCA1/2 and Rad51.

Conclusions

Our study revealed that HCQ and BKM120 synergistically increased DSBs in tumor cells and therefore augmented apoptosis, resulting in enhanced antitumor efficacy. Our findings provide a new insight into how HCQ exhibits antitumor efficacy and synergizes with PI3Ki BKM120, and warn that one should consider the “off target” effects of HCQ when used as autophagy inhibitor in the clinical treatment of cancer.
‘Green podiatry’ ‐ reducing our carbon footprints. Lessons from a sustainability panel
Authors: Evans Angela Margaret
Published: November 2021

Background

The eyes of the world will be on COP26 as it meets in Glasgow in November, 2021. Our planet is displaying weather extremes due to climate change which cannot be ignored, and which are deleterious for people's health. Ironically, healthcare contributes to climate change, contributing approximately 5% of carbon emissions globally. Climate change due to global warming is ‘the biggest global health threat of the 21st century’.

Main body

The Australian Podiatry Association conference held a sustainability panel, hearing perspectives of industry and science, medicine and sport, fashion, and retail. Content unified a broad planet and human health message, which is highly relevant for podiatrists. Key themes included waste as a resource, exercise as evidence‐based intervention, responsibility and circular economy recycling principles for end‐of‐life product (footwear) purchases, and wider ethical considerations of footwear and clothing.

The Anthropocene origin of climate change requires humanity to collaborate and to live more sustainably. Innovation is essential for better energy modes, cleaner air, human health and earth care.

Green Podiatry joins the concerted activity of medical and health groups within Australia. The UK's NHS is an exemplar in this area, having already reduced healthcare emissions by 35%, and aiming for net zero by 2045, and perhaps sooner.

Conclusion

People are increasingly concerned about climate change, and COP26 is an important and imminent meeting for human and planet health.

This commentary on Green Podiatry directs us all to lighten our carbon footprint. A final, and forthcoming commentary will outline practical ways of positively incorporating climate change communication into the clinical setting.
recount3: summaries and queries for large-scale RNA-seq expression and splicing
Authors: Wilks Christopher , Zheng Shijie C. , Chen Feng Yong , Charles Rone , Solomon Brad , Ling Jonathan P. , Imada Eddie Luidy , Zhang David , Joseph Lance , Leek Jeffrey T. , Jaffe Andrew E. , Nellore Abhinav , Collado-Torres Leonardo , Hansen Kasper D. , Langmead Ben
Published: November 2021

We present recount3, a resource consisting of over 750,000 publicly available human and mouse RNA sequencing (RNA-seq) samples uniformly processed by our new analysis pipeline. To facilitate access to the data, we provide the and R/Bioconductor packages as well as complementary web resources. Using these tools, data can be downloaded as study-level summaries or queried for specific exon-exon junctions, genes, samples, or other features. can be used to process local and/or private data, allowing results to be directly compared to any study in recount3. Taken together, our tools help biologists maximize the utility of publicly available RNA-seq data, especially to improve their understanding of newly collected data. recount3 is available from http://rna.recount.bio.
The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination
Authors: Hay Curtis M. , Jackson Stacey , Mitew Stanislaw , Scott Daniel J. , Koenning Matthias , Bensen AeSoon L. , Bujalka Helena , Kilpatrick Trevor J. , Emery Ben
Published: November 2021

Background

Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination.

Methods

To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo.

Results

We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood.

Conclusions

We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.
Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome
Authors: Gerossier Estelle , Nayar Saba , Froidevaux Sylvie , Smith Charlotte G. , Runser Celine , Iannizzotto Valentina , Vezzali Enrico , Pierlot Gabin , Mentzel Ulrich , Murphy Mark J. , Martinic Marianne M. , Barone Francesca
Published: November 2021

Background

Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren’s syndrome.

Methods

Cenerimod was administered in two established models of Sjögren’s syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test.

Results

In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands.

Conclusions

Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren’s syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.
Tracing TET1 expression in prostate cancer: discovery of malignant cells with a distinct oncogenic signature
Authors: Schagdarsurengin U. , Luo C. , Slanina H. , Sheridan D. , Füssel S. , Böğürcü-Seidel N. , Gattenloehner S. , Baretton G. B. , Hofbauer L. C. , Wagenlehner F. , Dansranjav T.
Published: November 2021

Background

Ten–eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in DNA demethylation and transcriptional regulation, plays a key role in the maintenance of stem cell pluripotency, and is dysregulated in malignant cells. The identification of cancer stem cells (CSCs) driving tumor growth and metastasis is the primary objective of biomarker discovery in aggressive prostate cancer (PCa). In this context, we analyzed TET1 expression in PCa.

Methods

A large-scale immunohistochemical analysis of TET1 was performed in normal prostate (NOR) and PCa using conventional slides (50 PCa specimens) and tissue microarrays (669 NOR and 1371 PCa tissue cores from 371 PCa specimens). Western blotting, RT-qPCR, and 450 K methylation array analyses were performed on PCa cell lines. Genome-wide correlation, gene regulatory network, and functional genomics studies were performed using publicly available data sources and bioinformatics tools.

Results

In NOR, TET1 was exclusively expressed in normal cytokeratin 903 (CK903)–positive basal cells. In PCa, TET1 was frequently detected in alpha-methylacyl-CoA racemase (AMACR)–positive tumor cell clusters and was detectable at all tumor stages and Gleason scores. Pearson’s correlation analyses of PCa revealed 626 TET1-coactivated genes (r > 0.5) primarily encoding chromatin remodeling and mitotic factors. Moreover, signaling pathways regulating antiviral processes (62 zinc finger, ZNF, antiviral proteins) and the pluripotency of stem cells were activated. A significant proportion of detected genes exhibited TET1-correlated promoter hypomethylation. There were 161 genes encoding transcription factors (TFs), of which 133 were ZNF-TFs with promoter binding sites in TET1 and in the vast majority of TET1-coactivated genes.

Conclusions

TET1-expressing cells are an integral part of PCa and may represent CSCs with oncogenic potential.
Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain
Authors: Yue Xiangpei , Zhou Yanzhao , Qiao Meng , Zhao Xingnan , Huang Xin , Zhao Tong , Cheng Xiang , Fan Ming , Zhao Yongqi , Chen Ruoli , Zhu Lingling
Published: November 2021

Background

Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT.

Methods

Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus.

Results

IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes.

Conclusions

This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.
Prevalence of anemia and its associated factors among married women in 19 sub-Saharan African countries
Authors: Zegeye Betregiorgis , Anyiam Felix Emeka , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena , Budu Eugene , Seidu Abdul-Aziz , Yaya Sanni
Published: November 2021

Background

Sub-Saharan Africa (SSA) remains the region with the highest burden of anemia globally. Since anemia has both health and non-health-related consequences, its reduction is one of the Sustainable Development Goals. Therefore, this study aimed to examine the prevalence of anemia and its associated factors among married women in SSA.

Methods

Using Stata version-14 software, the analysis was done on 89,029 married women from the Demographic and Health Surveys of 19 countries in SSA. Pearson Chi-Square test and Binary logistic regression analyses were used to examine the factors associated with anemia. The results were presented using adjusted Odds Ratio (aOR) at a 95% Confidence Interval (CI). A p-value less than or equal to 0.05 (p ≤ 0.05) was considered statistically significant.

Results

The pooled analysis showed that 49.7% of married women were anemic. Of these, 1.04% and 15.05% were severely and moderately anemic respectively, and the rest 33.61% were mildly anemic. Husband education (primary school-aOR = 0.84, 95% CI; 0.71–0.99), wealth index (middle-aOR = 0.81, 95% CI; 0.68–0.96, richer-aOR = 0.69, 95% CI; 0.57–0.84, richest-aOR = 0.68, 95% CI; 0.51–0.91), modern contraceptive use (yes-aOR = 0.68, 95% CI; 0.56–0.81) and religion (Muslim-aOR = 1.27, 95% CI; 1.11–1.46, others-aOR = 0.73, 95% CI; 0.59–0.90) were factors associated with anemia among married women.

Conclusion

The findings show that nearly half of the married women are affected by anemia. Enhancing partners’ educational levels, and economic empowerment of women, strengthening family planning services, and working with religious leaders to reduce the perception and religious beliefs related to food restrictions can be the main focus to reduce the burden of anemia among married women in SSA.