bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salidroside protects against diabetes mellitus‐induced kidney injury and renal fibrosis by attenuating TGF‐β1 and Wnt1/3a/β‐catenin signalling
Authors: Shati Ali A. , Alfaifi Mohammad Y. 
Published: May 2020

AbstractThis study evaluated if the nephroprotective effect of Salidroside in type 1 diabetes mellitus (T1DM) involves modulation of Wnt/β‐catenin signalling pathways. Control or Streptozotocin (STZ, 50 mg/kg, iv)‐induced T1DM adult male Wister rats were treated with the vehicle and Salidroside (100 mg/kg, orally) for 8 weeks daily. As compared to T1DM‐induced rats, Salidroside improved kidney structure, reduced urinary protein and albumin level, increased creatinine clearance, and suppressed renal fibrosis. It also decreased mRNA and protein levels of Wnt1, Wnt3, and TGF‐β1, phosphorylation of Smad‐3, total and nuclear levels of β‐catenin, and levels and activities of cleaved caspase‐3. Concomitantly, Salidroside significantly increased the levels of p‐β‐catenin (Ser33/37/Thr41) and suppressed protein levels of Axin‐2, fibronectin, and, mRNA and protein levels of collagen IIIa, the main targets of β‐catenin. In both control and T1DM rats, Salidroside significantly lowered fasting glucose levels and reduced renal levels of reactive oxygen species (ROS) p‐and GS3Kβ (Ser9) but significantly increased levels of SOD and GSH. In conclusion, Salidroside protected the kidney of rats against T1DM‐induced injury and fibrosis by activating GS3Kβ‐induced inhibition of Wnt1/Wnt3a β‐catenin. This was associated with hypoglycaemic and antioxidant effects.
Children's active outdoor play: ‘good’ mothering and the organisation of children's free time
Authors: Clark Emily , Dumas Alex 
Published: May 2020

AbstractThis qualitative study draws on the Foucault‐inspired notion of biopedagogies to examine and problematise the salient factors of contemporary motherhood impacting children's active outdoor play (AOP). The study positions mothering as a practice, through which children's health and bodies are constructed and disciplined. A discourse analysis of 21 interviews with Canadian mothers identified three discursive constructions of the ‘good mother’: mothers as time managers, risk managers and screen‐time managers. Each was characterised by discursive conflicts that compromised the provision of AOP by mothers. This study provides data necessary for successfully including AOP as a leisure practice within family‐centred health promotion.
A comparative analysis of current blood pressure management guidelines in people with and without diabetes
Authors: Xu Yu , Wu Shujing , Niu Jingya , Li Mian , Lu Jieli , Wang Weiqing , He Jiang , Solomon Henry A. , Bi Yufang , Ning Guang 
Published: May 2020

AbstractHypertension is the leading global risk factor for cardiovascular disease and premature death. Recommendations from current guidelines of blood pressure (BP) management differ in many ways; therefore, we did an overview and comparative analysis of major clinical guidelines of BP management in people with and without diabetes, including the definition and classification of hypertension, initiation of antihypertensive drug therapy, BP control targets, and antihypertensive treatment strategies. BP management in patients with diabetes was discussed in great detail using both hypertension and diabetes guidelines. We conclude that high‐level evidence from high‐quality clinical studies is urgently needed to settle uncertainties on BP management recommendations.
Global burden of noncommunicable diseases attributable to high fasting plasma glucose
Authors: Ye Lingxia , Xu Jingya , Zhang Tianyue , Lin Xiling , Pan Xiaowen , Zeng Wenheng , Ren Yuezhong , Shan Pengfei 
Published: May 2020

AbstractBackgroundHyperglycemia is a major public health concern. An understanding of the latest trends of the global burden of noncommunicable diseases (NCDs) by high fasting plasma glucose (HFPG) is critical for determining research priorities and planning health policy.MethodsThis is a comparative burden‐of‐disease study. We obtained global, regional, and national data on deaths and disability‐adjusted life years (DALYs) of NCDs attributable to HFPG from the Global Burden of Disease Study 2017, performed a secondary analysis of deaths and DALYs by time, age, gender, location, and specific causes, and analyzed their associations.ResultsIn 2017, 6.39 million deaths and 166.36 million DALYs from NCDs were attributable to HFPG, accounting for 15.6% and 10.7% of all deaths and DALYs, respectively. The burden's rate decreased with time, increased with age and was significantly higher in males. A negative association was found between the sociodemographic index (SDI) and disease burden, and a positive association was found between SDI and male superiority by gender difference and gender ratio.ConclusionsThe burden of NCDs attributable to HFPG has increased significantly since 1990 and varied widely across regions. Greater efforts are needed to prevent and control hyperglycemia, especially in less developed countries and among males.
A practical approach to measuring the biodiversity impacts of land conversion
Authors: Durán América P. , Green Jonathan M. H. , West Christopher D. , Visconti Piero , Burgess Neil D. , Virah‐Sawmy Malika , Balmford Andrew 
Published: May 2020

Abstract

Further progress in reducing biodiversity loss relies on the improved quantification of the connections between drivers of habitat loss and subsequent biodiversity impacts. To this end, biodiversity impact metrics should be able to report linked trends in specific human activities and changes in biodiversity state, accounting for both the ecology of different species and the cumulative effects of historical habitat losses. These characteristics are not currently captured within a single metric.

Here, we develop a globally applicable methodological framework that uses freely and publicly available datasets to quantify the relative impacts of anthropogenic activities on biodiversity. We use species‐specific habitat suitability models to link specific land uses to ensuing changes in the likelihood that local populations of those species will persist. To illustrate our approach, we assess the impacts of soy expansion and other land uses within the Brazilian Cerrado on over 2,000 species of amphibians, birds, mammals and plants for three periods between 2000 and 2014.

Our results showed that mammals and plants suffered the greatest overall reduction of suitable habitat. However, among endemic and near‐endemic species—which face greatest risk of global extinction from habitat conversion in the Cerrado—birds and mammals were the most affected groups. While conversion of natural vegetation to grassland and planted pastures were together responsible for most of the biodiversity impact of recent changes, soy expansion (via direct conversion of natural vegetation) had the greatest impact per unit area. The total biodiversity impact of recent land‐use change was concentrated in the southern states of the Cerrado—Minas Geráis, Goiás and Mato Grosso—but the impact on biodiversity of production of soy was greatest within the agricultural frontiers of Bahía and Piauí.

The flexibility of our approach to examine linkages between biodiversity loss and specific human activities has clear potential to better characterize the pathways by which habitat loss drivers operate. Its capacity to incorporate species‐specific ecological needs, through a globally applicable methodology, can improve the tangibility of biodiversity loss assessments.
Garbage as Racialization
Authors: Millar Kathleen M. 
Published: May 2020

SummaryThis essay examines parallels between the representation of garbage and the racialized production of the category of the human. In recent years, waste has become a ubiquitous metaphor for understanding the lives of the jobless poor, perceived as discarded by global capitalism and thereby rendered “disposable life.” The essay questions the conflation of waste with abjection through an ethnographic analysis of a film and art project produced on a garbage dump in Rio de Janeiro.
Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus
Authors: Chanoine Sébastien , Gautier‐Veyret Elodie , Pluchart Hélène , Tonini Julia , Fonrose Xavier , Claustre Johanna , Bedouch Pierrick , Stanke‐Labesque Françoise 
Published: May 2020

AimsA new formulation of posaconazole (PCZ), delayed‐release tablets (PCZ‐tab), increases PCZ bioavailability and plasma trough concentrations (Cmin) over those achieved with an oral suspension (PCZ‐susp). PCZ is an inhibitor of cytochrome P450 3A4 and P‐glycoprotein. We therefore investigated the impact of PCZ‐tab treatment on blood Cmin and doses of tacrolimus (TAC) and everolimus (EVR).MethodsEighteen lung transplant patients receiving TAC (n = 13) or TAC + EVR (n = 5) between June 2015 and March 2016 were retrospectively included. Ten of these patients received both PCZ‐tab and PCZ‐susp (i.e. switched patients); the other 8 received only PCZ‐tab. Plasma Cmin of PCZ (n = 64), blood Cmin of TAC (n = 299) and EVR (n = 80) were determined during routine therapeutic drug monitoring by liquid chromatography–tandem mass spectrometry.ResultsPCZ Cmin on PCZ‐tab treatment (n = 48) was 2.5 times higher than that on PCZ‐susp therapy (n = 16), for both PCZ patients (P < .0001) and for switched patients (P = .003). PCZ initiation, regardless of galenic form, increased TAC and EVR Cmin adjusted for dose (D), 3‐fold and 3.5‐fold, respectively (P < .0001 for both). PCZ‐tab treatment was associated with a higher TAC Cmin/D (PCZ‐tab vs PCZ‐susp: 0.004 ± 0.004 L−1 vs 0.009 ± 0.006 L−1, P < .0001) and lower TAC daily dose than PCZ‐susp (PCZ‐tab vs PCZ‐susp: 1.08 ± 0.92 vs 2.32 ± 1.62 mg d–1, P < .0001). EVR Cmin/D was higher and EVR dose tended to be lower on PCZ‐tab than on PCZ‐susp.ConclusionThe greater PCZ exposure achieved during PCZ‐tab treatment increased drug–drug interactions with TAC and EVR, resulting in greater exposure, potentially exposing patients to higher risks of adverse effects.
Primary care providers' use of and attitudes towards placebos: An exploratory focus group study with US physicians
Authors: Bernstein Michael H. , Locher Cosima , Stewart‐Ferrer Sif , Buergler Sarah , DesRoches Catherine M. , Dossett Michelle L. , Miller Franklin G. , Grose Deborah , Blease Charlotte R. 
Published: May 2020

ObjectiveTo examine how primary care physicians define placebo concepts, use placebos in clinical practice, and view open‐label placebos (OLPs).DesignSemi‐structured focus groups that were audio‐recorded and content‐coded.MethodsTwo focus groups with a total of 15 primary care physicians occurred at medical centres in the New England region of the United States. Prior experience using placebo treatments and attitudes towards open‐label placebos were explored. Themes were analysed using an inductive data‐driven approach.ResultsPhysicians displayed a nuanced understanding of placebos and placebo effects in clinical contexts which sometimes focused on relational factors. Some respondents reported that they prescribed treatments with no known pharmacological effect for certain conditions and symptoms (‘impure placebos’) and that such prescriptions were more common for pain disorders, functional disorders, and medically unexplained symptoms. Opinions about OLP were mixed: Some viewed OLPs favourably or considered them ‘harmless’; however, others strongly rejected OLPs as disrespectful to patients. Other issues in relation to OLPs included the following: lack of guidelines, legal and reputational concerns, and the notion that such treatments would run counter to customary medical practice.ConclusionsA number of physicians reported prescribing impure placebos in clinical care. Although some primary care physicians were resistant to the possibility of recommending OLPs, others regarded OLPs more favourably, viewing them as potential treatments, albeit with restricted potential.
Statement of contribution

What is already known?

Many physicians report prescribing drugs for the purposes of eliciting a placebo effect.

Initial evidence for the efficacy of open‐label placebos is promising.

What does this study add?

A more nuanced description of the circumstances under which primary care physicians report placebo prescribing.

A qualitative account of physician attitudes about using open‐label placebos in clinical practice.
Caregiving burden among informal caregivers of people with disability
Authors: Sit Hao Fong , Huang Lei , Chang Kay , Chau Wai I , Hall Brian J. 
Published: May 2020

ObjectiveChinese informal caregivers experience burden due to their caregiving responsibilities that violate their belief of reciprocal parent–child relationship, but little is known about this burden and coping processes among Chinese. It is believed that internal coping (i.e., self‐reliance) and external coping (i.e., seeking help from others) better captured cultural characteristics of coping styles observed among Chinese. Thus, the aim of this study was to estimate the prevalence of mental ill health, identify correlates, investigate the impact of caregiving burden on mental health, and explore the potentially moderating role of two coping strategies.DesignA purposive sample of 234 informal caregivers of family with intellectual or mental disability in Macao (SAR), China, from August to September 2018 was investigated.MethodsDASS‐21, Caregiving Burden Inventory (CBI), Perceived Difficulty Scale (PD), and a modified Chinese Coping Scale were used. Multiple regression analyses were conducted.ResultsCBI and PD were associated with depression, anxiety, and stress. Whereas internal coping buffered the effect of PD on depression and anxiety, external coping exacerbated the effect of PD on anxiety and the effect of CBI on depression and anxiety.ConclusionPoor mental health among caregivers is associated with greater caregiving challenges and burdens. Internal coping helped to buffer but external coping worsened the effect of burdens on mental health outcomes. Interventions that improve internal coping and mental health might be helpful for ageing informal caregivers.
Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy
Authors: Chen Long , Liao Fengying , Jiang Zhongyong , Zhang Chi , Wang Ziwen , Luo Peng , Jiang Qingzhi , Wu Jie , Wang Qing , Luo Min , Li Xueru , Leng Yu , Ma Le , Shen Gufang , Chen Zelin , Wang Yu , Tan Xu , Gan Yibo , Liu Dengqun , Liu Yunsheng , Shi Chunmeng 
Published: May 2020

Background and PurposeThere is an urgent but unmet need for mitigating radiation‐induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation‐induced intestinal toxicity and radiosensitivity of colorectal tumours.Experimental ApproachAcute and chronic histological injuries of the intestine from mice were used to assess radioprotection and IEC‐6 cell line was used to investigate the mechanisms in vitro. The fractionated abdominal radiation model of HCT116 and HT29 tumour grafts was used to determine the effects on colorectal cancer.Key ResultsMetformin alleviated radiation‐induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK‐dependent. In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo.Conclusion and ImplicationsMetformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation. Our findings provide a new strategy for further precise clinical trials for metformin on radiotherapy.
Clonal lineage from normal endometrium to ovarian clear cell carcinoma through ovarian endometriosis
Authors: Suda Kazuaki , Cruz Diaz Luis Antonio , Yoshihara Kosuke , Nakaoka Hirofumi , Yachida Nozomi , Motoyama Teiichi , Inoue Ituro , Enomoto Takayuki 
Published: May 2020

AbstractClear cell carcinoma of the ovary is thought to arise from endometriosis. In addition, retrograde menstruation of shed endometrium is considered the origin of endometriosis. However, little evidence supports cellular continuity from uterine endometrium to clear cell carcinoma through endometriosis at the genomic level. Here, we performed multiregional whole‐exome sequencing to clarify clonal relationships among uterine endometrium, ovarian endometriosis and ovarian clear cell carcinoma in a 56‐year‐old patient. Many somatic mutations including cancer‐associated gene mutations in ARID1A, ATM, CDH4, NRAS and PIK3CA were shared among epithelium samples from uterine endometrium, endometriotic lesions distant from and adjacent to the carcinoma, and the carcinoma. The mutant allele frequencies of shared mutations increased from uterine endometrium to distant endometriosis, adjacent endometriosis, and carcinoma. Although a splice site mutation of ARID1A was shared among the four epithelium samples, a frameshift insertion in ARID1A was shared by adjacent endometriosis and carcinoma samples, suggesting that the biallelic mutations triggered malignant transformation. Somatic copy number alterations, including loss of heterozygosity events at PIK3CA and ATM, were identified only in adjacent endometriosis and carcinoma, suggesting that mutant allele‐specific imbalance is another key factor driving malignant transformation. By reconstructing a clonal evolution tree based on the somatic mutations, we showed that the epithelium samples were derived from a single ancestral clone. Although the study was limited to a single patient, the results from this illustrative case could suggest the possibility that epithelial cells of ovarian endometriosis and clear cell carcinoma were descendants of uterine endometrial epithelium.
Highly expressed tumoral emmprin and stromal CD73 predict a poor prognosis for external auditory canal carcinoma
Authors: Miyazaki Masaru , Aoki Mikiko , Okado Yasuko , Koga Kaori , Hamasaki Makoto , Nakagawa Takashi , Sakata Toshifumi , Nabeshima Kazuki 
Published: May 2020

AbstractSquamous cell carcinoma of the external auditory canal (SCC‐EAC) is rare and has a poor prognosis. The SCC‐EAC cases with high‐grade tumor budding (TB) or poorly differentiated clusters (PDCs) are associated with shorter survival than those with low‐grade TB or PDCs. Extracellular matrix metalloproteinase inducer (emmprin) is a protein expressed in tumor cells that stimulates the production of MMP‐2 by stromal fibroblasts to facilitate tumor invasion. Recently, we reported that emmprin forms a complex with CD73 to regulate MMP‐2 production from fibroblasts in vitro. Here, we examined the association of emmprin and CD73 expression with TB or PDCs as well as with survival in 34 biopsy specimens of SCC‐EAC patients. High tumoral emmprin expression was associated with high­grade TB, whereas high stromal CD73 expression was associated with high‐grade PDCs. Furthermore, concurrent elevated expression of tumoral emmprin and stromal CD73 was determined to be an independent poor prognostic factor. In immunoprecipitation analyses, complex formation between emmprin and CD73 was demonstrated in vitro. Production of MMP‐2 from fibroblasts was more abundant when cocultured with tumor cells than from fibroblasts cultured alone. Furthermore, MMP‐2 production was reduced by the transfection of CD73 siRNA in fibroblasts cocultured with tumor cells. The colocalization of emmprin and CD73 was enhanced in not only the peripheral cells of the tumor cell clusters that interact with fibroblasts but also in the cells of intratumor clusters. Overall, this study provides novel insights into the roles of emmprin, CD73, and MMP‐2 in tumor invasiveness.
Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab
Authors: Upchurch Katherine , Wiest Matthew , Cardenas Jacob , Skinner Jason , Nattami Durgha , Lanier Bobby , Millard Mark , Joo HyeMee , Turner Jacob , Oh SangKon 
Published: May 2020

AbstractBackgroundAnti‐IgE (omalizumab) has been used for the treatment of moderate‐to‐severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits.ObjectiveTo investigate the transcriptional variations between omalizumab responders and non‐responders and to study the mechanisms of action of omalizumab.MethodsThe whole blood transcriptomes of moderate‐to‐severe adult asthma patients (N = 45:34 responders and 11 non‐responders) were analysed over the course of omalizumab treatment. Non‐asthmatic healthy controls (N = 17) were used as controls.ResultsTranscriptome variations between responders and non‐responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non‐responders tend to remain more similar to their pre‐treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up‐regulated in non‐responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non‐responders.Conclusion and Clinical RelevanceThis study provides not only transcriptional variations between omalizumab responders and non‐responders, but also molecular insights for controlling asthma by omalizumab.
Identifying research needs to inform white‐nose syndrome management decisions
Authors: Bernard Riley F. , Reichard Jonathan D. , Coleman Jeremy T. H. , Blackwood Julie C. , Verant Michelle L. , Segers Jordi L. , Lorch Jeffery M. , Paul White John , Moore Marianne S. , Russell Amy L. , Katz Rachel A. , Lindner Daniel L. , Toomey Rickard S. , Turner Gregory G. , Frick Winifred F. , Vonhof Maarten J. , Willis Craig K. R. , Grant Evan H. C. 
Published: May 2020

AbstractEcological understanding of host–pathogen dynamics is the basis for managing wildlife diseases. Since 2008, federal, state, and provincial agencies and tribal and private organizations have collaborated on bat and white‐nose syndrome (WNS) surveillance and monitoring, research, and management programs. Accordingly, scientists and managers have learned a lot about the hosts, pathogen, and dynamics of WNS. However, effective mitigation measures to combat WNS remain elusive. Host–pathogen systems are complex, and identifying ecological research priorities to improve management, choosing among various actions, and deciding when to implement those actions can be challenging. Through a cross‐disciplinary approach, a group of diverse subject matter experts created an influence diagram used to identify uncertainties and prioritize research needs for WNS management. Critical knowledge gaps were identified, particularly with respect to how WNS dynamics and impacts may differ among bat species. We highlight critical uncertainties and identify targets for WNS research. This tool can be used to maximize the likelihood of achieving bat conservation goals within the context and limitations of specific real‐world scenarios.