bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between lipid biomarkers and osteoporosis: a cross-sectional study
Authors: Kan Bo , Zhao Qianqian , Wang Lijuan , Xue Shanshan , Cai Hanqing , Yang Shuman
Published: September 2021

Background

Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis.

Methods

Using inpatients’ and outpatients’ electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis.

Results

The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06–2.07) and TG (OR: 1.67; 95 % CI: 1.16–2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10).

Conclusions

Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.
Temporomandibular dysfunction experience is associated with oral health-related quality of life: an Australian national study
Authors: Hanna Kamal , Nair Rahul , Amarasena Najith , Armfield Jason M. , Brennan David S.
Published: September 2021

Background

There are very few studies of the association between temporomandibular dysfunction (TMD) and oral health-related quality of life (OHRQoL) in a representative sample from the Asia–Pacific region. Accordingly, we aimed to quantify the association of TMD with OHRQoL dimensions and overall measurement scores in a representative sample of Australian adults while accounting for a range of confounders, and statistically estimating whether TMD experience is meaningfully associated with OHRQoL.

Method

Australia’s National Survey of Adult Oral Health 2004–2006 data were used. The outcome variables were the Oral Health Impact Profile (OHIP-14) domains and overall scores while the main exposure was self-reported Diagnostic Criteria Question for TMD. The analysis accounted for confounders including oral health status obtained from the oral examination, demographics, socioeconomics, health behaviours and health including perceived stress subscales of the PSS-14. We conducted complex samples analysis while using Cohen’s f2 effect size to estimate whether the association is meaningful.

Results

TMD prevalence was 9.9% (95% CI: 8.4–11.6%) among 4133 Australian adults. TMD experience was associated with impairments to the seven OHIP-14 OHRQoL domains (P < .05) with higher impairments observed in physical pain (B = 0.82, 95% CI: .45–1.20, P < .001), psychological discomfort (B = 0.68, 95% CI: .29–1.06, P = .001) and psychological disability (B = 0.52, 95% CI: .20–.84, P = .001) in adjusted multivariate analyses. The difference in the mean OHIP-14 scores for those reporting TMD (Mean = 13.1, 95% CI: 12.0–14.0) and those who did not (Mean = 6.6, 95% CI: 6.0–6.8) was significant (t = 7.51, P < .001). In an adjusted multivariable model for OHIP-14 scores, TMD experience was associated with higher OHIP-14 scores (B = 3.34, 95% CI: 1.94–4.75, P < .001) where the Cohen’s f2 was .022. Further, perceived stress subscales: perceived distress and perceived control were associated with TMD experience and OHIP-14 scores (P < .05).

Conclusion

Lower OHRQoL was observed in Australian adults who reported TMD experience but with small clinical importance which might support considering TMD in regular dental care. The higher impairments observed in physical pain, psychological discomfort and psychological disability domains of OHRQL can help clinicians and researchers focus their attention on these domains. The confounding effect exhibited by the perceived stress subscale might support their inclusion in future TMD and OHRQoL research.
Cultural adaptation and psychometric properties of the Jefferson empathy scale health professions students’ version in SpanishOccupational therapy students
Authors: Serrada-Tejeda Sergio , Sánchez-Herrera-Baeza Patricia , Rodríguez-Pérez Mª. Pilar , Máximo-Bocanegra Nuria , Martínez-Piédrola Rosa Mª. , Trugeda-Pedrajo Nuria , Huertas-Hoyas Elisabet , Pérez-de-Heredia-Torres Marta
Published: September 2021

Background

In occupational therapy, empathy is a fundamental concept and has a positive impact on health and quality of care outcomes for patients. It is a basic and essential concept that should prevail in the training of occupational therapy students. The aim of this study is to validate and cross-culturally adapt the Jefferson Medical Empathy Scale, version for health professionals (JSE-HPS) in a sample of Spanish university students of occupational therapy.

Methods

A cross-sectional descriptive study was conducted between 2019 and 2020. A convenience sample was selected, consisting of 221 students from the four courses of the Occupational Therapy degree at the Universidad Rey Juan Carlos during the 2019–20 academic year. Each of the participants voluntarily and anonymously completed a sociodemographic data sheet (including age and sex), in addition to the following assessment scales: JSE-HPS and the Interpersonal Reactivity Index (IRI).

Results

A culturally adapted version of the JSE-HPS that guarantees conceptual and grammatical equivalence specific to the study population was obtained. The psychometric analysis of the translated version showed a Cronbach coefficient α of 0.786. The test-retest reliability analysis showed an intraclass correlation coefficient of 0.90 (95% CI = 0.86–0.93, p < 0.0001). Confirmatory factor analysis (CFA) showed positive results (χ2 = 269.095, df = 167, p < 0.001, Confirmatory Fit Index [CFI] = 0.90, Root Mean Square Error of Approximation [RMSEA] = 0.04).

Conclusion

The cultural adaptation and psychometric results suggest that the Spanish version of the JSE-HPS is a valid and reliable way to evaluate the empathic ability of occupational therapy students.
Common patient-reported outcomes across ICHOM Standard Sets: the potential contribution of PROMIS®
Authors: Terwee Caroline B. , Zuidgeest Marloes , Vonkeman Harald E. , Cella David , Haverman Lotte , Roorda Leo D.
Published: September 2021

Background

The International Consortium for Health Outcomes Measurement (ICHOM) develops condition-specific Standard Sets of outcomes to be measured in clinical practice for value-based healthcare evaluation. Standard Sets are developed by different working groups, which is inefficient and may lead to inconsistencies in selected PROs and PROMs. We aimed to identify common PROs across ICHOM Standard Sets and examined to what extend these PROs can be measured with a generic set of PROMs: the Patient-Reported Outcomes Measurement Information System (PROMIS®).

Methods

We extracted all PROs and recommended PROMs from 39 ICHOM Standard Sets. Similar PROs were categorized into unique PRO concepts. We examined which of these PRO concepts can be measured with PROMIS.

Results

A total of 307 PROs were identified in 39 ICHOM Standard Sets and 114 unique PROMs are recommended for measuring these PROs. The 307 PROs could be categorized into 22 unique PRO concepts. More than half (17/22) of these PRO concepts (covering about 75% of the PROs and 75% of the PROMs) can be measured with a PROMIS measure.

Conclusion

Considerable overlap was found in PROs across ICHOM Standard Sets, and large differences in terminology used and PROMs recommended, even for the same PROs. We recommend a more universal and standardized approach to the selection of PROs and PROMs. Such an approach, focusing on a set of core PROs for all patients, measured with a system like PROMIS, may provide more opportunities for patient-centered care and facilitate the uptake of Standard Sets in clinical practice.
Exploring clinicians’ experiences and perceptions of end-user roles in knowledge development: a qualitative study
Authors: Verville Leslie , Cancelliere Carol , Connell Gaelan , Lee Joyce , Munce Sarah , Mior Silvano , Kay Robin , Côté Pierre
Published: September 2021

Background

End-user involvement in developing evidence-based tools for clinical practice may result in increased uptake and improved patient outcomes. Understanding end-user experiences and perceptions about the co-production of knowledge is useful to further the science of integrated knowledge translation (iKT) – a strategy for accelerating the uptake and impact of research. Our study had two main objectives: (1) explore end-user (clinician) experiences of co-producing an evidence-based practice tool; and (2) describe end-user perceptions in knowledge development.

Methods

We used a qualitative study design. We conducted semi-structured interviews with clinicians and used a transcendental phenomenological approach to analyze themes/phenomena. In addition, we explored the interrelated themes between the thematic maps of each objective.

Results

Four themes emerged from clinicians’ experiences in co-producing the practice tool: ease/convenience of participating, need for support and encouragement, understanding the value of participating, and individual skillsets yield meaningful contributions. Stakeholder roles in knowledge tool development and improving dissemination of evidence and knowledge tools were themes that related to clinician perceptions in knowledge development. The review of interrelated thematic maps depicts an intertwined relationship between stakeholders and dissemination.

Conclusions

End-users provide invaluable insight and perspective into the development of evidence-based clinical tools. Exploring the experiences and perceptions of end-users may support future research endeavours involving iKT, such as the co-production of clinical resources, potentially improving uptake and patient health outcomes.
Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation
Authors: Qiu Hu , Song Haixia , Luo Man , Ke Shaobo , Shi Wei , Chen Jiamei , Zhao Wensi , Luo Hesheng , Chen Yongshun
Published: September 2021

Objective

Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC.

Methods

The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC.

Results

A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence.

Conclusion

Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.
Immune classifier-based signatures provide good prognostic stratification and predict the clinical benefits of immune-based therapies for hepatocellular carcinoma
Authors: Xue Chen , Gu Xinyu , Li Lanjuan
Published: September 2021

Background

Hepatocellular carcinoma (HCC) is an aggressive cancer with a high rate of death globally. The use of bioinformatics may help to identify immune cell-related genes both as targets for potential immunotherapies and for their value associated with predicting therapy responses.

Methods

In this study, mRNA expression profiles of HCC samples from The Cancer Genome Atlas (TCGA) database were subjected to gene enrichment, cell type abundance, immune cell infiltration, and pathway enrichment analyses to determine immune cell gene features, cell type abundance, and functional annotation characteristics. We also evaluated their prognostic values using Cox regression and Kaplan–Meier analyses and assessed potential responses to chemotherapy. Four subgroups (Groups 1–4) were identified. Group 4 was associated with advanced clinical characteristics, high immune cell enrichment scores, and the poorest outcomes.

Results

Differentially expressed genes (DEGs) in the HCC samples were enriched in the following pathways: antigen binding, cell surface receptor signal transduction of the immune response, and cell surface activated receptor signal transduction of the immune response. Highly expressed genes in Group 4 were enriched in elements of the WNT signalling pathway. We identified five immune-related genes (SEMA3A, TNFRSF11B, GUCA2A, SAA1, and CALCR) that were significantly related to HCC prognosis. A prognostic model based on these five genes exhibited good predictive value, with 1-year and 5-year area under the curve (AUC) values of  >  0.66. Group 4 was also potentially more sensitive to EHT 1864, FH535, and lapatinib chemotherapies than the other groups.

Conclusions

We identified and validated four HCC subgroups based on immune system-related genes and identified five genes that may be used for an immune-based prognostic model for HCC treatment.
Evaluation of Xpert GBS assay and Xpert GBS LB assay for detection of Streptococcus agalactiae
Authors: Han Meng-Yi , Xie Chen , Huang Qing-Qing , Wu Qiao-Hua , Deng Qing-Yun , Xie Tian-Ao , Liu Ye-Ling , Li Zhuo-Lei , Zhong Jing-Hua , Wang Yan-Chao , Guo Xu-Guang
Published: September 2021

Background

Group B Streptococcal (GBS) infection is the primary agent of neonatal morbidity and mortality. Rapid and simple methods to detect GBS are Xpert GBS and GBS LB assays based on real-time polymerase chain reaction (PCR). However, since the diagnostic accuracy of the two techniques in diagnosing GBS remains unclear, we designed this study to appraise the diagnostic accuracy of the aforementioned.

Methods

A systematic search of all literature published before July 16, 2020 was conducted using Embase, PubMed, Web of Science, and Cochrane Library. The study quality was evaluated through Review Manager 5.3. Accordingly, data extracted in the included studies were analyzed using Meta-DiSc 1.4 and Stata 12.0 software. The diagnosis odds ratio (DOR) and bivariate boxplot were utilized to evaluate the heterogeneity. Publication bias was appraised by using Deeks’ funnel plot.

Results

A total of 13 studies were adopted and only 19 sets of data met the criteria. The sensitivity and specificity of Xpert GBS were 0.91 (95% CI 0.89–0.92) and 0.93 (95% CI 0.92–0.94). The area under the curve (AUC) was 0.9806. The sensitivity and specificity results of Xpert GBS LB were 0.96 (95% CI 0.95–0.98) and 0.94 (95% CI 0.92–0.95), respectively. The AUC was 0.9950. No publication bias was found.

Conclusions

The Xpert GBS and GBS LB assays are valuable alternative methods with high sensitivity and specificity. However, determining whether they can be used as clinical diagnostic standards for GBS is essential for the future.
Comparison of therapy with β-lactam/β-lactamase inhibitor combinations or carbapenems for bacteraemia of nonurinary source caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae
Authors: Luo Hong , Xiao Yanping , Hang Yaping , Chen Yanhui , Zhu Hongying , Fang Xueyao , Cao Xingwei , Zou Shan , Hu Xiaoyan , Xiong Jianqiu , Zhong Qiaoshi , Hu Longhua
Published: September 2021

Background

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a public health concern. This study aimed to compare the clinical outcomes of patients with nonurinary source bacteraemia caused by ESBL-producing Escherichia coli (E. coli) or Klebsiella pneumoniae (ESBL-producing EK) receiving β-lactam/β-lactamase inhibitor combinations (BLICs) versus carbapenem treatment and assess the risk factors of mortality with these two drugs.

Methods

We conducted a retrospective single-centre study of adult hospitalised patients with ESBL-producing EK bloodstream infection (BSI) from nonurinary source at our centre over a 4-year period. One hundred and eighty patients who received BLICs or carbapenems were included in the analysis. The outcome variables were 14-day treatment failure and 30-day mortality. For more reliable results, propensity score analysis was performed to compare the efficacy of the two drugs and analyse their risk factors for 30-day mortality.

Results

Out of 180 patients, 114 received BLICs, and 66 received carbapenem therapy. Compared to carbapenem-treated patients, those treated with BLICs were older and had higher age-adjusted Charlson comorbidity index, but they had shorter stay in the hospital. Additionally, their Pitt bacteraemia score, SOFA score, rate of leukaemia, and immune compromise were lower. After propensity score matching (PSM), the baseline characteristics of patients in the two treatment groups were balanced. BLICs were associated with a higher 14-day treatment failure rate (20.6%, 13/63) than carbapenems (16.3%, 7/43), although the difference was not significant in either univariate analysis (P = 0.429) or multivariate analysis (P = 0.122). And the 30-day mortality rate in BTG (11.1%, 7/63) and CTG (11.6%, 5/43) did not significantly differ (univariate analysis, P = 0.926; multivariate analysis, P = 0.420). In the multivariate analysis, after PSM, leukaemia was the only independent predictor of mortality in both BTG and CTG.

Conclusions

Our study showed that BLICs had higher 14-day treatment failure rate compared with carbapenems, although there were no statistically significant differences because of the small number of patients, therefore, further evaluation of the efficacy of BLICs is needed.
The role of dosimetry and biological effects in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study
Authors: Sciuto Rosa , Rea Sandra , Ungania Sara , Testa Antonella , Dini Valentina , Tabocchini Maria Antonella , Patrono Clarice , Soriani Antonella , Palma Valentina , Marconi Raffaella , Strigari Lidia
Published: September 2021

Background

223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize 223Ra treatment.

Methods

Out of 20 mCRPC patients who underwent standard 223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each 223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar 223Ra images were obtained at 2–4 and 18–24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after 223Ra injection and 2 months after last cycle.

Results

1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of 223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics.

Conclusions

This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate 223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during 223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose.

Trial registration

The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18–2111).
Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma
Authors: Kang Hyunkoo , Lee Sungmin , Kim Kyeongmin , Jeon Jaewan , Kang Seok-Gu , Youn HyeSook , Kim Hae Yu , Youn BuHyun
Published: September 2021

Background

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor in which the standard treatment, ionizing radiation (IR), achieves a median survival of about 15 months. GBM harbors glioblastoma stem-like cells (GSCs), which play a crucial role in therapeutic resistance and recurrence.

Methods

Patient-derived GSCs, GBM cell lines, intracranial GBM xenografts, and GBM sections were used to measure mRNA and protein expression and determine the related molecular mechanisms by qRT-PCR, immunoblot, immunoprecipitation, immunofluorescence, OCR, ECAR, live-cell imaging, and immunohistochemistry. Orthotopic GBM xenograft models were applied to investigate tumor inhibitory effects of glimepiride combined with radiotherapy.

Results

We report that GSCs that survive standard treatment radiation upregulate Speedy/RINGO cell cycle regulator family member A (Spy1) and downregulate CAP-Gly domain containing linker protein 3 (CLIP3, also known as CLIPR-59). We discovered that Spy1 activation and CLIP3 inhibition coordinately shift GBM cell glucose metabolism to favor glycolysis via two cellular processes: transcriptional regulation of CLIP3 and facilitating Glucose transporter 3 (GLUT3) trafficking to cellular membranes in GBM cells. Importantly, in combination with IR, glimepiride, an FDA-approved medication used to treat type 2 diabetes mellitus, disrupts GSCs maintenance and suppresses glycolytic activity by restoring CLIP3 function. In addition, combining radiotherapy and glimepiride significantly reduced GBM growth and improved survival in a GBM orthotopic xenograft mouse model.

Conclusions

Our data suggest that radioresistant GBM cells exhibit enhanced stemness and glycolytic activity mediated by the Spy1-CLIP3 axis. Thus, glimepiride could be an attractive strategy for overcoming radioresistance and recurrence by rescuing CLIP3 expression.
A systematic review and meta-analysis on prevalence and distribution of Taenia and Echinococcus infections in Ethiopia
Authors: Shumuye Nigus Abebe , Ohiolei John Asekhaen , Gebremedhin Mebrahtu Berhe , Yan Hong-Bin , Li Li , Li Wen-Hui , Zhang Nian-Zhang , Fu Bao-Quan , Jia Wan-Zhong
Published: September 2021

Background

Tapeworm infections are among the tropical neglected parasitic diseases endemically occurring in Ethiopia. This systematic review and meta-analysis aims at estimating the pooled prevalence and distribution ofTaeniaandEchinococcusinfections in humans and animals from reports from Ethiopia.

Methods

The systematic search was conducted in four bibliographic databases (PubMed, Google Scholar, Africa Journal Online and Science Direct). Additional data were retrieved from grey literature. Studies that met the inclusion criteria were considered for the systematic review and meta-analysis. The meta-analysis was conducted using MetaXL add-in for Microsoft Excel. Heterogeneity and inconsistency were evaluated using Cochran’sQandI2statistics, respectively.

Results

The study provides a country-based database ofTaeniaandEchinococcusinfections consisting of 311 datasets from 201 publications which were mostly abattoir surveys; of these, 251 datasets were subjected to meta-analysis. Most of the studies were from Oromia (32.8%) followed by Amhara (22.9%) regional states. The pooled prevalence of cystic echinococcosis in intermediate and accidental hosts was calculated as 22% (95% CI 18–26%) and high study variability (Q = 24,420.65,I2 = 100%,P = 0.000). Moreover, a pooled prevalence ofEchinococcusinfections in final hosts was calculated as 33% (95% CI 20–48%) and low study variability (Q = 17.24,I2 = 65%,P = 0.001). Similarly, study subjects (human, cattle, sheep, goat and wolf) were infected byTaeniaspp. with pooled prevalence of 3% (95% CI 2–4%) and moderate study variability (Q = 279.07,I2 = 89,P = 0.000). Meanwhile, the pooled prevalence ofTaenia hydatigena,T. ovisandT. multicepsinfections in intermediate hosts were calculated as 38%, 14% and 5%, respectively. The random effect meta-analysis of bovine cysticercosis showed a pooled prevalence of 7% (95% CI 5–9%) and high study variability was of (Q = 4458.76;I2 = 99%,P = 0.000). Significant differences in prevalence ofTaeniaandEchinococcusinfections between study sites or different livestock origins have been reported.

Conclusion

The study evidenced a comprehensive dataset on the prevalence and distribution ofTaeniaandEchinococcusinfections at different interfaces by regions and hosts and hence can aid in the design of more effective control strategies.

Graphical Abstract
The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis
Authors: Derrett-Smith Emma , Clark Kristina E. N. , Shiwen Xu , Abraham David J. , Hoyles Rachel K. , Lacombe Olivier , Broqua Pierre , Junien Jean Louis , Konstantinova Irena , Ong Voon H. , Denton Christopher P.
Published: September 2021

Background

The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype.

Methods

PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored.

Results

Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure.

Conclusions

In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications.
Chronic wasting disease: a cervid prion infection looming to spillover
Authors: Otero Alicia , Velásquez Camilo Duque , Aiken Judd , McKenzie Debbie
Published: September 2021

The spread of chronic wasting disease (CWD) during the last six decades has resulted in cervid populations of North America where CWD has become enzootic. This insidious disease has also been reported in wild and captive cervids from other continents, threatening ecosystems, livestock and public health. These CWD “hot zones” are particularly complex given the interplay between cervid PRNP genetics, the infection biology, the strain diversity of infectious prions and the long-term environmental persistence of infectivity, which hinder eradication efforts. Here, we review different aspects of CWD including transmission mechanisms, pathogenesis, epidemiology and assessment of interspecies infection. Further understanding of these aspects could help identify “control points” that could help reduce exposure for humans and livestock and decrease CWD spread between cervids.
RETRACTED ARTICLE: Implementation of MapReduce parallel computing framework based on multi-data fusion sensors and GPU cluster
Authors: Chang Dajun , Li Li , Chang Ying , Qiao Zhangquan
Published: September 2021

Nowadays, with the rapid growth of data volume, massive data has become one of the factors that plague the development of enterprises. How to effectively process data and reduce the concurrency pressure of data access has become the driving force for the continuous development of big data solutions. This article mainly studies the MapReduce parallel computing framework based on multiple data fusion sensors and GPU clusters. This experimental environment uses a Hadoop fully distributed cluster environment, and the entire programming of the single-source shortest path algorithm based on MapReduce is implemented in Java language. 8 ordinary physical machines are used to build a fully distributed cluster, and the configuration environment of each node is basically the same. The MapReduce framework divides the request job into several mapping tasks and assigns them to different computing nodes. After the mapping process, a certain intermediate file that is consistent with the final file format is generated. At this time, the system will generate several reduction tasks and distribute these files to different cluster nodes for execution. This experiment will verify the changes in the running time of the PSON algorithm when the size of the test data set gradually increases while keeping the hardware level and software configuration of the Hadoop platform unchanged. When the number of computing nodes increases from 2 to 4, the running time is significantly reduced. When the number of computing nodes continues to increase, the reduction in running time will become less and less significant. The results show that NESTOR can complete the basic workflow of MapReduce, and simplifies the process of user development of GPU positive tree order, which has a significant speedup for applications with large amounts of calculations.
Designated server-aided revocable identity-based keyword search on lattice
Authors: Guo Ying , Meng Fei , Cheng Leixiao , Dong Xiaolei , Cao Zhenfu
Published: September 2021

Public key encryption scheme with keyword search is a promising technique supporting search on encrypted data without leaking any information about the keyword. In real applications, it’s critical to find an effective revocation method to revoke users in multi-user cryptosystems, when user’s secret keys are exposed. In this paper, we propose the first designated server-aided revocable identity-based encryption scheme with keyword search (dSR-IBKS) from lattice. The dSR-IBKS model requires each user to keep just one private key corresponding with his identity and does not need to communicate with the key generation center or the server during key updating. We have proved that our scheme can achieve chosen keyword indistinguishability in the standard model. In particular, our scheme can designate a unique tester to test and return the search results, therefore no other entity can guess the keyword embedded in the ciphertext by generating search queries and doing the test by itself. We provide a formal security proof of our scheme assuming the hardness of the learning with errors problem on the standard model.
Circulating extracellular vesicles during pregnancy in women with type 1 diabetes: a secondary analysis of the CONCEPTT trial
Authors: Abolbaghaei Akram , Langlois Marc-André , Murphy Helen R , Feig Denice S. , Burger Dylan ,   on behalf of the CONCEPTT Collaborative Group
Published: September 2021

Background

Extracellular vesicles are membrane vesicles that are released into the extracellular environment and accumulate in the circulation in vascular disease. We aimed to quantify circulating extracellular vesicles in pregnant women with type 1 diabetes and to examine associations between extracellular vesicle levels, continuous glucose measures, and pregnancy outcomes.

Methods

We used plasma samples from the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial study and quantified circulating extracellular vesicles by flow cytometry (n = 163). Relationships with clinical variables were assessed by repeated measures correlation. Logistic regression was used to assess associations between elevated extracellular vesicle levels and pregnancy outcomes.

Results

Platelet extracellular vesicle levels were inversely associated with glucose time above range and glycaemic variability measures (P < 0.05). A weak positive association was observed between endothelial extracellular vesicles and mean amplitude of glycemic excursion (P < 0.05). In a univariate logistic regression model, high baseline endothelial extracellular vesicles was associated with increased risk of neonatal intensive care unit (NICU) admission (OR: 2.06, 1.03–4.10), and respiratory distress requiring ventilation (OR: 4.98, 1.04–23.92). After adjusting for HbA1c and blood pressure the relationship for NICU admission persisted and an association with hyperbilirubinemia was seen (OR: 2.56, 1.10–5.94). Elevated platelet extracellular vesicles were associated with an increased risk of NICU admission (OR: 2.18, 1.04–4.57), and hyperbilirubinemia (OR: 2.61, 1.11–6.12) after adjusting for HbA1c and blood pressure.

Conclusions

High levels of extracellular vesicles in early pregnancy were associated with adverse neonatal outcomes. Assessment of extracellular vesicles may represent a novel approach to personalized care in type 1 diabetes pregnancy.
Food and ecology or how dietary alterations can affect an aquatic ecosystem
Authors: Tsounis Lambros , Iliadi Katerina , Kehayias George
Published: September 2021

Fishing ensures necessary food for humans and is inextricably linked with the environment because coastal communities developed special fishing procedures to achieve better exploitation of the aquatic resources. Lake Trichonis, Greece’s largest natural lake, is a freshwater ecosystem in which a marine species (Atherina boyeri) has entered and dominate the ichthyofauna. This species is exploited by purse seine fishing with the use of light, and previous studies revealed that the fishing lights create a particular food chain reaction, which promotes predation among the attracted fish species, one of which is Scardinius acarnanicus that preys upon A. boyeri. The purse seine fishers typically return to the lake alive S. acarnanicus, due to its low market demand, although it is the main predator of their catch. This custom, apart from causing income losses, promotes instability in the fish populations, while eventually altered the foraging behaviour of S. acarnanicus and made it a fish-predator instead of a typical omnivorous species. Based on data from official fish landing recordings, interviews with local fishers, and responses to questionnaires completed by residents of villages around Lake Trichonis, the present study investigates how changes in the dietary habits of the lakeside communities over time have led to the low market demand for S. acarnanicus. The present findings revealed an interesting relation between the dietary preferences of the local population and their ecological consequences for the fish community of this lake. This will eventually lead to the increase in the top predator (S. acarnanicus) and an inevitable decrease in the main catch (A. boyeri), affecting not only the ecological status of the lake, but also the socioeconomic characteristics of the human populations in this area. From another perspective, the results demonstrate a paradigm of adapted evolution by a wild fish under the pressure of human activities.
Exposure to microplastic fibers does not change fish early life stage development of three-spined sticklebacks (Gasterosteus aculeatus)
Authors: Bunge Anja , Kammann Ulrike , Scharsack Jörn Peter
Published: September 2021

Microplastic fibers are frequent contaminants of aquatic ecosystems. Early life stages of aquatic organisms are predicted to be especially vulnerable to microplastic pollution. We hypothesized that microplastic fibers in the water column might interfere with fertilization and embryonic development of fish. We tested this with an in vitro fertilization system with three-spined sticklebacks. Six egg clutches were divided and one half was fertilized and bread out in water with polyester fibers (PET fibers; mean diameter 9.7 ± 2.3 μm; mean length 245.6 ± 163.1 μm) at a concentration of 1 × 104 fibers/L while the other half served as control without fibers.

Observation with a dissection microscope revealed that some polyester fibers stuck to the outside of the eggs in the fiber treatments. Yet, overall 67.4 ± 12.9% eggs were fertilized from which 97.2 ± 4.2% larvae hatched without any significant difference between treatments. Mortality and abnormal development of larvae was low and was not changed by microplastic fibers, as was the heart rate of developing embryos five days post fertilization.

The present study illustrates that polyester fibers, even at concentrations three to four orders above levels reported from the environment, do not impair fertilization success, embryonic and early larval development of sticklebacks. Accordingly, concentrations of microplastic fibers currently observed in aquatic habitats do not appear to be harmful to early live stages of fish.
Approach to the Patient: Pharmacological Management of Trans and Gender-Diverse Adolescents
Authors: O’Connell Michele A , Nguyen Thomas P , Ahler Astrid , Skinner S Rachel , Pang Ken C
Published: September 2021

Internationally, increasing numbers of children and adolescents with gender dysphoria are presenting for care. In response, gender-affirming therapeutic interventions that seek to align bodily characteristics with an individual’s gender identity are more commonly being used. Depending on a young person’s circumstances and goals, hormonal interventions may aim to achieve full pubertal suppression, modulation of endogenous pubertal sex hormone effects, and/or development of secondary sex characteristics congruent with their affirmed gender. This is a relatively novel therapeutic area and, although short-term outcomes are encouraging, longer term data from prospective longitudinal adolescent cohorts are still lacking, which may create clinical and ethical decision-making challenges. Here, we review current treatment options, reported outcomes, and clinical challenges in the pharmacological management of trans and gender-diverse adolescents.
Cyclical endometrial repair and regeneration
Authors: Salamonsen Lois A. , Hutchison Jennifer C. , Gargett Caroline E.
Published: September 2021

Uniquely among adult tissues, the human endometrium undergoes cyclical shedding, scar-free repair and regeneration during a woman's reproductive life. Therefore, it presents an outstanding model for study of such processes. This Review examines what is known of endometrial repair and regeneration following menstruation and parturition, including comparisons with wound repair and the influence of menstrual fluid components. We also discuss the contribution of endometrial stem/progenitor cells to endometrial regeneration, including the importance of the stem cell niche and stem cell-derived extracellular vesicles. Finally, we comment on the value of endometrial epithelial organoids to extend our understanding of endometrial development and regeneration, as well as therapeutic applications.
Membrane architecture and adherens junctions contribute to strong Notch pathway activation
Authors: Falo-Sanjuan Julia , Bray Sarah J.
Published: September 2021

The Notch pathway mediates cell-to-cell communication in a variety of tissues, developmental stages and organisms. Pathway activation relies on the interaction between transmembrane ligands and receptors on adjacent cells. As such, pathway activity could be influenced by the size, composition or dynamics of contacts between membranes. The initiation of Notch signalling in the Drosophila embryo occurs during cellularization, when lateral cell membranes and adherens junctions are first being deposited, allowing us to investigate the importance of membrane architecture and specific junctional domains for signalling. By measuring Notch-dependent transcription in live embryos, we established that it initiates while lateral membranes are growing and that signalling onset correlates with a specific phase in their formation. However, the length of the lateral membranes per se was not limiting. Rather, the adherens junctions, which assemble concurrently with membrane deposition, contributed to the high levels of signalling required for transcription, as indicated by the consequences of α-Catenin depletion. Together, these results demonstrate that the establishment of lateral membrane contacts can be limiting for Notch trans-activation and suggest that adherens junctions play an important role in modulating Notch activity.
Kinematic and dynamic aspects of chimpanzee knuckle walking: finger flexors likely do not buffer ground impact forces
Authors: Leijnse J. N. , Spoor C. W. , Pullens P. , Vereecke E. E.
Published: September 2021

Chimpanzees are knuckle walkers, with forelimbs contacting the ground by the dorsum of the finger's middle phalanges. As these muscular apes are given to high-velocity motions, the question arises of how the ground reaction forces are buffered so that no damage ensues in the load-bearing fingers. In the literature, it was hypothesized that the finger flexors help buffer impacts because in knuckle stance the metacarpophalangeal joints (MCPJs) are strongly hyperextended, which would elongate the finger flexors. This stretching of the finger flexor muscle–tendon units would absorb impact energy. However, EMG studies did not report significant finger flexor activity in knuckle walking. Although these data by themselves question the finger flexor impact buffering hypothesis, the present study aimed to critically investigate the hypothesis from a biomechanical point of view. Therefore, various aspects of knuckle walking were modeled and the finger flexor tendon displacements in the load-bearing fingers were measured in a chimpanzee cadaver hand, of which also an MRI was taken in knuckle stance. The biomechanics do not support the finger flexor impact buffering hypothesis. In knuckle walking, the finger flexors are not elongated to lengths where passive strain forces would become important. Impact buffering by large flexion moments at the MCPJs from active finger flexors would result in impacts at the knuckles themselves, which is dysfunctional for various biomechanical reasons and does not occur in real knuckle walking. In conclusion, the current biomechanical analysis in accumulation of previous EMG findings suggests that finger flexors play no role in impact buffering in knuckle walking.
Thermal stress induces tissue damage and a broad shift in regenerative signaling pathways in the honey bee digestive tract
Authors: Bach Dunay M. , Holzman Miriam A. , Wague Fatoumata , Miranda JJ L. , Lopatkin Allison J. , Mansfield Jennifer H. , Snow Jonathan W.
Published: September 2021

Honey bee colonies in the USA have suffered from increased die-off in the last few years with a complex set of interacting stresses playing a key role. With changing climate, an increase in the frequency of severe weather events, such as heat waves, is anticipated. Understanding how these changes may contribute to stress in honey bees is crucial. Individual honey bees appear to have a high capacity to endure thermal stress. One reason for this high-level endurance is likely their robust heat shock response (HSR), which contributes to thermotolerance at the cellular level. However, less is known about other mechanisms of thermotolerance, especially those operating at the tissue level. To elucidate other determinants of resilience in this species, we used thermal stress coupled with RNAseq and identified broad transcriptional remodeling of a number of key signaling pathways in the honey bee, including those pathways known to be involved in digestive tract regeneration in the fruit fly such as the Hippo and JAK/STAT pathways. We also observed cell death and shedding of epithelial cells, which likely leads to induction of this regenerative transcriptional program. We found that thermal stress affects many of these pathways in other tissues, suggesting a shared program of damage response. This study provides important foundational characterization of the tissue damage response program in this key pollinating species. In addition, our data suggest that a robust regeneration program may also be a critical contributor to thermotolerance at the tissue level, a possibility which warrants further exploration in this and other species.
Παραγωγή και χρήση στρατηγικών διδασκαλίας για τη συνεκπαίδευση μαθητών με ή χωρίς ειδικές ανάγκες
Authors: Τσαρούχα Βασιλική
Published: September 2021

Η μελέτη διερευνά τις στάσεις των εκπαιδευτικών της Πρωτοβάθμιας εκπαίδευσης απέναντι στις στρατηγικές διδασκαλίας που εφαρμόζουν στη συνεκπαίδευση μαθητών με και χωρίς ειδικές εκπαιδευτικές ανάγκες. Ειδικότερα, ερευνάται η αλληλεπίδραση μεταξύ των χαρακτηριστικών των εκπαιδευτικών (κατάρτιση, εμπειρία, στάσεις, συνεργασίες) και της εφαρμογής των στρατηγικών διδασκαλίας με βάση τέσσερα κυρίαρχα διδακτικά μοντέλα : συμπεριφορισμός, κοινωνιογνωστισμός, δομισμός, εποικοδομισμός. Η μελέτη είναι εμπειρική και συνδύασε στοιχεία ποιοτικών και ποσοτικών ερευνητικών προσεγγίσεων. Η βασική έρευνα πραγματοποιήθηκε με ερωτηματολόγιο στάσεων με κλειστές ερωτήσεις πολλαπλής επιλογής σε δείγμα 547 εκπαιδευτικών της Πρωτοβάθμιας εκπαίδευσης. Τα αποτελέσματα της έρευνας έδειξαν ότι οι εκπαιδευτικοί έχουν θετική στάση απέναντι στη συνεκπαίδευση και εφαρμόζουν ποικίλες στρατηγικές διδασκαλίας με έμφαση σε αυτές των δομικών μοντέλων (δομισμός, εποικοδομισμός). Διαπιστώθηκε επίσης υψηλός και στατιστικά σημαντικός βαθμός αλληλεπίδρασης μεταξύ ορισμένων χαρακτηριστικών των εκπαιδευτικών (κατάρτιση, εμπειρία, σχολείο, συνεργασίες) και των στρατηγικών διδασκαλίας που εφαρμόζουν κατά τη συνεκπαίδευση των μαθητών με και χωρίς ειδικές εκπαιδευτικές ανάγκες.