bluuebunny/crossref_metadata_2025 huggingface dataset:
Body mass index was linked with multi-cardiometabolic abnormalities in Chinese children and adolescents: a community-based survey
Authors: He Huijing , Pan Li , Du Jianwei , Jin Yuming , Jia Pengben , Shan Guangliang
Published: January 2022

Background

Evidence on how body mass index (BMI) influence cardiometabolic health remains sparse in Chinese children and adolescents, especially in south China. We aim to investigate the effect of overweight and/or obesity on high blood pressure (HBP), dyslipidemia, elevated serum uric acid (SUA) and their clustering among children and adolescents in an island in South China.

Methods

Using multi-stage cluster sampling method, 1577 children and adolescents aged 7–18 in Hainan province, south China, participated in the survey. The association between body mass index and cardiometabolic indexes were explored. Overweight and obesity were classified according to criteria of World Health Organization for children and adolescents aged 5 to 19. Restricted cubic spline models were used to examine the possible non-linear association between BMI and cardiometabolic profiles. Multivariable logistic regression models were fitted to examine the effect size of BMI on cardiometabolic disorders including HBP, elevated SUA and dyslipidemia. Comorbidity of at least two cardiometabolic abnormalities (HBP, dyslipidemia, elevated SUA) was defined as clustering of cardiometabolic risk factors.

Results

Comparing with normal weight and underweight subjects, overweight/obese youths had higher levels of BP, SUA, triglyceride, low-density lipoprotein but lower level of high-density lipoprotein. Overweight/obese youth had higher risk of dyslipidemia (OR:2.89, 95%CI: 1.65–5.06), HBP (OR:2.813, 95%CI: 1.20–6.59) and elevated SUA (OR: 2.493, 95%CI: 1.45–4.27), respectively, than their counterparts. The sex-, age-adjusted prevalence of abnormalities clustering was 32.61% (95% CI: 20.95% to 46.92%) in overweight/obesity group, much higher than in the under/normal weight group (8.85%, 95%CI: 7.44% to 10.48%).

Conclusion

Excess adiposity increased the risk of elevated serum uric acid, serum lipids, blood pressure and their clustering among children and adolescents in south China.
What makes children learn how to swim? – health, lifestyle and environmental factors associated with swimming ability among children in the city of Malmö, Sweden
Authors: Lõhmus Mare , Osooli Mehdi , Pilgaard Frida I. H. , Östergren Per-Olof , Olin Anna , Kling Stefan , Albin Maria , Björk Jonas
Published: January 2022

Background

Swimming ability among children in the city of Malmö, Sweden is strongly affected by socioeconomic differences. We investigated to what extent mediating health and lifestyle factors, such as children’s eating, sleeping and physical activity habits, as well as the characteristics of the social and working environment at both school and home, could explain the socioeconomic gradient in swimming ability.

Methods

Our study population included children who started their first-grade school-year in 2012 or 2013 at any of the public primary schools of Malmö, Sweden. Cross-sectional, self-reported questionnaire-based data about health status and swimming ability in the fourth grade (age 10) were included from the Pupil Health Database (ELSA) for 3468 children.

Results

Children’s self-reported swimming ability was strongly associated with both individual- and school-based sociodemographic variables. Nine health, lifestyle and environmental variables were identified as potential mediators and included in the final model. Four of these variables, “Activity”, “Outdoor time”, “Social relationships at home and on the free time”, and “Positivity about future”, were significantly and positively associated with children’s ability to swim.

Conclusions

Social support, optimism for the future and an active lifestyle were positively associated with children’s swimming skills; however, compared to the socioeconomic factors, these health- and lifestyle factors contributed very little. It is possible, that interventions concerning children’s swimming ability in lower socioeconomic neighbourhoods, should in addition to children’s swimming lessons, target the whole families with the goal of increasing their possibilities for socialising and engaging in different kinds of recreational activities.
Integrative transcriptomic and proteomic analysis reveals mechanisms of silica-induced pulmonary fibrosis in rats
Authors: Bo Cunxiang , Zhang Juan , Sai Linlin , Du Zhongjun , Yu Gongchang , Li Chao , Li Ming , Peng Cheng , Jia Qiang , Shao Hua
Published: January 2022

Background

Silicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis. Although great effort has been made to understand the pathogenesis of the disease, molecular mechanism underlying silicosis is not fully elucidated. This study was aimed to explore proteomic and transcriptomic changes in rat model of silicosis.

Methods

Twenty male Wistar rats were randomly divided into two groups with 10 rats in each group. Rats in the model group were intratracheally instilled with 50 mg/mL silicon dioxide (1 mL per rat) and rats in the control group were treated with 1.0 mL saline (1 mL per rat). Twenty-eight days later, transcriptomic analysis by microarray and tandem mass tags (TMT)-based proteomic analysis were performed to reveal the expression of mRNAs and proteins in lung tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze the altered genes and proteins. The integrated analysis was performed between transcriptome and proteome. The data were further verified by RT-qPCR and parallel reaction monitoring (PRM).

Results

In total, 1769 differentially expressed genes (DEGs) and 650 differentially expressed proteins (DEPs) were identified between the silicosis model and control groups. The integrated analysis showed 250 DEPs were correlated to the corresponding DEGs (cor-DEPs-DEGs), which were mainly enriched in phagosome, leukocyte transendothelial migration, complement and coagulation cascades and cellular adhesion molecule (CAM). These pathways are interrelated and converged at common points to produce an effect. GM2a, CHI3L1, LCN2 and GNAI1 are involved in the extracellular matrix (ECM) and inflammation contributing to fibrosis.

Conclusion

Our comprehensive transcriptome and proteome data provide new insights into the mechanisms of silicosis and helpful information for more targeted prevention and treatment of silicosis.
Application of the QFD-fuzzy-SERVQUAL methodology as a quality planning tool at the surgical centre of a public teaching hospital
Authors: Junior Jurandir Barreto Galdino , Hékis Hélio Roberto , Costa José Alfredo Ferreira , de Andrade Íon Garcia Mascarenhas , dos Santos Cabral Eric Lucas , Castro Wilkson Ricardo Silva , de Medeiros Florentino Davidson Rogério , de Oliveira Barreto Tiago , da Costa Júnior João Florêncio
Published: January 2022

Background

In Brazil, many public hospitals face constant problems related to high demand vis-à-vis an overall scarcity of resources, which hinders the operations of different sectors such as the surgical centre, as it is considered one of the most relevant pillars for the proper hospital functioning, due to its complexity, criticality as well as economic and social importance. Proper asset management based on well-founded decisions is, therefore, a sine-qua-non condition for addressing such demands. However, subjectivity and other difficulties present in decisions make the management of hospital resources a constant challenge.

Methods

Thus, the present work proposes the application of a hybrid approach, formed by the QFD tools, fuzzy logic and SERVQUAL as a decision support tool for the quality planning of the surgical centre of the Onofre Lopes Teaching Hospital (Hospital Universitário Onofre Lopes—HUOL). To accomplish such objective, it was necessary to discover and analyse the main needs of the medical team working in the operating room, through the application of the SERVQUAL questionnaire, associated with fuzzy logic.

Results

Then, the most relevant deficiencies were transformed into entries for the QFD-fuzzy, where they were translated into project requirements. Soon after, the analysis of the existing relationships between the inputs and these requirements was carried out, generating the ranking of actions with the greatest impact on the improvement of the surgical centre overall quality.

Conclusions

As a result, it was found that the proposed methodology can optimize the decision process to which hospital managers are submitted, improving the surgical centre operation efficiency.
Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors
Authors: Kovesdy Csaba , Schmedt Niklas , Folkerts Kerstin , Bowrin Kevin , Raad Hanaya , Batech Michael , Fried Linda
Published: January 2022

Background

Clinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), also referred to as diabetic kidney disease (DKD), who are at even higher risk. In this study, we sought to identify predictors of cardio-kidney events, cardio-kidney complications, and treatment failure (i.e., addition/initiation of a new T2D class, insulin, or discontinuation of SGLT2is) after new initiation of SGLT2is in patients with CKD and T2D (DKD).

Methods

In this retrospective cohort study, we identified adult patients with DKD who initiated SGLT2is between April 1, 2012, and June 30, 2019, in Optum claims data. Outcome rates per 1000 person-years (PY) are reported with 95% confidence intervals (CIs). Cox proportional hazards regression identified patient characteristics associated with each outcome.

Results

The study population consisted of 6389 initiators of SGLT2is. The rate of CV hospitalization was 26.0 (95% CI 21.6, 30.4) per 1000 PY. Baseline characteristics associated with higher risk of CV hospitalization included age, atrial fibrillation, peripheral vascular disease (PVD), and cancer. The rate of kidney hospitalization was 12.0 (95% CI 9.0, 15.0) per 1000 PY. The risk increased significantly with baseline evidence of heart failure, hyperkalemia, respiratory failure, depression, and use of loop diuretics. In total, 55.0% of all SGLT2i initiators discontinued treatment during the follow-up period. The rate of treatment failure was 510.5 (95% CI 492.9, 528.1) per 1000 PY. Analysis of key time-dependent SGLT2i-associated adverse events showed that experiencing diabetic ketoacidosis and volume depletion were associated with risk of treatment failure.

Conclusions

Our study demonstrated high rates of residual cardio-kidney outcomes and treatment failure in patients with DKD treated with SGLT2is. Patients with high baseline CV risk and the presence of certain conditions, such as atrial fibrillation, PVD, and heart failure, were at higher risk for cardio-kidney events. Further research is needed to assess the potential relationship between adverse events and SGLT2i treatment failure.
Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England
Authors: Abner Sophia , Gillies Clare L. , Shabnam Sharmin , Zaccardi Francesco , Seidu Samuel , Davies Melanie J. , Adeyemi Tobi , Khunti Kamlesh , Webb David R.
Published: January 2022

Objective

To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status.

Methods

Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated.

Results

696,255 (mean 4.9 years [95% CI, 2.02–7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47–18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%.

Conclusions

Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs.
Repairing boundaries along pathways to tuberculosis case detection: a qualitative synthesis of intervention designs
Authors: van Wyk Susanna S. , Medley Nancy , Young Taryn , Oliver Sandy
Published: January 2022

Background

Tuberculosis case-finding interventions often involve several activities to enhance patient pathways, and it is unclear which activity defines the type of case-finding intervention. When conducting studies to identify the most effective case-finding intervention it is important to have a clear understanding of these interventions for meaningful comparisons. This review aimed to construct a systems-based logic model of all pathways to tuberculosis case detection through a synthesis of intervention designs.

Methods

We identified an existing systematic review on the effectiveness of interventions to increase tuberculosis case detection and updated the search from December 2016 to October 2020. We included randomized controlled trials, as these designs encourage detailed description of interventions. Taking each study in turn, intervention descriptions were read in detail. The texts were analysed qualitatively by constantly comparing emerging codes to construct patient journeys, visualized as logical chains. Actions taken as part of interventions were positioned along patient journeys to theorize the sequence of outcomes. Patient journeys formed the basis of the model, which was refined through discussion.

Results

Based on intervention descriptions from 17 randomized controlled trials, our model distinguishes two care-seeking pathways and four screening pathways. An open invitation to people with tuberculosis symptoms creates care-seeking pathways. On care-seeking pathways, systematic screening can be conducted at general health services, but not at specific TB care services. People invited to tuberculosis services regardless of symptoms follow tuberculosis screening pathways and may be identified with presumptive tuberculosis even if they do not seek care for tuberculosis symptoms. Tuberculosis screening pathways include screening offered to all people accessing care at general health services, screening at a mobile clinic or health facility with open invitation to a whole population or tuberculosis contacts, screening personally offered to a whole population or tuberculosis contacts at home, work or school, and screening offered to people receiving care for human immunodeficiency virus or other clinical risk-group care.

Conclusion

This systems-based logic model of tuberculosis case-finding pathways may support standardized terminology, consistency, transparency and improved communication among researchers, policy-makers, health workers and community members when implementing and evaluating interventions to improve tuberculosis case detection.
Adapting and validating the log quadratic model to derive under-five age- and cause-specific mortality (U5ACSM): a preliminary analysis
Authors: Perin Jamie , Chu Yue , Villavicencio Francisco , Schumacher Austin , McCormick Tyler , Guillot Michel , Liu Li
Published: January 2022

Background

The mortality pattern from birth to age five is known to vary by underlying cause of mortality, which has been documented in multiple instances. Many countries without high functioning vital registration systems could benefit from estimates of age- and cause-specific mortality to inform health programming, however, to date the causes of under-five death have only been described for broad age categories such as for neonates (0–27 days), infants (0–11 months), and children age 12–59 months.

Methods

We adapt the log quadratic model to mortality patterns for children under five to all-cause child mortality and then to age- and cause-specific mortality (U5ACSM). We apply these methods to empirical sample registration system mortality data in China from 1996 to 2015. Based on these empirical data, we simulate probabilities of mortality in the case when the true relationships between age and mortality by cause are known.

Results

We estimate U5ACSM within 0.1–0.7 deaths per 1000 livebirths in hold out strata for life tables constructed from the China sample registration system, representing considerable improvement compared to an error of 1.2 per 1000 livebirths using a standard approach. This improved prediction error for U5ACSM is consistently demonstrated for all-cause as well as pneumonia- and injury-specific mortality. We also consistently identified cause-specific mortality patterns in simulated mortality scenarios.

Conclusion

The log quadratic model is a significant improvement over the standard approach for deriving U5ACSM based on both simulation and empirical results.
Development and validation of dietary and lifestyle insulinemic indices among Iranian adult population
Authors: Mokhtari Ebrahim , Teymoori Farshad , Farhadnejad Hossein , Mirmiran Parvin , Azizi Fereidoun
Published: January 2022

Background

There is no study regarding developing a valid index to predict insulin-related disorders in the Iranian population based on their dietary habits and lifestyle. In the current study, we aimed to develop and validate insulinemic potential indices of diet and lifestyle in Iranian adults.

Methods

In this cross-sectional study, we analysed data of 1063 men and women aged ≥ 25 years among participants of the examination three of Tehran lipid and glucose study (TLGS) (2006–2008). Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle indices were developed using stepwise linear regression analysis based on dietary intakes, body mass index, and physical activity data. Fasting serum insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) were used as biomarkers of hyperinsulinemia (HI) and insulin resistance (IR). Validation analyses were performed in examination four of TLGS.

Results

We developed four indices related to insulin homeostasis, including the dietary index for HI (DIH), the dietary index for IR (DIR), the lifestyle index for HI (LIH), and the lifestyle index for IR (LIR). Based on multivariable-adjusted models, the relative values of the biomarker in subjects in the highest quartile of indices were 45% for LIH (95% CI 1.36–1.55, Ptrend < 0.001), 28% for DIR (95% CI 1.13–1.42, Ptrend = 0.019), and 51% for LIR (95% CI 1.41–1.61, Ptrend < 0.001), higher than those in the reference quartile, respectively.

Conclusion

We designed and validated indices to determine the insulin potential of diet and lifestyle for the Iranian population, according to Iran’s demographic and dietary intake characteristics.
Multifocal EBV-associated smooth muscle tumors in a patient with cytomegalovirus infection after liver transplantation: a case report from Shiraz, Iran
Authors: Anbardar Mohammad Hossein , Soleimani Neda , Safavi Dornaz , Eshraghian Ahad , Ayoub Abbas
Published: January 2022

Introduction

Immunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein–Barr virus (EBV) is considered to be involved in the etiology of this neoplasm.

Case report

A 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions.

Conclusion

Although the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors.
Characteristics of HER2-negative breast cancers with FISH-equivocal status according to 2018 ASCO/CAP guideline
Authors: Kong Hui , Bai Qianming , Li Anqi , Zhou Xiaoyan , Yang Wentao
Published: January 2022

Background

According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.

Methods

195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0–4.4, 4.5–4.9, 5.0–5.4, 5.5–5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed.

Results

183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn’t receive targeted therapy.

Conclusions

In this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.
Correlation of MRI and arthroscopic findings with clinical outcome in temporomandibular joint disorders: a retrospective cohort study
Authors: Vervaeke Kobbe , Verhelst Pieter-Jan , Orhan Kaan , Lund Bodil , Benchimol Daniel , Van der Cruyssen Fréderic , De Laat Antoon , Jacobs Reinhilde , Politis Constantinus
Published: January 2022

Background

Arthroscopy is a minimally invasive diagnostic tool and treatment strategy in patients suffering from temporomandibular disorders (TMD) when conservative treatment fails. This study aimed to find specific variables on pre-operative MRI or during arthroscopy that could predict success of arthroscopic lysis and lavage.

Methods

This retrospective analysis compared pre-operative maximum interincisal opening (MIO), pain and main complaint (pain, limited MIO or joint sounds) with results at short-term and medium-term follow-up (ST and MT respectively). Different variables scored on MRI or arthroscopy were used to make a stepwise regression model, subsequently a combined analysis was conducted using variables from both MRI and arthroscopy.

Results

A total of 47 patients (50 joints) met the inclusion criteria. The main complaint improved by 62 and 53% at ST and MT respectively. The absolute or probable absence of a crumpled disc scored on MRI predicted success at ST and MT (p = 0.0112 and p = 0.0054), and remained significant at MT in the combined analysis (p = 0.0078). Arthroscopic findings of degenerative joint disease predicted success at ST (p = 0.0178), absolute or probable absence of discal reduction scored during arthroscopy significantly predicted success in the combined analysis at ST (p = 0.0474).

Conclusion

To improve selection criteria for patients undergoing an arthroscopic lysis and lavage of the TMJ, future research might focus on variables visualized on MRI. Although more research is needed, disc shape and in particular the absolute or probable absence of a crumpled disc might be used as predictive variable for success.
Pathological α-synuclein recruits LRRK2 expressing pro-inflammatory monocytes to the brain
Authors: Xu Enquan , Boddu Ravindra , Abdelmotilib Hisham A. , Sokratian Arpine , Kelly Kaela , Liu Zhiyong , Bryant Nicole , Chandra Sidhanth , Carlisle Samantha M. , Lefkowitz Elliot J. , Harms Ashley S. , Benveniste Etty N. , Yacoubian Talene A. , Volpicelli-Daley Laura A. , Standaert David G. , West Andrew B.
Published: January 2022

Background

Leucine rich repeat kinase 2 (LRRK2) and SNCA are genetically linked to late-onset Parkinson’s disease (PD). Aggregated α-synuclein pathologically defines PD. Recent studies identified elevated LRRK2 expression in pro-inflammatory CD16+ monocytes in idiopathic PD, as well as increased phosphorylation of the LRRK2 kinase substrate Rab10 in monocytes in some LRRK2 mutation carriers. Brain-engrafting pro-inflammatory monocytes have been implicated in dopaminergic neurodegeneration in PD models. Here we examine how α-synuclein and LRRK2 interact in monocytes and subsequent neuroinflammatory responses.

Methods

Human and mouse monocytes were differentiated to distinct transcriptional states resembling macrophages, dendritic cells, or microglia, and exposed to well-characterized human or mouse α-synuclein fibrils. LRRK2 expression and LRRK2-dependent Rab10 phosphorylation were measured with monoclonal antibodies, and myeloid cell responses to α-synuclein fibrils in R1441C-Lrrk2 knock-in mice or G2019S-Lrrk2 BAC mice were evaluated by flow cytometry. Chemotaxis assays were performed with monocyte-derived macrophages stimulated with α-synuclein fibrils and microglia in Boyden chambers.

Results

α-synuclein fibrils robustly stimulate LRRK2 and Rab10 phosphorylation in human and mouse macrophages and dendritic-like cells. In these cells, α-synuclein fibrils stimulate LRRK2 through JAK-STAT activation and intrinsic LRRK2 kinase activity in a feed-forward pathway that upregulates phosphorylated Rab10. In contrast, LRRK2 expression and Rab10 phosphorylation are both suppressed in microglia-like cells that are otherwise highly responsive to α-synuclein fibrils. Corroborating these results, LRRK2 expression in the brain parenchyma occurs in pro-inflammatory monocytes infiltrating from the periphery, distinct from brain-resident microglia. Mice expressing pathogenic LRRK2 mutations G2019S or R1441C have increased numbers of infiltrating pro-inflammatory monocytes in acute response to α-synuclein fibrils. In primary cultured macrophages, LRRK2 kinase inhibition dampens α-synuclein fibril and microglia-stimulated chemotaxis.

Conclusions

Pathologic α-synuclein activates LRRK2 expression and kinase activity in monocytes and induces their recruitment to the brain. These results predict that LRRK2 kinase inhibition may attenuate damaging pro-inflammatory monocyte responses in the brain.
Predictive factors of endometriosis progression into ovarian cancer
Authors: Varga Ján , Reviczká Alžbeta , Háková Hedviga , Švajdler Peter , Rabajdová Miroslava , Ostró Alexander
Published: January 2022

Background

In recent years, the endometriosis has overcome a noteworthy renaissance in the recognition of its potential. In certain patients, a demonstrable malignant progression of ectopic foci leading to development of ovarian cancer is seen. The knowledge of endometriosis overthrow background into endometriosis associated ovarian cancer is of paramount importance for selection of patients at risk. The goal of the presented study was to review a malignant potential of the endometriosis and to specify predictive factors of endometriosis progression into ovarian cancer. Altogether 189 patients were included in the study. Conventional cytogenetics as well as measurement of transcriptional activity of CTNNB1 (β-catenin) and HIF1A (HIF1-α) genes were prospectively studied in 60 endometriosis patients and 50 control group patients. The retrospective histopathological analysis was performed in 19 endometriosis associated ovarian cancer patients and 60 patients with histologically confirmed endometriosis.

Results

Five endometriosis patients showed a deviation from normal cytogenetics finding without affecting of their phenotype. In 6 cases of endometriosis associated ovarian cancer ectopic endometrium was not confirmed. The remaining 13 cases demonstrated either benign or atypical endometriosis or even structures of borderline carcinoma. Atypical endometriosis was histologically confirmed in 20% of 60 endometriosis patients. Determination of gene expression (CTNNB1, HIF1A) formed two subgroups. Transcriptionally incipient endometriosis subgroup with insignificant genes expression compared to control group. In transcriptionally evident endometriosis subgroup were genes expressions significantly higher compared to control group (p < 0.01) as well as transcriptionally incipient endometriosis subgroup (p < 0.05).

Conclusions

Significant structural abnormalities of chromosomes are not included in genetic rigging of endometriosis patients. Atypical endometriosis represents a histopathologically detectable intermediate of endometriosis progression. Determination of genes expression CTNNB1 and HIF1A helps to allocate risk patients with endometriosis where more precise management is needed.
LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway
Authors: Zhang Wei , Liang Feng , Li Qingfeng , Sun Hong , Li Fei , Jiao Zhibo , Lei Jie
Published: January 2022

Background

Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated.

Methods

MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells.

Results

MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway.

Conclusion

MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.
Awake prone positioning in nonintubated spontaneous breathing ICU patients with acute hypoxemic respiratory failure (PRONELIFE)—protocol for a randomized clinical trial
Authors: Morales-Quinteros L. , Schultz M. J. , Serpa-Neto A. , Antonelli M. , Grieco D. L. , Roca O. , Juffermans N. P. , de Haro C. , de Mendoza D. , Blanch Ll. , Camprubí-Rimblas M. , Gomà Gemma , Artigas-Raventós A. ,   for the PRONELIFE collaborative group
Published: January 2022

Background

It is uncertain whether awake prone positioning can prevent intubation for invasive ventilation in spontaneous breathing critically ill patients with acute hypoxemic respiratory failure. Awake prone positioning could benefit these patients for various reasons, including a reduction in direct harm to lung tissue, and prevention of tracheal intubation-related complications.

Design and methods

The PRONELIFE study is an investigator-initiated, international, multicenter, randomized clinical trial in patients who may need invasive ventilation because of acute hypoxemic respiratory failure. Consecutive patients admitted to participating ICUs are randomly assigned to standard care with awake prone positioning, versus standard care without awake prone positioning. The primary endpoint is a composite of tracheal intubation and all-cause mortality in the first 14 days after enrolment. Secondary endpoints include time to tracheal intubation and effects of awake prone positioning on oxygenation parameters, dyspnea sensation, and complications. Other endpoints are the number of days free from ventilation and alive at 28 days, total duration of use of noninvasive respiratory support, total duration of invasive ventilation, length of stay in ICU and hospital, and mortality in ICU and hospital, and at 28, 60, and 90 days. We will also collect data regarding the tolerance of prone positioning.

Discussion

The PRONELIFE study is among the first randomized clinical trials investigating the effect of awake prone positioning on intubation rate in ICU patients with acute hypoxemic failure from any cause. The PRONELIFE study is sufficiently sized to determine the effect of awake prone positioning on intubation for invasive ventilation—patients are eligible in case of acute hypoxemic respiratory failure without restrictions regarding etiology. The PRONELIFE study is a pragmatic trial in which blinding is impossible—however, as around 35 ICUs worldwide will participate in this study, its findings will be highly generalizable. The findings of the PRONELIFE study have the potential to change clinical management of patients who may need invasive ventilation because of acute hypoxemic respiratory failure.

Trial registration

ISRCTN ISRCTN11536318. Registered on 17 September 2021. The PRONELIFE study is registered at clinicaltrials.gov with reference number NCT04142736 (October, 2019).
Performance evaluation and comparison study of adaptive MANET service location and discovery protocols for highly dynamic environments
Authors: Ben Brahim Ghassen , Mohammad Nazeeruddin , El-Hajj Wassim , Parr Gerard , Scotney Bryan
Published: January 2022

A critical requirement in Mobile Ad Hoc Networks (MANETs) is its ability to automatically discover existing services as well as their locations. Several solutions have been proposed in various communication domains which could be classified into two categories: (1) directory based, and (2) directory-less. The former is efficient but suffers from the amount of control messages being exchanged to maintain all directories in an agile environment. However, the latter approach attempts to reduce the amount of control messages to update directories, by simply sending broadcast messages to discover services; which is also a non-desirable approach in MANETs. This research work builds on top of our prior work (Nazeeruddin et al. in IFIP/IEEE international conference on management of multimedia networks and services, Springer, Berlin, 2006)) where we introduced a new efficient protocol for service discovery in MANETs (MSLD); a lightweight, robust, scalable, and flexible protocol which supports node heterogeneity and dynamically adapts to network changes while not flooding the network with extra protocol messages—a major challenge in today’s network environments, such as Internet of Things (IoT). Extensive simulations study was conducted on MSLD to: (1) initially evaluate its performance in terms of latency, service availability, and overhead messages, then (2) compare its performance to Dir-Based, Dir-less, and PDP protocols under various network conditions. For most performance metrics, simulation results show that MSLD outperforms Dir-Based, Dir-less, and PDP by either matching or achieving high service availability, low service discovery latency, and considerably less communication overhead.
Two efficient modifications of AZPRP conjugate gradient method with sufficient descent property
Authors: Salleh Zabidin , Almarashi Adel , Alhawarat Ahmad
Published: January 2022

The conjugate gradient method can be applied in many fields, such as neural networks, image restoration, machine learning, deep learning, and many others. Polak–Ribiere–Polyak and Hestenses–Stiefel conjugate gradient methods are considered as the most efficient methods to solve nonlinear optimization problems. However, both methods cannot satisfy the descent property or global convergence property for general nonlinear functions. In this paper, we present two new modifications of the PRP method with restart conditions. The proposed conjugate gradient methods satisfy the global convergence property and descent property for general nonlinear functions. The numerical results show that the new modifications are more efficient than recent CG methods in terms of number of iterations, number of function evaluations, number of gradient evaluations, and CPU time.
Homologous tumor cell membrane vesicles active preferential self-recognition of tumor cells in vitro
Authors: Wu Chenghu , Yu Ailin , Chen Yue , Fan Mingbo
Published: January 2022

Cell membrane vesicles, as delivery carriers of drugs or biological agents in vivo, are an important therapeutic mode in the study of disease treatment. Tumor membrane-derived vesicles have been widely used in tumor therapy because of their good tumor enrichment effect. The most common method is the surface of nanoparticles coated with tumor cell membrane, which can effectively prolong the circulation time of particles in the blood and the enrichment of tumors. In this study, we prepared vesicles of different tumor cell membrane derivate and studied their targeting to tumors detailly. The results showed that homologous vesicles have high targeting to homologous tumor cells. The fluorescence of vesicles in homologous tumor cells was significantly higher than that in other tumor cells. This study will provide a new strategy and guidance for the clinical treatment of cancer based on the tumor cell membrane system.

Graphical Abstract
Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival
Authors: Ebrahimi Azadeh , Korshunov Andrey , Reifenberger Guido , Capper David , Felsberg Joerg , Trisolini Elena , Pollo Bianca , Calatozzolo Chiara , Prinz Marco , Staszewski Ori , Schweizer Leonille , Schittenhelm Jens , Harter Patrick N. , Paulus Werner , Thomas Christian , Kohlhof-Meinecke Patricia , Seiz-Rosenhagen Marcel , Milde Till , Casalini Belén M. , Suwala Abigail , Wefers Annika K. , Reinhardt Annekathrin , Sievers Philipp , Kramm Christof M. , Etminam Nima , Unterberg Andreas , Wick Wolfgang , Herold-Mende Christel , Sturm Dominik , Pfister Stefan M. , Sill Martin , Jones David T. W. , Schrimpf Daniel , Reuss David E. , Aldape Ken , Abdullaev Zied , Sahm Felix , von Deimling Andreas , Stichel Damian
Published: January 2022

Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.
Investigating the effect of bruxism on maxillary arch length and width in children using three-dimensional digital model analysis
Authors: Hazar Bodrumlu Ebru , Çakmak Özlü Fethiye , Yılmaz Hakan , Demiriz Levent
Published: January 2022

Background

Bruxism is defined as repetitive jaw-muscle activity characterized by the grinding and clenching of teeth. The prevalence of bruxism in children is extensive, and it can cause irregularities in dental arches. The study aimed to investigate the presence of any effects of bruxism on maxillary arch length and width in children using three-dimensional (3D) digital model analysis.

Method

This study evaluated 30 children with bruxism. For every child with bruxism, a case control without bruxism was selected and matched for gender, age, and dentition. Digital models of the patients’ maxilla were obtained with a 3D intraoral scanner, and width and length measurements between the reference points on the maxilla were obtained on the digital models.

Results

The mean age of the study group was 9.13 ± 1.27. Insıgnificance differences were found between females and males within and between groups in terms of maxillary width and length. Insignificant difference was found between the control and study groups when the lengths of 3R-3L, 4R-4L, 5R-5L, 6R-6L, and IP-M were compared (p > 0.05).

Conclusion

Based on the study results, there were no differences in the maxillary arch length and width in patients with bruxism and patients without bruxism.
Anterior cruciate ligament reconstruction, can an anatomic femoral tunnel be achieved with the trans-tibial technique? Cadaveric study
Authors: Acevedo Tobler Daniel , Hermosilla Santiago , Otero Natalia , Kenny Juan , Del Castillo Juan
Published: January 2022

Purpose

To evaluate the possibility to access the anatomic femoral insertion of the anterior cruciate ligament (ACL) through trans-tibial (TT) and trans-portal technique, for ACL reconstruction in an independent way. To register anatomical characteristics of the TT tunnels.

Methods

Ten formaldehyde preserved knee anatomic articular specimens were dissected. Femoral tunnels were confectioned reproducing the original topography of the ACL. First, the femoral tunnel was made with the independent trans-portal technique. Then, utilizing the tibial stump of the ACL and tibial guides at 45°, the TT tunnels were confectioned trying to match the previously made femoral tunnel by trans-portal technique.

Results

In all specimens, match between the TT tunnel with the independent trans-portal tunnel was achieved. Mean values for TT coronal angle was 53,0°, for transversal angle 43,3° and for distance from tunnel to joint line 2,55 cm. A horizontalization and medialization of the TT tunnels had to be made to adequately match with the femoral tunnel made by the independent trans-portal technique.

Conclusions

By macroscopic anatomic and independent means, an anatomic femoral tunnel was confectioned with the TT technique matching with the anatomic femoral tunnel made in an independent way. As clinical relevance, the present study allows to anatomically assess the possibility to perform an anatomic femoral tunnel through the TT technique.

Level of evidence

V