bluuebunny/crossref_metadata_2025 huggingface dataset:
“Current dementia care: what are the difficulties and how can we advance care globally?”
Authors: Giebel Clarissa
Published: May 2020

Background

Dementia is a growing global public health concern, with post-diagnostic care often very limited. Depending on where people live, both within a country and depending on high-, middle-, and low-income countries, they might also face barriers in accessing the right care at the right time. Therefore, it is important to highlight recent evidence on the facilitators and barriers to dementia care, but also evidence on how to move dementia care forward.

Main text

Current dementia care is subject to several inequalities, including living in rural regions and being from a minority ethnic background. Evidence in this collection highlights the issues that both people living with dementia and unpaid carers are facing in accessing the right care, with evidence from Australia, Canada, Uganda, to the Netherlands, and further afield. Providing improved dementia-specific training to health care professionals and supporting medication and reablement interventions have been identified as possible ways to improve dementia care for all.

Conclusions

This special issue focuses on recent evidence on inequalities in dementia care across the globe and how dementia care can be advanced in various areas.
A retrospective review of 10-year trends in general anesthesia for cesarean delivery at a university hospital: the impact of a newly launched team on obstetric anesthesia practice
Authors: Ikeda Takamitsu , Kato Atsuko , Bougaki Masahiko , Araki Yuko , Ohata Takuya , Kawashima Seiichiro , Imai Yousuke , Ninagawa Jun , Oba Koji , Chang Kyungho , Uchida Kanji , Yamada Yoshitsugu
Published: May 2020

Background

The indications for general anesthesia (GA) in obstetric settings, which are determined in consideration of maternal and fetal outcome, could be affected by local patterns of clinical practice grounded in unique situations and circumstances that vary among medical institutions. Although the use of GA for cesarean delivery has become less common with more frequent adoption of neuraxial anesthesia, GA was previously chosen for pregnancy with placenta previa at our institution in case of unexpected massive hemorrhage. However, the situation has been gradually changing since formation of a team dedicated to obstetric anesthesia practice. Here, we report the results of a review of all cesarean deliveries performed under GA, and assess the impact of our newly launched team on trends in clinical obstetric anesthesia practice at our institution.

Methods

Our original database for obstetric GA during the period of 2010 to 2019 was analyzed. The medical records of all parturients who received GA for cesarean delivery were reviewed to collect detailed information. Interrupted time series analysis was used to evaluate the impact of the launch of our obstetric anesthesia team.

Results

As recently as 2014, more than 10% of cesarean deliveries were performed under GA, with placenta previa accounting for the main indication in elective and emergent cases. Our obstetric anesthesia team was formed in 2015 to serve as a communication bridge between the department of anesthesiology and the department of obstetrics. Since then, there has been a steady decline in the percentage of cesarean deliveries performed under GA, decreasing to a low of less than 5% in the latest 2 years. Interrupted time series analysis revealed a significant reduction in obstetric GA after 2015 (P = 0.04), which was associated with decreased use of GA for pregnancy with placenta previa. On the other hand, every year has seen a number of urgent cesarean deliveries requiring GA.

Conclusions

There has been a trend towards fewer obstetric GA since 2015. The optimized use of GA for cesarean delivery was made possible mainly through strengthened partnerships between anesthesiologists and obstetricians with the support of our obstetric anesthesia team.
Does fine particulate matter (PM2.5) affect the benefits of habitual physical activity on lung function in adults: a longitudinal cohort study
Authors: Guo Cui , Bo Yacong , Chan Ta-Chien , Zhang Zilong , Lin Changqing , Tam Tony , Lau Alexis K. H. , Chang Ly-yun , Hoek Gerard , Lao Xiang Qian
Published: May 2020

Background

Physical activity (PA) increases a person’s inhalation of air pollutants due to greater ventilation, possibly leading to larger adverse health effects. This study aims to investigate the combined effects of long-term exposure to fine particulate matter (PM2.5) and habitual PA on lung function in adults.

Methods

This was a longitudinal cohort study that included 278,065 Taiwan residents with an age of 20 years old or above who joined a standard medical screening programme between 2001 and 2014. Each participant received at least one medical examination (including spirometric, blood, and urinary tests and a standard self-administered questionnaire survey) during the study period. We estimated the 2-year average PM2.5 concentrations at each participant’s address using a new physical model based on observational data. Information on the participants’ PA was collected using the standard self-administrated questionnaire. Generalised linear mixed models were used to investigate the combined effects of PM2.5 and PA on pulmonary function. We also performed stratified analyses by different levels of PM2.5 exposure and habitual PA.

Results

Each 10 MET-h increase in PA was associated with a higher level of 0.20%, 0.16%, and 0.19% in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum mid-expiratory flow (MMEF), respectively, after adjusting for PM2.5 exposure and a wide range of covariates including age, sex education, body mass index, lifestyles, and health conditions. Each 10 μg/m3 increase in PM2.5 was associated with a lower FVC, FEV1, and MMEF (2.43%, 2.78% and 3.10%, respectively). Negative interactions were observed, and PM2.5 exposure was associated with a greater reduction in lung function among the participants with higher PA levels.

Conclusions

We found significant negative interaction effects between long-term exposure to PM2.5 and habitual PA, suggesting that the increased intake of PM2.5 due to PA may attenuate the benefits of habitual PA on lung function. However, the PA benefits generally remained stable at different stratum of PM2.5 in the stratified analyses, and habitual PA may still be recommended to people residing in relatively polluted regions.
Association of sleep disturbance with risk of cardiovascular disease and all-cause mortality in patients with new-onset type 2 diabetes: data from the Korean NHIS-HEALS
Authors: Choi Young , Choi Jae Woo
Published: May 2020

Background

Sleep disturbance has been significantly associated with the incidence of cardiovascular disease (CVD) in the general population. However, despite the common prevalence of sleep disturbance in patients with type 2 diabetes, its relationship with the risk of CVD remains unclear. Here, we have examined the association of sleep disturbance with the incidence of all CVD and all-cause mortality in patients with newly-diagnosed type 2 diabetes.

Methods

We used the Korean National Health Insurance Service–Health Screening Cohort data and included 36,058 patients with new-onset type 2 diabetes aged ≥ 40 years between 2004 and 2007, along with follow-up examinations to 2013. We used the ICD-10 code to measure sleep disturbance as a primary diagnosis and the multivariable Cox proportional hazards regression models to estimate the adjusted hazard ratio (AHR) and 95% confidence interval (CI) of all CVD, coronary heart disease (CHD), stroke, and all-cause mortality.

Results

We identified 6897 cases of all CVD (CHD, n = 4138; stroke, n = 2759) and 2890 events of all-cause mortality during a mean follow-up period of 7.0 years. Sleep disturbance was associated with an increased risk of All CVD (AHR, 1.24; 95% CI, 1.06–1.46), CHD events (AHR, 1.24; 95% CI, 1.00–1.53), and all-cause mortality (AHR, 1.47; 95% CI, 1.15–1.87) in patients with new-onset type 2 diabetes. Furthermore, women (AHR, 1.33; 95% CI, 1.06–1.67) and middle-aged adults (AHR, 1.29; 95% CI, 1.02–1.64) with sleep disturbance had a significantly increased risk of CVD than those without; contrarily, men (AHR, 1.45; 95% CI, 1.09–1.95) and older adults (AHR, 1.51; 95% CI, 1.15–1.99) with sleep disturbance were associated with a significantly increased risk of all-cause mortality than those without.

Conclusions

Our findings suggest that sleep disturbance is significantly associated with an increased risk of CVD and all-cause mortality in patients with new-onset type 2 diabetes.
Autophagy-dependent and -independent modulation of oxidative and organellar stress in the diabetic heart by glucose-lowering drugs
Authors: Packer Milton
Published: May 2020

Autophagy is a lysosome-dependent intracellular degradative pathway, which mediates the cellular adaptation to nutrient and oxygen depletion as well as to oxidative and endoplasmic reticulum stress. The molecular mechanisms that stimulate autophagy include the activation of energy deprivation sensors, sirtuin-1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK). These enzymes not only promote organellar integrity directly, but they also enhance autophagic flux, which leads to the removal of dysfunctional mitochondria and peroxisomes. Type 2 diabetes is characterized by suppression of SIRT1 and AMPK signaling as well as an impairment of autophagy; these derangements contribute to an increase in oxidative stress and the development of cardiomyopathy. Antihyperglycemic drugs that signal through insulin may further suppress autophagy and worsen heart failure. In contrast, metformin and SGLT2 inhibitors activate SIRT1 and/or AMPK and promote autophagic flux to varying degrees in cardiomyocytes, which may explain their benefits in experimental cardiomyopathy. However, metformin and SGLT2 inhibitors differ meaningfully in the molecular mechanisms that underlie their effects on the heart. Whereas metformin primarily acts as an agonist of AMPK, SGLT2 inhibitors induce a fasting-like state that is accompanied by ketogenesis, a biomarker of enhanced SIRT1 signaling. Preferential SIRT1 activation may also explain the ability of SGLT2 inhibitors to stimulate erythropoiesis and reduce uric acid (a biomarker of oxidative stress)—effects that are not seen with metformin. Changes in both hematocrit and serum urate are the most important predictors of the ability of SGLT2 inhibitors to reduce the risk of cardiovascular death and hospitalization for heart failure in large-scale trials. Metformin and SGLT2 inhibitors may also differ in their ability to mitigate diabetes-related increases in intracellular sodium concentration and its adverse effects on mitochondrial functional integrity. Differences in the actions of SGLT2 inhibitors and metformin may reflect the distinctive molecular pathways that explain differences in the cardioprotective effects of these drugs.
Association of human XPA rs1800975 polymorphism and cancer susceptibility: an integrative analysis of 71 case–control studies
Authors: Yuan Maoxi , Yu Chunmei , Yu Kuiying
Published: May 2020

Background

The objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A (XPA) gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence.

Methods

We retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case–control studies for pooled assessment.P-values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg’s test and Egger’s test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses.

Results

In total, 71 case–control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (P < 0.05, OR > 1). A similar positive conclusion was also detected in the “skin cancer” or “skin basal cell carcinoma (BCC)” subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes ofXPAin the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (P < 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (P < 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between theXPArs1800975 A/G polymorphism and the risk of lung or colorectal cancer.

Conclusions

Our findings provide evidence of the close relationship between theXPArs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect ofXPArs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.
Item analysis of the Eating Assessment Tool (EAT-10) by the Rasch model: a secondary analysis of cross-sectional survey data obtained among community-dwelling elders
Authors: Hansen Tina , Kjaersgaard Annette
Published: May 2020

Background

The Eating Assessment Tool (EAT-10) is increasingly used to screen for self-perceived oropharyngeal dysphagia (OD) in community-dwelling elders. A summated EAT-10 total score ranges from 0 to 40, with a score ≥ 3 indicative of OD. When using cut-points of a summated score, important requirements for the measurements are specific objectivity, validity, and reliability. Analysis by the Rasch model allows investigation of whether scales like EAT-10 satisfy these requirements. Currently, a few studies have found that EAT-10 responses from clinical populations with OD do not adequately fit the Rasch model.

Purpose

The aim of this study was to determine whether measurements by EAT-10 fit the Rasch model when applied in screening self-perceived OD in non-clinical populations.

Methods

Secondary analysis was conducted on data from a cross-sectional survey of community-dwelling elders living in a municipal district of Tokyo, Japan, in which 1875 respondents completed the Japanese version of EAT-10 (J-EAT-10). Data were cleaned and recoded for the purpose of the analysis in this study, which resulted in inclusion of J-EAT-10 responses from 1144 respondents. Data were analyzed using RUMM2030 and included overall model fit, reliability, unidimensionality, threshold ordering, individual item and person fits, differential item functioning, local item dependency, and targeting.

Results

The analysis identified that the response categories from zero to four were not used as intended and did not display monotonicity, which necessitated reducing the five categories to three. Considerable floor effect was demonstrated and there was an inappropriate match between items’ and respondents’ estimates. The person separation reliability (PSI = 0.65) was inadequate, indicating that it is not possible to differentiate between different levels of OD. Several items displayed misfit with the Rasch model, and there were local item dependency and several redundant items.

Conclusions

J-EAT-10 performed less than optimally and exhibited substantial floor effect, low reliability, a rating scale not working as intended, and several redundant items. Different improvement strategies failed to resolve the identified problems. Use of J-EAT-10 in population-based surveys cannot therefore be recommended. For such purpose, alternative screening tools of self-perceived OD should be chosen or a new one should be developed and validated.
A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID)
Authors: Huth Teilah Kathryn , Eaton-Fitch Natalie , Staines Donald , Marshall-Gradisnik Sonya
Published: May 2020

Background

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been proposed that metabolomics may contribute to the illness pathogenesis of CFS/ME/SEID. In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID.

Methods

PubMed, Scopus, EBSCOHost (Medline) and EMBASE were searched using medical subject headings terms for Chronic Fatigue Syndrome, metabolomics and metabolome to source papers published from 1994 to 2020. Inclusion and exclusion criteria were used to identify studies reporting on metabolites measured in blood and urine samples from CFS/ME/SEID patients compared with healthy controls. The Joanna Briggs Institute Checklist was used to complete a quality assessment for all the studies included in this review.

Results

11 observational case control studies met the inclusion criteria for this review. The primary outcome of metabolite measurement in blood samples of CFS/ME/SEID patients was reported in ten studies. The secondary outcome of urine metabolites was measured in three of the included studies. No studies were excluded from this review based on a low-quality assessment score, however there was inconsistency in the scientific research design of the included studies. Metabolites associated with the amino acid pathway were the most commonly impaired with significant results in seven out of the 10 studies. However, no specific metabolite was consistently impaired across all of the studies. Urine metabolite results were also inconsistent.

Conclusion

The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.
Dysregulation of miR-3607 predicts prognosis of hepatocellular carcinoma and regulates tumor cell proliferation, migration and invasion
Authors: Dou Wenwen , Yang Min , Su Yan , Xie Ruizhu
Published: May 2020

Background

Hepatocellular carcinoma (HCC) is one of the most common global malignancies with increasing morbidity and mortality. The purpose of this study was to investigate the expression levels and prognostic value of microRNA-3607 (miR-3607) in patients with HCC.

Methods

The expression of miR-3607 was estimated by quantitative real-time RT-PCR. Survival analysis using the Kaplan-Meier method and Cox regression analysis was conducted to evaluate the prognostic value of miR-3607. The functional role of miR-3607 in HCC progression was further assessed using gain- and loss-of-function experiments. Bioinformatics analysis and a dual-luciferase reporter assay were used to explore the direct targets of miR-3607.

Results

miR-3607 expression was found to be significantly decreased in HCC tissues and cells compared with the matched tissues and cells (P < 0.001). The decreased expression of miR-3607 was associated with the patients’ tumor size and TNM stage (all P < 0.05). According to the survival curves, patients with low miR-3607 expression had poorer overall survival than those with high levels (log-rank P = 0.012). Moreover, the Cox analysis results indicated that miR-3607 expression was an independent prognostic factor for HCC. The results of cell experiments revealed that the overexpression of miR-3607 in HCC cells led to the inhibited cell proliferation, migration, and invasion. TGFBR1 was identified as a direct target of miR-3607.

Conclusion

The data of this study indicated that the decreased expression of miR-3607 in HCC predicts poor prognosis and the overexpression of miR-3607 in HCC cells can suppress the tumor progression by targeting TGFBR1. This study provides a novel insight into the prognosis and treatment of HCC, and miR-3607 serves as a candidate prognostic biomarker and therapeutic target of HCC.
Judicial outcome and follow up of abused child protection acts in a pediatric emergency department: 12-year experience in a third level pediatric hospital
Authors: Poropat Federico , Canuto Arianna , Caddeo Giulia , Predonzani Erica , Novello Laura , Zorzetto Alessandra , Germani Claudio , Barbi Egidio
Published: May 2020

Background

Italian laws allow the protection of a child who is suspected to be a victim of abuse through a procedure that can be put in motion by the attending physician in any Emergency Department (article nr. 403 Civil Code) with a temporarily suspension of parental authority.

This study aims at evaluating both the appropriateness of the activation of the protection procedure by ED doctors in cases of suspected child abuse in terms of judicial confirmation and how it impacts children in the long-term.

Methods

We selected cases in which the procedure was activated due to suspected child abuse. The children were admitted to the ED of a tertiary children hospital from 2006 to 2018. We then reviewed the medical charts and collected data from the social services through a questionnaire concerning the long-term outcomes .

Results

Twenty-eight patients were included (75% females, mean age 13.8 years). In 90% of cases the activation of the procedure in the ED was followed by a Court confirmation. Evaluation of long term outcome was possible in 22 cases. Among them, a positive social outcome was achieved in 15 cases (68.2%). The remaining abandoned the program or had critical reintegration in the family. Eighteen percent of patients developed major issues such as aberrant behaviours, substance abuse or psychiatric disorders.

Conclusions

This report identifies a good ability of ED doctors in the activation of an emergency procedure to protect the child. Overall, the social outcome was good for nearly 70% of the patients, highlighting the importance of activation of social support programs for child abuse.
Frequency and spectrum of PIK3CA somatic mutations in breast cancer
Authors: Martínez-Sáez Olga , Chic Nuria , Pascual Tomás , Adamo Barbara , Vidal Maria , González-Farré Blanca , Sanfeliu Esther , Schettini Francesco , Conte Benedetta , Brasó-Maristany Fara , Rodríguez Adela , Martínez Débora , Galván Patricia , Rodríguez Ana Belén , Martinez Antonio , Muñoz Montserrat , Prat Aleix
Published: May 2020

Purpose

The therascreenPIK3CAmutation assay and the alpha-specific PI3K inhibitor alpelisib are FDA-approved for identifying and treating patients with advancedPIK3CA-mutated (PIK3CAmut) breast cancer (BC). However, it is currently unknown to what extend this assay detects mostPIK3CAmutations in BC. This information is critical as patients and clinicians are using this and other genomic assays to indicate alpelisib.

Methods

Data from 6338 patients with BC was explored across 10 publicly available studies. The primary objective was to evaluate the proportion and distribution ofPIK3CAmutations in BC. Secondary objectives were (1) to evaluate in silico the spectrum ofPIK3CAmutations in BC that would be captured by the therascreen panel; (2) to evaluate the proportion and distribution ofPIK3CAmutations in hormone receptor-positive/HER2-negative (HR+/HER2−), HER2+, and triple-negative BC (TNBC); and (3) to explore the identification ofPIK3CAmutations in a cohort of 48 HR+/HER2− advanced BC patients by the Guardant B360 circulating tumor DNA (ctDNA) assay.

Results

Patients withPIK3CAmut tumors represented 35.7% (2261/6338). FivePIK3CAmutations comprised 73% of allPIK3CAmutations: H1047R (35%), E545K (17%), E542K (11%), N345K (6%), and H1047L (4%). Therascreen gene list would capture 72% of allPIK3CAmutations and 80% of patients with a knownPIK3CAmut BC. Among patients with doublePIK3CAmut tumors (12% of allPIK3CAmut), the therascreen panel would capture 78% as harboring 1 singlePIK3CAmutation, 17% asPIK3CAmut undetected, and 5% asPIK3CAdouble-mut.PIK3CAmutation rates were lower in TNBC (16%) compared to HR+/HER2 (42%) and HER2+ (31%) BC; however, the distribution of the 4 mainPIK3CAmutations across subtypes was similar. Finally, 28% ofPIK3CAmutations identified in ctDNA in 48 patients with advanced HR+/HER2− BC were not part of the therascreen panel.

Conclusion

PIK3CAmutations in BC are heterogenous and ~ 20% of patients with a knownPIK3CAmutation, and 95% with a known doublePIK3CAmut tumor, would not be captured by the therascreen panel. Finally, the clinical utility ofPIK3CAmutations not present in the therascreen companion diagnostic assay or identified by other sequencing-based assays needs further investigation.
Relocating a pediatric hospital: Does antimicrobial resistance change?
Authors: Schönfeld Annika , Ascherl Rudolf , Petzold-Quinque Stefanie , Lippmann Norman , Rodloff Arne C. , Kiess Wieland
Published: May 2020

Objective

Analyze the changes in antimicrobial drug resistance patterns due to hospital relocation. To this end, we conducted a retrospective analysis of microbiological results, especially minimum inhibitory concentrations (MIC) of all isolates from blood, urine and bronchial secretions, in our pediatric university hospital before and after moving to a new building.

Results

While the number of tests done did not change, the fraction of those positive increased, more MICs were determined and certain microbes (A. baumannii, E. faecalis, Klebsiella spp. and P. mirabilis) were detected more frequently. Most changes in MICs occurred in E. faecium (increases in 8 antimicrobials, decreases only in linezolid and gentamicin). For imipenem and aminopenicillins the MICs commonly rose after relocation, the opposite is true for gentamicin and trimethoprim/sulfamethoxazole. The other factors that alter by moving a hospital such as changes in medical personnel or case severity cannot be corrected for, but using MICs we are able to provide insights into changes down to the individual antimicrobial drug and even small changes usually undetectable to the common categorical reporting of resistance.
Microarray analysis of formalin-fixed, paraffin-embedded follicular thyroid carcinoma samples from patients who developed postoperative distant metastasis
Authors: Jikuzono Tomoo , Ishikawa Tomoko , Hirokawa Mitsuyoshi , Sugitani Iwao , Ishibashi Osamu
Published: May 2020

Objective

Although follicular thyroid carcinoma (FTC) generally has a good prognosis, it occasionally metastasises, leading to poor prognosis. Unfortunately, minimally invasive FTC (mi-FTC) and encapsulated angioinvasive FTC (ea-FTC) cannot be distinguished cytopathologically from thyroid follicular adenoma (FTA), a benign tumour with a good prognosis. Therefore, a molecular diagnosis to distinguish mi- or ea-FTC from FTA is needed for clinical treatment. Several transcriptomics/proteomics studies have searched for FTC biomarkers. However, the results of these studies were not consistent, which could be partly explained by inaccurate diagnosis of the specimens analysed.

Data description

We conducted a microarray-based genome-wide transcriptome analysis using formalin-fixed paraffin-embedded mi- or ea-FTC specimens from patients who developed distant metastasis up to 10 years postoperatively, which ensured the accuracy of diagnosis.
Relevance of biomarkers across different neurodegenerative diseases
Authors: Ehrenberg Alexander J. , Khatun Ayesha , Coomans Emma , Betts Matthew J. , Capraro Federica , Thijssen Elisabeth H. , Senkevich Konstantin , Bharucha Tehmina , Jafarpour Mehrsa , Young Peter N. E. , Jagust William , Carter Stephen F. , Lashley Tammaryn , Grinberg Lea T. , Pereira Joana B. , Mattsson-Carlgren Niklas , Ashton Nicholas J. , Hanrieder Jörg , Zetterberg Henrik , Schöll Michael , Paterson Ross W.
Published: May 2020

Background

The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For example, neuropathological investigations of Alzheimer’s disease pathogenesis can fall in disagreement with conclusions reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field.

Purpose of review

Along with separate review articles covering fluid and imaging biomarkers in this issue ofAlzheimer’s Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease research, commenting on appropriate use, interpretation, and considerations for implementation across different neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel modalities that have been proposed in the landscape of neurodegenerative disease research and care.
Increasing allergy: are antibiotics the elephant in the room?
Authors: Herman Rod A.
Published: May 2020

Antibiotics cause dramatic changes to the human microbiome. The composition of the microbiome has been associated with changes in the immune system and these changes are beginning to be linked to immune diseases. Thus, antibiotics have been implicated as a significant contributor to the continual rise of allergies and autoimmune disease in developed countries. This recognition will hopefully result in the development of post-antibiotic therapies that restore a healthy microbiome and reduce immune system disorders.
Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus
Authors: Nazki Salik , Khatun Amina , Jeong Chang-Gi , Mattoo Sameer ul Salam , Gu Suna , Lee Sim-In , Kim Seung-Chai , Park Ji-Hyo , Yang Myoun-Sik , Kim Bumseok , Park Choi-Kyu , Lee Sang-Myeong , Kim Won-Il
Published: May 2020

The host-associated defence system responsible for the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) from infected pigs is currently poorly understood. To better understand the dynamics of host–pathogen interactions, seventy-five of 100 pigs infected with PRRSV-JA142 and 25 control pigs were euthanized at 3, 10, 21, 28 and 35 days post-challenge (dpc). Blood, lung, bronchoalveolar lavage (BAL) and bronchial lymph node (BLN) samples were collected to evaluate the cellular immune responses. The humoral responses were evaluated by measuring the levels of anti-PRRSV IgG and serum virus-neutralizing (SVN) antibodies. Consequently, the highest viral loads in the sera and lungs of the infected pigs were detected between 3 and 10 dpc, and these resulted in moderate to mild interstitial pneumonia, which resolved accompanied by the clearance of most of the virus by 28 dpc. At peak viremia, the frequencies of alveolar macrophages in infected pigs were significantly decreased, whereas the monocyte-derived DC/macrophage and conventional DC frequencies were increased, and these effects coincided with the early induction of local T-cell responses and the presence of proinflammatory cytokines/chemokines in the lungs, BAL, and BLN as early as 10 dpc. Conversely, the systemic T-cell responses measured in the peripheral blood mononuclear cells were delayed and significantly induced only after the peak viremic stage between 3 and 10 dpc. Taken together, our results suggest that activation of immune responses in the lung could be the key elements for restraining PRRSV through the early induction of T-cell responses at the sites of virus replication.
Interleukin 4 inducible 1 gene (IL4I1) is induced in chicken phagocytes by Salmonella Enteritidis infection
Authors: Elsheimer-Matulova Marta , Polansky Ondrej , Seidlerova Zuzana , Varmuzova Karolina , Stepanova Hana , Fedr Radek , Rychlik Ivan
Published: May 2020

In attempt to identify genes that are induced in chickens by Salmonella Enteritidis we identified a new highly inducible gene, interleukin 4 induced 1 gene (IL4I1). IL4I1 reached its peak expression (458× induction) in the cecum of newly hatched chickens 4 days post-infection and remained upregulated for an additional 10 days. IL4I1 was expressed and induced in macrophages and granulocytes, both at the mRNA and protein level. IL4I1 was expressed and induced also in CD4 and γδ T-lymphocytes though at a 50-fold lower level than in phagocytes. Expression of IL4I1 was not detected in CD8 T lymphocytes or B lymphocytes. Mutation of IL4I1 in chicken HD11 macrophages did not affect their bactericidal capacity against S. Enteritidis but negatively affected their oxidative burst after PMA stimulation. We therefore propose that IL4I1 is not directly involved in bactericidal activity of phagocytes and, instead, it is likely involved in the control of inflammatory response and signaling to T and B lymphocytes.
Beneficial effect modification on survival outcome of sepsis between ART-123 and polymyxin B‑immobilised haemoperfusion: a nationwide Japanese registry study
Authors: Mochizuki Katsunori , Mori Kotaro , Kamijo Hiroshi , Ichikawa Michitaro , Nitta Kenichi , Imamura Hiroshi
Published: May 2020

Background

Although recently published randomised controlled trials did not confirm significant positive effect of ART-123 or polymyxin B‑immobilised haemoperfusion (PMX-HP) on survival outcome, previous studies using a dataset of 3195 patients with sepsis registered at 42 intensive care units throughout Japan revealed significantly reduced mortality following these treatments. A study has suggested the efficacy of combination therapy with ART-123 and PMX-HP; however, it did not evaluate the effect modification between them. We hypothesised that coadministration of ART-123 and PMX-HP has a significant positive effect modification on survival outcome. The purpose of this study was to evaluate the effect modification between ART-123 and PMX-HP treatment on the survival outcome of sepsis using post hoc analysis of the dataset of the Japan Septic Disseminated Intravascular Coagulation registry.

Results

Of the 3195 patients recorded in the registry, 2350 were analysed. The product term between ART-123 and PMX-HP was analysed by the Cox regression model to evaluate significance. The primary outcome of this study was hospital mortality. Although the administration of ART-123 was independently positively associated with survival outcome (adjusted hazard ratio [HR]: 0.834, 95% confidence interval [CI] 0.695–0.999;P = 0.049) in the model prior to the introduction of the product term, a significant effect modification on survival outcome was observed between the administration of ART-123 and PMX-HP treatment (adjusted HR: 0.667, 95% CI 0.462–0.961;P = 0.030).

Conclusions

The main effect of the administration of ART-123 may be beneficial for survival outcome in patients with sepsis. In addition, a significant beneficial effect modification on survival outcome was observed between the administration of ART-123 and PMX-HP treatment.
The role of passive immunization in the age of SARS-CoV-2: an update
Authors: Fischer Johannes C. , Zänker Kurt , van Griensven Martijn , Schneider Marion , Kindgen-Milles Detlef , Knoefel Wolfram Trudo , Lichtenberg Artur , Tamaskovics Balint , Djiepmo-Njanang Freddy Joel , Budach Wilfried , Corradini Stefanie , Ganswindt Ute , Häussinger Dieter , Feldt Torsten , Schelzig Hubert , Bojar Hans , Peiper Matthias , Bölke Edwin , Haussmann Jan , Matuschek Christiane
Published: May 2020

The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.
Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies
Authors:   the MoMar study group, Weber Daniel G. , Casjens Swaantje , Brik Alexander , Raiko Irina , Lehnert Martin , Taeger Dirk , Gleichenhagen Jan , Kollmeier Jens , Bauer Torsten T. , Brüning Thomas , Johnen Georg
Published: May 2020

Background

For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.

Methods

Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.

Results

GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel’s sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.

Conclusions

GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.
Trends and projections of kidney cancer incidence at the global and national levels, 1990–2030: a Bayesian age-period-cohort modeling study
Authors: Du Zhebin , Chen Wei , Xia Qier , Shi Oumin , Chen Qi
Published: May 2020

Background

Identifying the temporal trends of kidney cancer (KC) incidence in both the past and the future at the global and national levels is critical for KC prevention.

Methods

We retrieved annual KC case data between 1990 and 2017 from the Global Burden of Disease (GBD) online database. The average annual percentage change (AAPC) was used to quantify the temporal trends of KC age-standardized incidence rates (ASRs) from 1990 to 2017. Bayesian age-period-cohort models were used to predict KC incidence through 2030.

Results

Worldwide, the number of newly diagnosed KC cases increased from 207.3 thousand in 1990 to 393.0 thousand in 2017. The KC ASR increased from 4.72 per 100,000 to 4.94 per 100,000 during the same period. Between 2018 and 2030, the number of KC cases is projected to increase further to 475.4 thousand (95% highest density interval [HDI] 423.9, 526.9). The KC ASR is predicted to decrease slightly to 4.46 per 100,000 (95% HDI 4.06, 4.86). A total of 90, 2, and 80 countries or territories are projected to experience increases, remain stable, and experience decreases in KC ASR between 2018 and 2030, respectively. In most developed countries, the KC incidence is forecasted to decrease irrespective of past trends. In most developing countries, the KC incidence is predicted to increase persistently through 2030.

Conclusions

KC incidence is predicted to decrease in the next decade, and this predicted decrease is mainly driven by the decreases in developed countries. More attention should be placed on developing countries.
Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets
Authors:   on behalf of the Advancing Treatment for Pediatric Craniopharyngioma Consortium, Prince Eric , Whelan Ros , Donson Andrew , Staulcup Susan , Hengartner Astrid , Vijmasi Trinka , Agwu Chibueze , Lillehei Kevin O. , Foreman Nicholas K. , Johnston James M. , Massimi Luca , Anderson Richard C. E. , Souweidane Mark M. , Naftel Robert P. , Limbrick David D. , Grant Gerald , Niazi Toba N. , Dudley Roy , Kilburn Lindsay , Jackson Eric M. , Jallo George I. , Ginn Kevin , Smith Amy , Chern Joshua J. , Lee Amy , Drapeau Annie , Krieger Mark D. , Handler Michael H. , Hankinson Todd C.
Published: May 2020

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential therapies identified through the study of pediatric ACP may also have a role in adult ACP. Using our compiled transcriptome dataset of 27 pediatric and 9 adult ACPs, obtained through the Advancing Treatment for Pediatric Craniopharyngioma Consortium, we interrogated potential age-related transcriptional differences using several rigorous mathematical analyses. These included: canonical differential expression analysis; divisive, agglomerative, and probabilistic based hierarchical clustering; information theory based characterizations; and the deep learning approach, HD Spot. Our work indicates that there is no therapeutically relevant difference in ACP gene expression based on age. As such, potential therapeutic targets identified in pediatric ACP are also likely to have relvance for adult patients.
Together we unite: the role of the Commonwealth in achieving universal health coverage through pharmaceutical care amidst the COVID-19 pandemic
Authors: Chan Amy Hai Yan , Rutter Victoria , Ashiru-Oredope Diane , Tuck Chloe , Babar Zaheer-Ud-Din
Published: May 2020

The world currently faces unprecedented health challenges as COVID-19 poses a huge threat to health systems, economies and societies as we know it. The events of the current COVID-19 pandemic have further emphasised existing issues within our health systems. There is no better time than now to come together in global solidarity to tackle these evolving threats of COVID-19 pandemic. The Commonwealth is an ideally placed network to tackle these global health challenges, with its wide-reaching networks of governmental, non-governmental and civil society organisations across all continents. Although the biennial Commonwealth Heads of Government Meeting (CHOGM) originally scheduled to take place in Kigali in Rwanda 22–27 June 2020 has been postponed in view of COVID-19, Commonwealth country discussions are continuing, centred on the CHOGM key theme of ‘Delivering a Common Future: Connecting, Innovating, Transforming’, and five subthemes of Information and Communications Technology (ICT) and Innovation; Trade; Environment; Governance and the Rule of Law; and Youth. The planned CHOGM and Commonwealth itself provides all members a timely platform to consider innovative ways to connect, innovate and transform healthcare to meet the needs of their populations. This commentary considers these five CHOGM subthemes and how member nations can be supported to achieve universal health coverage through optimising medicines use and outcomes, in the midst of a global pandemic in line with the global health agenda.
Coulomb stress change on inland faults during megathrust earthquake cycle in southwest Japan
Authors: Mitogawa Tsukasa , Nishimura Takuya
Published: May 2020

In the subduction zone, megathrust earthquakes may modulate the shallow crustal seismicity in the overriding plate. Historical documents indicate the frequent occurrence of large shallow crustal earthquakes in the overriding continental plate 50 years before and 10 years after the megathrust earthquakes along the Nankai trough in southwest Japan. In this study, we model megathrust earthquake cycles in a simple oblique subduction zone considering the viscoelasticity, and calculate the temporal evolution of the Coulomb failure stress changes ($$\Delta {\text{CFS}}$$ΔCFS) on the crustal faults in the overriding plate. Further, we examine the variation of$$\Delta {\text{CFS}}$$ΔCFSdepending on the location and fault type, and the active period of crustal earthquakes in which$$\Delta {\text{CFS}}$$ΔCFSexceeds the previous maximum. Our viscoelastic model suggests that the dependency of the active period on the distance from the megathrust fault is less when the intrinsic loading rate of the inland fault is low. Moreover, it suggests that the viscoelastic stress evolution on faults with negative coseismic$$\Delta {\text{CFS}}$$ΔCFSrenders the active period longer or shorter than those in a pure elastic medium. The temporal evolution of$$\Delta {\text{CFS}}$$ΔCFSon most major active faults in southwest Japan can be categorized into two groups with the following different characteristics: one is that$$\Delta {\text{CFS}}$$ΔCFSis positive coseismically and peaks 10 years after a megathrust earthquake. The other is that$$\Delta {\text{CFS}}$$ΔCFSis negative coseismically, and does not recover to the preseismic one for more than 50 years after a megathrust earthquake. This can explain the temporal sequence of the historical earthquakes in southwest Japan. Our model which includes viscoelastic relaxation successfully expresses the activation of shallow crustal earthquakes in the overriding continental plate not only before the megathrust earthquake, but also after. If the apparent frictional coefficient is less than ~ 0.1, the coseismic$$\Delta {\text{CFS}}$$ΔCFSon the source faults of the 1943 Mj7.3 Tottori earthquake, 1596 M7.0 Keicho Iyo earthquake, and 1596 M7.5 Keicho Fushimi earthquake that occurred within 10 years before the megathrust earthquake along the Nankai trough is negative. Therefore, to explain the occurrence of these historical earthquakes, our model suggests that the apparent frictional coefficient must be less than ~ 0.1.