bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of a Patient Reported Experience Measure (PREM) to measure the rare disease patients and caregivers experience: a Spanish cross-sectional study
Authors: Guilabert Mercedes , Martínez-García Alba , Sala-González Marina , Solas Olga , Mira José Joaquín
Published: February 2021

Objective

To measure the experience of the person having a rare disease in order to identify objectives for optimal care in the health care received by these patients. Methods. A cross-sectional study was conducted in Spain involving patients associated with the Spanish Rare Diseases Federation [Federación Española de Enfermedades Raras] (FEDER). A modified version of the PREM IEXPAC [Instrumento para evaluar la Experiencia del Paciente Crónico] instrument was used (IEXPAC-rare-diseases). Scores ranged between 0 (worst experience) and 10 (best experience).

Results

A total of 261 caregivers (in the case of paediatric population) and patients with rare diseases (response rate 54.4%) replied. 232 (88.9%) were adult patients and 29 (11.1%) caregivers of minor patients. Most males, 227 (87%), with an average age of 38 (SD 13.6) years. The mean time since confirmation of diagnosis was 7.8 (SD 8.0) years. The score in this PREM was 3.5 points out to 10 (95%CI 3.2–3.8, SD 2.0). Caregivers of paediatric patients scored higher, except for coordination of social and healthcare services.

Conclusions

There are wide and important areas for improvement in the care of patients with rare diseases. This study involves a first assesment of the experience of patients with rare diseases in Spain.
Adapting evidence-based clinical practice guidelines for people with attention deficit hyperactivity disorder in Saudi Arabia: process and outputs of a national initiative
Authors: Bashiri Fahad A. , Albatti Turki H. , Hamad Muddathir H. , Al-Joudi Haya F. , Daghash Hadeel F. , Al-Salehi Saleh M. , Varnham Jeremy L. , Alhaidar Fatimah , Almodayfer Omar , Alhossein Abdulkarim , Aldhalaan Hesham , Ad-Dab’bagh Yasser A. , Al Backer Nouf , Altwaijri Waleed , Alburikan Khalid , Buraik Maysaa W. , Ghaziuddin Mohammad , Nester Michael J. , Wahabi Hayfaa A. , Alhabib Samia , Jamal Amr A. , Amer Yasser S.
Published: February 2021

Background

We recently adapted the published National Institute for Health and Care Excellence (NICE) Attention deficit hyperactivity disorder (ADHD) diagnosis and management guideline to the Saudi Arabian context. It has been postulated that adaptation of evidence-based clinical practice guidelines to the local healthcare context rather than de-novo development will improve their adoption and implementation without imposing a significant burden on resources. The objective of this paper is to describe the adaptation process methodology utilized for the generation of the first national guideline for management of people with ADHD in Saudi Arabia.

Methods

We used the KSU-Modified-ADAPTE methodology for the guideline adaptation process. We describe the full process in detail including the three phases of set-up, adaptation, and finalization. The process was conducted by a multidisciplinary guideline adaptation group in addition to an external review for the clinical content and methodology.

Results

The group adapted ten main categories of recommendations from one source CPG (NICE). The recommendations include: (i) service organisation and training, (ii) recognition, identification and referral, (iii) diagnosis, (iv) support, (v) managing ADHD, (vi) dietary advice, (vii) medication, (viii) maintenance and monitoring, (ix) adherence to treatment, and (x) review of medication and discontinuation. Several implementation tools were compiled and developed to enhance implementability including a clinical algorithm, quality measures, coding system, medication tables, translations, patient information, and online resources.

Conclusions

The finalized clinical practice guideline provides healthcare providers with applicable evidence-based guidance for the management of people with ADHD in Saudi Arabia. The project also demonstrated the effectiveness of KSU-Modified-ADAPTE, and emphasized the value of a collaborative clinical and methodological expert group for adaptation of national guidelines.
Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Italian Society of Pediatrics
Authors:   on behalf of the Rheumatology Study Group of the Italian Society of Pediatrics, Cattalini Marco , Taddio Andrea , Bracaglia Claudia , Cimaz Rolando , Paolera Sara Della , Filocamo Giovanni , La Torre Francesco , Lattanzi Bianca , Marchesi Alessandra , Simonini Gabriele , Zuccotti Gianvincenzo , Zunica Fiammetta , Villani Alberto , Ravelli Angelo
Published: February 2021

Background

Italy was the first Western country to be hit by the SARS-CoV-2 epidemic. There is now mounting evidence that a minority of children infected with SARS-CoV2 may experience a severe multisystem inflammatory syndrome, called Multisystem inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C). To date no universally agreed approach is available for this disease.

Main body

as Italy is now facing a second hity of COVID-19 cases, we fear a recrudescence of MIS-C cases. We have, therefore, decided to prepare a report that will help clinicians to face this novel and challenging disease. We propose a diagnostic algorithm, to help case definition and guide work-up, and a therapeutic approach. MIS-C should be promptly recognized, based on the presence of systemic inflammation and specific organ involvement. Early treatment is crucial, and it will be based on the combined use of corticosteroids, high-dose immunoglobulins and anti-cytokine treatments, depending on the severity of the disease. Ancillary treatments (such as. aspirin and thrombo-profilaxis) will be also discussed.

Conclusions

we propose a document that will help physicians to diagnose and treat MIS-C patients. Given the level of evidence available and the methodology used, this document should not be interpreted as a guideline; the final decision about the optimal management should still be taken by the caring physician, on an individual basis.
COHESION: core outcomes in neonatal encephalopathy (protocol)
Authors: Quirke Fiona A. , Healy Patricia , Bhraonáin Elaine Ní , Daly Mandy , Biesty Linda , Hurley Tim , Walker Karen , Meher Shireen , Haas David M. , Bloomfield Frank H. , Kirkham Jamie J. , Molloy Eleanor J. , Devane Declan
Published: February 2021

Background

Neonatal encephalopathy is a complex syndrome in infants that predominantly affects the brain and other organs. The leading cause is a lack of oxygen in the blood reaching the brain. Neonatal encephalopathy can result in mortality or complications later in life, including seizures, movement disorders and cerebral palsy. Treatment options for neonatal encephalopathy are limited mainly to therapeutic hypothermia, although other potential treatments are emerging. However, evaluations of the effectiveness of treatments are challenging because of heterogeneity and inconsistency in outcomes measured and reported between trials. In this paper, we detail how we will develop a core outcome set to standardise outcomes measured and reported upon for interventions for the treatment of neonatal encephalopathy.

Methods

We will systematically review the literature to identify outcomes reported previously in randomised trials and systematic reviews of randomised trials. We will identify outcomes important to parents or caregivers of infants diagnosed with and who have received treatment for neonatal encephalopathy. We will do this by conducting in person or by video teleconferencing interviews with parents or caregivers in high-income and low- to middle-income countries. Stakeholders with expertise in neonatal encephalopathy (parents/caregivers, healthcare providers and researchers) will rate the importance of identified outcomes in an online Delphi survey using either a three-round Delphi survey or a “Real-Time” Delphi survey to which stakeholders will be allocated at random. Consensus meetings will take place by video conference to allow for an international group of stakeholder representatives to discuss and vote on the outcomes to include in the final core outcome set (COS).

Discussion

More research is needed on treatments for neonatal encephalopathy. Standardising outcomes measured and reported in evaluations of the effectiveness of interventions for the treatment of neonatal encephalopathy will improve evidence synthesis and improve results reported in systematic reviews and meta-analysis in this area. Overall, this COS will allow for improved treatments to be identified, heterogeneity in research to be reduced, and overall patient care to be enhanced.

Trial registration

This study is registered in the Core Outcome Measures for Effectiveness (COMET) database http://www.comet-initiative.org/Studies/Details/1270.
Decreased insulin resistance in diabetic patients by influencing Sirtuin1 and Fetuin-A following supplementation with ellagic acid: a randomized controlled trial
Authors: Ghadimi Mahnaz , Foroughi Farshad , Hashemipour Sima , Nooshabadi Mohammadreza Rashidi , Ahmadi Mohammad Hossein , Yari Mojtaba Ghadimi , Kavianpour Maria , Haghighian Hossein Khadem
Published: February 2021

Background

The beneficial effects of polyphenols have been reported. This study aimed to investigate the effect of oral Ellagic acid (EA) supplement on insulin resistance (IR) and Fetuin-A and serum sirtuin1 (SIRT1) in type 2 diabetics.

Methods

In this double-blind, randomized clinical trial, 44 diabetic patients were selected. Patients were assigned to the intervention group (22 subjects) and placebo (22 subjects) and received a capsule containing 180 mg of EA per day or placebo for eight weeks, respectively. At the beginning and end of the study, anthropometric indices, fasting plasma glucose (FPG), plasma insulin level, IR, Fetuin-A, and SIRT1 were measured. Statistical analysis was performed using SPSS software.

Results

At the beginning and end of the study, there was no significant difference between the two groups regarding anthropometric indices (P > 0.05). At the end of the survey, EA supplementation significantly reduced FPG, insulin, IR, and Fetuin-A and increased SIRT1 levels compared with the placebo group (P < 0.05). However, these changes were not significant in the placebo group (P > 0.05).

Conclusion

EA with antioxidant properties plays an essential role in reducing the macrovascular and microvascular complications of diabetes by reducing inflammation and insulin resistance.

Trial registration The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials (http://www.IRCT.IR, identifier: IRCT20141025019669N13)
Assessing the feasibility of heart rate variability as an objective indicator of anxiety in older adults with dementia living in care homes
Authors: Quinci Milena A. , Astell Arlene J.
Published: February 2021

Objective

Anxiety is reportedly prevalent in older adults with dementia living in care homes and, within this population, is most often assessed through caregiver reports. Heart rate variability (HRV) is a physiological indicator of autonomic function, whereby reduced vagally-mediated HRV is associated with a variety of anxiety symptoms and disorders. This study evaluates the feasibility of collecting HRV data within this population, presents HRV data for older adults with dementia living in a care home, and examines HRV in the context of self-reported anxiety. These data were collected during a larger study examining an exercise intervention.

Results

HRV data, in the form of log-transformed root mean square of the successive differences (lnRMSSD), were in line with transformed data from previous research. These data provide a promising direction for the use of wrist-worn devices in future HRV research with people living with dementia in care homes.
Inhibition of Ref(2)P, the Drosophila homologue of the p62/SQSTM1 gene, increases lifespan and leads to a decline in motor function
Authors: Hurley Emily P. , Staveley Brian E.
Published: February 2021

Objective

Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time.

Results

Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
Shifts in soil and plant functional diversity along an altitudinal gradient in the French Alps
Authors: Stokes Alexia , Angeles Guillermo , Anthelme Fabien , Aranda-Delgado Eduardo , Barois Isabelle , Bounous Manon , Cruz-Maldonado Nereyda , Decaëns Thibaud , Fourtier Stéphane , Freschet Grégoire T. , Gabriac Quentin , Hernández-Cáceres Daniel , Jiménez Leonor , Ma Jing , Mao Zhun , Marín-Castro Beatriz Eugenia , Merino-Martín Luis , Mohamed Awaz , Piedallu Christian , Pimentel-Reyes Carlos , Reijnen Hans , Reverchon Frédérique , Rey Hervé , Selli Lavinia , Siebe-Grabach Christina Desireé , Sieron Katrin , Weemstra Monique , Roumet Catherine
Published: February 2021

Objectives

Altitude integrates changes in environmental conditions that determine shifts in vegetation, including temperature, precipitation, solar radiation and edaphogenetic processes. In turn, vegetation alters soil biophysical properties through litter input, root growth, microbial and macrofaunal interactions. The belowground traits of plant communities modify soil processes in different ways, but it is not known how root traits influence soil biota at the community level. We collected data to investigate how elevation affects belowground community traits and soil microbial and faunal communities. This dataset comprises data from a temperate climate in France and a twin study was performed in a tropical zone in Mexico.

Data description

The paper describes soil physical and chemical properties, climatic variables, plant community composition and species abundance, plant community traits, soil microbial functional diversity and macrofaunal abundance and diversity. Data are provided for six elevations (1400–2400 m) ranging from montane forest to alpine prairie. We focused on soil biophysical properties beneath three dominant plant species that structure local vegetation. These data are useful for understanding how shifts in vegetation communities affect belowground processes, such as water infiltration, soil aggregation and carbon storage. Data will also help researchers understand how plant communities adjust to a changing climate/environment.
Cerebrospinal fluid N-224 tau helps discriminate Alzheimer’s disease from subjective cognitive decline and other dementias
Authors: Cicognola Claudia , Hansson Oskar , Scheltens Philip , Kvartsberg Hlin , Zetterberg Henrik , Teunissen Charlotte E. , Blennow Kaj
Published: February 2021

Background

Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer’s disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls.

Methods

Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay.

Results

N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson’s disease (PD, p < 0.0001), Parkinson’s disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R2 = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824).

Conclusions

N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.
RETRACTED ARTICLE: Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer’s amyloidosis
Authors: Maiti Panchanan , Bowers Zackary , Bourcier-Schultz Ali , Morse Jarod , Dunbar Gary L.
Published: February 2021

Background

Synaptic failure is one of the principal events associated with cognitive dysfunction in Alzheimer’s disease (AD). Preservation of existing synapses and prevention of synaptic loss are promising strategies to preserve cognitive function in AD patients. As a potent natural anti-oxidant, anti-amyloid, and anti-inflammatory polyphenol, curcumin (Cur) shows great promise as a therapy for AD. However, hydrophobicity of natural Cur limits its solubility, stability, bioavailability, and clinical utility for AD therapy. We have demonstrated that solid lipid curcumin particles (SLCP) have greater therapeutic potential than natural Cur in vitro and in vivo models of AD. In the present study, we have investigated whether SLCP has any preservative role on affected dendritic spines and synaptic markers in 5xFAD mice.

Methods

Six- and 12-month-old 5xFAD and age-matched wild-type mice received oral administration of SLCP (100 mg/kg body weight) or equivalent amounts of vehicle for 2 months. Neuronal morphology, neurodegeneration, and amyloid plaque load were investigated from prefrontal cortex (PFC), entorhinal cortex (EC), CA1, CA3, and the subicular complex (SC). In addition, the dendritic spine density from apical and basal branches was studied by Golgi-Cox stain. Further, synaptic markers, such as synaptophysin, PSD95, Shank, Homer, Drebrin, Kalirin-7, CREB, and phosphorylated CREB (pCREB) were studied using Western blots. Finally, cognitive and motor functions were assessed using open-field, novel object recognition (NOR) and Morris water maze (MWM) tasks after treatment with SLCP.

Results

We observed an increased number of pyknotic and degenerated cells in all these brain areas in 5xFAD mice and SLCP treatment partially protected against those losses. Decrease in dendritic arborization and dendritic spine density from primary, secondary, and tertiary apical and basal branches were observed in PFC, EC, CA1, and CA3 in both 6- and 12-month-old 5xFAD mice, and SLCP treatments partially preserved the normal morphology of these dendritic spines. In addition, pre- and postsynaptic protein markers were also restored by SLCP treatment. Furthermore, SLCP treatment improved NOR and cognitive function in 5xFAD mice.

Conclusions

Overall, these findings indicate that use of SLCP exerts neuroprotective properties by decreasing amyloid plaque burden, preventing neuronal death, and preserving dendritic spine density and synaptic markers in the 5xFAD mice.
In vivo tau pathology is associated with synaptic loss and altered synaptic function
Authors: Coomans Emma M. , Schoonhoven Deborah N. , Tuncel Hayel , Verfaillie Sander C. J. , Wolters Emma E. , Boellaard Ronald , Ossenkoppele Rik , den Braber Anouk , Scheper Wiep , Schober Patrick , Sweeney Steven P. , Ryan J. Michael , Schuit Robert C. , Windhorst Albert D. , Barkhof Frederik , Scheltens Philip , Golla Sandeep S. V. , Hillebrand Arjan , Gouw Alida A. , van Berckel Bart N. M.
Published: February 2021

Background

The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease.

Methods

Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models.

Results

Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe.

Conclusions

These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.
Detecting Alzheimer’s disease biomarkers with a brief tablet-based cognitive battery: sensitivity to Aβ and tau PET
Authors: Tsoy Elena , Strom Amelia , Iaccarino Leonardo , Erlhoff Sabrina J. , Goode Collette A. , Rodriguez Anne-Marie , Rabinovici Gil D. , Miller Bruce L. , Kramer Joel H. , Rankin Katherine P. , La Joie Renaud , Possin Katherine L.
Published: February 2021

Background

β-amyloid (Aβ) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer’s disease (AD) in living people. Cognitive measures sensitive to Aβ and tau burden may help streamline identification of cases for confirmatory AD biomarker testing.

Methods

We examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aβ -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aβ-, 97 Aβ+). We also investigated the relationship between the BHA tests and regional patterns of tau-PET signal using voxel-wise regression analyses in a subsample of 60 Aβ+ individuals with MCI or dementia.

Results

Favorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aβ positivity (area under the curve [AUC] = 0.75 [95% CI 0.66–0.85]). We found significant associations with tau-PET signal in mesial temporal regions for Favorites, frontoparietal regions for Match, and occipitoparietal regions for Line Orientation (visuospatial skills) in a subsample of individuals with MCI and dementia.

Conclusion

The BHA measures are significantly associated with both Aβ and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.
Dysentery as the only presentation of COVID-19 in a child: a case report
Authors: Tariverdi Marjan , Farahbakhsh Nazanin , Gouklani Hamed , Khosravifar Fatemeh , Tamaddondar Mohammad
Published: February 2021

Introduction

The coronavirus disease 2019 (COVID-19) pandemic has caused irreparable damage to society, and the damage continues. Pediatricians are confronted with COVID-19 in a variety of presentations, which may lead to delayed diagnosis and treatment. Early diagnosis of the disease plays an important role in preventing transmission of the virus in the community.

Case presentation

Here we report a 27-month-old previously healthy Iranian female child who presented with fever and bloody diarrhea, diagnosed with COVID-19 based on contact history, exclusion of enteric bacterial pathogens and parasites, and positive stool and nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT-PCR) tests. The patient had viral shedding for more than a month.

Conclusions

The pediatric population usually does not present with typical clinical features of COVID-19, which are respiratory involvement. Dysentery may be the only presentation of this disease, and long-term isolation should be considered, as the viral shedding may last for more than a month.
Melatonin activates ABCA1 via the BiP/NRF1 pathway to suppress high-cholesterol-induced apoptosis of mesenchymal stem cells
Authors: Kim Jun Sung , Jung Young Hyun , Lee Hyun Jik , Chae Chang Woo , Choi Gee Euhn , Lim Jae Ryong , Kim Seo Yihl , Lee Joo Eun , Han Ho Jae
Published: February 2021

Background

Retarded wound healing in patients with obesity contributes to a risk of complications associated with vascular insufficiency and oxidative stress. The high cholesterol levels of patients with obesity are associated with apoptosis of engrafted umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). Melatonin contributes to the prevention of cholesterol accumulation in patients with obesity via a mechanism that is poorly understood. We therefore investigated the regulatory mechanism of melatonin in cholesterol-induced apoptosis.

Methods

The protective effects of melatonin on cholesterol-induced apoptosis were investigated in UCB-MSCs. We used a mouse model of induced obesity to show that melatonin treatment restored the survival rate of transplanted UCB-MSCs and their wound-healing capacity. The mean values of the treatment groups were compared with those of the control group using Student’s t test, and differences among three or more groups were analyzed using one-way analysis of variance with Dunnett’s multiple comparison test.

Results

Melatonin treatment increased the expression of ATP-binding cassette subfamily A member 1 (ABCA1), which reduced cholesterol accumulation and cholesterol-induced apoptosis. The mouse skin wound healing model showed that melatonin treatment restored the survival rate of transplanted UCB-MSCs and the wound-healing capacity of obese mice. Melatonin inhibited the expression of binding immunoglobulin protein (BiP) through the regulation of MT2/Sp1-dependent microRNA-597-5p. Melatonin decreased the co-localization of BiP with nuclear factor erythroid 2-related factor 1 (NRF1), which resulted in increased ABCA1 expression.

Conclusion

Melatonin induced the efflux of intracellular cholesterol through ABCA1 to decrease apoptosis of UCB-MSCs via an MT2-dependent BiP/NRF1 pathway.
The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure
Authors: Na Jingtao , Jin Haifeng , Wang Xin , Huang Kan , Sun Shuang , Li Qiang , Zhang Wenting
Published: February 2021

Background

Heart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating  targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3.

Methods

Firstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry.

Results

HDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and −dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined.

Conclusion

Collectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.
DDB2 regulates DNA replication through PCNA-independent degradation of CDT2
Authors: Wu Xiaojun , Yu Min , Zhang Zhuxia , Leng Feng , Ma Yue , Xie Ni , Lu Fei
Published: February 2021

Background

Targeting ubiquitin-dependent proteolysis is one of the strategies in cancer therapy. CRLCDT2 and CRLDDB2 are two key E3 ubiquitin ligases involved in DNA replication and DNA damage repair. But CDT2 and DDB2 are opposite prognostic factors in kinds of cancers, and the underlining mechanism needs to be elucidated.

Methods

Small interfering RNAs were used to determine the function of target genes. Co-immunoprecipitation (Co-IP) was performed to detect the interaction between DDB2 and CDT2. Immunofluorescence assays and fluorescence activating cell sorting (FACS) were used to measure the change of DNA content. In vivo ubiquitination assay was carried out to clarify the ubiquitination of CDT2 mediated by DDB2. Cell synchronization was performed to arrest cells at G1/S and S phase. The mechanism involved in DDB2-mediated CDT2 degradation was investigated by constructing plasmids with mutant variants and measured by Western blot. Immunohistochemistry was performed to determine the relationship between DDB2 and CDT2. Paired two-side Student’s t-test was used to measure the significance of the difference between control group and experimental group.

Results

Knockdown of DDB2 stabilized CDT2, while over-expression of DDB2 enhanced ubiquitination of CDT2, and subsequentially degradation of CDT2. Although both DDB2 and CDT2 contain PIP (PCNA-interacting protein) box, PIP box is dispensable for DDB2-mediated CDT2 degradation. Knockdown of PCNA had negligible effects on the stability of CDT2, but promoted accumulation of CDT1, p21 and SET8. Silencing of DDB2 arrested cell cycle in G1 phase, destabilized CDT1 and reduced the chromatin loading of MCMs, thereby blocked the formation of polyploidy induced by ablation of CDT2. In breast cancer and ovarian teratoma tissues, high level of DDB2 was along with lower level of CDT2.

Conclusions

We found that CRL4DDB2 is the novel E3 ubiquitin ligases of CDT2, and DDB2 regulates DNA replication through indirectly regulates CDT1 protein stability by degrading CDT2 and promotes the assembly of pre-replication complex. Our results broaden the horizon for understanding the opposite function of CDT2 and DDB2 in tumorigenesis, and may provide clues for drug discovery in cancer therapy.
Transcriptomic and metabolomic profiling reveal the p53-dependent benzeneacetic acid attenuation of silica‐induced epithelial–mesenchymal transition in human bronchial epithelial cells
Authors: Ju Zhao , Shao Jianlin , Zhou Meiling , Jin Jing , Pan Huiji , Ding Ping , Huang Ruixue
Published: February 2021

Background

Silica exposure underlies the development of silicosis, one of the most serious occupational hazards worldwide. We aimed to explore the interaction of the silica-induced epithelial–mesenchymal transition (EMT)-related transcripts with the cellular metabolism regulated by p53.

Methods

We knocked out p53 using CRISPR/Cas9 in the human bronchial epithelial (HBE) cell line. The transcriptomic and metabolomic analyses and integrative omics were conducted using microarrays, GC–MS, and MetaboAnalyst, respectively.

Results

Fifty-two mRNAs showed significantly altered expression in the HBE p53-KO cells post-silica exposure. A total of 42 metabolites were putatively involved in p53-dependent silica-mediated HBE cell dysfunction. Through integrated data analysis, we obtained five significant p53-dependent metabolic pathways including phenylalanine, glyoxylate, dicarboxylate, and linoleic acid metabolism, and the citrate cycle. Through metabolite screening, we further identified that benzeneacetic acid, a key regulation metabolite in the phenylalanine metabolic pathway, attenuated the silica-induced EMT in HBE cells in a p53-dependent manner. Interestingly, despite the extensive p53-related published literature, the clinical translation of these studies remains unsubstantial.

Conclusions

Our study offers new insights into the molecular mechanisms by which epithelial cells respond to silica exposure and provide fresh perspective and direction for future clinical biomarker research and potential clinically sustainable and translatable role of p53.
Levosimendan use in patients with acute heart failure and reduced ejection fraction with or without severe renal dysfunction in critical cardiac care units: a multi-institution database study
Authors: Chan Cze-Ci , Lee Kuang-Tso , Ho Wan-Jing , Chan Yi-Hsin , Chu Pao-Hsien
Published: February 2021

Background

Acute heart failure is a life-threatening clinical condition. Levosimendan is an effective inotropic agent used to maintain cardiac output, but its usage is limited by the lack of evidence in patients with severely abnormal renal function. Therefore, we analyzed data of patients with acute heart failure with and without abnormal renal function to examine the effects of levosimendan.

Methods

We performed this retrospective cohort study using data from the Chang Gung Research Database (CGRD) of Chang Gung Memorial Hospital (CGMH). Patients admitted for heart failure with LVEF ≤ 40% between January 2013 and December 2018 who received levosimendan or dobutamine in the critical cardiac care units (CCU) were identified. Patients with extracorporeal membrane oxygenation (ECMO) were excluded. Outcomes of interest were mortality at 30, 90, and 180 days after the cohort entry date.

Results

There were no significant differences in mortality rate at 30, 90, and 180 days after the cohort entry date between the levosimendan and dobutamine groups, or between subgroups of patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2and eGFR < 30 mL/min/1.73 m2or on dialysis. The results were consistent before and after propensity score matching.

Conclusions

Levosimendan did not increase short- or long-term mortality rates in critical patients with acute heart failure and reduced ejection fraction compared to dobutamine, regardless of their renal function. An eGFR less than 30 mL/min/1.73 m2was not necessarily considered a contraindication for levosimendan in these patients.
Barriers and facilitators to the implementation of social robots for older adults and people with dementia: a scoping review protocol
Authors: Koh Wei Qi , Felding Simone Anna , Toomey Elaine , Casey Dympna
Published: February 2021

Background

Psychosocial health issues such as depression and social isolation are an important cause of morbidity and premature mortality for older adults and people with dementia. Social robots are promising technological innovations to deliver effective psychosocial interventions to promote psychosocial wellbeing. Studies have reported positive findings regarding this technology on the psychosocial health of older adults and people with dementia. However, despite positive findings of the effects of social robots for older adults and people with dementia, little is known about factors affecting their implementation in practice.

Methods

This study follows Arksey and O’Malley’s approach and methodological enhancement by Levac et al. Relevant articles will be identified by searching electronic databases: MEDLINE, Embase, PsycINFO, Scopus, Web of Science, Compendex and PubMed. A two-phase screening process will be undertaken by two independent reviewers to determine articles’ inclusion. Findings will be summarised and reported thematically based on domains in the Consolidated Framework of Implementation Research (CFIR) and presented narratively. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) will guide the reporting of findings.

Discussion

Reporting the protocol in advance of conducting the review will ensure that rigorous and transparent methodological approach is undertaken. The outcomes of the review include identifying variants in terminologies used to describe implementation, identifying the scope of the literature regarding the barriers and facilitators affecting the implementation of social robots and identifying research gaps to guide further empirical research in this field. This evidence synthesis constitutes part of a bigger project aimed to develop implementation guidelines for social robotics for older adults with dementia. Since the methodological process consists of reviewing and collecting data from publicly available data, this study does not require approval from a research ethics board.

Scoping review registration

Our protocol is registered with the Open Science Framework (https://osf.io/2x3y9/) as an open access article, under the Creative Commons Attribution Non Commercial (CC BY-NC-4.0) license, which allows others to distribute, remix, adapt and build on this work on a non-commercial basis, and license their derivative work using different terms, on the basis that the original basis is properly cited and the use is non-commercial (http://creativecommons.org/licenses/by-nc/4.0/).
Electronic cigarettes’ withdrawal severity symptoms among users during intermittent fasting: a cross-sectional study
Authors: Barakat Muna M. , Al-Qudah Raja’a A. , Alfayoumi Ibrahim , Al-Obaidi Hala Jehad , Jirjees Feras Jassim , Basheti Iman
Published: February 2021

Background

Recently, electronic cigarette (e-cig) usage has increased significantly, making it a potentially effective smoking cessation tool. In Muslim countries, most people who use e-cigarettes fast the month of Ramadan, which results in intermittent fasting. This study aims to reveal the severity of e-cig withdrawal symptoms among users during this intermittent fasting period.

Methods

A self-administered survey was developed and validated to solicit anonymous responses from e-cig users living in Jordan, through a cross-sectional study design. Participants were recruited through social media resources. Severity scores of physical (out of 11) and psychological (out of 8) withdrawal symptoms for each participant were assessed and calculated for each participant, depending on the symptoms reported.

Results

A convenience sample (n = 523) of e-cig adult users were recruited. The majority of the participants were males (96.4%) aged between 18 and 40 years (86.4%). Many participants replaced tobacco smoking with e-cig (53.5%) in order to help them stop smoking. More than half of the participants experienced relatively weak physical (0.82 ± 1.78) and psychological (1.24 ± 1.89) withdrawal symptoms during the month of fasting. Most of the participants (63.2%) preferred to engage themselves with a busy schedule to tolerate the related withdrawal symptoms they experienced.

Conclusion

E-cigs could play a vital role in smoking cessation among tobacco smokers during intermittent fasting. Ramadan offers a good opportunity for smokers to quit, as the reported physical and psychological e-cig withdrawal symptoms were found to be relatively weak. Awareness and behavioral interventions would help clarify the effect of e-cigs and help determine alternative ways to cease smoking.
Design, synthesis, and evaluation of 4-chromenone derivatives combined with N-acylhydrazone for aurora kinase A inhibitor
Authors: Shin Soon Young , Lee Junho , Ahn Seunghyun , Yoo Miri , Lee Young Han , Koh Dongsoo , Lim Yoongho
Published: February 2021

There is accumulating evidence that compounds containingN-acylhydrazone or 4-chromenone moieties can be active against multiple cancer cell types, yet the combined effect of these chemical groups is unclear. This study aimed to develop more effective anti-cancer compounds by combining 4-chromenone andN-acylhydrazone. Thirteen derivatives were designed, synthesized, and characterized, and their structures were identified using nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Most of the derivatives exhibited moderate to high efficacy in inhibiting the clonogenicity of HCT116 colon cancer cells. In particular, derivative12, (E)-N'-((6-methoxy-4-oxo-4H-chromen-3-yl)methylene)isonicotinohydrazide, strongly inhibited clonogenicity (GI50 = 34.8 μM) of HCT116 cells and aurora kinase A (aurA) activity in vitro (IC50 = 1.4 μM). In silico docking experiment predicted that derivative12interacts with aurA based on computational docking and calculations of binding free energy. When derivative12was exposed to HCT116 cells, the phosphorylation of aurA at Thr288 was dose-dependently decreased within 60 min. Further analysis showed that derivative12destroyed the mitotic spindle in HCT116 cells. These results suggest that derivatives of 4-chromenone combined withN-acylhydrazone are feasible in the development of selective aurA inhibitor and could be considered potential chemotherapeutic agents.
Undoing resilience: immigrant status and poor health following incarceration
Authors: Kuper Julie L. , Turanovic Jillian J.
Published: February 2021

Background

In the United States, foreign-born persons often have better health outcomes than their native-born peers, despite exposure to adversity. Nevertheless, it is unclear whether this pattern extends to the consequences of life events, such as incarceration, that separate immigrants from their supportive networks and increase exposure to adversity. Accordingly, using four waves of data from the National Longitudinal Study of Adolescent to Adult Health, hierarchical generalized linear models were used to examine within-individual changes in self-rated health following first incarceration (N = 31,202 person-waves).

Results

The results showed that incarceration was associated with modest health declines that were similar in magnitude for immigrant and native-born persons. Supplemental analyses revealed that these effects did not vary by immigrant race or ethnicity, or by age at immigration. The only exception was for immigrants from low- and middle-income countries, who were marginally less likely to experience health declines following incarceration.

Conclusions

In general, incarceration appears to be similarly health damaging for immigrants and non-immigrants. These findings raise important questions about how incarceration is linked to health declines for foreign- and native-born populations and emphasize the importance of access to healthcare for individuals released from correctional facilities. More research is needed, however, to further examine the cumulative impacts of incarceration on immigrants’ health across the life course, and to assess a broader spectrum of health outcomes.
Influence network design via multi-level optimization considering boundedly rational user behaviours in social media networks
Authors: Yun Guanxiang , Zheng Qipeng P. , Boginski Vladimir , Pasiliao Eduardo L.
Published: February 2021

Social media networks have been playing an increasingly more important role for both socialization and information diffusion. Political campaign can gain more supporters by attracting more mass attention and influencing them directly, while commercial campaigns can increase their companies’ profits by expanding social media connection with new users. To build the optimal network structure to influence the whole, this paper studies mathematical models to simulate the users’ behaviours interacting with others in the information provider’s network. The behaviours of concerns include information re-posting and following/unfollowing other users. Linear threshold propagation model is used to determine the re-posting actions, Boundedly Rational User Equilibrium (BRUE) models are used to determine the following or unfollowing actions. Hence, the topology of the network changes and depends on the information provider’s plan to post various kinds of information. A three-level optimization model is proposed to maximize total number of connections, the goal of the top level. The second level simulates user behaviours under BRUE. The third level maximizes the each user’s utility defined in the second level. This paper solves this problem using exact algorithms for a small-scale synthetic network. For a large-scale problem, this paper uses heuristic algorithms based on large neighbourhood search. This paper also discusses possible reasons why the BRUE model may be a more accurate simulation of users’ actions compared to game theory. Comparisons from the BRUE model to game theoretical model show that the BRUE model performs significantly better than game theoretical model.