bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, attitude and acceptability of COVID-19 vaccine among residents in rural communities in Ghana: a multi-regional study
Authors: Amponsah-Tabi Seth , Djokoto Rex , Opoku Stephen , Senu Ebenezer , Boakye Derrick Kyei , Azanu Wisdom Klutse , Ankobea-Kokroe Frank , Owusu-Asubonteng Gerald , Ansah Richard Owusu , Owusu Emmanuel , Ackah-Avoh Emmanuel , Kwayie Afia Agyapomaa , Boateng Eric Appiah , Azavil Richard Pul , Ennin Frederick
Published: January 2023

Background

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic has continuously affected human life with several devastating effects. Currently, there are effective vaccines to protect people from COVID‐19 and the World Health Organization (WHO) has highlighted strategies to influence COVID-19 vaccine uptake in hard-to-reach communities in Ghana. However, prior studies on COVID-19 vaccine acceptability in Ghana are online surveys targeting the literates and those in urban areas, leaving residents in far-flung communities. We assessed knowledge, attitude and acceptability of COVID-19 vaccine among residents in rural communities in Ghana.

Methods

This study was a community-based cross-sectional study and was conducted at three selected regions in Ghana (Northern, Ashanti and Western North) from May to November, 2021. This study included residents 15–81 years, living in the selected rural communities for more than 1 year. Study participants were recruited and questionnaires administered to collect data on knowledge, attitude and acceptance of the COVID-19 vaccine. Statistical analyses were performed using Statistical Package for Social Science (SPSS) version 26.0 and GraphPad Prism Version 8.0 software.

Results

Of the 764 participants included in this study, more than half had inadequate knowledge (55.0%), poor attitudes (59.4%) and bad perception about COVID-19 vaccine (55.4%). The acceptability of COVID-19 vaccine in this study was 41.9%. The acceptability of COVID-19 vaccine in Ashanti, Northern and Western North regions were 32.5%, 26.2% and 29.6% respectively. In a multivariate logistic regression analysis, receiving recent or previous vaccine such as HBV vaccine [aOR = 1.57, 95% CI (1.23–3.29), p = 0.002], having good attitude towards COVID-19 vaccine [aOR = 61.47, 95% CI (29.55–127.86), p < 0.0001] and having good perception about the COVID-19 vaccine [aOR = 3.87, 95% CI (1.40–10.72), p < 0.0001] were independently associated with higher odds of accepting COVID-19 vaccine.

Conclusion

More than half of residents in Ghanaian rural communities have inadequate knowledge, poor attitudes and bad perception about COVID-19 vaccine. The acceptability of COVID-19 vaccine is generally low among rural residents in Ashanti, Northern and Western North regions of Ghana. Residents living in hard-to-reach communities must be educated about the benefits of COVID-19 vaccine to achieve effective vaccination program.
Lessons learned from a sporadic FUSopathy in a young man: a case report
Authors: García-Roldán Ernesto , Rivas-Infante Eloy , Medina-Rodríguez Manuel , Arriola-Infante José Enrique , Rodrigo-Herrero Silvia , Paradas Carmen , Rábano-Gutiérrez Alberto , Franco-Macías Emilio
Published: February 2023

Background

In frontotemporal dementia (FTD) spectrum, younger patients may correspond to fusopathy cases, and cognitive decline could be rapidly progressive. We present a clinical and neuropathological description of a patient.

Case presentation

A 37-year-old man, without a family history of neurodegenerative diseases, was brought by his family to consult for dysarthria and behavioural change. Initial exploration showed spastic dysarthria and disinhibition. He progressively worsened with a pseudobulbar syndrome, right-lateralized pyramidal signs, left hemispheric corticobasal syndrome and, finally, lower motor neuron signs in his right arm. He died four years after the initiation of the syndrome from bronchopneumonia. Laboratory tests (including blood and cerebrospinal fluid (CSF)) were normal. Magnetic resonance imaging (MRI) and fluorodeoxyglucose-containing positron emission tomography (PET-18F-FDG) showed left fronto-insular atrophy and hypometabolism. Subsequently, 123I-ioflupane (DaT-SCAN®) single-photon emission computed tomography (SPECT) was pathologic, manifesting bilaterally decreased activity with greater affection on the left side. Only a third electromyogram (EMG) detected denervation in the last year of evolution. No mutations were found in genes such as Tau, progranulin, C9orf72, FUS, TDP-43, CHMP2B, or VCP. In necropsy, severe frontotemporal atrophy with basophilic neuronal cytoplasmic and intranuclear inclusions, negative for tau and TAR DNA binding protein 43 (TDP-43), but positive for fused in sarcoma (FUS) consistent with specifically basophilic inclusions body disease (BIBD) type was found.

Conclusions

In patients affected by FTD, particularly the youngest, with rapidly progressive decline and early motor affection, fusopathy must be suspected. These cases can include motor signs described in the FTD spectrum. Lower motor neuron affection in EMG could be detected late.
Evaluating the impact of patient-reported outcome measures on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial
Authors: Chu Nathan Y. , Watson Kaitlyn E. , Al Hamarneh Yazid N. , Yushko Lily , Tsuyuki Ross T. , Smyth Penelope
Published: February 2023

Background

Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients’ lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient’s perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety.

Methods

A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient’s MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes.

Discussion

This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice.

Trial registration

This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.govNCT04979546. Registered on July 28, 2021.
The association between liver fibrosis and depression in patients after ischemic stroke
Authors: Zhang Yun , Yang Yao , Feng Yue , Chen Zhonglun , He Lin , Xie Shu , Shi Jian , Yang Bufan , Tang Yufeng
Published: January 2023

Background and objective

Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up.

Methods

We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories (< 2.67 versus ≥ 2.67). Patients with a 17-item Hamilton Depression Scale score > 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months.

Results

A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%–30.5%) of the cohort.

The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%;P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03–3.42;P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable.

Conclusions

This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.
Simple surgical punctal occlusion with high frequency radiowave electrosurgery
Authors: Park Jeong Woo , Han Jisang , Choi Wan Kyu , Kim Jaemin , Choi Chul Young
Published: February 2023

Background

To introduce and evaluate the efficacy of a simple punctal occlusion technique for dry eye patients.

Methods

Medical records of 79 eyes from 40 patients refractory to common dry eye conservative treatment who underwent multiple high-frequency radio-wave electro-punctal occlusion were retrospectively reviewed. Pre- and post-procedural ocular surface indices (Schirmer test, tear break-up time (TBUT), and corneal staining grade (Oxford scheme)) and subjective symptom scores (including frequency of artificial tear use, interval between procedures, and total repeat time) were analyzed.

Results

Average Schirmer test result was significantly (P < 0.05) improved from 4.10 ± 1.39 mm to 8.14 ± 3.13 mm at 6 weeks after the procedure (n = 79). A total of 32 eyes from 16 patients underwent repeated procedure with a mean interval of 8.00 ± 4.86 months, while 24 patients had a single procedure. Twenty-five of 30 patients showed improvement for subjective symptom scores. No complications related to the procedure were observed.

Conclusions

A simple, less-invasive punctal occlusion technique using a fine-needle tip with high-frequency radio-wave could significantly relieve subjective symptoms and improve ocular surface indices of patients with aqueous deficient dry eye without causing a major complication. This procedure may play a considerable role in treating dry eye refractory to common practices.
Characteristics and outcomes of neonates with intrapartum asphyxia managed with therapeutic hypothermia in a public tertiary hospital in South Africa
Authors: Nakwa Firdose Lambey , Sepeng Letlhogonolo , van Kwawegen Alison , Thomas Reenu , Seake Karabo , Mogajane Tshiamo , Ntuli Nandi , Ondongo-Ezhet Claude , Kesting Samantha , Kgwadi Dikeledi Maureen , Kamanga Noela Holo Bertha , Coetser Annaleen , Van Rensburg Jeanne , Pepper Michael S. , Velaphi Sithembiso C.
Published: January 2023

Background

In randomized clinical trials, therapeutic hypothermia (TH) has been shown to reduce death and/or moderate-to-severe disability in neonates with hypoxic ischemic encephalopathy (HIE) in high-income countries, while this has not consistently been the case in low-and middle-income countries (LMICs). Many studies reporting on outcomes of neonates with HIE managed with TH are those conducted under controlled study conditions, and few reporting in settings where this intervention is offered as part of standard of care, especially from LMICs. In this study we report on short-term outcomes of neonates with moderate-to-severe HIE where TH was offered as part of standard of care.

Objective

To determine characteristics and mortality rate at hospital discharge in neonates with moderate-to-severe HIE.

Methods

Hospital records of neonates with intrapartum asphyxia were reviewed for clinical findings, management with TH (cooled or non-cooled) and mortality at hospital discharge. Inclusion criteria were birthweight ≥ 1800 g, gestational age ≥ 36 weeks and moderate-to-severe HIE. Comparisons were made between survivors and non–survivors in cooled and/or non-cooled neonates.

Results

Intrapartum asphyxia was diagnosed in 856 neonates, with three having no recorded HIE status; 30% (258/853) had mild HIE, and 595/853 (69%) with moderate-to-severe HIE. The overall incidence of intrapartum asphyxia was 8.8/1000 live births. Of the 595 with moderate-to-severe HIE, three had no records on cooling and 67% (399/592) were cooled. Amongst 193 non-cooled neonates, 126 (67%) had documented reasons for not being cooled with common reasons being a moribund neonate (54.0%), equipment unavailability (11.1%), pulmonary hypertension (9.5%), postnatal age > 6 h on admission (8.7%), and improvement in severity of encephalopathy (8.7%). Overall mortality was 29.0%, being 17.0% and 53.4% in cooled and non-cooled infants respectively. On multivariate analysis, the only factor associated with mortality was severe encephalopathy.

Conclusion

Overall mortality in neonates with moderate-to-severe HIE was 29.0% and 17.0% in those who were cooled. Cooling was not offered to all neonates mainly because of severe clinical illness, equipment unavailability and delayed presentation, making it difficult to assess overall impact of this intervention. Prospective clinical studies need to be conducted in LMIC to further assess effect of TH in short and long-term outcomes.
Sociodemographic and clinical characteristics of children with tic disorders and behavioral problems: A real-world study and development of a prediction model
Authors: Liu Fang , Wang Gaohua , Ye Jingping , Yao Baozhen , Wang Junling , Wang Huaqian , Liu Hong
Published: February 2023

Background

Tic disorders (TD) are complex neuropsychiatric disorders frequently associated with a variety of comorbid problems, whose negative effects may exceed those of the tics themselves. In this study, we aimed to explore the sociodemographic and clinical characteristics of children with TD and behavioral problems, and develop a prediction model of behavioral problems based on the predictors under real-world conditions.

Methods

A hospital-based cross-sectional study was conducted on children with TD. Behavioral problems were surveyed using the Achenbach Child Behavior Checklist (CBCL). Sociodemographic information was collected from face-to-face interviews using an electronic questionnaire administered during the initial ambulatory visit. Clinical data were collected from medical records, and quality control was performed. The sociodemographic and clinical characteristics of patients with and without behavioral problems were statistically compared, and a nomogram prediction model was developed based on multivariate logistic regression analysis. The discriminatory ability and clinical utility of the nomogram were assessed by concordance index (C-index), receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve (CIC).

Results

A total of 343 TD cases were included in the final analysis, of which 30.32% had behavioral problems. The prediction model showed age 12–16 years, abnormal birth history, parenting pattern of indulgence, parent/close relatives with psychiatric disorders, chronic motor or vocal tic disorder (CTD)/Tourette syndrome (TS) and moderate/severe tic severity were associated with behavioral problems in children with TD. The C-index of the prediction model (nomogram) was 0.763 (95% confidence interval, 0.710 ~ 0.816). The nomogram was feasible for making beneficial clinical decisions, according to the satisfactory results of the DCA and CIC.

Conclusions

A nomogram prediction model for comorbid behavioral problems in children with TD was established. The prediction model demonstrated a good discriminative ability and predictive performance for beneficial clinical decisions. This model further provides a comprehensive understanding of associated sociodemographic and clinical characteristics by visual graphs and allows clinicians to rapidly identify patients with a higher risk of behavioral problems and tailor necessary interventions to improve clinical outcomes.
Systematic review of structured care pathways in major depressive disorder and bipolar disorder
Authors: Kim Helena Kyunghee , Banik Suman , Husain Muhammad Ishrat , Tang Victor , Levitan Robert , Daskalakis Zafiris J. , Kloiber Stefan
Published: February 2023

Background

Structured care pathways (SCPs) consist of treatment algorithms that patients advance through with the goal of achieving remission or response. These SCPs facilitate the application of current evidence and adequate treatment, which potentially benefit patients with mood disorders. The aim of this systematic review was to provide an updated synthesis of SCPs for the treatment of depressive disorders and bipolar disorder (BD).

Method

PubMed, PsycINFO, and Embase were searched through June 2022 for peer-reviewed studies examining outcomes of SCPs. Eligibility criteria included being published in a peer-reviewed journal in the English language, reporting of intervention used in the SCP, and having quantitative outcomes. Studies Cochrane risk of bias tool was used to assess quality of RCTs.

Results

Thirty-six studies including 15,032 patients were identified for qualitative synthesis. Six studies included patients with BD. The studies were highly heterogeneous in design, outcome measures, and algorithms. More than half of the studies reported superiority of SCPs over treatment as usual, suggesting that the standardized structure and consistent monitoring inherent in SCPs may be contributing to their effectiveness. We also found accumulating evidence supporting feasibility of SCPs in different settings, although dropout rates were generally higher in SCPs. The studies included were limited to being published in peer-reviewed journals in English language. The heterogeneity of studies did not allow quantitative evaluation.

Conclusions

The findings of our study suggest that SCPs are equally or more effective than treatment as usual in depression and BD. Further studies are required to ascertain their effectiveness, particularly for BD, and to identify factors that influence their feasibility and success.
Trends in hospital admissions and prescribing due to chronic obstructive pulmonary disease and asthma in England and Wales between 1999 and 2020: an ecological study
Authors: Alwafi Hassan , Naser Abdallah Y. , Ashoor Deema Sami , Aldhahir Abdulelah M. , Alqahtani Jaber S. , Minshawi Faisal , Salawati Emad , Samannodi Mohammed , Dairi Mohammad Saleh , Alansari Aisha Khaled , Ekram Rakan
Published: February 2023

Objective

To investigate the trends in hospital admissions and medication prescriptions related to asthma and chronic obstructive pulmonary disease (COPD) in England and Wales.

Methods

An ecological study was conducted between April 1999 and April 2020 using data extracted from the hospital episode statistics database in England and the patient episode database for Wales. The Office of National Statistics mid-year population estimates for 1999 through 2020 were collected, and medication prescription data for 2004–2020 were extracted from the prescription cost analysis database.

Results

The total annual number of COPD and asthma hospital admissions for various causes increased by 82.2%, from 210,525 in 1999 to 383,652 in 2020, representing a 59.1% increase in hospital admission rate (from 403.77 in 1999 to 642.42 per 100,000 persons in 2020, p < 0.05). Chronic obstructive pulmonary disease with acute lower respiratory infection accounted for 38.7% of hospital admissions. Around 34.7% of all hospital admissions involved patients aged 75 and older. Around 53.8% of all COPD and asthma hospital admissions were attributable to females. The annual number of prescriptions dispensed for COPD and asthma medications increased by 42.2%.

Conclusions

Throughout the study period, hospital admissions due to chronic obstructive pulmonary disease and asthma, as well as medication prescriptions, increased dramatically among all age groups. Hospitalization rates were higher for women. Further observational and epidemiological research is required to identify the factors contributing to increased hospitalization rates.
Infrared thermographic changes after decompression surgery in patients with carpal tunnel syndrome
Authors: Park Yeo Eun , Lee Sang-Eok , Eom Yoon Sik , Cho Jae Man , Yang Joong Won , Kim Man Su , Kwon Heum Dai , Lee Jang Woo , Park Dougho
Published: January 2023

Background

Digital infrared thermal imaging (DITI), which detects infrared rays emitted from body surface to create a body heat map, has been utilized at various musculocutaneous conditions. Notably, DITI can demonstrate autonomic vasomotor activity in the nerve-innervated area, and thus may be of use in carpal tunnel syndrome (CTS). In this study, we compared DITI findings before and after carpal tunnel release (CTR) surgery in patients with unilateral CTS to investigate the corresponding neurophysiological changes.

Methods

In this retrospective cohort study, DITI parameters such as the temperature differences between the median and ulnar nerve territories and median nerve-innervated digital anisometry were measured. Subjective symptom duration, pain scale, and ultrasonographic findings were also compared before and after CTR. Patients were evaluated before and 6 weeks after CTR, respectively.

Results

A total of 27 patients aged 59.0 ± 11.2 years were finally included. After CTR, median nerve-innervated thermal anisometry was improved (2.55 ± 0.96 °C to 1.64 ± 1.34 °C; p = 0.003). The temperature differences between the median and ulnar nerve territories were not significantly changed. Subjective pain, the Simovic Weinberg Clinical Scale, and palmar bowing of the flexor retinaculum were also significantly improved (p <  0.001 for all comparisons).

Conclusions

Our results demonstrated that DITI findings could reflect an improvement in autonomic function after CTR. Therefore, DITI can be an objective method to assess pre- and post-operative neurophysiologic changes in CTS.
Circadian Timing, Information processing and Metabolism (TIME) study: protocol of a longitudinal study of sleep duration, circadian alignment and cardiometabolic health among overweight adults
Authors: Baron Kelly Glazer , Appelhans Bradley M. , Burgess Helen J. , Quinn Lauretta , Greene Tom , Allen Chelsea M.
Published: January 2023

Background

Both short sleep duration and circadian rhythm misalignment are risk factors for metabolic dysfunction, but the underlying mechanisms are unknown. The goal of this study is to examine how sleep duration and circadian alignment predict changes in cardiometabolic risk factors over a 12-month period, and test cognitive function and hedonic eating tendencies as potential mechanisms.

Methods

We will recruit a sample of 120 working aged adults with BMI 25–35 kg/m2 (overweight to class I obesity). The protocol includes 5 visits over a 12-month period. Study visits include wrist actigraphy to measure sleep behaviors, 24-h diet recalls, dim light melatonin collection, a computerized neurobehavioral assessment, eating in the absence of hunger task, and frequently sampled IV glucose tolerance test.

Discussion

The results of the TIME study will advance the understanding of how both short sleep duration and circadian misalignment contribute to behavioral aspects of obesity and metabolic dysfunction.

Trial registration

ClinicalTrials.Gov, NCT04759755, registered retrospectively February 13, 2021.
The effects of a low carbohydrate diet on erectile function and serum testosterone levels in hypogonadal men with metabolic syndrome: a randomized clinical trial
Authors: da Silva Schmitt Caio , da Costa Carla Martins , Souto José Carlos Stumpf , Chiogna Lorenzo Miron , de Albuquerque Santos Zilda Elizabeth , Rhoden Ernani Luis , Neto Brasil Silva
Published: February 2023

Purpose

Metabolic syndrome is a risk factor for several diseases. The relationship between metabolic syndrome and hypogonadism is well known. Our objetive is to assess whether a low carbohydrate diet can increase total serum testosterone and improve erectile function in hypogonadal men with metabolic syndrome.

Methods

An open label randomized clinical trial was conducted comparing a low carbohydrate diet and controls, during three months, in hypogonadal men with metabolic syndrome. Anthropometric measurements were evaluated as well as total serum testosterone levels, and symptoms of hypogonadism, using the ADAM and AMS scores, and sexual function using IIEF-5 score.

Results

Eighteen men were evaluated. Anthropometric measures were improved only in low carbohydrate diet group. The intervention group also had a statistically increase in IIEF-5 score and a significant reduction in AMS and ADAM scores (p < 0.001). The increase in serum total testosterone levels was statistically significant in the low carbohydrate group compared to the control group as well as calculated free testosterone (p < 0.001).

Conclusions

Low carbohydrate diet may increase serum levels of testosterone and improve erectile function in hypogonadal men with metabolic syndrome. However, larger studies are necessary to strongly prove the effectiveness of low carbohydrate diet in treating male hypogonadism.
Effect of shelf-storage temperature on degree of conversion and microhardness of composite restorative materials
Authors: El-Maksoud Omar Abd , Hamama Hamdi Hosni Hamdan , Wafaie Ramy Ahmed , El-Wassefy Noha , Mahmoud Salah Hasab
Published: January 2023

Background

The pre-cure temperature is considered an important parameter that affects the polymerization kinetics and the properties of composite restoration. As dissension exists about the effect of storing composite restorative materials in refrigerator, this study aimed to assess the effect of shelf-storage temperature on degree of conversion (DC) and microhardness of three composite restorative materials with different matrix systems.

Methods

Three commercially-available composite restorative materials were used in this study; an Ormocer-based composite (Admira Fusion, Voco GmbH), a nanoceramic composite, (Ceram.X SphereTEC One, Dentsply Sirona GmbH), and a nanohybrid composite (Tetric N-Ceram, Ivoclar Vivadent AG). Regarding DC and microhardness tests, 60 disc-shaped composite specimens for each test were randomly divided into 3 groups (n = 20) according to the restorative material used. Each group was divided into 2 subgroups (n = 10) according to the composite storage temperature; stored at room temperature or stored in the refrigerator at 4°–5 °C. DC was evaluated using a Fourier-transform infrared spectrometer coupled to an attenuated total reflectance accessory. Microhardness was evaluated using micro-Vickers hardness tester under a load of 50 g with a dwell time of 10 s. The results were analyzed by ANOVA, post-hoc LSD, and independent t-tests at a significance level of p < 0.05.

Results

Regarding DC test all groups showed statistically significant differences at both storage temperature. The Ormocer-based composite had the highest mean values. There was a statistically significant difference between all room-stored groups and their corresponding groups stored at refrigerator (p < 0.05). For microhardness test, all groups exhibited also statistically significant differences at both storage temperatures with the Ormocer-based composite having the highest mean values. A statistically significant difference between both room-stored and refrigerator-stored groups has been observed also (p < 0.05).

Conclusions

Refrigeration of resin-composite might have a deleterious effect on DC and microhardness of the tested composite restorative materials with different matrix systems. Moreover, the differences in the formulations of composite matrix have a potential impact on DC and microhardness.
Learners’ characteristics and the mastery of digital education during the COVID-19 pandemic in students of a medical faculty in Germany
Authors: Roick Julia , Poethke Paul , Richter Matthias
Published: February 2023

Background

In response to the spread of the coronavirus, educational institutions have been closed and digital education has become a new teaching method to ensure the continuity of medical education. Since this format was a new form of learning for students at medical faculties in Germany, little is known about the perception of it and the factors that contribute to successful mastery. The current study aimed to analyze students’ learning experiences during the first online semester and to identify associations between learners’ characteristics and enjoyment, mastery experiences, as well as the perceived stress level.

Methods

In this cross-sectional study, students of a medical faculty from Germany answered an online questionnaire including information about perceptions towards digital education and learners’ characteristics (study skills and dispositions). Data were analyzed using multivariate linear regression analysis.

Results

In total, 383 students responded to the online survey. A majority of students felt at least somewhat worse about their studies compared to before the pandemic. Success of study tasks was related to preferences for cooperative learning (B = − 0.063, p < .001) and success of study organization was associated to the use of metacognitive learning strategies (B = 0.019, p = .04). Enjoyment of studying in times of digital education was positively related to the use of metacognitive strategies (B = 0.049, p = .04) and self-efficacy (B = 0.111, p = .02). The perceived stress was influenced by cognitive strategies (B = 0.401, p = .02) and test anxiety (B = 0.466, p < .001).

Conclusions

Although students perceive digital teaching as a good alternative for big courses, those with low self-efficacy beliefs and low self-regulation have problems in coping with the demands of this learning format and need further support.
Understanding mentoring relationships between mentees, peer and senior mentors
Authors: Venktaramana Vaishnavi , Ong Yun Ting , Yeo Jun Wei , Pisupati Anushka , Krishna Lalit Kumar Radha
Published: January 2023

Background

Mentoring relationships play a critical but poorly understood role in mentoring’s overall success. To overcome these knowledge gaps, a study of mentee experiences in the Palliative Medicine Initiative, a structured research-based mentoring program, is proposed. The program’s clearly described mentoring approach, competency-based mentoring stages and curated mentoring environment ensure a consistent mentoring experience. It provides a unique platform to study mentoring relationships longitudinally and its implications on professional identity formation.

Methodology

The Tool Design Systematic Evidence-Based Approach methodology is used to map and employ current understanding. A review of recent reviews on mentoring processes, mentoring’s effects, professional identity formation and professional identity formation assessment tools lay the foundation for the design of semi-structured interviews and mentoring diaries to evaluate the characteristics of successful mentoring relationships and mentoring’s impact on professional identity formation. The data accrued from these tools were evaluated using this methodology whilst changes in professional identity formation were assessed using the Ring Theory of Personhood.

Results

The semi-structured interviews revealed four themes: stakeholders, mentoring stages, mentoring relationships and professional identity formation whilst the mentoring diaries revealed two: mentoring processes and mentoring relationships. Two final domains emerged – mentoring relationships and professional identity formation.

Conclusions

The Palliative Medicine Initiative’s structured stage-based mentoring approach, trained stakeholders, curated environment, assessment-directed and personalized mentoring support reveal seven developmental stages of mentoring relationships. These culminate in changes to the values, beliefs and principles that shape how mentees see, feel and act as professionals. These findings suggest that mentoring programs may help to further develop and fine-tune their professional identity formation.
Mapping patient pathways and understanding clinical decision-making in dengue management to inform the development of digital health tools
Authors: Nguyen Quang Huy , Ming Damien K. , Luu An Phuoc , Chanh Ho Quang , Tam Dong Thi Hoai , Truong Nguyen Thanh , Huy Vo Xuan , Hernandez Bernard , Van Nuil Jennifer Ilo , Paton Chris , Georgiou Pantelis , Nguyen Nguyet Minh , Holmes Alison , Tho Phan Vinh , Yacoub Sophie ,   the Vietnam ICU Translational Applications Laboratory (VITAL) investigators
Published: February 2023

Background

Dengue is a common viral illness and severe disease results in life-threatening complications. Healthcare services in low- and middle-income countries treat the majority of dengue cases worldwide. However, the clinical decision-making processes which result in effective treatment are poorly characterised within this setting. In order to improve clinical care through interventions relating to digital clinical decision-support systems (CDSS), we set out to establish a framework for clinical decision-making in dengue management to inform implementation.

Methods

We utilised process mapping and task analysis methods to characterise existing dengue management at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. This is a tertiary referral hospital which manages approximately 30,000 patients with dengue each year, accepting referrals from Ho Chi Minh city and the surrounding catchment area. Initial findings were expanded through semi-structured interviews with clinicians in order to understand clinical reasoning and cognitive factors in detail. A grounded theory was used for coding and emergent themes were developed through iterative discussions with clinician-researchers.

Results

Key clinical decision-making points were identified: (i) at the initial patient evaluation for dengue diagnosis to decide on hospital admission and the provision of fluid/blood product therapy, (ii) in those patients who develop severe disease or other complications, (iii) at the point of recurrent shock in balancing the need for fluid therapy with complications of volume overload. From interviews the following themes were identified: prioritising clinical diagnosis and evaluation over existing diagnostics, the role of dengue guidelines published by the Ministry of Health, the impact of seasonality and caseload on decision-making strategies, and the potential role of digital decision-support and disease scoring tools.

Conclusions

The study highlights the contemporary priorities in delivering clinical care to patients with dengue in an endemic setting. Key decision-making processes and the sources of information that were of the greatest utility were identified. These findings serve as a foundation for future clinical interventions and improvements in healthcare. Understanding the decision-making process in greater detail also allows for development and implementation of CDSS which are suited to the local context.
Rural and urban differences in quality of dementia care of persons with dementia and caregivers across all domains: a systematic review
Authors: Arsenault-Lapierre Geneviève , Bui Tammy X. , Le Berre Mélanie , Bergman Howard , Vedel Isabelle
Published: January 2023

Background

There are challenges in healthcare service delivery in rural areas, and this may be especially true for persons with dementia, who have higher needs to access to the healthcare system, and may have difficulties to commute easily and safely to these services. There is a growing body of literature regarding geographical disparities, but there is no comprehensive systematic review of geographical differences in persons with dementia across all domains of care quality. Therefore, the objective of this study is to conduct a systematic review of the literature on rural and urban differences in quality of dementia care outcomes of persons with dementia across all quality-of-care domains.

Methods

We performed a digital search in Ovid MEDLINE on July 16, 2019, updated on May 3, 2021, for French or English records. We selected studies that reported outcome from at least one domain of quality of dementia care (Access, Integration, Effective Care, Efficient Care, Population Health, Safety, and Patient-Centered) in both rural and urban persons with dementia or caregivers. We used rigorous, systematic methods for screening, selection, data extraction and we analyzed outcomes reported by at least two studies using vote counting and appraised the certainty of evidence. Finally, we explored sources of heterogeneity.

Results

From the 38 included studies, we found differences in many dementia care domains. Rural persons with dementia had higher mortality rates (Population Health), lower visits to any physicians (Access), more hospitalizations but shorter stays (Integration), higher antipsychotic medications (Safety), lower use of home care services and higher use of nursing home (Patient-Centered Care) compared to urban persons with dementia.

Conclusions

This comprehensive portrait of rural–urban differences in dementia care highlights possible geographically based inequities and can be used by researchers and decision makers to guide development of more equitable dementia care policies.
BRD4 is involved in viral exacerbation of chronic obstructive pulmonary disease
Authors: Duan Yifei , Zhou Siyi , Wang Jianmiao
Published: January 2023

Background

Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD.

Methods

BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant.

Results

BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression.

Conclusions

Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.
Acid sphingomyelinase promotes diabetic cardiomyopathy via NADPH oxidase 4 mediated apoptosis
Authors: Liu Ruijiao , Duan Tengfei , Yu Li , Tang Yongzhong , Liu Shikun , Wang Chunjiang , Fang Wei-Jin
Published: February 2023

Background

Increased acid sphingomyelinase (ASMase) activity is associated with insulin resistance and cardiac dysfunction. However, the effects of ASMase on diabetic cardiomyopathy (DCM) and the molecular mechanism(s) underlying remain to be elucidated. We here investigated whether ASMase caused DCM through NADPH oxidase 4-mediated apoptosis.

Methods and results

We used pharmacological and genetic approaches coupled with study of murine and cell line samples to reveal the mechanisms initiated by ASMase in diabetic hearts. The protein expression and activity of ASMase were upregulated, meanwhile ceramide accumulation was increased in the myocardium of HFD mice. Inhibition of ASMase with imipramine (20 mg Kg−1 d−1) or siRNA reduced cardiomyocyte apoptosis, fibrosis, and mitigated cardiac hypertrophy and cardiac dysfunction in HFD mice. The similar effects were observed in cardiomyocytes treated with high glucose (HG, 30 mmol L−1) + palmitic acid (PA, 100 μmol L−1) or C16 ceramide (CER, 20 μmol L−1). Interestingly, the cardioprotective effect of ASMase inhibition was not accompanied by reduced ceramide accumulation, indicating a ceramide-independent manner. The mechanism may involve activated NADPH oxidase 4 (NOX4), increased ROS generation and triggered apoptosis. Suppression of NOX4 with apocynin prevented HG + PA and CER incubation induced Nppb and Myh7 pro-hypertrophic gene expression, ROS production and apoptosis in H9c2 cells. Furthermore, cardiomyocyte-specific ASMase knockout (ASMaseMyh6KO) restored HFD-induced cardiac dysfunction, remodeling, and apoptosis, whereas NOX4 protein expression was downregulated.

Conclusions

These results demonstrated that HFD-mediated activation of cardiomyocyte ASMase could increase NOX4 expression, which may stimulate oxidative stress, apoptosis, and then cause metabolic cardiomyopathy.
In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer
Authors: Ge Chun , Huang Xintong , Zhang Sujie , Yuan Man , Tan Zhaoyi , Xu Chen , Jie Qiong , Zhang Jingjing , Zou Jianjun , Zhu Yubing , Feng Dong , Zhang Yue , Aa Jiye
Published: January 2023

Background

As a prodrug of 5-fluorouracil (5-FU), orally administrated capecitabine (CAP) undergoes preliminary conversion into active metabolites in the liver and then releases 5-FU in the gut to exert the anti-tumor activity. Since metabolic changes of CAP play a key role in its activation, a single kind of intestinal or hepatic cell can never be used in vitro to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) nature. Hence, we aimed to establish a novel in vitro system to effectively assess the PK and PD of these kinds of prodrugs.

Methods

Co-culture cellular models were established by simultaneously using colorectal cancer (CRC) and hepatocarcinoma cell lines in one system. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to evaluate cell viability and apoptosis, respectively. Apoptosis-related protein expression levels were measured using western blot analysis. A selective liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed for cellular PK in co-culture models.

Results

CAP had little anti-proliferative effect on the five monolayer CRC cell lines (SW480, LoVo, HCT-8, HCT-116 and SW620) or the hepatocarcinoma cell line (HepG2). However, CAP exerted marked anti-tumor activities on each of the CRC cell lines in the co-culture models containing both CRC and hepatocarcinoma cell lines, although its effect on the five CRC cell lines varied. Moreover, after pre-incubation of CAP with HepG2 cells, the culture media containing the active metabolites of CAP also showed an anti-tumor effect on the five CRC cell lines, indicating the crucial role of hepatic cells in the activation of CAP.

Conclusion

The simple and cost‑effective co-culture models with both CRC and hepatocarcinoma cells could mimic the in vivo process of a prodrug dependent on metabolic conversion to active metabolites in the liver, providing a valuable strategy for evaluating the PK and PD characteristics of CAP-like prodrugs in vitro at the early stage of drug development.
Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network
Authors: Yang Zihan , Zhou Li , Si Tongxu , Chen Siyuan , Liu Chengxi , Ng Kelvin Kaki , Wang Zesheng , Chen Zhiji , Qiu Chan , Liu Guopan , Wang Qingliang , Zhou Xiaoyu , Zhang Liang , Yao Zhongping , He Song , Yang Mengsu , Zhou Zhihang
Published: January 2023

Background

Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear.

Methods

LC–MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 μm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC–MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype.

Results

Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis.

Conclusions

LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization.
Plasma derived extracellular vesicle biomarkers of microglia activation in an experimental stroke model
Authors: Roseborough A. D. , Myers S. J. , Khazaee R. , Zhu Y. , Zhao L. , Iorio E. , Elahi F. M. , Pasternak S. H. , Whitehead S. N.
Published: January 2023

Chronic microglia activation post-stroke is associated with worse neurological and cognitive outcomes. However, measurement of microglia activation in vivo is currently limited. Plasma derived extracellular vesicles (EVs) are cell-specific indicators that may allow for non-invasive measurement of microglia phenotype. The aim of this study was to identify activation-state specific microglia EVs (MEVs) in vitro followed by validation in an experimental stroke model. Following pro-inflammatory activation, MEVs contain the microglia protein TMEM119 alongside increased expression of the Toll-like receptor 4 co-receptor CD14. Immunoprecipitation followed by fluorescent nanoparticle tracking analysis (ONI Nanoimager) was used to confirm the isolation of TMEM119+/CD14+ EVs from rat plasma. Electron microscopy confirmed that TMEM119 and CD14 localize to the MEV membrane. To model ischemia, plasma was collected from 3-month wildtype Fischer344 rats prior to, 7 and 28 days after endothelin-1 or saline injection into the dorsal right striatum. Fluorescently labelled MEVs were directly measured in the plasma using nanoflow cytometry (Apogee A60 Microplus). We report a significant increase in circulating TMEM119+/CD14+ EVs 28-days post-stroke in comparison to baseline levels and saline-injected rats, which correlated weakly with stroke volume. TMEM119+/MHC-II+ EVs were also increased post-stroke in comparison to baseline and saline-injected animals. This study is the first to describe an EV biomarker of activated microglia detected directly in plasma following stroke and represents a future tool for the measurement of microglia activity in vivo.