bluuebunny/crossref_metadata_2025 huggingface dataset:
Missense variants causing Wiedemann-Steiner syndrome preferentially occur in the KMT2A-CXXC domain and are accurately classified using AlphaFold2
Authors: Reynisdottir Tinna , Anderson Kimberley Jade , Boukas Leandros , Bjornsson Hans Tomas
Published: June 2022

Wiedemann-Steiner syndrome (WDSTS) is a neurodevelopmental disorder caused by de novo variants in KMT2A, which encodes a multi-domain histone methyltransferase. To gain insight into the currently unknown pathogenesis of WDSTS, we examined the spatial distribution of likely WDSTS-causing variants across the 15 different domains of KMT2A. Compared to variants in healthy controls, WDSTS variants exhibit a 61.9-fold overrepresentation within the CXXC domain–which mediates binding to unmethylated CpGs–suggesting a major role for this domain in mediating the phenotype. In contrast, we find no significant overrepresentation within the catalytic SET domain. Corroborating these results, we find that hippocampal neurons from Kmt2a-deficient mice demonstrate disrupted histone methylation (H3K4me1 and H3K4me3) preferentially at CpG-rich regions, but this has no systematic impact on gene expression. Motivated by these results, we combine accurate prediction of the CXXC domain structure by AlphaFold2 with prior biological knowledge to develop a classification scheme for missense variants in the CXXC domain. Our classifier achieved 92.6% positive and 92.9% negative predictive value on a hold-out test set. This classification performance enabled us to subsequently perform an in silico saturation mutagenesis and classify a total of 445 variants according to their functional effects. Our results yield a novel insight into the mechanistic basis of WDSTS and provide an example of how AlphaFold2 can contribute to the in silico characterization of variant effects with very high accuracy, suggesting a paradigm potentially applicable to many other Mendelian disorders.
Marital rape and its impact on the mental health of women in India: A systematic review
Authors: Agarwal Nandini , Abdalla Salma M. , Cohen Gregory H.
Published: June 2022

This systematic review aims to describe the prevalence of marital rape in India, the analytic methods employed in its study, and its implications on mental health of victims. Online databases, PubMed, Embase, Web of Science and APA Psych, were systematically searched for articles published up until November 2020. Selected articles included those published from or studies conducted in India where the primary exposure was marital rape. The primary outcomes of interest are Post Traumatic Stress Disorder (PTSD) and Depression. Secondary outcomes related to PTSD and depression (e.g., suicidality) included in identified studies were also described. 11 studies were included after excluding studies based on our selection criteria: 9 quantitative studies and 2 qualitative studies. Sexual coercion by intimate partner was highly prevalent, ranging from 9%-80% and marital rape ranged from 2%-56%. Many of the studies reported statistically significant associations between marital rape and mental health outcomes, including clinical depression (7 of 8); PTSD (1 of 3). Quantitative studies were assessed for quality and risk of bias using the NIH Quality Assessment Scale and the modified Newcastle Ottawa Scale for cross-sectional and observational cohort studies, and most exhibited a low risk of bias. Qualitative studies identified a broad range of exposures and psychological sequlae of marital rape not captured by quantitative studies. Included publications exhibit a low to moderate association between marital rape and adverse mental health outcomes. Qualitative data also supplements these findings and provide relevant context. Further research on marital rape, its prevalence and consequences, is needed to advance policy, and health infrastructure on the subject.
Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique
Authors: Santano Rebeca , Rubio Rocío , Grau-Pujol Berta , Escola Valdemiro , Muchisse Osvaldo , Cuamba Inocência , Vidal Marta , Ruiz-Olalla Gemma , Aguilar Ruth , Gandasegui Javier , Demontis Maria , Jamine Jose Carlos , Cossa Anélsio , Sacoor Charfudin , Cano Jorge , Izquierdo Luis , Chitnis Chetan E. , Coppel Ross L. , Chauhan Virander , Cavanagh David , Dutta Sheetij , Angov Evelina , van Lieshout Lisette , Zhan Bin , Muñoz José , Dobaño Carlota , Moncunill Gemma
Published: June 2022

Background

Soil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure.

Methodology

We evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference.

Principal findings

IgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed.

Conclusions

We provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.
Bothrops lanceolatus snake venom impairs mitochondrial respiration and induces DNA release in human heart preparation
Authors: Cano-Sanchez Mariola , Ben-Hassen Kais , Louis Olivier Pierre , Dantin Fabienne , Gueye Papa , Roques Francois , Mehdaoui Hossein , Resiere Dabor , Neviere Remi
Published: June 2022

Introduction

Envenomations by Bothrops snakebites can induce overwhelming systemic inflammation ultimately leading to multiple organ system failure and death. Release of damage-associated molecular pattern molecules (DAMPs), in particular of mitochondrial origin, has been implicated in the pathophysiology of the deregulated innate immune response.

Objective

To test whether whole Bothrops lanceolatus venom would induce mitochondrial dysfunction and DAMPs release in human heart preparations.

Methods

Human atrial trabeculae were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing routine coronary artery bypass surgery. Cardiac fibers were incubated with vehicle and whole Bothrops lanceolatus venom for 24hr before high-resolution respirometry, mitochondrial membrane permeability evaluation and quantification of mitochondrial DNA.

Results

Compared with vehicle, incubation of human cardiac muscle with whole Bothrops lanceolatus venom for 24hr impaired respiratory control ratio and mitochondrial membrane permeability. Levels of mitochondrial DNA increased in the medium of cardiac cell preparation incubated with venom of Bothrops lanceolatus.

Conclusion

Our study suggests that whole venom of Bothrops lanceolatus impairs mitochondrial oxidative phosphorylation capacity and increases mitochondrial membrane permeability. Cardiac mitochondrial dysfunction associated with mitochondrial DAMPs release may alter myocardium function and engage the innate immune response, which may both participate to the cardiotoxicity occurring in patients with severe envenomation.
Dynamics of reproductive genetic technologies: Perspectives of professional stakeholders
Authors: van Dijke Ivy , van El Carla G. , Lakeman Phillis , Goddijn Mariëtte , Rigter Tessel , Cornel Martina C. , Henneman Lidewij
Published: June 2022

Reproductive and genetic medicine are evolving rapidly, and new technologies are already impacting current practices. This includes technologies that can identify a couples’ risk of having a child with a genetic disorder. Responsible implementation of new technologies requires evaluation of safety and ethics. Valuable insights for shaping governance processes are provided by various stakeholders involved, including healthcare professionals. Their willingness to adopt these technologies and guide the necessary systemic changes is required for the successful implementation of these technologies. In this study, twenty-one semi-structured interviews were conducted with professionals from different disciplines in the field of reproductive and genetic healthcare in the Netherlands. Three emerging technologies were discussed: expanded carrier screening (ECS), non-invasive prenatal diagnosis (NIPD) and germline genome editing (GGE). By probing stakeholders’ views, we explored how culture, structure and practice in healthcare is being shaped by innovations and changing dynamics in genetic and reproductive medicine. The general consensus was that the implementation of reproductive genetic technologies nationwide is a slow process in Dutch healthcare. A “typical Dutch approach” emerged that is characterized by restrictive legislation, broad support for people living with disabilities, values of an egalitarian society and limited commercialisation. Different scenarios for embedding ECS in future practice were envisioned, while implementation of NIPD in clinical practice was considered obvious. Views on GGE varied among stakeholders. Previous implementation examples in the Netherlands suggest introduction of new technology involves an organized collective learning process, with pilot studies and stepwise implementation. In addition, introducing and scaling up new technologies is complex due to perceived barriers from the legislative framework and the complex relationship between the government and stakeholders in this area. This paper describes how the international trends and advances of technologies are expected to manifest itself in a national setting.
Awareness of and attitudes towards public involvement in research on ageing and health among older people in Sweden
Authors: Frögren Joakim , Schmidt Steven M. , Kylén Maya , Jonsson Oskar , Slaug Björn , Iwarsson Susanne
Published: June 2022

Background

While the importance of involving older people in research is increasingly acknowledged, quantitative studies exploring the perspectives of larger samples of older people who take an active role in research on ageing and health are scarce. The aim of this study was to investigate the awareness of and attitudes towards public involvement in research on ageing and health among older people in Sweden.

Materials and methods

Data derived from a survey (N = 881) of people aged 60 years or older in Sweden. Demographics, self-rated health, and attitudes were analysed using descriptive statistics. Awareness of and previous active involvement in research were analysed using chi-square tests and Mann Whitney tests. Factors associated with willingness to be actively involved in research were determined by logistic regressions.

Results

Of the 26% who responded (N = 881), 39% (n = 343) were aware that they could be actively involved in research. Awareness and previous active involvement in research were significantly associated with a higher level of education. Public involvement was believed to enhance research communication and enable valuable contributions related to ageing. The proportion of respondents who were willing to be actively involved in research was significantly higher for respondents with previous experience and a higher level of education.

Conclusions

Engaging older people in Sweden in research targeting active involvement in research presents a challenge. The study shows an over-representation of people with higher education, who tend to be more aware, have previous experience, and are more willing to be involved in research with public involvement. This implies a risk that groups with lower education are not represented, and that knowledge co-produced with mostly highly educated groups will lead to a biased picture. Further studies are needed to understand how an increased awareness of research and willingness to participate can be achieved.

IRRID: RR2-10.2196/17759.
Early neurological development and nutritional status in Mexican socially deprived contexts
Authors: Serván-Mori Edson , Fuentes-Rivera Evelyn , Quezada Amado D. , Pineda-Antunez Carlos , del Carmen Hernández-Chávez María , García-Martínez Angélica , Madrigal Abby , García-Feregrino Raquel , Santiago-Angelino Tania , Hernández-Serrato María , Schnaas Lourdes
Published: June 2022

Early childhood development (ECD) is a critical stage in the intergenerational process of human development. Targeted interventions depend on accurate and up-to-date ECD measurements. This paper presents estimates for the nutritional and neurodevelopmental status of socially marginalized children in Mexico. We performed a cross-sectional study based on data collected in 2019–2020 during home visits to 1,176 children aged 0–38 months across 24 highly marginalized locations in Oaxaca. We assessed nutritional status according to the World Health Organization 2006 child-growth standards and ECD status using the Child Development Evaluation Test, 2ndEdition. We stratified results by sex. Prevalence of stunting was 5.3 percentage points (p.p.) higher (p= 0.023) in males (25.3%; 95% CI: 20.2%, 31.1%) compared to females (20.0%; 95% CI: 15.0%, 26.1%). Overall prevalence rates stood at 5.7% (95% CI: 4.0%, 8.1%) for underweight, 1.5% (95% CI: 0.9%, 2.7%) for wasting and 3.6% (95% CI: 2.3%, 5.7%) for overweight/obesity, with no significant differences by sex. Prevalence of normal development was 8.3 p.p. lower (p= 0.001) in males (39.3%; 95% CI: 34.5%, 44.4%) compared to females (47.6%; 95% CI: 41.6%, 53.6%). By development area, the highest prevalence of suboptimal outcomes among children with developmental lag or at risk of delay was observed in their gross motor and language skills: 24.1% (95% CI: 20.0%, 28.8%) and 38.6% (95% CI: 34.0%, 43.3%), respectively. The largest difference between the sexes was found in the language area. Our results show that childhood development strategies have been insufficient thus far in the studied population. Programs specifically designed to prevent ECD lags and bridge inequality gaps are urgently needed.

Trial registration:ClinicalTrials.gov ID:NCT04210362.
The effect of red/blue color stimuli on temporal perception under different pupillary responses induced by different equiluminant methods
Authors: Kinzuka Yuya , Sato Fumiaki , Minami Tetsuto , Nakauchi Shigeki
Published: June 2022

As time plays a fundamental role in our social activities, scholars have studied temporal perception since the earliest days of experimental psychology. Since the 1960s, the ubiquity of color has been driving research on the potential effects of the colors red and blue on temporal perception and on its underlying mechanism. However, the results have been inconsistent, which could be attributed to the difficulty of controlling physical properties such as hue and luminance within and between studies. Therefore, we conducted a two-interval duration-discrimination task to evaluate the perceived duration of color stimuli under different equiluminant conditions: subjective or pupillary light reflex (PLR)-based equiluminance. The results, based on psychometric functional analyses and simultaneous pupillary recordings, showed that the perceived duration of red was overestimated compared with blue even when the intensity of the stimulus was controlled based on subjective equiluminance (Experiment 1). However, since blue is known to induce a larger PLR than red despite equiluminance, we conducted a controlled study to distinguish the indirect effect of pupillary response to temporal perception. Interestingly, the effect observed in Experiment 1 faded when the luminance levels of the two stimuli were matched based on PLR response (Experiment 2). These results indicate that duration judgement can be affected not only by the hue but also by different equiluminance methods. Furthermore, this causality between the equiluminance method and temporal perception can be explained by the fluctuations in incident light entering the pupil.
Comparing artificial intelligence and human coaching goal attainment efficacy
Authors: Terblanche Nicky , Molyn Joanna , de Haan Erik , Nilsson Viktor O.
Published: June 2022

The history of artificial intelligence (AI) is filled with hype and inflated expectations. Notwithstanding, AI is finding its way into numerous aspects of humanity including the fast-growing helping profession of coaching. Coaching has been shown to be efficacious in a variety of human development facets. The application of AI in a narrow, specific area of coaching has also been shown to work. What remains uncertain, is how the two compare. In this paper we compare two equivalent longitudinal randomised control trial studies that measured the increase in clients’ goal attainment as a result of having received coaching over a 10-month period. The first study involved human coaches and the replication study used an AI chatbot coach. In both studies, human coaches and the AI coach were significantly more effective in helping clients reach their goals compared to the two control groups. Surprisingly however, the AI coach was as effective as human coaches at the end of the trials. We interpret this result using AI and goal theory and present three significant implications: AI coaching could be scaled to democratize coaching; AI coaching could grow the demand for human coaching; and AI could replace human coaches who use simplistic, model-based coaching approaches. At present, AI’s lack of empathy and emotional intelligence make human coaches irreplicable. However, understanding the efficacy of AI coaching relative to human coaching may promote the focused use of AI, to the significant benefit of society.
The sustainable health Agenda in the Americas: Pre-pandemic gaps and 2030 estimates of the SDGs indicators
Authors: Silveira Fabrício , da Matta Machado Fernandes Luísa , Paes-Sousa Rômulo
Published: June 2022

The preliminary assessments of the impact of the COVID-19 pandemic have recently rekindled worries about the feasibility of the Sustainable Development Goals (SDGs). Notwithstanding the concern voiced by key academic and political actors, the actual evidence on the current gaps and distance from the goals is still very much unknown. This study estimates the global evolution curves for each health-related SDGs indicator in the World Health Organization’s SDGs platform. These curves synthesize the transnational trends at play in the evolution of each health-related topic, offering an average global counterfactual to compare with the actual information for each country. The empirical investigation focuses on the American continent, highlighting the health gaps before the COVID-19 outbreak in 33 countries of the region. The study also extrapolates these trends to predict the evolution of the health-related SDGs in each of these countries over the next decade using as the baseline scenario the International Monetary Fund’s economic forecasts. The results show a widening gap in the region, associated with the differential economic capacity of these countries. Some bottlenecks are shared by most countries in the continent, especially in the themes of violence and infectious diseases. The latter is likely to improve faster than other health themes in the next decade, whereas improvements in the theme non-communicable diseases can be more challenging. The findings provide much needed comparative evidence to guide the countries in the region to set priorities and concentrate efforts to accelerate progress in the health-related SDGs.
Selective modulation of cell surface proteins during vaccinia infection: A resource for identifying viral immune evasion strategies
Authors: Depierreux Delphine M. , Altenburg Arwen F. , Soday Lior , Fletcher-Etherington Alice , Antrobus Robin , Ferguson Brian J. , Weekes Michael P. , Smith Geoffrey L.
Published: June 2022

The interaction between immune cells and virus-infected targets involves multiple plasma membrane (PM) proteins. A systematic study of PM protein modulation by vaccinia virus (VACV), the paradigm of host regulation, has the potential to reveal not only novel viral immune evasion mechanisms, but also novel factors critical in host immunity. Here, >1000 PM proteins were quantified throughout VACV infection, revealing selective downregulation of known T and NK cell ligands including HLA-C, downregulation of cytokine receptors including IFNAR2, IL-6ST and IL-10RB, and rapid inhibition of expression of certain protocadherins and ephrins, candidate activating immune ligands. Downregulation of most PM proteins occurred via a proteasome-independent mechanism. Upregulated proteins included a decoy receptor for TRAIL. Twenty VACV-encoded PM proteins were identified, of which five were not recognised previously as such. Collectively, this dataset constitutes a valuable resource for future studies on antiviral immunity, host-pathogen interaction, poxvirus biology, vector-based vaccine design and oncolytic therapy.
Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis
Authors: Johnson Bryan A. , Zhou Yiyang , Lokugamage Kumari G. , Vu Michelle N. , Bopp Nathen , Crocquet-Valdes Patricia A. , Kalveram Birte , Schindewolf Craig , Liu Yang , Scharton Dionna , Plante Jessica A. , Xie Xuping , Aguilar Patricia , Weaver Scott C. , Shi Pei-Yong , Walker David H. , Routh Andrew L. , Plante Kenneth S. , Menachery Vineet D.
Published: June 2022

While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203–205 in the SARS-CoV-2 nucleocapsid protein. Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. The R203K+G204R mutant corresponds with increased viral RNA and protein both in vitro and in vivo. Importantly, the R203K+G204R mutation increases nucleocapsid phosphorylation and confers resistance to inhibition of the GSK-3 kinase, providing a molecular basis for increased virus replication. Notably, analogous alanine substitutions at positions 203+204 also increase SARS-CoV-2 replication and augment phosphorylation, suggesting that infection is enhanced through ablation of the ancestral ‘RG’ motif. Overall, these results demonstrate that variant mutations outside spike are key components in SARS-CoV-2’s continued adaptation to human infection.
Social Capital, Basic Life Satisfaction and Happiness in Local Government
Authors:   Crisis and Emergency Management: Theory and Praxis, Choi Yena
Published: June 2022

This study is to analyze the effect of social capital and basic life satisfaction on citizens' happiness, focusing on moderating effect of volunteering and giving. As a result of the analysis, satisfactions of family relationship, income and consumption have no effect on happiness. And basic life infrastructure, social security institution, culture and leisure have no effect on happiness. Besides, social capitals have positive effects on happiness in part. In other words, citizen trust does not affect happiness but community sense, associate activities, giving and volunteering affect happiness. And as the results of moderating effect of charitable behaviors, interaction between volunteering and healthcare service, interaction between giving and citizen trust and interaction between giving and self-respect for region have positive effects on happiness. Based on this, policy directions to enhance charitable behaviors as a risk management tool and to promote happiness are as follows. First, role sharing through public-private partnerships is necessary. Second, the vitalization of civil society is important to enhance philanthropic activities.
Examining the Performance Measurement Factors Impacting on the Effectiveness of Disaster Management System
Authors:   Crisis and Emergency Management: Theory and Praxis, Kim Dong Wook , Kim Hyun Woo , Lee Chang Kil
Published: June 2022

Body The purpose of this study is to examine the direction of disaster management by administration change in Korea and identify factors that could accommodate the public's demand for an effective disaster management system. Keyword network analysis is conducted for the 3rd and 4th National Emergency Management Plan to explore the changes in the direction of disaster management policies. Through the analysis, topic words, their frequency, and matrixes for co-occurrence between keywords are extracted. Based on the extracted matrix, the degree centrality (connectivity of keywords) is identified and cluster analysis has been conducted afterward. The findings show that education training, on-site disaster response, improvement of legal system, professional training, and cooperation among related agencies are detected as key topic words. The direction of the plan is also changing to cope with the unexpected disaster situation due to the climate change.
Celiac Disease and Serious Infections: A Nationwide Cohort Study From 2002 to 2017
Authors: Röckert Tjernberg Anna , Mårild Karl , Söderling Jonas , Lebwohl Benjamin , Roelstraete Bjorn , Bonnedahl Jonas , Green Peter H.R. , Ludvigsson Jonas F.
Published: June 2022

INTRODUCTION:

Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century.

METHODS:

We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002–2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities.

RESULTS:

During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25–1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17–1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20–1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09–1.45) and gastrointestinal infections (1.60; 95% CI = 1.47–1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections.

DISCUSSION:

This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care.
RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study
Authors: Calvaruso Vincenza , Celsa Ciro , D'Ambrosio Roberta , Simone Fabio , Petta Salvatore , Cacciola Irene , Enea Marco , Battaglia Salvatore , Pandolfo Alessandra , Licata Massimo , Degasperi Elisabetta , Cabibbo Giuseppe , Di Marco Lorenza , Pennisi Grazia , Borghi Marta , Di Martino Vincenzo , Filomia Roberto , Abdel-Hadi Yasmin , Crapanzano Luciano , Raimondo Giovanni , Lampertico Pietro , Craxì Antonio , Cammà Calogero , Di Marco Vito
Published: June 2022

INTRODUCTION:

Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia–HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria).

METHODS:

All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 109/L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 109/L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated.

RESULTS:

The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%–13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65–0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria.

DISCUSSION:

Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.
Transcutaneous Electrical Acustimulation Improves Irritable Bowel Syndrome With Constipation by Accelerating Colon Transit and Reducing Rectal Sensation Using Autonomic Mechanisms
Authors: Huang Zhihui , Lin Zhenghua , Lin Chenhong , Chu Hua , Zheng Xia , Chen Binrui , Du Lijun , Chen Jiande D.Z. , Dai Ning
Published: June 2022

INTRODUCTION:

Slow colon transit and visceral hypersensitivity are recognized as major pathophysiological mechanisms in irritable bowel syndrome with constipation (IBS-C). However, there is a lack of therapies targeting both abdominal pain and colonic motility. This study was designed to investigate the long-term effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) in patients with IBS-C.

METHODS:

Fifty-two patients with IBS-C were randomized into 2 groups: daily TEA for 4 weeks (n = 26) and daily sham-TEA for 4 weeks (n = 26). The number of complete spontaneous bowel movements per week (CSBMs/week, primary outcome), Irritable Bowel Syndrome Severity Scoring System, Patient Assessment of Constipation Quality of Life, visual analog scale (VAS) pain score, colonic transit time, and anorectal physiology were evaluated before treatment and at the end of the treatment. Colonic transit was assessed with radiopaque markers. Electrocardiograms were recorded for assessing autonomic functions.

RESULTS:

(i) TEA improved constipation and abdominal pain. After the treatment, the number of CSBMs/week during the last week in the TEA group was higher than that in the sham-TEA group (3.5 ± 1.6 vs 2.3 ± 0.6, P = 0.002). Similar effects were also noted in the visual analog scale pain score (P = 0.002) and Irritable Bowel Syndrome Severity Scoring System score (P = 0.025). In addition, there was a significant improvement in the quality of life of patients with constipation. The Patient Assessment of Constipation Quality of Life total score was significantly decreased in the TEA group (P = 0.004). (ii) Compared with sham-TEA, TEA improved colon transit (P = 0.002) and increased the threshold of rectal sensation (desire to defecate, P = 0.004; maximum tolerability, P < 0.001). (iii) TEA increased vagal activity, compared with sham-TEA (P < 0.05); at the end of the treatment, the vagal activity was significantly correlated with colon transit and the CSBMs/week.

DISCUSSION:

TEA improves constipation and symptoms of IBS by accelerating colon transit and reducing rectal sensation, possibly mediated by using the autonomic mechanisms.
Outcomes of Exercise Interventions in Patients With Advanced Liver Disease: A Systematic Review of Randomized Clinical Trials
Authors: Jamali Taher , Raasikh Taaj , Bustamante Gabriel , Sisson Amy , Tandon Puneeta , Duarte-Rojo Andres , Hernaez Ruben
Published: June 2022

INTRODUCTION:

Frailty and sarcopenia are common complications of advanced liver disease. Owing to associated morbidity/mortality, there have been targeted efforts to prevent and/or improve both by enrolling these patients in focused exercise programs. This review systematically analyzes the data of randomized clinical trials (RCTs) on anthropometric, physical fitness, quality-of-life, and safety outcomes of exercise interventions in patients with advanced liver disease.

METHODS:

Two authors independently searched trials on PubMed and EMBASE from inception up to November 18, 2021. A third independent arbitrator adjudicated all disagreements. We qualitatively summarized these outcomes as follows: (i) muscular fitness (maximal inspiratory/expiratory pressures, muscle size, muscle strength, and bioimpedance testing), (ii) cardiorespiratory fitness (cardiopulmonary exercise testing and 6-minute walk distance), (iii) quality of life, and (iv) others (safety or frailty indices).

RESULTS:

There were 11 RCTs (4 home-based interventions) with 358 participants. Interventions ranged from 8 to 14 weeks and included cycling, walking, resistance exercises, balance and coordination training, and respiratory exercises. All described outcomes compared preintervention with postintervention measurements. Nine studies showed statistically significant improvements in at least 1 physical fitness variable. Ten studies showed statistically significant improvements in at least 1 muscular fitness variable. Six studies showed statistically significant improvements in at least 1 quality-of-life variable. Attrition rates ranged from 5% to 36%, and adherence rates ranged very widely from 14% to 100%. Only 1 study reported frailty indices. Notably, no complications of portal hypertension were seen in intervention groups in the 9 studies that reported these data.

DISCUSSION:

A review of 11 RCTs with 358 participants with advanced liver disease demonstrates that exercise interventions can have favorable outcomes on muscular/cardiorespiratory fitness and quality of life. Although attrition and adherence varied, these interventions seem to be safe in patients with cirrhosis and are well tolerated.
Concordance of ICD-10 Codes and the Clinical Diagnosis of Alcoholic Hepatitis
Authors: Geng Calvin X. , Gudur Anuragh R. , Patterson Daniel R. , Stotts Matthew J.
Published: June 2022

INTRODUCTION:

Many studies on alcoholic hepatitis (AH) use the International Classification of Disease (ICD) coding to identify patients. Data regarding the diagnostic accuracy of ICD codes for AH are limited.

METHODS:

A total of 151 patients with ICD-10 codes for AH were reviewed for the presence or absence of AH using standardized diagnostic criteria.

RESULTS:

Sixty-eight of the 151 patients met AH criteria, corresponding to a positive predictive value of 45%. Patients with AH experienced higher model for end-stage liver disease and mortality than those who did not (P < 0.05).

DISCUSSION:

Our results suggest ICD-10 codes are not reliable for identifying AH. Studies using the ICD codes should be interpreted cautiously.
A Combined Baveno VII and Spleen Stiffness Algorithm to Improve the Noninvasive Diagnosis of Clinically Significant Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease
Authors: Dajti Elton , Ravaioli Federico , Marasco Giovanni , Alemanni Luigina Vanessa , Colecchia Luigi , Ferrarese Alberto , Cusumano Caterina , Gemini Stefano , Vestito Amanda , Renzulli Matteo , Golfieri Rita , Festi Davide , Colecchia Antonio
Published: June 2022

INTRODUCTION:

A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease.

METHODS:

This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were >90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported.

RESULTS:

One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 109/L to rule out CSPH and LSM >25 kPa to rule in CSPH) was validated; however, 40%–60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%–15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the “rule-in” zone of the model including SSM.

DISCUSSION:

The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.
Anamnestic, clinical and laboratory features of the acute period of ischemic stroke in young patients
Authors: Gusev V. V. , Kovtun O. P. , Lvova O. A. , Partylova E. A. , Sergeev A. P. , Sergeeva M. V. , Yanchuk I. T. , Dobrazova D. A. , Suvorkov P. A. , Shamalov N. A.
Published: June 2022

Objective: to study the anamnestic, clinical and laboratory features of the acute period of ischemic stroke (IS) and to determine the risk factors for its development in young patients.

Patients and methods. Clinical and statistical processing of data of 256 patients aged 18 to 44 years included, who had IS, confirmed by computed and/or magnetic resonance imaging of the brain in the acute period, was carried out. Furthermore, in 154 patients and in 117 healthy participants, who made up the control group, eight polymorphisms of the thrombophilic spectrum genes were determined – FGB: -455G>A, F2: 20210G>A, F5: 1691G>A, F7: 10976G>A, F13: 103 G>T, ITGA2: 807C>T, ITGB3: 1565 T>C, PAI-1: -675 5G>4G.

Results and discussion. 154 (60.15%) patients demonstrated good recovery (achievement of a level of ≤2 points on the Rankin scale by the patient). None of the patients died during their hospitalization. In the evaluated group of patients, we identified allelic variants of the thrombophilic spectrum genes and gene-gene combinations, the carriage of which increased the likelihood of IS development at the young age by 1.74 and 2.19 times, respectively. Taking into consideration additional examination methods, the pathogenetic variant of IS according to the TOAST classification was verified in 226 (88%) patients.

Conclusion. In IS at a young age a detailed assessment of risk factors is required, including an analysis of carrier variants and combinations of procoagulant and prothrombotic spectrum gene polymorphisms.
Acute and long-term neurological disorders in patients with coronavirus infection
Authors: Parfenov V. A. , Kulesh A. A.
Published: June 2022

Currently, patients who attribute their complaints and disorders to the past COVID-19 are turning to a neurologist for a consultation. One should consider dangerous complications of COVID-19 such as stroke, including cerebral venous thrombosis, autoimmune encephalitis and myelitis, posterior reversible encephalopathy syndrome, Guillain–Barre’ syndrome. Disorders of consciousness, disorders of smell and taste, headache and dizziness are significantly more often present in the acute period of COVID-19. Long-term persistence of complaints and disorders after COVID-19 is regarded as post-COVID syndrome (PCS). Neurological complaints and disorders in a patient who has had COVID-19 are often caused by the development or exacerbation of a comorbid disease, including primary headache, musculoskeletal pain in the neck and back, various vestibular disorders, Alzheimer's disease, anxiety and depressive disorders. Unfortunately, in real clinical practice, these diseases are often not diagnosed, patients are observed with a diagnosis of PCS, and it is not taken into account that the basis for diagnosing PCS is the exclusion of other diseases that can explain complaints and disorders in a patient who has suffered from COVID-19.
Zadovoljstvo študentov zdravstvene nege s kliničnim usposabljanjem
Authors: Rožnik Anet , Božič Anika , Prosen Mirko , Ličen Sabina
Published: June 2022

Uvod: Na kliničnem usposabljanju ima podpora kliničnih mentorjev ključno vlogo pri zadovoljstvu študentov. Namen raziskave je bil raziskati zadovoljstvo študentov zdravstvene nege s kliničnim usposabljanjem in oceniti stopnjo podpore, ki so je bili deležni.Metode: Uporabljena je bila kvantitativna neeksperimentalna metoda empiričnega raziskovanja. Instrument raziskave je bil vprašalnik zaprtega tipa (CLEI-19) z 19 trditvami. Raziskava je potekala na priložnostnem vzorcu študentov dodiplomskega študijskega programa zdravstvene nege (n = 106) ene izmed fakultet v Sloveniji. Pri statistični analizi podatkov sta bili uporabljeni  deskriptivna ter interferenčna statistika (Mann- Whitneyjev U-test).Rezultati: Rezultati kažejo zadovoljstvo študentov zdravstvene nege s kliničnim usposabljanjem ( = 3,55, s = 1,064, p < 0,001) in zaznano podporo kliničnih mentorjev ( = 3,70, s = 0,856, p < 0,001). Med študenti zdravstvene nege ni opaziti statistično pomembnih razlik med spoloma, načinoma študija in letnikoma študija (p > 0,05) tako v povezavi z zadovoljstvom z zadnjim kliničnim usposabljanjem kot z zaznano podporo kliničnega mentorja.Diskusija in zaključek: Študenti izkazujejo zadovoljstvo s kliničnim usposabljanjem in med njegovim izvajanjem občutijo podporo kliničnega mentorja. Z namenom ohranjanja tovrstne kakovosti klinične izkušnje in njene nadgradnje bi bilo smiselno v usposabljanje kliničnih mentorjev vključiti več vsebin o mentorskih kompetencah, ki bi izboljšale zadovoljstvo študentov s kliničnim usposabljanjem in povečale podporo mentorjev.
PENGARUH MODAL KERJA, RASIO LIKUIDITAS, SOLVABILITAS DAN AKTIVITAS TERHADAP PROFITABILITAS PADA PERUSAHAAN INDEKS PEFINDO i-GRADE PERIODE 2007-2018
Authors: Virgantara Dika Zanuar
Published: June 2022

This study aims to determine the effect of working capital liquidity ratios, solvency and activity on profitability at PEFINDO i-GRADE index companies listed on the Indonesia Stock Exchange (BEI) for the period 2007-2018. Profitability is the net profit after tax obtained by a company. The PEFINDO i-GRADE index is an index that measures the price performance of 30 listed companies with investment grade ratings from PEfINDO (iDAAA to idBBB) which have the largest market capitalization. The GAP in this study is that there is a discrepancy between the results of the research and the inconsistent theory and results of previous research. In this study, the financial ratios of Working Capital (NWC), Liquidity (CR), Solvency (DER) and Activities (TATO) are taken. This study uses a causal associative method with a quantitative approach, the data used are secondary data from the company's financial statements, the PEFIND i-GRADE Index for 12 years from 2007-2018. The sample was determined by purposive sampling technique. The sample in this study were 14 companies and were analyzed using EVIEWS version 10. The data testing techniques used in this study included classical assumption tests, correlation tests, simple regression tests, and multiple regression tests. Furthermore, testing the hypothesis using the coefficient of determination, t test and F test.                The results of the analysis show that the Net Working Capita (NWC) variable produces a t count of (-0.017) < t table of (-1.974) and a probability value of (0.96) > (0.05) which means that the Net Working Capital (NWC) partially has no effect on Profitability (ROA). The variable Curren Ratio (CR) produces t count of (-3.4212) > t table of (-1.974) and the value of probability is equal (0.0046) < (0.05), which means that Current Ratio (CR) partially affects profitability (ROA). to Equity Ratio (DER) produces t count of (-0.8288) > t table of (-1.974) and the value of probability (0.423) > (0.05) which means that partially the Debt to Equity Ratio (DER) has no effect on profitability (ROA) The Total Asset Turn Over (TATO) variable produces t count (-0.3762) < t table (-1.974) and a probability value (0.712) > (0.05) which means that partially Total Asset Turn Over (TATO) has no effect on profitability ( ROA) .From all the independent variable testing simultaneously, it is obtained that F count is (3.86) > F table (2.66) and the value of probability is equal (0.028) < (0.05) which means together the Net Working Capita (NWC), Curren Ratio ( CR), Dept. Equity Ratio (DER) and Total Asset Turn Over (TATO) has a significant effect on profitability (ROA).It can be concluded that the CR variable partially has a significant effect on profitability (ROA). While the variables of NWC, DER and TATO partially do not have a significant effect on profitability (ROA). Simultaneously NWC, CR, DER and TATO have a significant effect on Profitability (ROA).
PENGARUH CAR, FDR, DAN BOPO DENGAN NPF SEBAGAI VARIABEL MODERATING TERHADAP KINERJA KEUANGAN PERBANKAN SYARIAH DI INDONESIA (Studi Empiris pada Bank Umum Syariah di Indonesia Periode 2014 Q1 – 2018 Q4)
Authors: Kurnia Taufik , Wahyudi Sugeng
Published: June 2022

The purpose of this study was to determine the effect of CAR, FDR, and BOPO with NPF as a moderating variable on the Profitability of Islamic Commercial Banks in Indonesia in the period 2014 to 2018. Profitability is proxied by ROA as a measure of the amount of profit generated.The sample in this study is Islamic commercial bank in Indonesia during the period 2014-2018. The number of samples were 11 banks taken by purposive sampling method. The analytical method of this study uses MRA (Moderated Regression Analysis) with the SPSS 25 program which previously passed the classic assumption test.The results of this study indicate that CAR has a positive and significant effect on ROA. FDR has a positive no significant effect on ROA. BOPO has a negative and significant effect on ROA. NPF able to moderate CAR relationship effect on ROA. NPF not being able to moderate FDR relationship effect on ROA. NPF able to moderate BOPO relationship effect on ROA.