bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct neurocomputational mechanisms support informational and socially normative conformity
Authors: Mahmoodi Ali , Nili Hamed , Bang Dan , Mehring Carsten , Bahrami Bahador
Published: March 2022

A change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive, and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of 2 different social roles and 2 different social partners revealed distinct behavioural and neural markers for informational and normative conformity. Dorsal anterior cingulate cortex (dACC) BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with humans. A network of brain areas (dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ)) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind.
Estimates of the basic reproduction number for rubella using seroprevalence data and indicator-based approaches
Authors: Papadopoulos Timos , Vynnycky Emilia
Published: March 2022

The basic reproduction number (R0) of an infection determines the impact of its control. For many endemic infections, R0 is often estimated from appropriate country-specific seroprevalence data. Studies sometimes pool estimates from the same region for settings lacking seroprevalence data, but the reliability of this approach is unclear. Plausibly, indicator-based approaches could predict R0 for such settings. We calculated R0 for rubella for 98 settings and correlated its value against 66 demographic, economic, education, housing and health-related indicators. We also trained a random forest regression algorithm using these indicators as the input and R0 as the output. We used the mean-square error to compare the performances of the random forest, simple linear regression and a regional averaging method in predicting R0 using 4-fold cross validation. R0 was <5, 5–10 and >10 for 81, 14 and 3 settings respectively, with no apparent regional differences and in the limited available data, it was usually lower for rural than urban areas. R0 was most correlated with educational attainment, and household indicators for the Pearson and Spearman correlation coefficients respectively and with poverty-related indicators followed by the crude death rate considering the Maximum Information Coefficient, although the correlation for each was relatively weak (Pearson correlation coefficient: 0.4, 95%CI: (0.24,0.48) for educational attainment). A random forest did not perform better in predicting R0 than simple linear regression, depending on the subsets of training indicators and studies, and neither out-performed a regional averaging approach. R0 for rubella is typically low and using indicators to estimate its value is not straightforward. A regional averaging approach may provide as reliable an estimate of R0 for settings lacking seroprevalence data as one based on indicators. The findings may be relevant for other infections and studies estimating the disease burden and the impact of interventions for settings lacking seroprevalence data.
How does a small molecule bind at a cryptic binding site?
Authors: Shan Yibing , Mysore Venkatesh P. , Leffler Abba E. , Kim Eric T. , Sagawa Shiori , Shaw David E.
Published: March 2022

Protein-protein interactions (PPIs) are ubiquitous biomolecular processes that are central to virtually all aspects of cellular function. Identifying small molecules that modulate specific disease-related PPIs is a strategy with enormous promise for drug discovery. The design of drugs to disrupt PPIs is challenging, however, because many potential drug-binding sites at PPI interfaces are “cryptic”: When unoccupied by a ligand, cryptic sites are often flat and featureless, and thus not readily recognizable in crystal structures, with the geometric and chemical characteristics of typical small-molecule binding sites only emerging upon ligand binding. The rational design of small molecules to inhibit specific PPIs would benefit from a better understanding of how such molecules bind at PPI interfaces. To this end, we have conducted unbiased, all-atom MD simulations of the binding of four small-molecule inhibitors (SP4206 and three SP4206 analogs) to interleukin 2 (IL2)—which performs its function by forming a PPI with its receptor—without incorporating any prior structural information about the ligands’ binding. In multiple binding events, a small molecule settled into a stable binding pose at the PPI interface of IL2, resulting in a protein–small-molecule binding site and pose virtually identical to that observed in an existing crystal structure of the IL2-SP4206 complex. Binding of the small molecule stabilized the IL2 binding groove, which when the small molecule was not bound emerged only transiently and incompletely. Moreover, free energy perturbation (FEP) calculations successfully distinguished between the native and non-native IL2–small-molecule binding poses found in the simulations, suggesting that binding simulations in combination with FEP may provide an effective tool for identifying cryptic binding sites and determining the binding poses of small molecules designed to disrupt PPI interfaces by binding to such sites.
Tumor immune cell clustering and its association with survival in African American women with ovarian cancer
Authors: Wilson Christopher , Soupir Alex C. , Thapa Ram , Creed Jordan , Nguyen Jonathan , Segura Carlos Moran , Gerke Travis , Schildkraut Joellen M. , Peres Lauren C. , Fridley Brooke L.
Published: March 2022

New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME. Therefore, we have developed a framework for the spatial analysis of the TIME using Ripley’sK, coupled with a permutation-based framework to estimate and measure the departure from complete spatial randomness (CSR) as a measure of the interactions between immune cells. This approach was then applied to epithelial ovarian cancer (EOC) using mIF collected on intra-tumoral regions of interest (ROIs) and tissue microarrays (TMAs) from 160 high-grade serous ovarian carcinoma patients in the African American Cancer Epidemiology Study (AACES) (94 subjects on TMAs resulting in 263 tissue cores; 93 subjects with 260 ROIs; 27 subjects with both TMA and ROI data). Cox proportional hazard models were constructed to determine the association of abundance and spatial clustering of tumor-infiltrating lymphocytes (CD3+), cytotoxic T-cells (CD8+CD3+), and regulatory T-cells (CD3+FoxP3+) with overall survival. Analysis was done on TMA and ROIs, treating the TMA data as validation of the findings from the ROIs. We found that EOC patients with high abundance and low spatial clustering of tumor-infiltrating lymphocytes and T-cell subsets in their tumors had the best overall survival. Additionally, patients with EOC tumors displaying high co-occurrence of cytotoxic T-cells and regulatory T-cells had the best overall survival. Grouping women with ovarian cancer based on both cell abundance and spatial contexture showed better discrimination for survival than grouping ovarian cancer cases only by cell abundance. These findings underscore the prognostic importance of evaluating not only immune cell abundance but also the spatial contexture of the immune cells in the TIME. In conclusion, the application of this spatial analysis framework to the study of the TIME could lead to the identification of immune content and spatial architecture that could aid in the determination of patients that are likely to respond to immunotherapies.
CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism
Authors: Ajazi Arta , Choudhary Ramveer , Tronci Laura , Bachi Angela , Bruhn Christopher
Published: March 2022

Glutamine analogs are potent suppressors of general glutamine metabolism with anti-cancer activity. 6-diazo-5-oxo-L-norleucine (DON) is an orally available glutamine analog which has been recently improved by structural modification for cancer treatment. Here, we explored the chemogenomic landscape of DON sensitivity using budding yeast as model organism. We identify evolutionarily conserved proteins that mediate cell resistance to glutamine analogs, namely Ura8CTPS1/2, Hpt1HPRT1, Mec1ATR, Rad53CHK1/CHK2 and Rtg1. We describe a function of Ura8 as inducible CTP synthase responding to inhibition of glutamine metabolism and propose a model for its regulation by CTP levels and Nrd1-dependent transcription termination at a cryptic unstable transcript. Disruption of the inducible CTP synthase under DON exposure hyper-activates the Mec1-Rad53 DNA damage response (DDR) pathway, which prevents chromosome breakage. Simultaneous inhibition of CTP synthase and Mec1 kinase synergistically sensitizes cells to DON, whereas CTP synthase over-expression hampers DDR mutant sensitivity. Using genome-wide suppressor screening, we identify factors promoting DON-induced CTP depletion (TORC1, glutamine transporter) and DNA breakage in DDR mutants. Together, our results identify CTP regulation and the Mec1-Rad53 DDR axis as key glutamine analog response pathways, and provide a rationale for the combined targeting of glutamine and CTP metabolism in DDR-deficient cancers.
Deficiency in Lyst function leads to accumulation of secreted proteases and reduced retinal adhesion
Authors: Ji Xiaojie , Zhao Lihong , Umapathy Ankita , Fitzmaurice Bernard , Wang Jieping , Williams David S. , Chang Bo , Naggert Jürgen K. , Nishina Patsy M.
Published: March 2022

Chediak–Higashi syndrome, caused by mutations in the Lysosome Trafficking Regulator (Lyst) gene, is a recessive hypopigmentation disorder characterized by albinism, neuropathies, neurodegeneration, and defective immune responses, with enlargement of lysosomes and lysosome-related organelles. Although recent studies have suggested that Lyst mutations impair the regulation of sizes of lysosome and lysosome-related organelle, the underlying pathogenic mechanism of Chediak–Higashi syndrome is still unclear. Here we show striking evidence that deficiency in LYST protein function leads to accumulation of photoreceptor outer segment phagosomes in retinal pigment epithelial cells, and reduces adhesion between photoreceptor outer segment and retinal pigment epithelial cells in a mouse model of Chediak–Higashi syndrome. In addition, we observe elevated levels of cathepsins, matrix metallopeptidase (MMP) 3 and oxidative stress markers in the retinal pigment epithelium of Lyst mutants. Previous reports showed that impaired degradation of photoreceptor outer segment phagosomes causes elevated oxidative stress, which could consequently lead to increases of cysteine cathepsins and MMPs in the extracellular matrix. Taken together, we conclude that the loss of LYST function causes accumulation of phagosomes in the retinal pigment epithelium and elevation of several extracellular matrix-remodeling proteases through oxidative stress, which may, in turn, reduce retinal adhesion. Our work reveals previously unreported pathogenic events in the retinal pigment epithelium caused by Lyst deficiency. The same pathogenic events may be conserved in other professional phagocytic cells, such as macrophages in the immune system, contributing to overall Chediak–Higashi syndrome pathology.
Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress
Authors: de Oliveira Rodolpho Pereira , de Andrade José Simões , Spina Marianna , Chamon João Vítor , Silva Paulo Henrique Dias , Werder Ana Keyla , Ortolani Daniela , Thomaz Lucas de Santana Cardoso , Romariz Simone , Ribeiro Daniel Araki , Longo Beatriz Monteiro , Spadari Regina Célia , Viana Milena de Barros , Melo-Thomas Liana , Céspedes Isabel Cristina , da Silva Regina Cláudia Barbosa
Published: March 2022

In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.
Clinicopathologic characteristics of severe COVID-19 patients in Mexico City: A post-mortem analysis using a minimally invasive autopsy approach
Authors: Nava-Santana Carlos , Rodríguez-Armida María , Jiménez José Víctor , Vargas-Parra Nancy , León Diana E. Aguilar , Campos-Murguia Alejandro , Macías-Rodriguez Ricardo , Arteaga-Garrido Andrés , Hernández-Villegas Antonio C. , Dominguez-Cherit Guillermo , Rivero-Sigarroa Eduardo , Gamboa-Dominguez Armando , Gullias-Herrero Alfonso , Sifuentes-Osornio José , Uribe-Uribe Norma Ofelia , Morales-Buenrostro Luis E.
Published: March 2022

Objective

Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies.

Design

Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature.

Setting

Single-center COVID-19 reference center in Mexico City.

Results

Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed.

Conclusion

Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.
The cost of noise: Stochastic punishment falls short of sustaining cooperation in social dilemma experiments
Authors: Salahshour Mohammad , Oberhauser Vincent , Smerlak Matteo
Published: March 2022

Identifying mechanisms able to sustain costly cooperation among self-interested agents is a central problem across social and biological sciences. One possible solution is peer punishment: when agents have an opportunity to sanction defectors, classical behavioral experiments suggest that cooperation can take root. Overlooked from standard experimental designs, however, is the fact that real-world human punishment—the administration of justice—is intrinsically noisy. Here we show that stochastic punishment falls short of sustaining cooperation in the repeated public good game. As punishment noise increases, we find that contributions decrease and punishment efforts intensify, resulting in a 45% drop in gains compared to a noiseless control. Moreover, we observe that uncertainty causes a rise in antisocial punishment, a mutually harmful behavior previously associated with societies with a weak rule of law. Our approach brings to light challenges to cooperation that cannot be explained by economic rationality and strengthens the case for further investigations of the effect of noise—and not just bias—on human behavior.
A hybrid Neural Network-SEIR model for forecasting intensive care occupancy in Switzerland during COVID-19 epidemics
Authors: Delli Compagni Riccardo , Cheng Zhao , Russo Stefania , Van Boeckel Thomas P.
Published: March 2022

Anticipating intensive care unit (ICU) occupancy is critical in supporting decision makers to impose (or relax) measures that mitigate COVID-19 transmission. Mechanistic approaches such as Susceptible-Infected-Recovered (SIR) models have traditionally been used to achieve this objective. However, formulating such models is challenged by the necessity to formulate equations for plausible causal mechanisms between the intensity of COVID-19 transmission and external epidemic drivers such as temperature, and the stringency of non-pharmaceutical interventions. Here, we combined a neural network model (NN) with a Susceptible-Exposed-Infected-Recovered model (SEIR) in a hybrid model and attempted to increase the prediction accuracy of existing models used to forecast ICU occupancy. Between 1stof October, 2020 - 1stof July, 2021, the hybrid model improved performances of the SEIR model at different geographical levels. At a national level, the hybrid model improved, prediction accuracy (i.e., mean absolute error) by 74%. At the cantonal and hospital levels, the reduction on the forecast’s mean absolute error were 46% and 50%, respectively. Our findings illustrate those predictions from hybrid model can be used to anticipate occupancy in ICU, and support the decision-making for lifesaving actions such as the transfer of patients and dispatching of medical personnel and ventilators.
Perspectives on linkage to care for patients diagnosed with HIV: A qualitative study at a rural health center in South Western Uganda
Authors: Opio Mark , Akello Florence , Twongyeirwe Doreen Kagina , Opio David , Aceng Juliet , Namagga Jane Kasozi , Kabakyenga Jerome Kahuma
Published: March 2022

Linkage to care for newly diagnosed human immunodeficiency virus (HIV) patients is important to ensure that patients have good access to care. However, there is little information about factors influencing linkage to care for HIV patients. We aimed to identify existing measures in place that promote linkage to care and to explore facilitators and barriers to linkage to care for clients diagnosed with HIV/acquired immune deficiency syndrome at a rural health center in Uganda. This descriptive qualitative study enrolled 33 purposively selected participants who included expert clients, linkage facilitators, heads of families with people living with HIV, and health workers. Data were collected using in-depth interviews that were audio-recorded, transcribed, and translated. The data were manually analyzed to generate themes. The following four themes were generated: 1) availability of services that include counseling, testing, treatment, follow-up, referral, outreach activities, and support systems. 2) Barriers to linkage to care were at the individual, health facility, and community levels. Individual-level barriers were socioeconomic status, high transport costs, fear of adverse drug effects, fear of broken relationships, and denial of positive results or treatment, while health facility barriers were reported to be long waiting time, negative staff attitude, and drug stock outs. Community barriers were mostly due to stigma experienced by HIV clients, resulting in discrimination by community members. 3) Facilitators to linkage to care were positive staff attitudes, access to information, fear of death, and support from others. 4) Suggestions for improving service delivery were shortening waiting time, integrating HIV services, increasing staff numbers, and intensifying outreaches. Our findings highlight the importance of stakeholder involvement in linkage to care. Access and linkage to care are positively and negatively influenced at the individual, community, and health facility levels. However, integration of HIV services and intensifying outreaches are key to improving linkage to care.
Transgenerational changes in pod maturation phenology and seed traits of Glycine soja infested by the bean bug Riptortus pedestris
Authors: Adachi-Fukunaga Shuhei , Nakabayashi Yui , Tokuda Makoto
Published: March 2022

Land plants have diverse defenses against herbivores. In some cases, plant response to insect herbivory may be chronological and even transgenerational. Feeding by various stink bugs, such as the bean bugRiptortus pedestris(Hemiptera: Alydidae), induce physiological changes in soybean, called as green stem syndrome, which are characterized by delayed senescence in stems, leaves, and pods. To investigate the plant response to the bean bug feeding in the infested generation and its offspring, we studied the effects ofR.pedestrisinfestation onGlycine soja, the ancestral wild species of soybean. Field surveys revealed that the occurrence of the autumnR.pedestrisgeneration coincided withG.sojapod maturation in both lowland and mountainous sites. Following infestation byR.pedestris, pod maturation was significantly delayed inG.soja. WhenG.sojaseeds obtained from infested and non-infested plants were cultivated, the progeny of infested plants exhibited much earlier pod maturation and larger-sized seed production than that of control plants, indicating thatR.pedestrisfeeding induced transgenerational changes. Because earlier seed maturity results in asynchrony with occurrence ofR.pedestris, the transgenerational changes in plant phenology are considered to be an adaptive transgenerational and chronological defense for the plant against feeding by the stink bug.
Discover your potential: The influence of kinematics on a muscle’s ability to contribute to the sit-to-stand transfer
Authors: Roelker Sarah A. , Schmitt Laura C. , Chaudhari Ajit M. W. , Siston Robert A.
Published: March 2022

Existing methods for estimating how individual muscles contribute to a movement require extensive time and experimental resources. In this study we developed an efficient method for determining how changes to lower extremity joint kinematics affect the potential of individual muscles to contribute to whole-body center-of-mass vertical (support) and anteroposterior (progression) accelerations. A 4-link 2-dimensional model was used to assess the effect of kinematic changes on muscle function. Joint kinematics were systematically varied throughout ranges observed during the momentum transfer phase of the sit-to-stand transfer. Each muscle’s potential to contribute to support and progression was computed and compared to simulated potentials estimated by traditional dynamic simulation methods for young adults and individuals with knee osteoarthritis. The new method required 4-10s to compute muscle potentials per kinematic state and computed potentials were consistent with simulated potentials. The new method identified differences in muscle potentials between groups due to kinematic differences, particularly decreased anterior pelvic tilt in young adults, and revealed kinematic and muscle strengthening modifications to increase support. The methods presented provide an efficient, systematic approach to evaluate how joint kinematic adjustments alter a muscle’s ability to contribute to movement and can identify potential sources of pathologic movement and rehabilitation strategies.
Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection
Authors: O’Laughlin Kelli N. , Thompson Matthew , Hota Bala , Gottlieb Michael , Plumb Ian D. , Chang Anna Marie , Wisk Lauren E. , Hall Aron J. , Wang Ralph C. , Spatz Erica S. , Stephens Kari A. , Huebinger Ryan M. , McDonald Samuel A. , Venkatesh Arjun , Gentile Nikki , Slovis Benjamin H. , Hill Mandy , Saydah Sharon , Idris Ahamed H. , Rodriguez Robert , Krumholz Harlan M. , Elmore Joann G. , Weinstein Robert A. , Nichol Graham ,   for the INSPIRE Investigators
Published: March 2022

Background

Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

Methods

INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.

Results

Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.

Conclusions

This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.
Why people vote for thin-centred ideology parties? A multi-level multi-country test of individual and aggregate level predictors
Authors: Çakal Hüseyin , Altınışık Yasin , Gökcekuş Ömer , Eraslan Ertugrul Gazi
Published: March 2022

The present research investigates the individual and aggregate level determinants of support for thin-centred ideology parties across 23 European countries. Employing a multilevel modelling approach, we analysed European Social Survey data round 7 2014 (N = 44000). Our findings show that stronger identification with one’s country and confidence in one’s ability to influence the politics positively but perceiving the system as satisfactory and responsive; trusting the institutions and people, and having positive attitudes toward minorities, i.e., immigrants and refugees, negatively predict support for populist and single issue parties. The level of human development and perceptions of corruption at the country level moderate these effects. Thus, we provide the first evidence that the populist surge is triggered by populist actors’ capacity to simultaneously invoke vertical, “ordinary” people against “the elites”, and horizontal, “us” against “threatening aliens”, categories of people as well as the sovereignty of majority over minorities. These categories and underlying social psychological processes of confidence, trust, and threats are moderated by the general level of human development and corruption perceptions in a country. It is, therefore, likely that voting for populist parties will increase as the liberally democratic countries continue to prosper and offer better opportunities for human development. Stronger emphasis on safeguarding the integrity of the economic and democratic institutions, as our findings imply, and preserving their ethical and honest, i.e., un-corrupt, nature can keep this surge under check.
Prevalence and associated factors of overweight/obesity among severely ill psychiatric patients in Eastern Ethiopia: A comparative cross-sectional study
Authors: Fentie Dilnessa , Derese Tariku
Published: March 2022

Background

Globally, the burden of overweight and obesity is a major cardiovascular disease risk factor and is even higher among patients with psychiatric disorders compared to the general population. This is mainly due to the deleterious lifestyles characterized by physical inactivity, excessive substance use, and unhealthy diets common among patients with psychiatric disorders, as well as the negative metabolic effects of psychotropic medications. Despite these conditions being a high burden among patients with psychiatric illness, little attention is given to them during routine reviews in psychiatric clinics in most African nations, including Ethiopia. Therefore, this study aimed to estimate and compare the prevalence of and associated risk factors for overweight and obesity among patients with psychiatric illnesses.

Methods

A comparative cross-sectional study was conducted between severely ill psychiatric patients and non-psychiatric patients in Dire Dawa, Eastern Ethiopia. The study included 192 study participants (96 psychiatric patients and 96 non-psychiatric controls). Weight and height were measured for 192 study participants. Baseline demographic and clinical characteristics of psychiatric and non-psychiatric patients were described. The data were cleaned and analyzed using the Statistical Package for Social Sciences, Version 21. The intergroup comparisons were performed using an independent sample t-test and Chi-square tests. Logistic regression analysis was used to identify the association between overweight/obesity and the associated variables.

Results

The magnitude of overweight/obesity was significantly higher in the severely ill psychiatric groups (43.8%) than in the non-exposed controls (20.80%). The prevalence of overweight/obesity was highest in major depressive disorders (40%), followed by schizophrenia (32%), and bipolar disorder (28%).

Conclusions

There was a high prevalence of obesity/overweight among psychiatric patients. Educational status, unemployment, and late stages of the disease were significant predictors of overweight/ obesity. Clinicians should be aware of the health consequences of overweight/obesity, and considering screening strategies as a part of routine psychiatric care is strongly recommended.
Gross domestic product and logistics performance index drive the world trade: A study based on all continents
Authors: Jayathilaka Ruwan , Jayawardhana Chanuka , Embogama Nilupul , Jayasooriya Shalini , Karunarathna Navodika , Gamage Thisara , Kuruppu Nethmali
Published: March 2022

The purpose of this study was to examine the impact of Gross Domestic Product (GDP) and Logistics Performance Index (LPI) on international trade of nations across each continent and worldwide. Secondary data collected on 142 countries—37 Asian, 41 European, 41 African, 3 Oceania, 14 Middle East, 11 North American and 9 South American–were analysed across the years 2007, 2010, 2012, 2014, 2016, and 2018. Panel regression technique was applied and the random effect (RE) model was chosen based on the results of the Hausman tests and Breusch–Pagan Lagrange Multiplier test. The findings revealed that the LPI has a positive relationship with net exports globally and specifically within the continents of Asia, Europe, and Oceania. Moreover, while the GDP appears to have a significant negative impact on net exports, specifically within Asia, in contrast, countries in Oceania and the Middle East present a positive relationship. Also on the African continent, GDP has a significant negative impact on the net exports. Findings provide a holistic picture of the impact of LPI & GDP on net exports, which will assist governments in the formulation and revision of its strategies and policies to expedite the growth of exports and in turn, the economy. This study was the first of its kind to explore the impact of GDP and LPI on international trade of nations across worldwide.
Individual, community, and structural factors associated with linkage to HIV care among people diagnosed with HIV in Tennessee
Authors: Ahonkhai Aima A. , Rebeiro Peter F. , Jenkins Cathy A. , Rickles Michael , Cook Mekeila , Conserve Donaldson F. , Pierce Leslie J. , Shepherd Bryan E. , Brantley Meredith , Wester Carolyn
Published: March 2022

Objective

We assessed trends and identified individual- and county-level factors associated with individual linkage to HIV care in Tennessee (TN).

Methods

TN residents diagnosed with HIV from 2012–2016 were included in the analysis (n = 3,751). Individuals were assigned county-level factors based on county of residence at the time of diagnosis. Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used modified Poisson regression to estimate probability of 30-day linkage to care at the individual-level and the contribution of individual and county-level factors to this outcome.

Results

Both MSM (aRR 1.23, 95%CI 0.98–1.55) and women who reported heterosexual sex risk factors (aRR 1.39, 95%CI 1.18–1.65) were more likely to link to care within 30-days than heterosexual males. Non-Hispanic Black individuals had poorer linkage than White individuals (aRR 0.77, 95%CI 0.71–0.83). County-level mentally unhealthy days were negatively associated with linkage (aRR 0.63, 95%CI: 0.40–0.99).

Conclusions

Racial disparities in linkage to care persist at both individual and county levels, even when adjusting for county-level social determinants of health. These findings suggest a need for structural interventions to address both structural racism and mental health needs to improve linkage to care and minimize racial disparities in HIV outcomes.
Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
Authors: Sivertsson Ebba , Friederich-Persson Malou , Persson Patrik , Nangaku Masaomi , Hansell Peter , Palm Fredrik
Published: March 2022

The proposed mechanisms for the development of nephropathy are many, complex and often overlapping. Although recent literature strongly supports a role of kidney hypoxia as an independent pathway to nephropathy, the evidence remains inconclusive since the role of hypoxia is difficult to differentiate from confounding factors such as hyperglycemia, hypertension and oxidative stress. By increasing kidney oxygen consumption using triiodothyronine (T3) and, thus, avoiding these confounding factors, the aim of the present study was to investigate renal hypoxia per se as a causal pathway for the development of nephropathy. Healthy Sprague-Dawley rats were treated with T3 (10 μg/kg/day) and the angiotensin II AT1-receptor antagonist candesartan (1 mg/kg in drinking water) to eliminate effects of T3-induced renin release; and compared to a candesartan treated control group. After 7 weeks of treatment in vivo kidney function, oxygen metabolism and mitochondrial function were evaluated. T3 did not affect glomerular filtration rate or renal blood flow, but increased total kidney oxygen consumption resulting in cortical hypoxia. Nephropathy, demonstrated as albuminuria and tubulointerstitial fibrosis, developed in T3-treated animals. Mitochondria uncoupling mediated by uncoupling protein 2 and the adenosine nucleotide transporter was demonstrated as a mechanism causing the increased kidney oxygen consumption. Importantly, blood glucose levels, mean arterial blood pressure and oxidative stress levels were not affected by T3. In conclusion, the present study provides further evidence for increased kidney oxygen consumption causing intrarenal tissue hypoxia, as a causal pathway for development of nephropathy.
Clinical characteristics and risk factors for mortality among COVID-19 hospitalized patients in UAE: Does ethnic origin have an impact
Authors: AbuRuz Salah , Al-Azayzih Ahmad , ZainAlAbdin Sham , Beiram Rami , Al Hajjar Mohammed
Published: March 2022

Background

The relationship between COVID-19 patient’s clinical characteristics and disease manifestation remains incompletely understood. The impact of ethnicity on mortality of patients with COVID-19 infection is poorly addressed in the literature. Emerging evidence suggests that many risk factors are related to symptoms severity and mortality risk, emphasizing the necessity of fulfilling this knowledge gap that may help reducing mortality from COVID-19 infections through tackling the risk factors.

Aims

To explore epidemiological and demographic characteristics of hospitalized COVID-19 patients from different ethnic origins living in the UAE, compare them to findings reported across the globe and determine the impact of these characteristics and ethnicity on mortality during hospitalization.

Methods

A single center, retrospective chart review study of hospitalized COVID-19 patients was conducted in a large COVID-19 referral hospital in UAE. The following outcomes were assessed: patients’ clinical characteristics, disease symptoms and severity, and association of ethnicity and other risk factors on 30-day in hospital mortality.

Results

A total of 3296 patients were recruited in this study with an average age of 44.3±13.4 years old. Preliminary data analysis indicated that 78.3% (n = 2582) of cases were considered mild. Average duration of hospital stay was 6.0±7.3 days and 4.3% (n = 143) were admitted to ICU. The most frequently reported symptoms were cough (32.6%, n = 1075) and fever (22.2%, n = 731). The 30-day mortality rate during hospitalization was 2.7% (n = 90). Many risk factors were associated with mortality during hospitalization including: age, respiratory rate (RR), creatinine, and C-reactive protein, oxygen saturation (SaO2), hemoglobin, hematocrit, ferritin, creatinine, C-reactive protein, anemia, COPD, Chronic kidney disease, dyslipidemia, Vitamin-D Deficiency, and ethnic origin (p <0.05). Multiple logistic regression analysis showed that higher mortality rates during hospitalization was associated with anemia, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and Middle Eastern origin (p<0.05).

Conclusion

The results indicated that most COVID-19 cases were mild and morality rate was low compared to worldwide reported mortality. Mortality rate during hospitalization was higher in patients from Middle East origin with preexisting comorbidities especially anemia, COPD, and chronic kidney disease. Due to the relatively small number of mortality cases, other identified risk factors from univariate analysis such as age, respiratory rate, and Vitamin-D (VitD) deficiency should also be taken into consideration. It is crucial to stratify patients on admission based on these risk factors to help decide intensity and type of treatment which, possibly, will reduce the risk of death.
Q fever expertise among human and veterinary health professionals in Germany – A stakeholder analysis of knowledge gaps
Authors: Winter Fenja , Campe Amely
Published: March 2022

Q fever is a zoonosis caused by Coxiella burnetii. In Germany, the common sources of human infections include small ruminants that excrete the pathogen. Q fever in humans can be asymptomatic or nonspecific. However, severe disease progression is also possible, which can lead to death. Q fever in small ruminants is usually asymptomatic, although reproductive disorders may occur. To protect humans from Q fever, it is important that human and veterinary health professionals (practitioners/health authority employees) have comprehensive knowledge of the diagnosis, control and prevention of Q fever, and its zoonotic potential. To ensure and enhance this understanding, this stakeholder analysis assessed Q fever expertise in human and veterinary health professionals in Germany and investigated how these knowledge gaps can best be resolved. For this purpose, an online survey and two focus group discussions were conducted with 836 and 18 participants, respectively. Knowledge gaps are due to a lack of awareness of Q fever, especially among human health practitioners. Moreover, colleagues who have heard about Q fever still lack the necessary cross-species knowledge to successfully diagnose, control and prevent this zoonosis. Additionally, differences exist between stakeholders regarding their work context and the region in which they work. In this study, stakeholders in southwestern Germany had slightly better Q fever knowledge than their colleagues in northeastern Germany. In addition, information sources aimed at resolving knowledge gaps involve direct conversations between the stakeholders, as well as reading materials and seminars. Each of these information sources should focus on interdisciplinary resources to strengthen the cooperation between human and veterinary health professionals and to raise awareness of the strengths of each stakeholder group. These results have already been implemented by the Q-GAPS project, with goals of raising awareness of Q fever and filling knowledge gaps.
Insulin secretory and antidiabetic actions of Heritiera fomes bark together with isolation of active phytomolecules
Authors: Ansari Prawej , Flatt Peter R. , Harriott Patrick , Abdel-Wahab Yasser H. A.
Published: March 2022

In folklore, Heritiera fomes (H. fomes) has been extensively used in treatment of various ailments such as diabetes, cardiac and hepatic disorders. The present study aimed to elucidate the antidiabetic actions of hot water extract of H. fomes (HWHF), including effects on insulin release from BRIN BD11 cells and isolated mouse islets as well as glucose homeostasis in high-fat-fed rats. Molecular mechanisms underlying anti-diabetic activity along with isolation of active compounds were also evaluated. Non-toxic concentrations of HWHF stimulated concentration-dependent insulin release from isolated mouse islets and clonal pancreatic β-cells. The stimulatory effect was potentiated by glucose and isobutyl methylxanthine (IBMX), persisted in presence of tolbutamide or a depolarizing concentration of KCl but was attenuated by established inhibitors of insulin release such as diazoxide, verapamil, and Ca2+ chelation. HWHF caused depolarization of the β-cell membrane and increased intracellular Ca2+. The extract also enhanced glucose uptake and insulin action in 3T3-L1 differentiated adipocytes cells and significantly inhibited in a dose-dependent manner starch digestion, protein glycation, DPP-IV enzyme activity, and glucose diffusion in vitro. Oral administration of HWHF (250 mg/5ml/kg b.w.) to high-fat fed rats significantly improved glucose tolerance and plasma insulin responses and it inhibited plasma DPP-IV activity. HWHF also decreased in vivo glucose absorption and intestinal disaccharidase activity while increasing gastrointestinal motility and unabsorbed sucrose transit. Compounds were isolated from HWHF with similar molecular weights to quercitrin (C21 H20 O11) ranging from 447.9 to 449.9 Da which stimulated the insulin release in vitro and improved both glucose tolerance and plasma insulin responses in mice. In conclusion, H. fomes and its water-soluble phytochemicals such as quercitrin may exert antidiabetic actions mediated through a variety of mechanisms which might be useful as dietary adjunct in the management of type 2 diabetes.
Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits
Authors: Charan Jaykaran , Riyad Priyanka , Ram Heera , Purohit Ashok , Ambwani Sneha , Kashyap Priya , Singh Garima , Hashem Abeer , Abd_Allah Elsayed Fathi , Gupta Vijai Kumar , Kumar Ashok , Panwar Anil
Published: March 2022

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.