bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells
Authors: Bosma Esmeralda K. , Darwesh Shahan , Zheng Jia Y. , van Noorden Cornelis J.F. , Schlingemann Reinier O. , Klaassen Ingeborg
Published: July 2022

Endothelial cells (ECs) form a precisely regulated polarized monolayer in capillary walls. Vascular endothelial growth factor-A (VEGF-A) induces endothelial hyperpermeability, and VEGF-A applied to the basolateral side, but not the apical side, has been shown to be a strong barrier disruptor in blood–retinal barrier ECs. We show here that VEGF-A presented to the basolateral side of human umbilical vein ECs (HUVECs) induces higher permeability than apical stimulation, which is similar to results obtained with bovine retinal ECs. We investigated with immunocytochemistry and confocal imaging the distribution of VEGF receptor-2 (VEGFR2) and neuropilin-2 (NRP2) in perinuclear apical and basolateral membrane domains. Orthogonal z-sections of cultured HUVECs were obtained, and the fluorescence intensity at the apical and basolateral membrane compartments was measured. We found that VEGFR2 and NRP2 are evenly distributed throughout perinuclear apical and basolateral membrane compartments in unstimulated HUVECs grown on Transwell inserts, whereas basolateral VEGF-A stimulation induces a shift toward basolateral VEGFR2 and NRP2 localization. When HUVECs were grown on coverslips, the distribution of VEGFR2 and NRP2 across the perinuclear apical and basolateral membrane domains was different. Our findings demonstrate that HUVECs dynamically regulate VEGFR2 and NRP2 localization on membrane microdomains, depending on growth conditions and the polarity of VEGF-A stimulation.
Graphia: A platform for the graph-based visualisation and analysis of high dimensional data
Authors: Freeman Tom C. , Horsewell Sebastian , Patir Anirudh , Harling-Lee Josh , Regan Tim , Shih Barbara B. , Prendergast James , Hume David A. , Angus Tim
Published: July 2022

Graphia is an open-source platform created for the graph-based analysis of the huge amounts of quantitative and qualitative data currently being generated from the study of genomes, genes, proteins metabolites and cells. Core to Graphia’s functionality is support for the calculation of correlation matrices from any tabular matrix of continuous or discrete values, whereupon the software is designed to rapidly visualise the often very large graphs that result in 2D or 3D space. Following graph construction, an extensive range of measurement algorithms, routines for graph transformation, and options for the visualisation of node and edge attributes are available, for graph exploration and analysis. Combined, these provide a powerful solution for the interpretation of high-dimensional data from many sources, or data already in the form of a network or equivalent adjacency matrix. Several use cases of Graphia are described, to showcase its wide range of applications in the analysis biological data. Graphia runs on all major desktop operating systems, is extensible through the deployment of plugins and is freely available to download from https://graphia.app/.
Nexus between constructs of social cognitive theory model and diabetes self-management among Ghanaian diabetic patients: A mediation modelling approach
Authors: Obirikorang Yaa , Acheampong Emmanuel , Anto Enoch Odame , Afrifa-Yamoah Ebenezer , Adua Eric , Taylor John , Fondjo Linda Ahenkorah , Lokpo Sylvester Yao , Adu Evans Asamoah , Adutwum Bernard , Antwi Enoch Ofori , Acheampong Emmanuella Nsenbah , Gyamfi Michael Adu , Aidoo Freeman , Owiredu Eddie-Williams , Obirikorang Christian
Published: July 2022

The promotion of Diabetes Self-Management (DSM) practices, education, and support is vital to improving the care and wellbeing of diabetic patients. Identifying factors that affect DSM behaviours may be useful to promote healthy living among these patients. The study assessed the determinants of DSM practices among Type 2 diabetes mellitus (T2DM) patients using a model-based social cognitive theory (SCT). This cross-sectional study comprised 420 (T2DM) patients who visited the Diabetic Clinic of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana. Data was collected using self-structured questionnaires to obtain socio-demographic characteristics, T2DM-related knowledge, DSM practices, SCT constructs; beliefs in treatment effectiveness, level of self-efficacy, perceived family support, and healthcare provider-patient communication. Path analysis was used to determine direct and indirect effects of T2DM-related knowledge, perceived family support, and healthcare provider service on DSM practices with level of self-efficacy mediating the relationships, and beliefs in treatment effectiveness as moderators. The mean age of the participants was 53.1(SD = 11.4) years and the average disease duration of T2DM was 10 years. Most of the participants (65.5%) had high (>6.1mmol/L) fasting blood glucose (FBG) with an average of 6.93(SD = 2.41). The path analysis model revealed that age (p = 0.176), gender (p = 0.901), and duration of T2DM (p = 0.119) did not confound the relationships between the SCT constructs and DSM specified in the model. A significant direct positive effect of family and friends’ support (Critical ratio (CR) = 5.279, p < 0.001) on DSM was observed. Self-efficacy was a significant mediator in this relationship (CR = 4.833, p < 0.001). There were significant conditional indirect effects (CIE) for knowledge of T2DM and family and friends’ support at medium and high levels of belief in treatment effectiveness (p < 0.05) via level of self-efficacy on DSM practices. However, no evidence of moderated-mediation was observed for the exogenous variables on DSM. Diabetes-related knowledge of T2DM, family and friends’ support, level of self-efficacy, and belief in treatment effectiveness are crucial in DSM practices among Ghanaian T2DM patients. It is incumbent to consider these factors when designing interventions to improve DSM adherence.
In-silico discovery of dual active molecule to restore synaptic wiring against autism spectrum disorder via HDAC2 and H3R inhibition
Authors: Raja Anupam , Shekhar Nishant , Singh Harvinder , Prakash Ajay , Medhi Bikash
Published: July 2022

Metal-dependent histone deacetylases (HDACs) are essential epigenetic regulators; their molecular and pharmacological roles in medically critical diseases such as neuropsychiatric disorders, neurodegeneration, and cancer are being studied globally. HDAC2’s differential expression in the central nervous system makes it an appealing therapeutic target for chronic neurological diseases like autism spectrum disorder. In this study, we identified H3R inhibitor molecules that are computationally effective at binding to the HDAC2 metal-coordinated binding site. The study highlights the importance of pitolisant in screening the potential H3R inhibitors by using a hybrid workflow of ligand and receptor-based drug discovery. The screened lead compounds with PubChem SIDs 103179850, 103185945, and 103362074 show viable binding with HDAC2 in silico. The importance of ligand contacts with the Zn2+ ion in the HDAC2 catalytic site is also discussed and investigated for a significant role in enzyme inhibition. The proposed H3R inhibitors 103179850, 103185945, and 103362074 are estimated as dual-active molecules to block the HDAC2-mediated deacetylation of the EAAT2 gene (SLC1A2) and H3R-mediated synaptic transmission irregularity and are, therefore, open for experimental validation.
Molecular characterization of gastric adenocarcinoma diagnosed in patients previously treated for Hodgkin lymphoma or testicular cancer
Authors: Rigter Lisanne S. , Snaebjornsson Petur , Rosenberg Efraim H. , Altena Estelle , van Grieken Nicole C. T. , Aleman Berthe M. P. , Kerst Jan M. , Morton Lindsay , Schaapveld Michael , Meijer Gerrit A. , van Leeuwen Flora E. , van Leerdam Monique E. ,   PALGA group
Published: July 2022

Introduction

The risk of developing gastric cancer is increased in patients treated with radiotherapy for Hodgkin lymphoma (HL) or testicular cancer (TC). This study aims to assess if gastric adenocarcinoma after treatment for HL/TC (t-GC) is molecularly different from gastric adenocarcinoma in the general population.

Methods

Patients were diagnosed with t-GC ≥5 years after treatment for HL/TC. Four molecular subtypes were identified using immunohistochemical and molecular analyses: Epstein-Barr virus (EBV), mismatch repair (MMR) deficiency or microsatellite instability (MSI), aberrant p53 staining as surrogate for chromosomal instability (sCIN), and a surrogate for genomic stability (sGS) without these aberrations. Results were compared with gastric cancer in the general population (p-GC) described in literature.

Results

Molecular subtyping of 90 t-GCs resulted in 3% EBV, 8% MSI, 36% sCIN and 53% sGS. 3/6 of MSI t-GCs had MLH1 promoter methylation and 2/6 were explained by double somatic mutations in MMR genes. T-GCs were more frequently sGS than p-GCs (53% vs. 38%, p = 0.04). T-GC was more frequently sGS in HL/TC patients diagnosed before 1990, than after 1990 (63% vs. 38%, p = 0.03). T-GCs located in the antrum, an area that receives high irradiation doses, were more frequently sGS (61% vs. 28% in p-GCs, p = 0.02).

Conclusion

Our results demonstrate that t-GCs are more frequently of the sGS subtype than p-GCs. An association of t-GC of the sGS subtype with prior anticancer treatment is suggested by the high frequency in HL/TC patients who were treated before 1990, a time period in which HL/TC treatments were more extensive.
Hand size estimates of fibromyalgia patients are associated with clinical and experimental pain
Authors: Staud Roland , Carpenter Rachel , Godfrey Melyssa , Robinson Michael E.
Published: July 2022

Introduction

Simply inspecting one’s own body can reduce clinical pain and magnification of body parts can increase analgesia. Thus, body perceptions seem to play an important role for analgesia. Conversely, pain may also affect bodily perceptions. Therefore, we evaluated the effects of clinical and/or experimental pain on perceived hand size in fibromyalgia patients (FM) and healthy controls (HC).

Methods

To investigate the effects of chronic and/or acute pain on size perception we compared hand size estimates of 35 HC and 32 FM patients at baseline and during tonic mechanical pain stimuli applied to one ear lobe. Mechanical stimuli were adjusted for each individual pain sensitivity to achieve a rating of 4 ± 1 VAS (0–10) units. Photographs of each subject’s hands were digitally manipulated to produce a monotonic series of 5 images larger and 6 smaller than actual size which were then presented to the participants in ascending and descending order (total number of images: 12).

Results

FM and HC participants’ clinical pain ratings at baseline were 3.3 (3.1) and .3 (.8) VAS units, respectively. At baseline, FM participants selected significantly smaller hand images than HC as representative of their actual size (p < .02). During application of tonic experimental pain, the image size chosen to represent their actual hand size decreased significantly in FM participants and HC (p < .001) but this decrease was not different between groups (p > .05). Hand size estimates of FM participants correlated negatively with their clinical pain ratings (p < .04).

Conclusion

The decreased hand size perception of FM patients and HC was associated with their clinical and/or experimental pain, supporting the hypothesis that pain can result in visual body distortions.
Testing the expectancy-disconfirmation theory: Geography, employment status and household size of local communities determine their perspectives of a local mine business in South Africa
Authors: Boihang Mothusi , Yessoufou Kowiyou
Published: July 2022

Local communities’ perspectives on mining businesses are a matter of endless debate, particularly in developing countries. If misunderstood or mismanaged by authorities (local and national), these perspectives may lead to violent and deadly reactions, which are unaffordable given the tremendous contribution of mining businesses to socio-economic development. The recurrence of these violent events means that authorities and mining businesses may have been failing to understand the dynamic of local people’s expectations. Here, to explain the complexity of the interactions of local people with mine businesses, we collected socio-economic data along with data on people’s satisfaction levels towards the services delivered by a local mining business in theMose KotaneLocal Municipality in South Africa. Data collected were analyzed by fitting a Structural Equation Model (SEM). We found that only 4–8% of communities’ expectations were met by the local mine business, and that closest communities to the mine do not benefit significantly more services than away-communities (Chi-square = 2.71, df = 4, P = 0.60). However, the proportion of moderately satisfied people (in relation to the services delivered by the mine) tends to increase when moving away from the mine while the proportion of dissatisfied people decreases. Our SEM, linking socio-economic data to communities’ perspectives, shows a good fit (Fisher C value = 0; P = 1.00, n = 158). In communities away from the mine, residents who were initially happy about the establishment of the mining business tend to be satisfied with the services delivered by the mine (β = 2.69±0.41, P<0.001) but these residents are likely to be employed people (P<0.05). In communities close to the mine, large-sized households tend to be satisfied with the mine-delivered services (P = 0.04). This is potentially due to the fact that a large household is more likely to have at least one person working for the mine. Collectively, these findings reveal how socio-economic variables determine people’s perspectives on the mining business.
Swimming behavior and hydrodynamics of the Chinese cavefish Sinocyclocheilus rhinocerous and a possible role of its head horn structure
Authors: Lei Fakai , Xu Mengzhen , Ji Ziqing , Rose Kenneth Alan , Zakirov Vadim , Bisset Mike
Published: July 2022

The blind troglobite cavefish Sinocyclocheilus rhinocerous lives in oligotrophic, phreatic subterranean waters and possesses a unique cranial morphology including a pronounced supra-occipital horn. We used a combined approach of laboratory observations and Computational Fluid Dynamics modeling to characterize the swimming behavior and other hydrodynamic aspects, i.e., drag coefficients and lateral line sensing distance of S. rhinocerous. Motion capture and tracking based on an Artificial Neural Network, complemented by a Particle Image Velocimetry system to map out water velocity fields, were utilized to analyze the motion of a live specimen in a laboratory aquarium. Computational Fluid Dynamics simulations on flow fields and pressure fields, based on digital models of S. rhinocerous, were also performed. These simulations were compared to analogous simulations employing models of the sympatric, large-eyed troglophile cavefish S. angustiporus. Features of the cavefish swimming behavior deduced from the both live-specimen experiments and simulations included average swimming velocities and three dimensional trajectories, estimates for drag coefficients and potential lateral line sensing distances, and mapping of the flow field around the fish. As expected, typical S. rhinocerous swimming speeds were relatively slow. The lateral line sensing distance was approximately 0.25 body lengths, which may explain the observation that specimen introduced to a new environment tend to swim parallel and near to the walls. Three-dimensional simulations demonstrate that just upstream from the region under the supra-occipital horn the equipotential of the water pressure and velocity fields are nearly vertical. Results support the hypothesis that the conspicuous cranial horn of S. rhinocerous may lead to greater stimulus of the lateral line compared to fish that do not possess such morphology.
Comparing timelines and evidence available to support new TB, HIV, and HCV drug approvals: The same, only different
Authors: LaHood Allison , Rahman Rifat , McKenna Lindsay , Frick Mike , Mitnick Carole D.
Published: July 2022

Background

Tuberculosis (TB), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) share a global presence and propensity to disproportionately affect marginalized populations. However, over recent decades, many fewer drugs have been brought to market for TB than for the others. Although three new anti-TB drugs have been approved in the US or Europe in the last 10 years, uptake of these drugs has been limited. Using case examples of drugs developed recently for TB, HIV, and HCV, we explore possible reasons. We examine the use and effect of regulatory pathways intended to address weak economic incentives in the face of urgent, unmet needs; evaluate the extent of data underpinning authorizations for these indications; document development timelines and evidence available at the time of each approval; consider explanations for observed differences; and discuss the implications for clinical guidelines and use.

Methods and findings

For each indication, we selected two drugs: one recently approved and one approved between 2012 and 2014, when the first new anti-TB drug from a novel class in more than 40 years received marketing authorization. We calculated time from first published peer-reviewed evidence of activity to date of approval; the number of phase 1, 2, and 3 trials; the number of trial participants randomized to treatment arms containing the drug; and the total number of participants in each trial from the individual drug approval packages. We found that the two TB drugs took longer to gain approval (8.0 and 19.2 years for bedaquiline and pretomanid, respectively) despite availing of special regulatory pathways meant to expedite approval, when compared to the HIV (2.6 years for dolutegravir and 4.7 years for doravirine) and HCV drugs (3.2 and 1.6 years for sofosbuvir and glecaprevir/pibrentasvir, respectively). Moreover, fewer participants were studied prior to TB drug approvals (380 and 879) than prior to approvals for HIV (1598 and 979) and for HCV (2291 and 2448) drugs.

Conclusions

The dramatic disparities observed in TB drug development reaffirm the importance of several actions. Increased investment in TB research and development is necessary to rapidly advance drugs through the pipeline. Development plans and partnerships must provide safety and efficacy evidence on combinations and durations that are relevant to real-world use in heterogeneous populations. Reliable, validated surrogate markers of relapse-free cure are essential to decrease the duration and cost of TB treatment trials and increase the confidence and speed with which new regimens can advance. Lastly, regulators and normative bodies must maintain high evidentiary standards for authorization while ensuring timely and broad approval for TB drugs and regimens.
The role of information in consumer preferences for sustainable certified palm oil products in Germany
Authors: Richartz Christoph , Abdulai Awudu
Published: July 2022

Food products are often subject to information asymmetries, which are commonly supposed to be reduced by labels and certifications. However, as the number of labels increases, consumers tend to get confused, bored or impatient and stop using them to make product choices. This study uses data from a discrete choice experiment, conducted in Germany, to analyze consumers’ preferences and willingness-to-pay (WTP) for sustainability indicators on products that contain palm oil as an ingredient. Since information is crucial to the assessment and awareness of, or attendance to, labels on consumer products, this study assesses the effect of factual information on preferences as well as attribute-processing strategies. We use a hybrid latent variable model that allows us to jointly examine the response to the stated choice component and the responses to attribute processing questions, thus capturing attribute non-attendance (ANA) to specific labels while controlling for heterogenous preferences. Our results reveal that the attribute ‘organic’ receives the highest monetary valuation in the overall sample as well as in the information intervention, and the no-information intervention groups. The results also show that providing additional information tends to change consumers’ non-attendance patterns as well as WTP values. In particular, the information intervention tends to increase consumers’ WTP and decreases their ANA for sustainability-indicating attributes. The findings suggest that the attribute ‘organic’ has the potential to be ranked highest across the entire latent variable structure, making it the most promising attribute for promoting sustainable palm oil use across consumer groups.
Parent and child mental health during COVID-19 in Australia: The role of pet attachment
Authors: Bennetts Shannon K. , Crawford Sharinne B. , Howell Tiffani J. , Burgemeister Fiona , Chamberlain Catherine , Burke Kylie , Nicholson Jan M.
Published: July 2022

Restrictions, social isolation, and uncertainty related to the global COVID-19 pandemic have disrupted the ways that parents and children maintain family routines, health, and wellbeing. Companion animals (pets) can be a critical source of comfort during traumatic experiences, although changes to family routines, such as those caused by COVID-19, can also bring about challenges like managing undesirable pet behaviours or pet-human interactions. We aimed to examine the relationship between pet attachment and mental health for both parents and their children during the COVID-19 pandemic in Australia. A total of 1,034 parents living with a child under 18 years and a cat or dog completed an online cross-sectional survey between July and October 2020. Path analysis using multivariate linear regression was conducted to examine associations between objective COVID-19 impacts, subjective worry about COVID-19, human-pet attachment, and mental health. After adjusting for core demographic factors, stronger pet-child attachment was associated with greater child anxiety (parent-reported, p < .001). Parent-pet attachment was not associated with self-reported psychological distress (p = .42), however, parents who reported a strong emotional closeness with their pet reported greater psychological distress (p = .002). Findings highlight the role of pets during times of change and uncertainty. It is possible that families are turning to animals as a source of comfort, during a time when traditional social supports are less accessible. Alternatively, strong pet attachment is likely to reflect high levels of empathy, which might increase vulnerability to psychological distress. Longitudinal evidence is required to delineate the mechanisms underpinning pet attachment and mental health.
DES-Amyloidoses “Amyloidoses through the looking-glass”: A knowledgebase developed for exploring and linking information related to human amyloid-related diseases
Authors: Bajic Vladan P. , Salhi Adil , Lakota Katja , Radovanovic Aleksandar , Razali Rozaimi , Zivkovic Lada , Spremo-Potparevic Biljana , Uludag Mahmut , Tifratene Faroug , Motwalli Olaa , Marchand Benoit , Bajic Vladimir B. , Gojobori Takashi , Isenovic Esma R. , Essack Magbubah
Published: July 2022

More than 30 types of amyloids are linked to close to 50 diseases in humans, the most prominent being Alzheimer’s disease (AD). AD is brain-related local amyloidosis, while another amyloidosis, such as AA amyloidosis, tends to be more systemic. Therefore, we need to know more about the biological entities’ influencing these amyloidosis processes. However, there is currently no support system developed specifically to handle this extraordinarily complex and demanding task. To acquire a systematic view of amyloidosis and how this may be relevant to the brain and other organs, we needed a means to explore "amyloid network systems" that may underly processes that leads to an amyloid-related disease. In this regard, we developed the DES-Amyloidoses knowledgebase (KB) to obtain fast and relevant information regarding the biological network related to amyloid proteins/peptides and amyloid-related diseases. This KB contains information obtained through text and data mining of available scientific literature and other public repositories. The information compiled into the DES-Amyloidoses system based on 19 topic-specific dictionaries resulted in 796,409 associations between terms from these dictionaries. Users can explore this information through various options, including enriched concepts, enriched pairs, and semantic similarity. We show the usefulness of the KB using an example focused on inflammasome-amyloid associations. To our knowledge, this is the only KB dedicated to human amyloid-related diseases derived primarily through literature text mining and complemented by data mining that provides a novel way of exploring information relevant to amyloidoses.
Poor glycemic control, cardiovascular disease risk factors and their clustering among patients with type 2 diabetes mellitus: A cross-sectional study from Nepal
Authors: Khanal Mahesh Kumar , Bhandari Pratiksha , Dhungana Raja Ram , Gurung Yadav , Rawal Lal B. , Pandey Gyanendra , Bhandari Madan , Devkota Surya , Courten Maximilian de , Courten Barbora de
Published: July 2022

Background

Cardiovascular disease (CVD) is the most common complication of diabetes mellitus (DM). To prevent morbidity and mortality among patients with type 2 diabetes mellitus (T2DM), optimization of glycemic status and minimizing CVD risk factors is essential. As Nepal has limited data on these CVD risk parameters, we assessed the prevalence of poor glycemic control, CVD risk factors, and their clustering among patients with T2DM.

Methods

Using a cross-sectional study design, we collected data of 366 patients with T2DM. We applied a multistage cluster sampling technique and used the WHO STEPS tools. Binary logistic and Poisson regression was applied to calculate odds and prevalence ratio of clustering of risk factors, considering P< 0.05 statistically significant.

Results

The mean age of participants was 54.5±10.7 years and 208 (57%) were male. The prevalence of poor glycemic control was 66.4% (95% C.I: 61.5–71.2). The prevalence of smoking, alcohol users, inadequate fruit and vegetables intake and physical inactivity were 18% (95% C.I:14 to 21.9), 14.8% (95% C.I:11.1 to 18.4), 98.1% (95% C.I: 96.7–99.4), and 9.8% (95% C.I:6.7–12.8), respectively. Overall, 47.3% (95% C.I: 42.1–52.4) were overweight and obese, 59% (95% C.I: 52.9–63) were hypertensive, and 68% (95% C.I: 63.2–72.7) had dyslipidemia. Clustering of two, three, four, five and more than five risk factors was 12.6%, 30%, 30%,19%, and 8.7%, respectively. Four or more risk factors clustering was significantly associated with gender, age, level of education, T2DM duration, and use of medication. Risk factors clustering was significantly higher among males and users of anti-diabetic medications with prevalence ratio of 1.14 (95% C.I:1.05–1.23) and 1.09 (95% C.I: 1.09–1.18)], respectively.

Conclusions

The majority of the patients with T2DM had poor glycemic control and CVD risk factors. Policies and programs focused on the prevention and better management of T2DM and CVD risk factors should be implemented to reduce mortality in Nepal.
An epidemic model for SARS-CoV-2 with self-adaptive containment measures
Authors: Marchetti Sabina , Borin Alessandro , Conteduca Francesco Paolo , Ilardi Giuseppe , Guzzetta Giorgio , Poletti Piero , Pezzotti Patrizio , Bella Antonino , Stefanelli Paola , Riccardo Flavia , Merler Stefano , Brandolini Andrea , Brusaferro Silvio
Published: July 2022

During the COVID-19 pandemic, several countries have resorted to self-adaptive mechanisms that tailor non-pharmaceutical interventions to local epidemiological and health care indicators. These mechanisms reinforce the mutual influence between containment measures and the evolution of the epidemic. To account for such interplay, we develop an epidemiological model that embeds an algorithm mimicking the self-adaptive policy mechanism effective in Italy between November 2020 and March 2022. This extension is key to tracking the historical evolution of health outcomes and restrictions in Italy. Focusing on the epidemic wave that started in mid-2021 after the diffusion of Delta, we compare the functioning of alternative mechanisms to show how the policy framework may affect the trade-off between health outcomes and the restrictiveness of mitigation measures. Mechanisms based on the reproduction number are generally highly responsive to early signs of a surging wave but entail severe restrictions. The emerging trade-off varies considerably depending on specific conditions (e.g., vaccination coverage), with less-reactive mechanisms (e.g., those based on occupancy rates) becoming more appealing in favorable contexts.
Do pupillary responses during authentic slot machine use reflect arousal or screen luminance fluctuations? A proof-of-concept study
Authors: Kim Andy J. , Murch W. Spencer , Limbrick-Oldfield Eve H. , Ferrari Mario A. , MacDonald Kent I. , Fooken Jolande , Cherkasova Mariya V. , Spering Miriam , Clark Luke
Published: July 2022

Modern slot machines are among the more harmful forms of gambling. Psychophysiological measures may provide a window into mental processes that underpin these harms. Here we investigated pupil dilation derived from eye tracking as a means of capturing changes in sympathetic nervous system arousal following outcomes on a real slot machine. We hypothesized that positively reinforcing slot machine outcomes would be associated with increases in arousal, reflected in larger pupil diameter. We further examined the contribution of game luminance fluctuations on pupil diameter. In Experiment 1A, experienced slot machine gamblers (N = 53) played a commercially-available slot machine in a laboratory for 20 minutes while wearing mobile eye tracking glasses. Analyses differentiated loss outcomes, wins, losses-disguised-as-wins, and (free-spin) bonus features. Bonus features were associated with rapid increases in pupil diameter following the onset of outcome-related audiovisual feedback, relative to losses. In Experiment 1B, luminance data were extracted from captured screen videos (derived from Experiment 1A) to characterize on-screen luminance changes that could modulate pupil diameter. Bonus features and wins were associated with pronounced and complex fluctuations in screen luminance (≈50 L and ≈25L, respectively). However, the pupil dilation that was observed to bonus features in Experiment 1A coincided temporally with only negligible changes in screen luminance, providing partial evidence that the pupil dilation to bonus features may be due to arousal. In Experiment 2, 12 participants viewed pairs of stimuli (scrambled slot machine images) at luminance difference thresholds of ≈25L, ≈50L, and ≈100L. Scrambled images presented at luminance differences of ≈25L and greater were sufficient to cause pupillary responses. Overall, pupillometry may detect event-related changes in sympathetic nervous system arousal following gambling outcomes, but researchers must pay careful attention to substantial in-game luminance changes that may confound arousal-based interpretations.
IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α
Authors: Van Dis Erik , Fox Douglas M. , Morrison Huntly M. , Fines Daniel M. , Babirye Janet Peace , McCann Lily H. , Rawal Sagar , Cox Jeffery S. , Stanley Sarah A.
Published: July 2022

The prevailing model of protective immunity to tuberculosis is that CD4 T cells produce the cytokine IFN-γ to activate bactericidal mechanisms in infected macrophages. Although IFN-γ-independent CD4 T cell based control ofM.tuberculosisinfection has been demonstratedin vivoit is unclear whether CD4 T cells are capable of directly activating macrophages to control infection in the absence of IFN-γ. We developed a co-culture model using CD4 T cells isolated from the lungs of infected mice andM.tuberculosis-infected murine bone marrow-derived macrophages (BMDMs) to investigate mechanisms of CD4 dependent control of infection. We found that even in the absence of IFN-γ signaling, CD4 T cells drive macrophage activation, M1 polarization, and control of infection. This IFN-γ-independent control of infection requires activation of the transcription factor HIF-1α and a shift to aerobic glycolysis in infected macrophages. While HIF-1α activation following IFN-γ stimulation requires nitric oxide, HIF-1α-mediated control in the absence of IFN-γ is nitric oxide-independent, indicating that distinct pathways can activate HIF-1α during infection. We show that CD4 T cell-derived GM-CSF is required for IFN-γ-independent control in BMDMs, but that recombinant GM-CSF is insufficient to control infection in BMDMs or alveolar macrophages and does not rescue the absence of control by GM-CSF-deficient T cells. In contrast, recombinant GM-CSF controls infection in peritoneal macrophages, induces lipid droplet biogenesis, and also requires HIF-1α for control. These results advance our understanding of CD4 T cell-mediated immunity toM.tuberculosis, reveal important differences in immune activation of distinct macrophage types, and outline a novel mechanism for the activation of HIF-1α. We establish a previously unknown functional link between GM-CSF and HIF-1α and provide evidence that CD4 T cell-derived GM-CSF is a potent bactericidal effector.
Influence of nano edible coating & films combined with zinc oxide and active phenol compounds from pomegranate peel to prolong shelf life of minimally processed pomegranate
Authors: Aboul anean hosam El din
Published: July 2022

The effect of edible coating and film from chitosan and incorporating it with the action of ZnONPs on active phenol compounds from extracts of pomegranate peel(PPE). The edible film's physical and chemical properties were determined, consisting of zinc oxide ZnONPs with active phenol compounds from extracted pomegranate peel(PPE). Adding ZnONPs with active phenol compounds from extracted pomegranate peel(PPE) to chitosan films can provide safe edible films, decrease microbial growth and consequently prolong the shelf life of pomegranate, as well as improve the physiochemical changes properties of the pomegranate. The substances used in this experiment were, film with a (A) Extracts pomegranate peels (PPE), 5 % (0.1%), (B)ZnONPs 1% (0.02%), (C) ZnONPs 2%(0.04%), (D) ZnONPs 3%(0.06%), (E) ZnONPs1% / PPE1% (0.02%), (F) ZnONPs 2% / PPE2% (0.04%), (G) ZnONPs 3% / PPE3%(0.06%) wt% of chitosan on quality attributes and prolong shelf- life of pomegranate were stored in plastic containers at 2°C and 90-95% relative humidity for 20 days. The treatments of (G) ZnONPs 3% / PPE3%(0.06%) loaded on chitosan as well as chitosan and (D) ZnONPs 3%(0.06%) reduced the weight loss%, have excellent microbial count until 20 days of storage, recorded the lowest microbial count and mold & yeast colonies. Other chemical properties were studied, e.g., Total soluble solids content, acidity, anthocyanin %, firmness and ascorbic acid. Results indicated that ZnONPs 3% / PPE3%(0.06%) loaded on chitosan or ZnONPs 3%(0.06%) are the best treatment for preserving pomegranate arils. It was found that the best measurements were that the film-forming nan emulsion solutions decreased E% 110 nm, B% 134 nm. Nano followed treatment, F% 188.7 nm, compared to nano edible films, which were A0% 1312nm. Acceptable sensory properties are suitable for barrier properties (carbon dioxide, oxygen and water). Thus, the stability and efficiency of these barriers to carrying antioxidant additives could indicate that these results may be useful in the domain of the food industry and simple technology for low-cost the production process
ROCK: digital normalization of whole genome sequencing data
Authors: Legrand Véronique , Kergrohen Thomas , Joly Nicolas , Criscuolo Alexis
Published: July 2022

Due to advances in high-throughput sequencing technologies, generating whole genome sequencing (WGS) data with high coverage depth (e.g. ≥500×) is now becoming common, especially when dealing with non-eukaryotic genomes. Such high coverage WGS data often fulfills the expectation that most nucleotide positions of the genome are sequenced a sufficient number of times without error. However, performing bioinformatic analyses (e.g. sequencing error correction, whole genome
de novo assembly) on such highly redundant data requires substantial running times and memory footprint.

To reduce redundancy within a WGS dataset, randomly downsampling high-throughput sequencing reads (HTSR) is trivial. Nevertheless, this first-in-mind strategy is not efficient as it does not minimize variation in sequencing depth, thereby eroding the coverage depth of genome regions that are under-covered (if any). To cope with this problem, a simple greedy algorithm, named digital normalization, was designed to efficiently downsample HTSRs over genome regions that are over-covered. Given an upper-bound threshold
κ>1, it returns a subset of HTSRs inducing an expected coverage depth of at most
εκ across the genome (where
ε>1 is a small constant). By discarding highly redundant HTSRs while retaining sufficient and homogeneous coverage depth (≈
εκ), this algorithm strongly decreases both running times and memory required to subsequently analyze WGS data, with often little impact on the expected results.

Interestingly, the digital normalization algorithm can be easily enhanced in several ways, so that the final subset contains fewer but more qualitative HTSRs. ROCK (Reducing Over-Covering K-mers) was therefore developed with the key purpose of implementing a fast, accurate and easy-to-use digital normalization procedure. Developed in C++, ROCK enables to observe fast running times using only a unique thread. To improve the digital normalization procedure, ROCK also implements two novel strategies: (i) downsampling the HTSRs based on their Phred scores, and (ii) implementing a final step that filters out low-covering HTSRs. Thanks to these improvements, ROCK can be used as a preprocessing step prior to performing fast genome
de novo assembly. The source code is available under GNU Affero General Public License v3.0 at
https://gitlab.pasteur.fr/vlegrand/ROCK.

[
In: Lemaitre C, Becker E, Derrien T (eds),
Proceedings of JOBIM 2022, Posters & Demos, Rennes, France, 5-8 July, p. 21]
How Online Reviews Affect Consumer’s Quality Belief: Ex-ante and Ex-post Preference of Consumption Decision
Authors: Li Yiyang
Published: July 2022

Many researchers focused on the impact of online reviews on sales, only a few researchers investigate consumer satisfaction following the purchasing decision. I hypothesised that online reviews would have an impact on both sales and returns. I first elaborated on the hypotheses with an analytical model that demonstrates how risk-neutral reference-dependent consumers form a quality belief and their consumption utility after consumption. Further, I empirically tested the hypotheses using cross-sectional data set collected from Taobao.com. By controlling the effect of types of products, and adding monetary incentiveas the instrumental variable for positive review rates, I ran 2SLS regressions of sales and returns on reviews. The result supports the proposition that the positive review rate is positively associated with both returns and sales, while the negative review rate is negatively associated with both returns and sales. Consumers tend to overestimate true product quality with positive reviews, while negative reviews tend to be more informative about the true quality of products. This is because sellers generally manipulate positive reviews and ratings to attract potential buyers. The result suggests that consumers could discount their quality beliefs before making the purchasing decision. This would not only increase the reference-dependent consumption utility but also reduce the transportation cost of returning products. Thus, achieving a more efficient allocation of resources.
Silver Lining in Looming Storm: Examining China’s Population Aging Crisis, Expansionary Population Policy, and Alternate Solutions
Authors: Zhang Tianyi
Published: July 2022

Home to over 1.4 billion residents, China has been the world’s most populous country for centuries. While population growth had been largely natural in China’s long history, population policies and controls had become an integral part of Chinese policymaking since the late 19th century. After the Communist Party overtook the regime in 1949, population policies became even more pivotal, if volatile and willful at times. In this essay, I will first show that there is indeed a significant population aging crisis brewing within China, which could mark a fundamental metamorphosis that decimates China’s population dividend. I will further state that this belated policy turnaround is already highly unlikely to prepare the Chinese population for the looming population aging crisis, nor is it a promising idea to play this population catch-up game, because it will incur an even heavier burden for the working age population in the next decade. And finally, I will propose alternate solutions to the looming population crisis that look beyond simply boosting birth rates, in the form of a fairer redistribution system and pension system reform that alleviates anxieties and burdens of the working class as well as elderly population.
Potential risk factors for diabetes mellitus type 1
Authors: Korneva K. G. , Strongin L. G. , Nazarova K. Yu. , Zagainov V. E.
Published: July 2022

Diabetes mellitus type 1 (T1D) develops as a result of the interaction of genetic and environmental factors. Genetic predisposition to T1D turns into clinical reality only in half of hereditary cases, which indirectly indicates the importance of external factors, the significance of which is periodically reviewed. Retrospective and prospective clinical foreign and national studies were included. PubMed, Medline and eLibrary were searched. Modern ideas about the possible impact of the main prenatal and postnatal environmental factors on the development of autoimmune response against insulin-producing islet cells and T1D were discussed. The risk of developing type 1 diabetes is determined by the complex interaction of environmental factors and genetic predisposition. The mechanisms of their influence remain rather unknown. Further research is needed to determine strategies of primary and secondary prevention of T1D.
Assessment of the relationship between prediabetes and low skeletal mass based on blood creatinine level
Authors: Ibragimova S. I. , Nuskabayeva G. O. , Shalkharova Z. N. , Sadykova K. Zh. , Junusbekova G. A. , Oran M.
Published: July 2022

BACKGROUND: Low muscle mass increases the risk of developing type 2 diabetes mellitus (DM 2) and prediabetes. Nutrition is an important factor in the study of the relationship between low muscle mass and the development of glucose metabolic disorders.

AIM: The present study was conducted to assess the relationship between prediabetes and low muscle mass on the basis of serum creatinine levels, taking into account patient nutrition.

MATERIALS AND METHODS: The study included 551 patients aged 18–69 years without DM 2. The glucose level was determined based on fasting glucose and after an oral glucose tolerance test (OGTT). Hyperglycemia is assessed according to the classification of the World Health Organization. The MedDietScore questionnaire was used to assess the nutritional factor, which determines the adherence of patients to the Mediterranean diet. In order to assess odds ratios (OR) and 95% confidence interval (CI), a binary logistic regression was performed.

RESULTS: The prevalence of prediabetes in the group with the lowest and highest blood creatinine level was 31.9% and 17.5% respectively (p=0.016). As a result of the conducted regression analysis, a statistically significant relationship was found between low creatinine levels and the chances of having prediabetes (crude OR 2,07, 95% CI 1,21; 3,56), which persisted after adjusting for socio-demographic, anthropometric factors, stress level and physical activity as well as muscle strength. After adding the data on MedDietScore to the statistical model, the revealed relationship was lost (p = 0.187).

CONCLUSION: Low serum creatinine increases the chances of the presence of prediabet regardless of gender, age, body weight index, the volume of the hips, the ratio of the volume of the waist to growth, as well as physical activity, the level of stress and muscular power. However, the chances of the presence of prediabet do not differ in persons with low creatinine blood depending on the commitment to the Mediterranean diet among the population of those living in the Turkestan region.
Oxidative stress and changes in liver sialoglycoconjugate metabolic parameters in rats with alloxanic diabetes mellitus
Authors: Volkhina I. V. , Butolin E. G.
Published: July 2022

BACKGROUND: Oxidative stress may be one of the mechanisms for the development of complications in DM and many forms of CKD. However, the influence of this factor on the metabolism of sialoglycoconjugates, which actively participates in the regulatory processes of the body, is unknown.

AIM: comparative study of the effect of lipoic acid on the parameters of liver sialoglycoconjugate metabolism in rats with alloxan diabetes mellitus.

MATERIALS AND METHODS: Studies were conducted on white male rats weighing 180–220 grams. The animals were divided into three groups: in the animals of the first and second groups, alloxan diabetes mellitus (DM) was caused by a single subcutaneous injection of alloxan tetrahydrate (AT). Animals of the second group received lipoic acid intramuscularly; the third group consisted of intact rats. On 5, 10, 20, 30 and 40 days after the injection of AT, a comprehensive examination of the animal’s condition was performed: 1) determination of the level of glycemia; 2) assessment of the degree of development of oxidative stress by the content of TBK-active products in the liver; 3) study of the dynamics of the exchange of sialoglycoconjugates in the liver (free, oligo-and protein-bound sialic acids, sialidase activity).

RESULTS: The study was conducted on 106 rats, each experimental group had 48 animals, control — 10. It was found that the administration of α-lipoic acid to rats with alloxan diabetes leads to a decrease in the level of glycemia. The introduction of lipoic acid in experimental animals did not reduce the sialidase activity and the content of all sialic acid fractions in the liver, although it reduced the degree of oxidative stress in the body.

CONCLUSION: Supplementation of lipoic acid in experimental animals did not significantly decrease sialidase activity and content of the sialic acid fractions under study in the liver, although it did reduce the degree of oxidative stress development in the organism. The increased rate of sialic acid metabolism in the liver of alloxan-diabetic rats may indicate a restructuring of hepatocyte metabolism to adapt the whole organism to prolonged hyperglycemia under insulin deficiency conditions.