bluuebunny/crossref_metadata_2025 huggingface dataset:
A polyherbal remedy of Chamomile, Cinnamon, Oregano, Ginger, and Anise (CCOGA) combined with physician-prescribed medication is a promising COVID-19 therapy.
Authors: Ali Ayad M. , Rashid Peshnyar M.A. , M.Ali Kamaran , Dana Omer I , Mahmood Asaad M. , Rostam Hassan M.
Published: September 2023

Introduction: The world has been on high pandemic alert subsequent to the severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak. In the first two years of the pandemic, there was no definitive treatment for coronavirus disease 2019 (COVID-19). Traditionally, herbal remedies were seen as a means of treating respiratory infections. The objective of this study is to evaluate the effect of a polyherbal remedy made of chamomile, cinnamon, oregano, ginger, and anise (CCOGA) on curing the COVID-19 infection.
Methods: This study used randomized, parallel control and treatment arms of COVID-19 outpatients. The control group receives only physician prescribes medications, whereas the treatment group receives physician prescribes medication plus CCOGA polyherbal remedy once a day for one week. The patients were evaluated at baseline and on day 7 for several biomarker tests, including: PCR cycle threshold values (PCR-Ct), total WBC count, lymphocyte count, C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and peripheral oxygen saturation (SpO2).
Result: CCOGA significantly reduces the viral load in the patients of the treatment arm. In addition, CCOGA significantly improves leukocyte, lymphocyte, and CRP levels in the middle-aged and elderly groups of the treatment arm. Older individuals who did not undergo CCOGA treatment had a significantly higher ESR and lower SpO2 than the corresponding age in treatment group.
Conclusion: The CCOGA polyherbal remedy reduces viral load and improves the prognostic biomarker of inflammation in COVID-19 outpatients, and it may be a promising remedy for elder patients.
Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans
Authors: Mudd Philip , Borcherding Nicholas , Kim Wooseob , Quinn Michael , Han Fangjie , Zhou Julian , Sturtz Alexandria , Schmitz Aaron , Lei Tingting , Schattgen Stefan , Klebert Michael , Suessen Teresa , Middleton William , Goss Charles , Liu Chang , Crawford Jeremy , Thomas Paul , Teefey Sharlene , Presti Rachel , O'Halloran Jane , Turner Jackson , Ellebedy Ali
Published: September 2023

SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.
Exploring influence factors on regional ozone formation for air quality guarantee by analysis on historical monitoring data
Authors: Huang Yan , Wang Qingqing , Ou Xiaojie , Sheng Dongping , Yao Shengdong , Zhang Shihan , Wang Qiaoli
Published: September 2023

Air quality assurance is an essential component of significant events and daily life alike. A comprehensive long-term analysis was carried out based on the observation data of air quality and meteorological elements in Deqing county in 2021, which serves as a sub-venue of 2022 Hangzhou Asian Games during 23, Sep. to 8 Oct. 2023. O3 is the key pollutant that should be take consideration in air quality guarantee for the Asian Games and daily air quality control. O3 exhibited the strongest correlation with RH, followed by Temp and NO2. Extremely high O3 concentration mostly occurred at stricter conditions of high Temp above 30℃, and RH between 30–60%, at the NO2 concentration ranging from 10 to 30 µg·m− 3. The ratio of VOCs and NO2 mostly distributed at 13.0 with an averagely ratio of 28.3. In addition, when NO2 concentration was lower enough, the atmospheric condition belonged to transition zone, while NO2 concentration was higher, the atmospheric condition belonged to NO2-sensitive zone. Historical contemporaneous analysis conducted similar expressions. The results are helpful to supplement and improve the local O3 formation mechanism in the complex environment, and scientifically and effectively guide the rapid, comprehensive and precise control of air pollution for important events.
Detection of distant relatedness in biobanks for identification of undiagnosed carriers of a Mendelian disease variant: application to Long QT Syndrome
Authors: Below Jennifer , Lancaster Megan , Chen Hung-Hsin , Shoemaker M. Benjamin , Fleming Matthew , Baker James , Evans Grahame , Polikowsky Hannah , Samuels David , Huff Chad , Roden Dan
Published: September 2023

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we developed a generalizable method of genotype inference based on distant relatedness and deployed this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identified 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncovered recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identified 22 additional subjects sharing this haplotype, subsequently confirmed to carry p.Asp76Asn. Referral and non-referral carriers had prolonged QTc compared to controls, and, among carriers, QTc polygenic score additively associated with QTc prolongation. Thus, our novel analysis of shared chromosomal segments identified undiagnosed cases of genetic disease and refined the understanding of LQT5 penetrance and phenotype.
Physiological and metabolic changes in Selaginella tamariscina in response to desiccation and resurrection
Authors: Xi Yi , Cai Yiming , Li Zhou
Published: September 2023

As a typical resurrection plant, Selaginella tamariscina exhibits remarkable drought tolerance and resurrection capacity. However, the mechanism of resurrection associated with the alteration of global organic metabolites in S. tamariscina has not been fully elucidated. Objectives of the study were to investigate drought tolerance and recovery capacity of S. tamariscina based on physiological response and to further reveal potential mechanism of resurrection related to changes in antioxidant defense and differential metabolites under drought stress and after rehydration. Results showed that severe drought reduced leaf relative water content from 90–18%, resulting in extreme declines in chlorophyll content and photochemical efficiency as well as a significant increase in malondialdehyde content in leaves, but S. tamariscina plants could rapidly recover within 3 days of rehydration. Superoxide dismutase, peroxidase, and catalase were significantly activated by dehydration and rehydration. In addition, drought-induced accumulations of citric acid and ribitol could be maintained at higher levels in response to rehydration. Although most of organic metabolites were not affected significantly by dehydration (lactic acid, ribonic acid, arabinitol, and erythritol) or decreased sharply under drought stress (glycine, alanine, γ-aminobutyric acid, proline, glyceric acid, vanillic acid, arabinose, and rhamnose), but S. tamariscia has the ability to quickly recover or increase the contents of these organic metabolite after rehydration. Current findings indicated that enhanced antioxidant defense system could be one of the main pathways for acquisition of desiccation tolerance and resurrection capacity, thereby alleviating oxidative damage to S. tamariscina plants. The accumulation of various organic metabolites played critical roles in underlying mechanism of resurrection due to their positive function associated with osmotic adjustment, osmoprotection, antioxidant, and energy metabolism.
Clinical significance of blocking novel immune checkpoint B7-H4 in Urothelial Carcinoma of Bladder as a potential therapeutic target
Authors: Raja David , Singh Aishwarya , Kurra Santosh , Nayak Brusabhanu , Kaushal Seema , Sharma Alpana , Singh Prabhjot
Published: September 2023

Urothelial Carcinoma of Bladder is complex disease with high mortality and recurrence rates. Current standard regimes have exhibited anti-tumor activity but still, a proportion of patients are non-responsive or in-eligible to receive such treatments. Immune checkpoints have emerged as potential class of therapeutics to be tested in UCB patients. Clinical trials targeting PD-1/PD-L1 axis have been tested in UCB but still a proportion of patients are non-responsive to it which stresses upon identifying new targets. New immune checkpoint B7-H4 has been shown to negatively regulate T cell activity in cancer and is a poor prognostic factor in various solid tumors. In this study we assessed the novel immune checkpoint B7-H4 status in UCB patients. We observed elevated expression of B7-H4 and PD-L1 on CD8+T cells in circulation of UCB patients. Relative mRNA expression and immunohistochemistry displayed upregulation in bladder tumor tissue. Increased expression of B7-H4 along with PD-L1 in periphery and tumor of UCB patients highlights involvement of B7-H4 in disease progression. Combinatorial blocking of B7-H4 and PD-L1 enhanced IFN-γ and granzyme B in CD-8 T cells functional T cell immune response in UCB patients.Also, B7-H4 was significantly associated with clinico-pathological parameters. Our findings highlight B7-H4 as potential therapeutic target for treatment of UCB patients in future after further validation.
Octupole Moment Driven Free Charge Generation in Partially Chlorinated Subphthalocyanine for Planar Heterojunction Organic Photodetectors
Authors: Durrant James , Rana Aniket , Park Song , Labanti Chiara , Fang Feifei , Yun Sungyoung , Dong Yifan , Yang Emily , Nodari Davide , Gasparini Nicola , Park Jeong-Il , Shin Jisoo , Minami Daiki , Park Kyung-Bae , Kim Ji-Seon
Published: September 2023

In this study, high-performance organic photodetectors (OPDs) are presented which utilize a pristine chlorinated subphthalocyanine (Cl6-SubPc) photoactive layer. Optical and optoelectronic analyses indicate that the device photocurrent is primarily generated through direct charge generation within the Cl6-SubPc layer, rather than exciton separation at layer interfaces. Molecular modelling suggests that this direct charge generation is facilitated by Cl6-SubPc’s high octupole moment (-80 DÅ2), which generates a 200 meV shift in molecular energetics. Increasing the thickness of Cl6-SubPc leads to faster OPD response times, correlated with a decrease in trap density. Notably, PHJ OPDs with a 50 nm thick Cl6-SubPc photoactive layer exhibit detectivities approaching 1013 Jones, with a dark current below 10− 7 A cm− 2 up to -5 V. Based on these findings, we conclude that Cl6-SubPc is a promising material for high-performance OPDs employing a single-component photoactive layer.
The key role of TDP-43 in amyotrophic lateral sclerosis propagation and the disease-modifying profile of CK-1 inhibitors
Authors: Cuevas Eva P. , Martinez-Gonzalez Loreto , Gordillo Clara , Tosat Carlota , Lastra Carmen Pérez de la , Sáenz Amets , Gil Carmen , Palomo Valle , Martin-Requero Angeles , Martinez Ana
Published: September 2023

Background
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease without any cure nor effective treatment to reverse its progression. The main hallmark of the disease is the nuclear protein TDP-43. It suffers different post-translational modifications leading to a lack of function in the nucleus and gain of toxicity in the cytoplasm. Previous reports indicated that pathogenic TDP-43 shows prion-like propagation in several different settings. With the aim of advancing therapeutics focused on the prevention of the propagation of TDP-43 pathology, we here study the potential role of pathogenic TDP-43 in immortalized lymphocytes from sporadic ALS patients
Methods
We used lymphoblastoid cell lines from sporadic ALS patients as source of pathogenic forms of TDP-43, and healthy cells (lymphoblasts, myoblasts or human neuroblastoma SH-SY5Y or osteosarcoma U2OS cell lines) as recipient cells to first investigate the seeding and spread of the TDP-43 proteinopathy. Furthermore, we have evaluated the potential of targeting TDP-43 phosphorylation by CK-1 inhibitors in preventing the propagation of the pathology.
Results
The results herein presented indicate that pathogenic TDP-43 forms are secreted to the extracellular medium of sporadic ALS lymphoblasts and could be transported by extracellular vesicles spreading TDP-43 pathology to healthy cells. Moreover, tunnelling nanotubes (TNTs) have been also discovered in sick cells transporting TDP-43 between the cells. Interestingly, targeting TDP-43 phosphorylation by an in-house designed benzothiazole-based CK-1 inhibitor, namely IGS2.7, was enough to stop cell-to-cell transmission in addition to its known effects on restoring phosphorylation levels, mislocalization and functionality of TDP-43 protein in patients-derived cells.
Conclusions
Our data show the key role of TDP-43 in cell-to-cell disease propagation in sporadic ALS lymphoblasts model and the relevant therapeutic role of CK-1 inhibitors, specifically the small heterocyclic molecule called IGS2.7, not only in restore the functional homeostasis of TDP-43 but also in avoiding the disease transmission. These outstanding data merits the translation of this small molecule to the clinical setting where all these results may be confirmed.
Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating the NLRP3 inflammasome and exosome secretion in M1 macrophages after UVB irradiation-induced skin injury
Authors: W Bour-Jr , Chen Yu-Ying , Chang Hui-Hsuan , Chen Rong-Jane , Wang Ying-Jan , Lee Yu-Hsuan
Published: September 2023

Background:
Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs.
Results:
We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release.However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion.
Conclusions:
Our findings propose a new concept for ZnONP-induced skin toxicity mechanismsand the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.
Key informants perspectives on creating a high impact research department in family and community medicine: a qualitative project
Authors: Gayapersad Allison , O’Brien Mary Ann , Meaney Christopher , Aditya Ishan , Baxter Julia , Selby Peter
Published: September 2023

Background
Primary care is integral to the health system and population health. Primary care research is still in development and most academic programs lack effective research investments. High impact primary care research programs are needed to advance the field to ensure a robust primary care system for the future. The project objective was to understand key informants’ views of structures, functions, and processes required to create a high impact research program in an academic primary care department.
Methods
A descriptive qualitative project with key informants from research programs in primary care. Participants included international research leaders in primary care (n = 10), department of family and community researchers (n = 37) and staff (n = 9) in an academic primary care department, other university leaders (n = 3) and members of the departmental executive leadership team (1 department; 25 members). Semi-structured interviews (n = 27), and focus groups (n = 6) were audio recorded, transcribed, and analyzed using thematic analysis. We used a socioecological framework which described macro, meso, micro levels of influence.
Results
At the micro level despite barriers with respect to funding, protected time and lack of formal mentorship, personal motivation was a key factor. At the meso level, the organizational structure that promoted collaboration and a sense of connection emerged as a key factor. Specifically research leaders identified a research faculty development pipeline based on equity, diversity, inclusion, indigeneity, and accessibility principles with thematic areas of focus as key enablers. Lastly, at the macro level, an overarching culture and policies that promoted funding and primary care research was associated with high impact programs.
Conclusion
The alignment/complementarity of micro, meso, and macro level factors influenced the creation of a high impact research department in primary care. High impact research in primary care is facilitated by the development of researchers through formalized and structured mentorship/sponsorship and a department culture that promote primary care research.
“I'm a failure again I can't do it”: Attitudes towards, and experiences of, exercise participation in adults with class III obesity
Authors: Orange Samuel , Roebuck Jessica , Marshall Phil , Madden Leigh , Vince Rebecca , Bell Beth
Published: September 2023

Background Exercise is first-line treatment for class III obesity. However, living within a larger body brings unique and non-trivial challenges to exercise participation, which are not well understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. Methods We recruited 30 adults with class III obesity (mean ± SD: age: 45.0 ± 12.5 years; body mass index: 45.8 ± 8.6 kg/m2) who were participating in a 6-month home-based aerobic and resistance exercise intervention. Participants took part in semi-structured interviews after they completed the first 3-months of the intervention. Open-ended questions were used flexibly to explore their experiences of exercise participation, encompassing perceived barriers, motivations, preferences, and benefits of exercise. Interview transcripts were analysed using reflexive thematic analysis. Results Three themes were developed that encapsulate participants’ views and experiences of exercise participation: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; (3) a desire to live well. People with class III obesity have a strong perception that they are unable to do exercise; a view that is attributed to a lifetime of perceived judgement by others, restrictions in mobility, pain during every day activities, and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value is placed on tailored exercise that accommodates for the unique needs of moving in a larger body. A desire to live a normal life and be free to carry out basic activities of daily living underpins motivations for exercise. Conclusions Our findings suggest that multicomponent obesity interventions should move away from generic exercise prescriptions designed to maximise energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored, person-centred, and weight-neutral exercise interventions.
Health service provider views on measuring patient involvement in healthcare: an interview study with researchers, clinicians, managers, and policymakers
Authors: Toft Bente Skovsby , Ellegaard Trine , Nielsen Berit Kjærside , Rossen Camilla Blach , Hørlück Jens Thusgaard , Ludvigsen Mette Spliid , Bekker Hilary Louise , Rodkjær Lotte Ørneborg
Published: September 2023

Background Strategies aimed at promoting patient involvement vary in purpose across different healthcare settings and are assessed using a wide range of outcomes. However, there is no consensus on the most appropriate measurement tools or ways to evaluate patient involvement initiatives.
This qualitative study aimed to explore the perspectives of stakeholders from micro, meso, and macro levels within the Danish healthcare system on patient involvement and its measurement.
MethodsThis descriptive, explorative study employed semi-structured interviews with open-ended questions to elicit participants’ views and experiences of patient involvement and measurement tools. A purposeful sample of participants was identified, to include decision makers, researchers, and health professionals (n=20) with experiences of patient involvement in healthcare at micro, meso, and macro levels across Danish organizations. Data underwent reflexive thematic analysis.
Results Three main themes were identified: 1) Determining the purpose of patient involvement and measurement alignment; 2) Reflecting on the qualities, fit, and usefulness of measures; 3) Recognizing conflicting stakeholder paradigms. Despite the interest in and positive attitudes toward patient involvement, views on the meaning and value of evaluating involvement and innovating varied; in part, this was attributable to challenges in selecting criteria, methods, and measures for evaluation.
Conclusion The findings indicate the need to integrate the perspectives of all key stakeholders in designing the evaluation of patient involvement initiatives. The application of a multiple stakeholder approach and co-production of a multidimensional evaluation may provide some common ground for selecting evaluation criteria and measurement tools in the healthcare setting.
Trial registration Danish Data Protection Agency (1-16-02-400-21) 15 October 2021.
International Journal of Information Security: A Bibliometric Study, 2007-2023
Authors: Dwivedi Rahul
Published: September 2023

This study employs various bibliometric analysis techniques to examine the intellectual structure of the International Journal of Information Security from 2007 to 2023. The aim is to identify the most cited journals, underlying research themes within the article corpus, and gradual changes in the research themes over time. “Lecture Notes on Computer Science” is the most referenced knowledge source. In addition, articles on the theme of encryption techniques received the highest average citations, followed by key management and authentication protocols. Moreover, machine learning, blockchain, and the Internet of Things are emerging topics of interest among published authors in the International Journal of Information Security. Qualitative and quantitative comparisons between open-access and regular articles suggested a few notable differences in author keywords but no differences in the number of citations received. Furthermore, regression analysis found a negative correlation between citation counts with the length of the article abstract and article title and a positive correlation with page count, being published in a special issue, and if at least the affiliation of one of the authors is different from others. Finally, we also identified prominent authors, articles, institutions, and countries published in this journal.
Are Deaf College Students More Sensitive to Unfair Information？
Authors: Du Xue , Gong Yuqi , Chen Xiaoyi , Jiang Jun
Published: September 2023

To investigate whether fairness decision among deaf college students is the sameto the normal hearing college students, we recorded event-related potentials (ERPs) to examine how the brain affected when the deaf college students perform the ultimatum gaming task.
For the behavioral outcomes, a main effect of proposal type was found for both deaf and normal hearing college students, the more unfair of the offer, the lower of acceptance rate have, which indicated that the deaf college students have the same unfairness aversion and fair decision-making as normal hearing college students at the behavioral level.
The ERPs results revealed there was a significant interaction between group and proposal type at the early stage (N1). Interestingly, only in the deaf college group, the mean wave amplitude of N1 induced by moderately and very unfair offers were significantly greater than that of fair offers. In addition, we found that the deaf college students had smaller amplitudes on P2 and P3 than normal hearing college students, which showed the deaf college students are more strongly motivated to be fair. Based on these, we should provide more fairness information and attention to the mental health of the deaf people.
Akkermansia muciniphila may mediate the association between prenatal metal mixture exposure and childhood depressive symptoms
Authors: Nagdeo Kiran , Midya Vishal , Lane Jamil M. , Torres-Olascoaga Libni A. , Martínez Gabriela Gil , Horton Megan K. , Gennings Chris , Téllez-Rojo Martha Maria , Wright Robert O. , Arora Manish , Eggers Shoshannah
Published: September 2023

Background: Prenatal metal exposure may be associated with childhood depressive symptoms. Emerging research suggests links between gut microbiome (GM) disruptions and depressive disorders. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in mediating the association between prenatal metal exposures and depressive symptoms in later childhood is not known. We aim to estimate the associations between prenatal mixed metal exposures, A. mucinipnila presence in the gut microbiome at 9-11 years old, and concurrent depressive symptoms.
Methods: We leverage existing data from a subset of 112 participants in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort. Metal concentrations (Pb, As, Cd, Cr, Zn, Se, Sb, Cu, Cs, Co, Mn) were measured in 2nd and 3rd trimester maternal whole blood. Stool samples were collected at 9–11 years of age and underwent metagenomic sequencing to assess the GM. The presence of A. muciniphila was detected using GM data. Children’s Depression Inventory (CDI) was administered at 9-11 years. We used weighted quantile sum (WQS) regression to separately estimate associations between prenatal metal mixture exposure at 2nd and 3rd trimesters and CDI. We used a nonparametric bootstrap approach to estimate the proportion of these associations mediated by A. muciniphila.
Results: A. muciniphila was detected in 24% of participants. The presence of A. muciniphila was associated with a significantly decreased log-transformed, t-score normalized CDI score (log tCDI) (ß=-0.13, 95%CI=[-0.21,-0.04]), suggesting a protective effect. Second and 3rd-trimester metal mixtures were associated with increased log tCDI (ß=0.06 per increase in quartile, 95%CI=[0.01,0.10] and ß=0.03 per increase in quartile, 95%CI=[-0.02,0.09], respectively). A quartile increase in these metal mixtures trended towards decreased odds of A. muciniphila (OR=0.54, 95%CI=[0.23,1.24] and OR=0.58, 95%CI=[0.23,1.49] at 2nd and 3rd trimesters respectively). The presence of A. muciniphila may mediate the association between the 2nd-trimester metal mixture and log tCDI by 34%.
Conclusion: We found suggestive evidence that A. muciniphila may attenuate the association between prenatal metal exposures and childhood depressive symptoms. A. muciniphila supplementation may be a promising intervention strategy to mitigate metal-associated depressive symptoms. Additional studies are needed to confirm these findings.
Association of ITGA2 Dual Site Variants with Recurrent Ischemic Events in Patients Undergoing Stenting for Symptomatic Intracranial Atherosclerotic StenosisAuthor list
Authors: Dong Yiwen , Ye Jiadan , Cheng Sheng , Yang Hongge , Li Ze , Di Xuan , Lou Xin , Li Xingang , Ma Ning
Published: September 2023

Objective
We aimed to investigate the relationship between gene polymorphisms and the occurrence of adverse clinical events following dual antiplatelet therapy in Patients with Symptomatic Intracranial Atherosclerotic Stenosis.
Methods
A total of 195 patients were enrolled, categorized into 32 cases (those with clinical adverse events) and 163 controls (without events). Genotyping of 20 SNPs from 17 genes was executed. Statistical analyses (Fisher’s exact test, logistic regression) were applied to determine associations.
Results
The ITGA2 rs1126643 (C807T) and rs1062535 (G873A) polymorphisms were significantly correlated with adverse clinical events. Specifically, the mutant frequency of allele C (ITGA2 rs1126643) and allele G (ITGA2 rs1062535) was significantly higher in cases compared to controls (OR = 2.97, 95%CI = 1.702–5.172, P = 0.0001; OR = 3.27, 95%CI = 1.762–6.066, P = 0.0002, respectively). Other genotypes showed no significant differences between the groups.
Conclusion
The ITGA2 C807T and G873A polymorphisms may elevate the risk of vascular events in Chinese patients. Detecting these polymorphisms may be valuable in identifying patients at risk of recurrent ischemic events.
xCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis
Authors: Wilhelm Elena D. , Wiesehöfer Marc , Dankert Jaroslaw Thomas , Wach Sven , Wagner Mathias , Spahn Martin , de Julio Marianna Kruithof , Wennemuth Gunther
Published: September 2023

Purpose
Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Interaction via soluble factors previously revealed a reduction in the expression of xCT and AL122023.1 in prostate carcinoma cells LNCaP after seven days of co-culture with stromal primary p21 cells. Furthermore, xCT is known to be a putative target for miR-26a, miR-30d and miR-30e which in turn potentially interact with the lncRNA AL122023.1.
Methods
We validated the repression of xCT and AL122023.1 at RNA level by quantitative real-time PCR and at protein level by Western Blotting. The lncRNA-miRNA-interaction was analyzed by luciferase reporter assays whereas the localization and distribution of xCT in prostate tissue of different developmental stages was evaluated by immunostaining.
Results
The interaction between AL122023.1 and miR-26a/-30d/-30e was verified and further investigated at protein level regarding xCT. An indirect inhibitory effect of AL122023.1 on the xCT expression could be shown, but miR-26a/-30d/-30e caused no inhibition. Moreover, immunostaining displayed a precise xCT expression in neuroendocrine cells ranging from fetal, healthy juvenile and adult prostate tissue to benign prostatic hyperplasia and finally advanced prostate cancer.
Conclusion
This study explores the relevance and function of xCT and AL122023.1 in the prostate and exposes xCT as a potential marker or therapeutic target in high-risk prostate cancer.
GOIZ ZAINDU trial: a FINGER-like multidomain lifestyle intervention feasibility study to prevent dementia in Southern Europe.
Authors: Tainta Mikel , Ecay-Torres Mirian , de Arriba Maria , Barandiaran Myriam , Otaegui-Arrazola Ane , Iriondo Ane , Garcia-Sebastian Maite , Estanga Ainara , Saldias Jon , Clerigue Montserrat , Gabilondo Alazne , Ros Naia , Mugica Justo , Barandiaran Aitziber , Mangialasche Francesca , Kivipelto Miia , Arrospide Arantzazu , Mar Javier , Martinez-Lage Pablo
Published: September 2023

Background:
GOIZ ZAINDU ("caring early" in Basque) is a pilot study to adapt the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) methodology to the Basque population and evaluate feasibility and adherence to a FINGER-like multidomain intervention program. Additional aims included the assessment of efficacy on cognition and collecting data to design a large efficacy trial.
Method:
GOIZ ZAINDU is a one-year, randomized, controlled trial of a multidomain intervention in persons aged 60+ years, with Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score ≥ 6, no dementia, and below-than-expected performance in at least one of three cognitive screening tests. Randomization to a Multidomain intervention (MD-Int) or Regular Health Advice (RHA) was stratified by sex, age (>/≤ 75), and cognitive status (Mild Cognitive Impairment (MCI)/normal cognition). MD-Int included cardiovascular risk factors control, nutritional counseling, physical activity, and cognitive training. The primary outcome was retention rate and adherence to the intervention program. Exploratory cognitive outcomes included Neuropsychological Test Battery z-scores change. Analyses were carried out by intention to treat.
Results:
One hundred twenty-five participants were recruited (mean age: 75.64 (±6.46); 58% women). MD-Int (n=61) and RHA (n=64) groups were balanced in demographics and cognition. 52 (85%) participants from RHA and 56 (88%) from the MD-Int group completed the study. More than 70% of participants presented good overall adherence to intervention activities. The risk of cognitive decline was higher in the RHA group compared with MD-Int regarding executive function (p=.019) and processing speed scores (p=.026).
Conclusions:
The GOIZ-ZAINDU study has proved that the FINGER methodology is adaptable and feasible in a different socio-cultural environment. Exploratory efficacy results show a lower risk of decline in executive function and processing speed. These results support the design of a large-scale efficacy trial.
XBNet and Text Mining-based Genetic Diseases Classification
Authors: Abd Dhafar Hamed , Jassim Mustafa Abdalrassual , Omri Mohamed Nazih , Hussain Abir
Published: September 2023

Text mining can be used for various biological and medical purposes. In this work, we have used text mining to analyze various papers related to Alzheimer's, Asthma, Cancer, Diabetes, Fabry, and various syndrome diseases using their abstracts and extracting from the text the related gene to those diseases. In this case, the data set collected from the various sources was generated manually in this pilot study. The text was collected from various articles searched through PubMed, Web of Science, and Medline. Extremely Boosted Neural Network is a new machine learning (ML) algorithm that has been developed recently to train a new optimization technique and can integrate tree-based models with Neural networks (NN). In this paper, an extremely boosted neural network was utilized as a novel application for the analysis of text data to extract information about the diseases. We benchmark the proposed model with 17 other ML models, achieving 98% accuracy. This is a significant improvement given that most of the benchmark techniques received less than 97%.
Zonular Fibre Insertion-to-Limbus Distance as a Diagnostic Parameter for Ectopia Lentis
Authors: Rohrberg Max , Lussac Vanessa , Salchow Daniel J.
Published: September 2023

Purpose: Subluxation of the crystalline lens (ectopia lentis, EL) can lead to significant visual impairment and serves as a diagnostic criterion for genetic disorders such as the Marfan syndrome. There is no established criterion to diagnose and quantify EL. We prospectively investigated the distance between the zonular fibre insertion and the limbus (ZLD) in healthy subjects as a parameter to assess the position of the lens, quantify EL and provide normative data.
Methods: This prospective, observational, cross-sectional study includes one-hundred-fifty eyes of 150 healthy participants (mean age 28 years, range 4-68). Pupils were dilated with tropicamide 0.5% and phenylephrine 2.5% eyedrops. ZLD was measured in mydriasis at the slit lamp as the distance between the most central visible insertions of the zonular fibres on the lens surface and the corneoscleral limbus. Vertical pupil diameter (PD) and refractive error were recorded. If zonular fibre insertions were not visible, the distance between limbus and the pupillary margin was recorded as the ZLD.
Results: 145 right and 5 left eyes were examined. 93% of study subjects were Caucasian, 7% were Asian. In eyes with visible zonular fibre insertions (n = 76 eyes), ZLD was 1.30 ± 0.28 mm (mean ± SD, range 0.7-2.1) and PD was 8.79 ± 0.57 mm (7.5-9.8 mm). In the remaining 74 eyes, ZLD was 1.38 ± 0.28 mm (0.7-2.1 mm), and PD was 8.13 ± 0.58 mm (6.7-9.4 mm). For all eyes, ZLD was 1.34 ± 0.29 mm (0.7- 2.1 mm), and PD was 8.47 ± 0.66 mm (6.7 to 9.8 mm). Refractive error and sex did not significantly affect ZLD. Smaller PD and older age were associated with larger ZLD (P < 0.001 and P = 0.036, respectively).
Conclusion: Average ZLD was 1.34 mm in eyes of healthy subjects. Older age correlated with larger ZLD. These normative data will aid in diagnosing and quantifying EL.
Circuit complexity and functionality: a thermodynamic perspective
Authors: Chamon Claudio , Ruckenstein Andrei , Mucciolo Eduardo , Canetti Ran
Published: September 2023

Circuit complexity, defined as the minimum circuit size required for implementing a particular Boolean computation, is a foundational concept in computer science. Determining circuit complexity is believed to be itself a hard problem [1]. Furthermore, placing general lower bounds on circuit complexity would allow distinguishing computational classes, such as P and NP, an unsolved problem [2]. Recently, in the context of black holes, circuit complexity has been promoted to a physical property, wherein the growth of complexity is reflected in the time evolution of the Einstein-Rosen bridge (“wormhole”) connecting the two sides of an AdS “eternal” black hole [3]. Here we explore another link between complexity and physics for circuits of given functionality. Taking advantage of the connection between circuit counting problems and the derivation of ensembles in statistical mechanics, we tie the entropy of circuits of a given functionality and fixed number of gates to circuit complexity. We use thermodynamic relations to connect the quantity analogous to the equilibrium temperature to the exponent describing the exponential growth of the number of distinct functionalities as a function of complexity. This connection is intimately related to the finite compressibility of typical circuits. Finally, we use the thermodynamic approach to formulate a framework for the obfuscation of programs of arbitrary length – an important problem in cryptography – as thermalization through recursive mixing of neighboring sections of a circuit, which can viewed as the mixing of two containers with “gases of gates”. This recursive process equilibrates the average complexity and leads to the saturation of the circuit entropy, while preserving functionality of the overall circuit. The thermodynamic arguments hinge on ergodicity in the space of circuits which we conjecture is limited to disconnected ergodic sectors due to fragmentation. The notion of fragmentation has important implications for the problem of circuit obfuscation as it implies that there are circuits with same size and functionality that cannot be connected via local moves. Furthermore, we argue that fragmentation is unavoidable unless the complexity classes NP and coNP coincide, a statement that implies the collapse of the polynomial hierarchy of complexity theory to its first level.
Phytotoxicity and Genotoxicity Study of Reactive Red 141 Dye in Mung Bean (Vigna radiata (L.) Wilczek)
Authors: Sompark Chalermwoot , Damrianant Somchit , Sakkayawong Niramol
Published: September 2023

An assessment of the phytotoxicity and genotoxicity of reactive red (RR) 141 dye was conducted using mung bean seedlings (Vigna radiata (L.) Wilczek). The dye exhibited phytotoxic effects, causing delayed germination and growth inhibition in pot plants. Plant parameters such as percentage of germination and seedling vigor index (SVI) were significantly reduced in mung beans treated with the dye at concentrations of 50 and 100 ml/L compared to the control group. Pot plant experiments were conducted with short-term (14 days) and long-term (60 days) exposures in paddy soil pot culture. In the short-term exposure, both plumule and radical lengths were significantly and dose-dependently decreased. In the long-term exposure, the dye affected plant length and grain weight, but had no impact on pod number, pod length, and seed number. To evaluate genotoxicity, high annealing temperature-random amplified polymorphic DNA (HAT-RAPD) analysis was used to detect DNA damage. Five RAPD primers with 58–75% GC content were utilized, resulting in the detection of polymorphic band patterns. A total of 116 bands were generated, with molecular sizes ranging from 433 to 2857 bp in the plant leaves exposed to the dye. Polymorphisms were observed as the disappearance and/or appearance of DNA bands in both concentration treatments compared to the control, and decreased genomic template stability (GTS) values indicated changes in the HAT-RAPD profiles, indicating DNA damage and mutation. These findings demonstrate that mung beans exposed to RR 141 dye experience significant effects on genomic template stability (GTS) and exhibit phytotoxic and genotoxic responses. This study highlights the potential of RR 141 dye as a harmful agent in plant model systems
Recent variability and trends and projected changes in precipitation in the southeastern United States: A focus on the Apalachicola-Chattahoochee-Flint River Basin
Authors: Diem Jeremy E. , Bonsu Prince Osei
Published: September 2023

Changes in precipitation impacts water availability in river basins; therefore, it is important to perform detailed analyses of precipitation variables within regions to better understand drivers of precipitation variability. This study, which focuses on the Apalachicola-Chattahoochee-Flint River Basin in the southeastern United States, provides an analysis of precipitation variability during 1980–2021 and connects that information to circulation variables while also exploring the alignment between recent and projected precipitation changes. Data include daily precipitation totals from 33 stations, monthly values for circulation indices, and downscaled precipitation projections from climate models. Results show the pressure gradient across the southwestern North Atlantic Ocean and southeastern United States – which is a function of the strength and position of the Bermuda High – is strongly correlated with the precipitation variables and is an important control of precipitation variability in the basin. In contrast, most teleconnection indices are relatively weakly correlated with precipitation. The basin has generally been getting wetter, with summer having the largest increases in precipitation totals and precipitation days and thus large decreases in maximum consecutive dry days. Increases in heavy-precipitation variables are relatively small, with the largest increases in the northern portion of the basin. Precipitation is projected to increase in the next several decades compared to recent decades, with heavy precipitation expected to have the largest increase. Since the Bermuda High is the dominant driver of precipitation in the basin, more information is needed about specific changes to the Bermuda High in upcoming decades to produce better precipitation projections.
Associations of Sleep Time, Quality of Life, and Obesity Indicators on Physical Literacy Components: A Structural Equation Model
Authors: Lemes Vanilson Batista , Sehn Ana Paula , Reuter Cézane Priscila , Burns Ryan , Gaya Anelise Reis , Gaya Adroaldo Cezar Araujo , Brand Caroline
Published: September 2023

Aim
To verify the association between ideal sleep time and physical literacy components while also considering multiple mediators such as quality of life and obesity, using a sample of adolescents.
Methods
This was a cross-sectional study that consisted of 470 adolescents aged 11–17 years from southern Brazil. Sleep time, health-related quality of life, and physical literacy components (i.e., physical education enjoyment, sports participation, sedentary behavior, moderate to vigorous physical activity, sex, and age) were evaluated through self-reported questionnaires. In addition, body mass index (BMI) was obtained by dividing body mass by height (in meters) squared, and waist circumference was measured using a metallic tape. The theoretical/statistical support of the structural equation model was evaluated according to fit parameters and strength of association.
Results
A direct association was observed between more sleep time and lower levels of obesity. The obesity indicators also had a negative association with HqOL, and HqOL had a positive association with physical literacy. The indirect associations indicated that the ideal sleep time was positively associated with HqOL and physical literacy components, considering the negative mediation effect of obesity. The model explaining physical literacy explained 31% of the variance (R = 0.31).
Conclusion
There was an indirect association between ideal sleep duration and quality of life, and between both variables with physical literacy. These relationships occur even considering the negative influence of obesity. Therefore, a child who sleeps adequately has a higher likelihood of being physically active, regardless of obesity, potentially enhancing overall quality of life across various domains.