bluuebunny/crossref_metadata_2025 huggingface dataset:
ICG-Functionalized Gold Nanostars As An Effective Contrast Agent For Real-time Tumor Localization with Dynamic Optical Contrast Imaging (DOCI) and Enhanced Radiation Therapy
Authors: Alhiyari Yazeed , Liu Yang , Mukdad Laith , Odion Ren A. , Evans Lauran K. , Shori Ramesh , Vo-Dinh Tuan , John Maie St.
Published: September 2023

The primary management of head and neck squamous cell carcinoma relies on complete surgical resection of the tumor. However, the establishment of negative margin complete resection is often difficult given the devastating side effects of aggressive surgery and the anatomic proximity to vital structures. Positive margin status is associated with significantly decreased survival. Currently, surgeons determine where the tumor cuts are made, by palpating the edges of the tumor and using prior imaging. After a tumor is presumed to be removed in its entirety, the surrounding tissues are sampled by frozen section histologic pathology to ensure that no microscopic disease is left behind, the efficacy of which varies and is subject to sampling error. The methodology by which frozen sections are collected whether tumor bed driven or specimen driven can also alter margin outcome. Thus, improving intraoperative detection of tumor margins is key to optimizing treatment and outcomes. Our group has developed a possible solution for this unmet clinical need. We have previously designed Dynamic Optical Contrast Imaging (DOCI), a novel imaging modality that acquires temporally dependent measurements of tissue autofluorescence. Furthermore, we demonstrated that DOCI can distinguish HNSCC from adjacent healthy tissue with a high degree of accuracy. DOCI images are captured in real time and offer an operatively wide field of view. With the addition of ICG conjugated gold nanostars (GNS) we can improve DOCI image contrast between tumors vs normal tissues as well as use the GNS for CT imaging and radiotherapeutic treatment.
Racial Disparities in Knowledge of Cardiovascular Disease by a Chat-Based Artificial Intelligence Model
Authors: Eromosele Oseiwe B. , Sobodu Temitope , Olayinka Olakeyede , Ouyang David
Published: September 2023

Background

Patients and their families often explore the information available online for information about health status. A dialogue-based artificial intelligence (AI) language model (ChatGPT) has been developed for complex question and answer. We sought to assess whether AI model had knowledge of cardiovascular disease (CVD) racial disparities, including disparities associated with CVD risk factors and associated diseases.

Methods

To assess ChatGPT’s responses to topic in cardiovascular disease disparities, we created six questions of twenty sets, with each set consisting of three questions with changes to text prompt based on differences in patient demographics. Each question was asked three times to assess variability in responses.

Results

A total of 180 responses were tabulated from ChatGPT’s responses to 60 questions asked in triplicate to assess. Despite some variation in wording, all responses to the same prompt were consistent across different sessions. ChatGPT’s responses to 63.4% of the questions (38 out of 60 questions) were appropriate, 33.3% (20 out of 60 questions) were inappropriate and 3.3% unreliable (2 out of 60 questions). Of the 180 prompt entries into ChatGPT, 141 (78.3%) were correct, 28 (15.5%) were hedging or indeterminate responses that could not be binarized into a correct or incorrect response, and 11 (6.1%) were incorrect. There were consistent themes in incorrect or hedging responses by ChatGPT, with 91% and 79% of incorrect and hedging responses related to a cardiovascular disease disparity that affects a minority or underserved racial group.

Conclusion

Our study showed that an online chat-based AI model has a broad knowledge of CVD racial disparities, however persistent gaps in knowledge about minority groups. Given that these models might be used by the general public, caution should be advised in taking responses at face value.
Transmission dynamics of symbiotic protist communities in the termite gut: association with host adult eclosion and dispersal
Authors: Inagaki Tatsuya , Igai Katsura , Takahashi Kazuki , Hongoh Yuichi
Published: September 2023

The fidelity of vertical transmission is a critical factor in maintaining mutualistic associations with microorganisms. The obligate mutualism between termites and intestinal protist communities has been maintained for over 130 million years, suggesting the faithful transmission of diverse protist species across host generations. Although a severe bottleneck can occur when alates disperse with gut protists, how protist communities are maintained during this process remains largely unknown. In this study, we examined the dynamics of intestinal protist communities during adult eclosion and alate dispersal in the termiteReticulitermes speratus. We found that the protist community structure in last-instar nymphs differed significantly from that in workers and persisted intact during adult eclosion, in contrast to moults between workers, in which all protists disappeared from the gut. The number of protists in nymphs and alates was substantially lower than in workers, whereas the proportion of protist species exhibiting low abundance in workers was higher in nymphs and alates. Using a simulation-based approach, we demonstrate that such changes in the protist community composition of nymphs and alates improve the transmission efficiency of whole protist species. This study thus provides novel insights into how termites have maintained mutualistic relationships with diverse gut microbiota for generations.
Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions
Authors: Chen Guan-Hua , Dai Yu-Ching , Hsieh Szu-Chia , Tsai Jih-Jin , Sy Ava Kristy , Jiz Mario , Pedroso Celia , Brites Carlos , Netto Eduardo Martins , Kanki Phyllis J. , Saunders Danielle R. D. , Vanlandingham Dana L. , Higgs Stephen , Huang Yan-Jang S. , Wang Wei-Kung
Published: September 2023

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.
Public perceptions of synthetic cooling agents in electronic cigarettes on Twitter
Authors: Liu Andrew H. , Hootman Julia , Li Dongmei , Xie Zidian
Published: September 2023

Amid a potential menthol ban, electronic cigarette (e-cigarette) companies are incorporating synthetic cooling agents like WS-3 and WS-23 to replicate menthol/mint sensations. This study examines public views on synthetic cooling agents in e-cigarettes via Twitter data. From May 2021 to March 2023, we used Twitter Streaming API, to collect tweets related to synthetic cooling agents with keywords such as ‘WS-23,’ ’ice,’ and ’frozen.’ Two deep learning roBERTa models, classified attitudes expressed in tweets about synthetic cooling agents and identified e-cigarette users. The BERTopic deep-learning model identified major topics of positive and negative tweets. Two proportion Z-tests were used to compare the proportions of positive and negative attitudes between e-cigarette users (vapers) and non-e-cigarette-users (non-vapers). Of 6,940,065 e-cigarettes related tweets, 5,788 non-commercial tweets related to synthetic cooling agents. The longitudinal trend analysis showed a clear upwards trend in discussions. Vapers posted most of the tweets (73.05%, 4,228/5,788). Nearly half (47.87%, 2,771/5,788) held a positive attitude toward synthetic cooling agents, which is significantly higher than those with a negative attitude (19.92%,1,153/5,788) with a P-value < 0.0001. The likelihood of Vapers expressing positive attitudes (60.17%, 2,544/4,228) was significantly higher (P< 0.0001) than that from non-vapers (14.55%, 227/1,560). Conversely, negative attitudes from non-vapers (30%, 468/1,560) was significantly (P< 0.0001) higher than vapers (16.2%, 685/4,228). Prevalent topics from positive tweets included “enjoyment of specific vape flavors,” “preference for lush ice vapes,” and “liking of minty/icy feelings.” Major topics from negative tweets included “disliking certain vape flavors” and “dislike of others vaping around them.” On Twitter, vapers are more likely to have a positive attitude toward synthetic cooling agents than non-vapers. Our study provides important insights into how the public perceives synthetic cooling agents in e-cigarettes, insights that are crucial for shaping future FDA regulations aimed at safeguarding public health.
Locating heterogeneity in Menstrual Hygiene Scheme impact on Indian adolescent girls
Authors: Sarkar Olivia , Dutta Arijita
Published: September 2023

India has seen Menstrual Hygiene Scheme for 15-19 aged adolescents as a mass movement in 2011 with Intervention, Education, Communication (IEC) interventions and subsidized menstrual product. While the phenomenal increase in hygienic menstrual usage during 2010-20 is celebrated, it leaves us to question if this is the MHS in play or a gradual transition due to overall developmental drive. As the age-cohorts move out of the beneficiary net over time, sustainability of the program can only be reflected if there is a behavioral change which is captured through difference in choice patterns over duration of program exposure. Using triple difference-in- difference methodology on unit level data from NFHS 4, the results find that overall the program fails to mark any significant effect on choice of hygienic product in India. However, the low rung of the cohorts in terms of education and media exposure reap the benefit of the scheme, leaving the better-off counterparts unaffected. This concludes that the issues targeted through the scheme is holistic to reach the lowest strata of the society, but a proper choice of target cohort can considerably reduce the project cost, free it of supply side inefficiencies and enhance targeting of IEC techniques, thereby making the scheme more effective.
Kidney Damage and Associated Risk Factors in the Rural Eastern Cape, South Africa: A Cross-Sectional Study
Authors: Gonzalez Ernesto Rosales , Yogeswaran Parimalanie , Chandia Jimmy , Pulido Estrada Guillermo Alfredo , Adeniyi Oladele Vincent
Published: September 2023

Background

The colliding epidemic of infectious and non-communicable diseases in South Africa could potentially increase the prevalence of kidney disease. This study determines the prevalence of kidney damage and known risk factors in a rural community of the Eastern Cape province, South Africa.

Methods

This observational cross-sectional study was conducted in the outpatient department of the Mbekweni Community Health Centre in the Eastern Cape between May and July 2022. Relevant data on demography, medical history, anthropometry and blood pressure were obtained. The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration Creatinine (CKD-EPICreatinine) equation and the re-expressed four-variable Modification of Diet in Renal Disease (MDRD) equation, without any adjustment for black ethnicity. Significant kidney damage was defined as low eGFR (<60mL/min per 1.73m2) and/or the presence of proteinuria. We used the logistic regression model analysis to identify the independent risk factors for significant kidney damage.

Results

The mean (±standard deviation) age of the 389 participants was 52.3 (± 17.5) years. The prevalence of significant kidney damage was 17.2% (n=67), as estimated by the CKD-EPICreatinine,with slight difference from the MDRD equation (17.7%; n=69), while the prevalence of proteinuria was 7.2%. Risk factors for significant kidney damage were older age (OR=0.94, 95% CI 0.91 - 0.96, p<0.001) and the presence of proteinuria (OR=0.98, 95% CI 0.97 - 0.99, p 0.002). Proteinuria was strongly associated with hypertension (OR=4.46, 95% CI 1.33 - 14.92, p<0.015) and elevated serum creatinine (OR=1.01, 95% CI 1 - 1.02, p=0.004).

Conclusions

This study found a high prevalence of kidney damage (17.2%) and proteinuria (7.2%) in this rural community, largely attributed to advanced age and hypertension, respectively. Early detection of proteinuria and decreased renal function could lead to prompt preventative measures and management to delay the progression to end-stage kidney failure and mortality.
Individual and community level factors associated with home delivery after adequate antenatal care visits: a multilevel analysis of the Ethiopian Demographic and Health Survey 2019
Authors: Gomora Degefa , Beressa Girma , Seyoum Kenbon , Tekalegn Yohannes , Sahiledengle Biniyam , Atlaw Daniel , Ejigu Neway , Kene Chala , Mesfin Telila , Mwanri Lillian
Published: September 2023

Background

Despite the reported increased antenatal care (ANC) utilization in Ethiopia, large numbers of women give birth at home without skilled personnel attendance, even after attending an adequate antenatal care schedule (≥ four antenatal visits) as recommended by the World Health Organization (WHO). This study aimed to assess individual and community-level factors associated with home delivery after adequate antenatal care visits in Ethiopia.

Methods

We analyzed the 2019 Ethiopian mini demographic and health survey data. A total weighted sample of 1,643 women who had full antenatal care visits for their last childbirth/index birth was included in the analysis. Model comparison was done by using intra-cluster correlation, median odds ratio, and proportional change in variance. A multivariable multilevel logistic regression analysis was conducted to identify the effect of individual and community-level factors on the outcome variable (home delivery). Adjusted odds ratios (AOR), along with a 95% confidence interval (CI) were used to estimate the strength of the associations.

Results

The intra cluster correlation (ICC) in the null model was 59%, showing that there was a significant difference in the prevalence of home delivery after adequate antenatal care at the community level, and the variability declined to 36.5% in the final model. Therefore, multilevel logistic regression model was utilized. At individual-level, secondary educational level was negatively associated with home delivery [AOR = 0.37; 95%CI: (0.17, 0.80)], and having a household of ≥ 5 members [AOR = 1.70; 95%CI: (1.09, 2.66)], poorest (vs. richest) wealth index [AOR = 6.98; 95%CI (2.89, 16.83)], poorer (vs. richest) wealth index [AOR = 2.77, 95%CI :(1.19,6.45)], and 2-3 birth order [AOR = 2.48; 95% CI(1.45, 4.21)] were associated with home delivery after attending the required adequate ANC visits. Community-level variables associated with home delivery after full antenatal care visits included: poor communities [AOR = 2.13; 95%CI (1.03, 4.40)], and living in a rural area [AOR = 2.74; 95%CI (1.19, 6.30)].

Conclusion

The findings of the current study indicate that in women who had the required number of ANC visits, having a larger household and poorest and poorer (vs. rich) wealth index, being the 2ndor 3rdbirth, residing in a rural area, and living in poor communities were predictors of home delivery. Having a secondary education was supportive, against delivering at home. Strategies to improve household’s socioeconomic empowerment were recommended.
Could Anti-retroviral treatment affects the profile of hepatitis B vaccine specific antibody in vertically HIV-infected children?
Authors: Tchouangueu T.F. , Kouitcheu L.B.M. , Lissom A. , Tchuandom S.B. , Tchadji J.C. , Sake C.S. , Ambada G. , Ngu L. , Ouambo H.F. , Esimone C.O. , Chae Gyu Park C.G. , Alain Bopda W.A. , Nchinda G.W.
Published: September 2023

Paediatric immunisation had been relevant in reducing the widespread of Hepatitis B virus, as an outcome of the induction of hepatitis B surface antigen specific-IgG antibodies (anti-HBs). Studies revealed alteration effects of memory B cells during antiretroviral therapy (ART). We aimed at assessing anti-HBs response profile with respect to the most prominently used ART regimens in children.

a cross-sectional study was conducted in 116 participants made up of 72 HIV-exposed and infected children, subdivided into 20 antiretroviral-naïve on one hand and on another hand 52 ARV treated children made up of regimen subgroups, including 8 ABC-3TC-EFV/NVP (ART-R1), 19 ABC-3TC-LPV/r (ART-R2), 21 AZT-3TC-NVP (ART-R3) and 4 AZT-3TC-LPV/r (ART-R4), and 44 HIV-uninfected and unexposed (HUx or control group) children. Participants included in this study were regularly vaccinated children aged between 4 months and 5 years old, born to HIV-infected mothers. An optimized and adapted home-made ELISA and BioELISA® Biohit kit were used to measure specific IgM, IgG and IgG subclasses to HBs in children.

As result, this study showed that the rates of vaccine protective response in children treated with ART under regimens R1, R2, R3 and R4 were 25%, 38%, 51% and 75%, respectively. These protective response rates were significantly lower (p<0.0001) in children under R1, R2 and R3 than the control group (92%). When comparing anti-HBs specific IgM and IgG response medians; IgM response levels were similar in both control and ARV treated children, whereas R1 (p=0.0045), R2 (p=0.0016), and R4 (p<0.0001) showed significantly lower IgG level compared to the control group. Anti-HBs IgG subclass profile pattern in the control was IgG3≈IgG1≈IgG4>IgG2. However, IgG3≈IgG1≈IgG4>IgG4 profile pattern was estimated for children submitted to R1, R2 and R4, and the profile pattern of IgG3>IgG1≈IgG4≈IgG2 in those treated with R3 which also showed the most prominent anti-HBs IgG response mean rank level.
Comparison of Omicron Breakthrough Infection Versus Monovalent SARS-CoV-2 Intramuscular Booster Reveals Differences in Mucosal and Systemic Humoral Immunity
Authors: Nantel Sabryna , Sheikh-Mohamed Salma , Chao Gary Y. C. , Kurtesi Alexandra , Hu Queenie , Wood Heidi , Colwill Karen , Li Zhijie , Liu Ying , Seifried Laurie , Bourdin Benoîte , McGeer Allison , Hardy William R. , Rojas Olga L. , Ostrowski Mario A. , Brockman Mark A. , Piccirillo Ciriaco A. , Quach Caroline , Rini James M. , Gingras Anne-Claude , Decaluwe Hélène , Gommerman Jennifer L.
Published: September 2023

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show that mild BT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary IgG and IgA levels against the Omicron Spike and enhanced reactivity to the ancestral Spike for the IgA isotype, which also reacted with SARS-CoV-1. Serum neutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for mucosal vaccines to emulate the enhanced mucosal and humoral immunity induced by Omicron without exposing individuals to the risks associated with SARS-CoV-2 infection.

ONE SENTENCE SUMMARY

Omicron breakthrough elicits cross-reactive systemic and mucosal immune responses in fully vaccinated adults.

Graphical Abstract
Occurrence of human infection withSalmonellaTyphi in sub-Saharan Africa
Authors: Kim Jong-Hoon , Parajulee Prerana , Nguyen Thuy Tien , Wasunkar Shreeya , Mogasale Vittal , Park Se Eun , Panzner Ursula , Mogeni Ondari D. , Im Justin , Marks Florian
Published: September 2023

Typhoid fever, caused bySalmonella entericaserovar Typhi, results in over 1.2 million cases and 29 thousand deaths annually from sub-Saharan Africa. Combating this disease requires various intervention approaches, such as typhoid conjugate vaccines and improving water, sanitation, and hygiene. Enhancing the effectiveness of these strategies necessitates a deeper understanding of the variation of the typhoid fever across the target region. Although the magnitude and variation of typhoid fever at the country level have been studied globally, sub-national variation remains underexplored. To address this gap, we collected data from 265 published reports on typhoid fever occurrences in sub-Saharan Africa between January 2000 and December 2020. The dataset includes information on the year and geographical location of observation, diagnostic tests used, and the type of studies in which typhoid fever was reported. By analyzing this dataset, we can gain insights into the sub-national heterogeneity of typhoid fever’s burden in the region. This knowledge will be instrumental in designing more effective intervention strategies to combat the disease.
Assessment of Knowledge and Attitude towards Blood Donation among Blood Donors in Jordan
Authors: Omaish R.S. , Al-Fayyadh Z.A. , Al-Habashneh S.M. , Al-Mashhdi S.Y. , Khasawneh S.Y. , Naber I.A. , Bourghli S.L. , Al-Adily T.N. , Mahafzah A.M. , Al-Fararjeh F.M. , Sughayer M.A
Published: September 2023

Objectives

This study will identify blood donor characteristics in Jordan. The study aims to investigate the extent of awareness and knowledge regarding blood donation among blood donors and to explore their attitudes towards blood donation in general. It also highlights various motivational factors and obstacles which impact the decision to donate blood among Jordanian donors.

Background

Recruitment of low risk blood donors can be challenging. Efforts should be made to increase the level of awareness and positive attitude toward blood donation. An essential step to achieve this is obtaining comprehensive data about the current situation of awareness, knowledge, and attitudes of the population towards blood donation.

Methods/Materials

The present study was conducted at two blood donation centers in Amman, Jordan, during 2021. A total of 535 whole blood donors were included. Data regarding their demographic characteristics, blood donation history as well as their knowledge and attitudes regarding blood donation was collected by a questionnaire.

Results

Four hundred ninety participants (91.6%) were males while 45 only (8.4%) were females. One hundred forty subjects (19.4%) were first time donors while 431 subjects (80.6%) had previous donations. The participants’ median score in the knowledge section was 19.0 points (range 5-25 points). There was no significant correlation between participants’ overall attitude score and their corresponding demographic characteristics or their overall knowledge score.

Conclusion

Measures to improve knowledge and attitude toward blood donation should be implemented in order to meet the increasing demand for blood and blood components. Targeted campaigns, correction of some misconceptions, and using different motivations are suggested.
Correction for Collider Bias in the Genome-wide Association Study of Diabetes-Related Heart Failure due to Bidirectional Relationship between Heart Failure and Type 2 Diabetes
Authors: Sun Yan V , Liu Chang , Hui Qin , Zhou Jin J , Gaziano J Michael , Wilson Peter WF ,   the Million Veteran Program, Joseph Jacob , Phillips Lawrence S
Published: September 2023

Aims

Type 2 diabetes (T2D) is a major risk factor for heart failure (HF) across demographic groups. On the other hand, metabolic impairment, including elevated T2D incidence is a hallmark of HF pathophysiology. We investigated the bidirectional relationship between T2D and HF, and identified genetic associations with diabetes-related HF after correction for potential collider bias.

Methods

We performed a genome-wide association study (GWAS) of HF to identify genetic instrumental variables (GIVs) for HF, and to enable bidirectional Mendelian Randomization (MR) analysis between T2D and HF. Since genetics and HF can independently influence T2D, collider bias may occur when T2D (i.e., collider) is controlled for by design or analysis. Thus, we conducted GWAS of diabetes-related HF with correction for collider bias.

Results

We first identified 61 genomic loci, including 24 novel loci, significantly associated with all-cause HF in 114,275 HF cases and over 1.5 million controls of European ancestry. Combined with the summary statistics of a T2D GWAS, we obtained 59 and 82 GIVs for HF and T2D, respectively. Using a two-sample bidirectional MR approach, we estimated that T2D increased HF risk (OR 1.07, 95% CI 1.04-1.10), while HF also increased T2D risk (OR 1.60, 95% CI 1.36-1.88). Then we performed a GWAS of diabetes-related HF corrected for collider bias due to prevalent HF affecting incidence of T2D. After removing the spurious association ofTCF7L2locus due to collider bias, we identified two genome-wide significant loci close toPITX2(chromosome 4) andCDKN2B−AS1(chromosome 9) associated with diabetes-related HF in the Million Veteran Program, and replicated the associations in the UK Biobank study.

Conclusion

We identified novel HF-associated loci to enable bidirectional MR study of T2D and HF. Our MR findings support T2D as a HF risk factor and provide strong evidence that HF increases T2D risk. As a result, collider bias leads to spurious genetic associations of diabetes-related HF, which can be effectively corrected to identify true positive loci. Evaluation of collider bias should be a critical component when conducting GWAS of complex disease phenotypes such as diabetes-related cardiovascular complications.
Inhibitory control and its modification in spider phobia – study protocol for an antisaccade training trial
Authors: Hildebrand Anne Sophie , Breuer Fabian , Leehr Elisabeth Johanna , Finke Johannes B. , Bucher Leandra , Klucken Tim , Dannlowski Udo , Roesmann Kati
Published: September 2023

Objectives

Inhibitory control deficits are considered a key pathogenic factor in anxiety disorders. To assess inhibitory control, the antisaccade task is a well-established measure, assessing antisaccade performance via latencies and error rates. The present study follows three aims: (1) to investigate inhibitory control via antisaccade latencies and errors in an antisaccade task, and their associations with multiple measures of fear in patients with spider phobia (SP) versus healthy controls (HC), (2) to investigate the modifiability of antisaccade performance via a fear-specific antisaccade training in patients with SP and HC, and (3) to explore associations between putative changes in antisaccade performance in SPs and diverse measures of fear following the training.

Methods

Towards aim 1, we assess antisaccade latencies (primary outcome) and error rates (secondary outcome) in an emotional antisaccade task. Further, the baseline assessment includes assessments of psychophysiological, behavioral, and psychometric indices of fear in patients with SP and HCs. To address aim 2, we compare effects of a fear-specific antisaccade training with effects of a prosaccade training as a control condition. The primary and secondary outcomes are reassessed at a post-1-assessment in both SPs and HCs. Aim 3 employs a cross-over design and is piloted in patients with SP, only. Towards this aim, primary and secondary outcomes, as well as psychophysiological, behavioral, and psychometric measures of fear are reassessed at a post-2-assessment after the second training block.

Conclusion

This study aims to better understand inhibitory control processes and their modifiability in spider phobia. If successful, antisaccade training may assist in the treatment of specific phobia by directly targeting the putative underlying inhibitory control deficits. This study has been preregistered with ISRCTN (ID:ISRCTN12918583) on 28th February 2022.
High prevalence of hepatitis B and HIV among women survivors of sexual violence in South Kivu province, eastern Democratic Republic of Congo
Authors: Bisimwa Parvine Basimane , Masemo Dieudonné Bihehe , Byabene Aline Kusinza , Besulani Georges Kikuni , Mitima Théophile Kashosi , Matabishi Cadeau Mugisho , Misuka Bienfait Mitima , Mukanga Omari , Mukonkole Jean Paulin , Nachega Jean Bisimwa , Mukwege Denis , Narcisse Patrice Joseph Komas
Published: September 2023

Introduction

Limited data are available on the prevalence rates of hepatitis B and acquired immunodeficiency syndrome (AIDS) among women survivors of sexual violence(WSSV)in South Kivu province, in the eastern part of the Democratic Republic of Congo (DRC), where armed conflicts persist. Here, we aimed to assess the prevalence of these two diseases in this vulnerable local population.

Methods

A total of 1002 WSSV, aged from 18 to 70 years old were enrolled from May 2018 to May 2020 at three one-stop centers, set up at the Panzi, Mulamba and Bulenga hospitals. Blood samples were collected and tested for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) antigens and antibodies using enzyme-linked immunoassay (ELISA) methods. Viral load quantification for HBV and HIV were performed using the GeneXpert.

Results

For HBV, overall prevalence was 8.9% (95% CI [7.2–10.8%]), 32.1% [29.3–35.0%], and 14.5% [12.3–16.8%] for HBsAg, anti-HBc and anti-HBs antibodies, respectively. Among the 89 HBsAg-positive patients, 17 (19.1%) were HBeAg-positive. The mean age was 40.57±14.99 years in the HBsAg-positive group (p=0.025). Risk factors for HBV infection were age (≥35 years) (AOR=1.83 [1.02-3.32];p=0.041), having no schooling (AOR=4.14 [1.35-12.62];p=0.012) or only primary school-level (AOR=4.88 [1.61-14.75];p=0.005), and multiple aggressors (AOR=1.76 [1.09-2.84],p=0.019). The prevalence of HIV was 4.3% [3.1–5.7%]. HIV/HBV co-infection occurred only in 5 individuals (0.5%). The HBV viral load was detectable (>2,000 copies/mL) in 61.8% of HBsAg-positive subjects and 64.8% HIV-positive subjects had a high viral load (>1,000 copies/mL).

Conclusion

This study revealed a high prevalence of HBV and HIV infections among WSSV in South Kivu. These results highlight the urgent need for systematic screening of HBV and HIV by integrating fourth-generation ELISA tests in HIV and HBV control programs.
Association of Electrocardiographic Left Ventricular Hypertrophy with Future Renal Function Decline in the General Population
Authors: Ikeda Shota , Shinohara Keisuke , Tagawa Koshiro , Tohyama Takeshi , Kishimoto Junji , Kazurayama Masaya , Tanaka Shinji , Yamaizumi Masamitsu , Nagayoshi Hirokazu , Toyama Kensuke , Matsushima Shouji , Tsutsui Hiroyuki , Kinugawa Shintaro
Published: September 2023

Background

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcome in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline of renal function in the general population.

Methods

This retrospective cohort study included individuals who received population-based health checkups from 2010 to 2019 in Japan. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥25% in the estimated glomerular filtration rate from baseline to <60 mL/min/1.73 m2. Multivariate adjusted Cox regression analysis was employed to evaluate the association between electrocardiographic LVH at baseline and renal function decline.

Results

Of the 19,825 study participants, 1,263 exhibited electrocardiographic LVH at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in both unadjusted analysis (hazard ratio 2.50, 95% confidence interval 1.73–3.60, P < 0.001) and adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14–2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein.

Conclusions

In the general population, electrocardiographic LVH was associated with future renal function decline. To detect high-risk individuals for renal function decline, electrocardiographic LVH may be useful in the setting of health checkups in the general population.

Clinical Perspectives

What is new?

This longitudinal study using a population-based annual health checkup data revealed that electrocardiographic LVH was associated with future renal function decline in the general population.

The association between electrocardiographic LVH and future renal function decline was consistent regardless of individual characteristics.

What are the clinical implications?

Renal dysfunction is a risk factor for cardiovascular disease and death as well as renal failure.

This study shows the prognostic value of electrocardiographic LVH to predict future renal dysfunction in the general population under annual health checkups.

Individuals with electrocardiographic LVH may require careful follow-up to prevent and detect the progression of renal dysfunction even if they do not have hypertension.
Physical activity reduces the effect of adiposity genetic liability on hypertension risk in the UK Biobank cohort
Authors: Hezekiah Chukwueloka , Blakemore Alexandra I , Bailey Daniel P , Pazoki Raha
Published: September 2023

Background and Purpose

Hypertension is a leading risk factor for cardiovascular disease (CVD) and is modulated by genetic variants. This study aimed to assess the effect of gene and environmental interaction focusing on adiposity genetic liability and physical activity on hypertension among European and African ancestry individuals within the UK Biobank (UKB).

Methods

Participants were 230,115 individuals of European ancestry and 3,239 individuals of African ancestry from UKB. Genetic liability for adiposity were estimated using previously published data including the list of genetic variants and effect sizes for body mass index (BMI), waist-hip ratio (WHR) and waist circumference (WC) using Plink software. The outcome was defined as stage 2 hypertension (systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the use of anti-hypertensive medications). The association between adiposity genetic liability and the outcome was assessed across categories of self-reported physical activity using logistic regression.

Results

Among European ancestry participants, there was up to a 20% hypertension risk difference between participants with a combination of high genetic liability and low physical activity compared with participants with a combination of low genetic liability and high physical activity (P<0.001). There was an interaction effect of physical activity on the association between BMI genetic liability and hypertension (Pinteraction=0.04). There was no evidence of an association between adiposity genetic liability and hypertension in individuals of African ancestry (P> 0.05).

Conclusion

This study suggests that engaging in physical activity may reduce the risk of stage 2 hypertension among European ancestry individuals who carry high genetic liability for adiposity. This cannot be inferred for individuals of African ancestry, possibly due to the low African ancestry sample size within the UKB.
Long non-coding RNA TUG1 is down-regulated in Friedreich’s ataxia
Authors: Koka Mert , Li Hui , Akther Rumana , Perlman Susan , Wong Darice , Fogel Brent L , Lynch David R , Chandran Vijayendran
Published: September 2023

Friedreich’s Ataxia (FRDA) is a neurodegenerative disorder caused by reduced frataxin (FXN) levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia with no cure, FRDA lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials. This study identifies long non-coding RNA Tug1 as a potential blood-based FRDA biomarker.

In a previous study using a frataxin knockdown mouse model (FRDAkd), we observed several hallmark FRDA symptoms and abnormalities in various tissues. Building on this, we hypothesized that a dual-source approach—comparing the data from peripheral blood samples from FRDA patients with tissue samples from affected areas in FRDAkd mice, tissues usually unattainable from patients—would effectively identify robust biomarkers.

A comprehensive reanalysis was conducted on gene expression data from 183 age- and sex-matched peripheral blood samples of FRDA patients, carriers, and controls, as well as 192 tissue datasets from FRDAkd mice. Blood and tissue samples underwent RNA isolation and qRT-PCR, and frataxin knockdown was confirmed through ELISA. Tug1 RNA interaction was explored via RNA pull-down assays. Validation was performed in serum and blood samples on an independent set of 45 healthy controls, 45 FRDA patients; 66 heterozygous carriers, and 72 FRDA patients. Tug1 and Slc40a1 emerged as potential blood-based biomarkers, confirmed in the FRDAkd mouse model (One-way ANOVA, p ≤ 0.05).

Tug1 was consistently downregulated after Fxn knockdown and correlated strongly with Fxn levels (R2= 0.71 during depletion, R2= 0.74 during rescue). Slc40a1 showed a similar but tissue-specific pattern. Further validation of Tug1’s downstream targets strengthened its biomarker candidacy. In additional human samples, TUG1 levels were significantly downregulated in both whole blood and serum of FRDA patients compared to controls (Wilcoxon signed-rank test, p < 0.05). Regression analyses revealed a negative correlation between TUG1 levels and disease onset (p < 0.0037), and positive correlations with disease duration and Functional Disability Stage score (p < 0.04). This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases.

In summary, this study highlights Tug1 as a crucial blood-based biomarker for FRDA. Tug1’s consistent expression variance across human and mouse tissues is closely associated to disease severity and key FRDA pathways. It also correlates strongly with Fxn levels, making it a promising early, non-invasive marker. TUG1 offers potential for FRDA monitoring and therapeutic development, warranting further clinical research.
The winner’s curse under dependence: repairing empirical Bayes using convoluted densities
Authors: Hawinkel Stijn , Thas Olivier , Maere Steven
Published: September 2023

The winner’s curse is a form of selection bias that arises when estimates are obtained for a large number of features, but only a subset of most extreme estimates is reported. It occurs in large scale significance testing as well as in rank-based selection, and imperils reproducibility of findings and follow-up study design. Several methods correcting for this selection bias have been proposed, but questions remain on their susceptibility to dependence between features since theoretical analyses and comparative studies are few. We prove that estimation through Tweedie’s formula is biased in presence of strong dependence, and propose a convolution of its density estimator to restore its competitive performance, which also aids other empirical Bayes methods. Furthermore, we perform a comprehensive simulation study comparing different classes of winner’s curse correction methods for point estimates as well as confidence intervals under dependence. We find a bootstrap method by Tan et al. (2015) and empirical Bayes methods with density convolution to perform best at correcting the selection bias, although this correction generally does not improve the feature ranking. Finally, we apply the methods to a comparison of single-feature versus multi-feature prediction models in predictingBrassica napusphenotypes from gene expression data, demonstrating that the superiority of the best single-feature model may be illusory.
Life in a Central European warm-temperate to subtropical open forest: paleoecology of the rhinocerotids from Ulm-Westtangente (Aquitanian, early Miocene, Germany)
Authors: Hullot Manon , Martin Céline , Blondel Cécile , Rößner Gertrud
Published: September 2023

The locality of Ulm-Westtangente yielded the richest vertebrate fauna from the Aquitanian of Germany. Its dating to the Mammal Neogene Zone 2a, a turnover in Cenozoic climate, makes it a crucial source for the understanding of faunal, palaeoecological and palaeoenvironmental specifics of the European Aquitanian. However, if most taxa from Ulm-Westtangente have been studied, very little to nothing has been done on the large herbivores and notably on the two rhinocerotidsMesaceratherium paulhiacenseandProtaceratherium minutum. Here, we used a multi-proxy approach to investigate the paleoecology of these two species. The remains of the smaller speciesP. minutum(442 to 667 kg) are twice as abundant as those of the largerM. paulhiacense(1687 to 2576 kg), but both display a similar age structure (∼ 10 % of juveniles, 20 % of subadults and 70 % of adults), mortality curves, and mild prevalence of hypoplasia (∼ 17 %). Results from dental mesowear, microwear, and carbon isotopes indicate different feeding preferences: both were C3 feeders butM. paulhiacensehad a more abrasive diet and was probably a mixed feeder. Our study on rhinocerotids also yielded new paleoenvironmental insights, such as the mean annual temperature (15.8 °C) and precipitation (317 mm/year) suggesting rather warm and dry conditions.

Statements and Declarations

The authors have no relevant financial or non-financial interests to disclose. This study was funded by a post doctoral fellowship of the Alexander von Humboldt Foundation (Germany).
Association of homelessness and diet on the gut microbiome: A United States-Veteran Microbiome Project (US-VMP) study
Authors: Hoisington Andrew J. , Stearns-Yoder Kelly A. , Stamper Christopher E. , Holliday Ryan , Brostow Diana P. , Penzenik Molly E. , Forster Jeri E. , Postolache Teodor T. , Lowry Christopher A. , Brenner Lisa A.
Published: September 2023

Military Veterans account for 8% of homeless individuals living in the United States. To highlight associations between history of homelessness and the gut microbiome, we compared the gut microbiome of Veterans who reported having a previous experience of homelessness to those from individuals who reported never having experienced a period of homelessness. Moreover, we examined the impact of the cumulative exposure of prior and current homelessness to understand possible associations between these experiences and the gut microbiome. Microbiome samples underwent genomic sequencing and were analyzed based on alpha diversity, beta diversity, and taxonomic differences. Additionally, demographic information, dietary data, and mental health history were collected. A lifetime history of homelessness was found to be associated with alcohol use disorder, substance use disorder, and healthy eating index compared to those without such a history. In terms of differences in gut microbiota, beta diversity was significantly different between Veterans that had experienced homelessness and Veterans that had never been homeless (p= 0.047, Weighted UniFrac), while alpha diversity was similar. The microbial community differences were, in part, driven by a lower relative abundance ofAkkermansiain Veterans that had experienced homelessness (mean ± SD; 1.07 ± 3.85) compared to Veterans that had never been homeless (2.02 ± 5.36) (p= 0.014, ancom-bc2). Additional research is required to facilitate understanding regarding complex associations between homelessness, the gut microbiome, and mental and physical health conditions, with a focus on increasing understanding regarding the longitudinal impact of housing instability throughout the lifespan.

Importance

Although there are known stressors related to homelessness, as well as chronic health conditions experienced by those without stable housing, there has been limited work evaluating the associations between microbial community composition and homelessness. We analyzed, for the first time, bacterial gut microbiome associations among those with experiences of homelessness on alpha diversity, beta diversity, and taxonomic differences. Additionally, we characterized the influences of diet, demographic characteristics, military service history and mental health conditions on the microbiome of Veterans with and without any lifetime history of homelessness. Future longitudinal research to evaluate the complex relationships between homelessness, the gut microbiome, and mental health outcomes is recommended. Ultimately, differences in the gut microbiome of individuals experiencing and not experiencing homelessness could assist in identification of treatment targets to improve health outcomes.