bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional enrichment analysis of mutated genes in children with hyperthyroidism
Authors: Mao Xiaojian , Tang Liangliang , Li Hongyi , Zhang Wen , Liu Li , Wang Heyong , Headar Abdalbari 
Published: October 2023

ObjectiveHyperthyroidism in Chinese children is relatively high and has been increasing in recent years, which has a significant impact on their healthy development. Hyperthyroidism is a polygenic disorder that presents greater challenges in terms of prediction and treatment than monogenic diseases. This study aims to elucidate the associated functions and gene sets of mutated genes in children with hyperthyroidism in terms of the gene ontology through GO enrichment analysis and in terms of biological signaling pathways through KEGG enrichment analysis, thereby enhancing our understanding of the expected effects of multiple mutated genes on hyperthyroidism in children.MethodsWhole-exome sequencing was performed on the DNA samples of children with hyperthyroidism. Screening for pathogenic genes related to hyperthyroidism in affected children was performed using the publicly available disease databases Malacards, MutationView, and Clinvar, and the functions and influences of the identified pathogenic genes were analyzed using statistical analysis and the gene enrichment approach.ResultsThrough GO enrichment analysis, it was found that the most significant gene ontology enrichment was the function “hormone activity” in terms of gene ontology molecular function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included TG, CALCA, POMC, CGA, PTH, GHRL, FBN1, TRH, PRL, LEP, ADIPOQ, INS, GH1. The second most significant gene ontology enrichment was the function “response to peptide hormone” in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included LRP6, TSC2, KANK1, COL1A1, CDKN1B, POMC, STAT1, MEN1, APC, GHRL, TSHR, GJB2, FBN1, GPT, LEP, ADIPOQ, INS, GH1. Through KEGG enrichment analysis, it was found that the most significant biological signaling pathway enrichment was the pathway “Thyroid hormone signaling pathway” function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included NOTCH3, MYH7, TSC2, STAT1, MED13L, MAP2K2, SLCO1C1, SLC16A2, and THRB. The second most significant biological signaling pathway enrichment was the pathway “Hypertrophic cardiomyopathy” in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included IGF1, CACNA1S, MYH7, IL6, TTN, CACNB2, LAMA2, and DMD.ConclusionThe mutated genes in children with hyperthyroidism were closely linked to function involved in “hormone activity” and “response to peptide hormone” in terms of the biological signaling pathway, and to the functional pathways involved in “Thyroid hormone signaling pathway” and “Hypertrophic cardiomyopathy” in terms of the biological signaling pathway.
Role of anthropometric indices as a screening tool for predicting metabolic syndrome among apparently healthy individuals of Karachi, Pakistan
Authors: Adil Syed Omair , Musa Kamarul Imran , Uddin Fareed , Shafique Kashif , Khan Asima , Islam Md Asiful 
Published: October 2023

IntroductionAnthropometric indices are affordable and non-invasive methods for screening metabolic syndrome (MetS). However, determining the most effective index for screening can be challenging.ObjectiveTo investigate the accuracy of anthropometric indices as a screening tool for predicting MetS among apparently healthy individuals in Karachi, Pakistan.MethodsA community-based cross-sectional survey was conducted in Karachi, Pakistan, from February 2022 to August 2022. A total of 1,065 apparently healthy individuals aged 25 years and above were included. MetS was diagnosed using International Diabetes Federation guidelines. Anthropometric indices were defined based on body mass index (BMI), neck circumference (NC), mid-upper arm circumference (MUAC), waist circumference (WC), waist to height ratio (WHtR), conicity index, reciprocal ponderal index (RPI), body shape index (BSI), and visceral adiposity index (VAI). The analysis involved the utilization of Pearson’s correlation test and independent t-test to examine inferential statistics. The receiver operating characteristic (ROC) analysis was also applied to evaluate the predictive capacities of various anthropometric indices regarding metabolic risk factors. Moreover, the area under the curve (AUC) was computed, and the chosen anthropometric indices’ optimal cutoff values were determined.ResultsAll anthropometric indices, except for RPI in males and BSI in females, were significantly higher in MetS than those without MetS. VAI [AUC 0.820 (95% CI 0.78–0.86)], WC [AUC 0.751 (95% CI 0.72–0.79)], WHtR [AUC 0.732 (95% CI 0.69–0.77)], and BMI [AUC 0.708 (95% CI 0.66–0.75)] had significantly higher AUC for predicting MetS in males, whereas VAI [AUC 0.693 (95% CI 0.64–0.75)], WHtR [AUC 0.649 (95% CI 0.59–0.70)], WC [AUC 0.646 (95% CI 0.59–0.61)], BMI [AUC 0.641 (95% CI 0.59–0.69)], and MUAC [AUC 0.626 (95% CI 0.57–0.68)] had significantly higher AUC for predicting MetS in females. The AUC of NC for males was 0.656 (95% CI 0.61–0.70), while that for females was 0.580 (95% CI 0.52–0.64). The optimal cutoff points for all anthropometric indices exhibited a high degree of sensitivity and specificity in predicting the onset of MetS.ConclusionBMI, WC, WHtR, and VAI were the most important anthropometric predictors for MetS in apparently healthy individuals of Pakistan, while BSI was found to be the weakest indicator.
Modulating β-catenin/BCL9 interaction with cell-membrane-camouflaged carnosic acid to inhibit Wnt pathway and enhance tumor immune response
Authors: Gao Ruqing , Zheng Xiaoqiang , Jiang Aimin , He Wangxiao , Liu Tianya 
Published: October 2023

IntroductionLung adenocarcinoma (LUAD) therapies are plagued by insufficient immune infiltration and suboptimal immune responses in patients, which are closely associated with the hyperactive Wnt/β-catenin pathway. Suppressing this signaling holds considerable promise as a potential tumor therapy for LUAD, but Wnt suppressor development is hindered by concerns regarding toxicity and adverse effects due to insufficient targeting of tumors.MethodsWe have synthesized a tumor-specific biomimetic Wnt pathway suppressor, namely CM-CA, by encapsulating carnosic acid within Lewis lung carcinoma (LLC) cell membranes. It possesses nano-size, allowing for a straightforward preparation process, and exhibits the ability to selectively target the Wnt/β-catenin pathway in lung adenocarcinoma cells. To evaluate its in vivo efficacy, we utilized the LLC Lewis homograft model, and further validated its mechanism of action through immunohistochemistry staining and transcriptome sequencing analyses.ResultsThe findings from the animal experiments demonstrated that CM-CA effectively suppressed the Wnt/β-catenin signaling pathway and impeded cellular proliferation, leading to notable tumor growth inhibition in a biologically benign manner. Transcriptome sequencing analyses revealed that CM-CA promoted T cell infiltration and bolstered the immune response within tumor tissues.ConclusionThe utilization of CM-CA presents a novel and auspicious approach to achieve tumor suppression and augment the therapeutic response rate in LUAD, while also offering a strategy for the development of Wnt/β-catenin inhibitors with biosafety profile.
Immunogenicity and effectiveness of COVID-19 booster vaccination among people living with HIV: a systematic review and meta-analysis
Authors: Cheng Meng-Qun , Li Rong , Weng Zhi-Ying , Song Gao 
Published: October 2023

BackgroundThe effect of booster vaccinations with the coronavirus virus disease (COVID-19) vaccine on people living with HIV (PLWH) remains unknown. In this study, we aimed to investigate the immunogenicity and effectiveness of booster doses of the COVID-19 vaccine in PLWH.MethodsLiterature research was done through the PubMed, Embase, Cochrane Review, and Web of Science databases up to 4 July 2023. Pooled estimates were calculated and compared using the DerSimonian and Laird method for a random effects model. Randomized control trials and observational studies were both considered for inclusion.ResultsWe included 35 eligible studies covering 30,154 PLWH. The pooled immune response rate (IRR) of PLWH after the COVID-19 booster vaccination was 97.25% (95% confidence interval [CI], 93.81–99.49), and similar to healthy control (HC) (risk ratio [RR] = 0.98, 95% CI, 0.96–1.00). The pooled IRR for PLWH with CD4+ T-cell counts ≤ 200 was 86.27 (95% CI, 65.35–99.07). For Omicron variants, the pooled IRR for PLWH after booster dose was 74.07% (95% CI, 58.83–89.30), and the risk of IRR was reduced by 10% in PLWH compared with HC (RR = 0.90, 95% CI, 0.80–1.00). The T-cell immune response of PLWH was found to be comparable to HC (p ≥ 0.05). Subgroup analyses revealed that mRNA vaccines produced a relatively high IRR in PLWH compared to other vaccines. In addition, the results showed that booster vaccination appeared to further reduce the risk of COVID-19-related infections, hospitalizations, and deaths compared with the primary vaccination.ConclusionIt was shown that booster vaccination with the COVID-19 vaccine provided a high IRR in PLWH and still produced a desirable moderate IRR in PLWH with a CD4+ T-cell count of ≤ 200. Importantly, the humoral and T-cell responses to booster vaccination in PLWH were comparable to HC, and similar results were observed with the SARS-CoV-2 Omicron variant. Our review strongly emphasizes the effect of mRNA vaccine booster vaccination in PLWH on eliciting desirable protective IRR. Furthermore, booster vaccination appears to further reduce the risk of COVID-19 infection, hospitalization, and death in PLWH compared to primary vaccination. However, more evidence is needed to confirm its effectiveness.
Awareness and knowledge of female genital schistosomiasis in a population with high endemicity: a cross-sectional study in Madagascar
Authors: Rausche Pia , Rakotoarivelo Rivo Andry , Rakotozandrindrainy Raphael , Rakotomalala Rivo Solotiana , Ratefiarisoa Sonya , Rasamoelina Tahinamandranto , Kutz Jean-Marc , Jaeger Anna , Hoeppner Yannick , Lorenz Eva , May Jürgen , Puradiredja Dewi Ismajani , Fusco Daniela 
Published: October 2023

IntroductionFemale genital schistosomiasis (FGS) is a neglected disease with long-term physical and psychosocial consequences, affecting approximately 50 million women worldwide and generally representing an unmet medical need on a global scale. FGS is the chronic manifestation of a persistent infection with Schistosoma haematobium. FGS services are not routinely offered in endemic settings with a small percentage of women at risk receiving adequate care. Madagascar has over 60% prevalence of FGS and no guidelines for the management of the disease. This study aimed to determine FGS knowledge among women and health care workers (HCWs) in a highly endemic area of Madagascar.MethodsA convenience sampling strategy was used for this cross-sectional study. Descriptive statistics including proportions and 95% confidence intervals (CI) were calculated, reporting socio-demographic characteristics of the population. Knowledge sources were evaluated descriptively. Binary Poisson regression with robust standard errors was performed; crude (CPR) and adjusted prevalence ratio (APR) with 95% CIs were calculated.ResultsA total of 783 participants were included in the study. Among women, 11.3% (n = 78) were aware of FGS while among the HCWs 53.8% (n = 50) were aware of FGS. The highest level of knowledge was observed among women in an urban setting [24%, (n = 31)] and among those with a university education/vocational training [23% (n = 13)]. A lower APR of FGS knowledge was observed in peri-urban [APR 0.25 (95% CI: 0.15; 0.45)] and rural [APR 0.37 (95% CI 0.22; 0.63)] settings in comparison to the urban setting. Most HCWs reported other HCWs [40% (n = 20)] while women mainly reported their family [32% (n = 25)] as being their main source of information in the 6 months prior to the survey.Discussion and conclusionsOur study shows limited awareness and knowledge of FGS among population groups in the highly endemic Boeny region of Madagascar. With this study we contribute to identifying an important health gap in Madagascar, which relates to a disease that can silently affect millions of women worldwide. In alignment with the targets of the NTD roadmap, addressing schistosomiasis requires a paradigm shift for its control and management including a greater focus on chronic forms of the disease.
Differential effects on TDP-43, piezo-2, tight-junction proteins in various brain regions following repetitive low-intensity blast overpressure
Authors: Heyburn Lanier , Dahal Shataakshi , Abutarboush Rania , Reed Eileen , Urioste Rodrigo , Batuure Andrew , Wilder Donna , Ahlers Stephen T. , Long Joseph B. , Sajja Venkatasivasai Sujith 
Published: October 2023

IntroductionMild traumatic brain injury (mTBI) caused by repetitive low-intensity blast overpressure (relBOP) in military personnel exposed to breaching and heavy weapons is often unrecognized and is understudied. Exposure to relBOP poses the risk of developing abnormal behavioral and psychological changes such as altered cognitive function, anxiety, and depression, all of which can severely compromise the quality of the life of the affected individual. Due to the structural and anatomical heterogeneity of the brain, understanding the potentially varied effects of relBOP in different regions of the brain could lend insights into the risks from exposures.MethodsIn this study, using a rodent model of relBOP and western blotting for protein expression we showed the differential expression of various neuropathological proteins like TDP-43, tight junction proteins (claudin-5, occludin, and glial fibrillary acidic protein (GFAP)) and a mechanosensitive protein (piezo-2) in different regions of the brain at different intensities and frequency of blast.ResultsOur key results include (i) significant increase in claudin-5 after 1x blast of 6.5 psi in all three regions and no definitive pattern with higher number of blasts, (ii) significant increase in piezo-2 at 1x followed by significant decrease after multiple blasts in the cortex, (iii) significant increase in piezo-2 with increasing number of blasts in frontal cortex and mixed pattern of expression in hippocampus and (iv) mixed pattern of TDP-3 and GFAP expression in all the regions of brain.DiscussionThese results suggest that there are not definitive patterns of changes in these marker proteins with increase in intensity and/or frequency of blast exposure in any particular region; the changes in expression of these proteins are different among the regions. We also found that the orientation of blast exposure (e.g. front vs. side exposure) affects the altered expression of these proteins.
Not all bad decisions are alike: approach and avoidant bad decisions are associated with distinct network organization
Authors: Lyons Siraj , Depue Brendan Eliot 
Published: October 2023

IntroductionDecisions under ambiguity occurs daily for everyone. Subsequently, we all deliberate upon options to initiate an action most appropriate for current goal demands. Researchers has attempted to identify factors which contribute to risk taking, alongside the neurocircuitry underpinning it. Empirically, uncertain decision making is frequently assessed using the Iowa Gambling Task (IGT). Research have reliably identified varying regions implicating two broader circuits known as the reward and salience networks. However, considerable work has focused on contrasting “good” versus “bad” decisions.MethodsThe present investigation attempted a unique approach to analyzing the modified IGT acquired during fMRI (n = 24) and focused on active and passive bad decisions to identify potential internetwork connectivity, dissociable connectivity patterns between approach and avoidant bad decisions, and their relationship with personality traits, which can be linked with behavioral approach styles.ResultsNetwork cluster analyses revealed general internetwork connectivity when passing (avoiding) good decks; however, the OFC was functionally disconnected from the rest of the selected brain regions when playing (approaching) bad decks. Decreased reward responsiveness was linked to increased functional connectivity between the lateral OFC and aSMG, while drive was associated with increased functional connectivity between dACC and aINS.DiscussionWe report evidence that approach and avoidant bad decisions are associated with distinct neural communication patterns. Avoidant decisions were marked by substantial network integration and coherence, contrasted with the general scarcity of internetwork communication observed for approach decisions. Furthermore, the present investigation observed preliminary evidence of personality traits linked with neural communication between salience and reward evaluative networks.
Alteration of static and dynamic intrinsic brain activity induced by short-term spinal cord stimulation in postherpetic neuralgia patients
Authors: Bu Chunxiao , Ren Huan , Lv Qingqing , Bu Huilian , Gao Xinyu , Zheng Ruiping , Huang Huiyu , Wang Weijian , Wei Yarui , Cheng Jingliang , Zhang Yong 
Published: October 2023

IntroductionShort-term spinal cord stimulation (stSCS) is an effective treatment for postherpetic neuralgia (PHN). However, how exactly stSCS affects time-dynamic intrinsic brain activity in PHN patients is not clear. The purpose of this study was to examine the static and dynamic variability of neural activity in PHN patients after stSCS.MethodsIn this study, 10 patients with PHN underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline and after SCS. The amplitude of low-frequency fluctuations (ALFF) and dynamic ALFF (dALFF) were used to investigate the static and dynamic variability of neural activity in PHN patients after stSCS. We additionally examined the associations between clinical parameters and functional changes in the brain.ResultsThere was a significant increase in dALFF in the left precuneus and right superior parietal gyrus, and a decrease in dALFF in the left inferior temporal gyrus, right gyrus rectus, left superior temporal gyrus, right orbitofrontal cortex, and left orbitofrontal cortex. There was significantly increased ALFF in the right inferior temporal gyrus, and decreased ALFF in the right lingual gyrus, left superior parietal gyrus, right superior parietal gyrus, and left precuneus. Furthermore, Pittsburgh sleep quality index scores were positively associated with dALFF changes in the left superior temporal gyrus and left orbitofrontal cortex. Hospital anxiety and depression scale scores and continuous pain scores exhibited significant negative correlation with dALFF changes in the right superior parietal gyrus.ConclusionThis study indicated that stSCS is able to cause dALFF changes in PHN patients, thus stSCS might alter brain functions to relieve pain, sleep, and mood symptoms. The findings provide new insights into the mechanisms of stSCS efficacy in the treatment of patients with PHN.
Weight stigma and fat phobia in Poland – attitudes towards people living with obesity and the level of knowledge about obesity among the social media internet respondents and medical professionals
Authors: Świder Karolina , Baska Alicja , Babicki Mateusz , Mastalerz-Migas Agnieszka , Kłoda Karolina 
Published: October 2023

IntroductionObesity often subjects individuals to stigmatization, impacting self-esteem, contributing to depression, social isolation, and even exacerbating weight gain. Our research aimed to evaluate weight stigma, fat phobia, their expressions, and obesity-related knowledge among social media internet respondents and medical practitioners in Poland.MethodsConducted through Computer-Assisted Web Interview (CAWI), our study employed the Fat Phobia Scale (FPS) and tailored questions, analyzing 1705 questionnaires.ResultsThe respondents averaged a score of 3.60  ±  0.62 on the FPS. Interestingly, men exhibited higher stigma levels than women. Variables like BMI, residency, and interactions with people having obesity did not significantly impact stigma levels. Approximately 74.0% of respondents found individuals with obesity less attractive than those with normal weight, while 32.2% identified obesity as a cause of shame. Only 69.1% were aware of the BMI-based obesity diagnosis criterion.ConclusionGiven limited knowledge of Poland’s weight stigma landscape, our research yields crucial insights for shaping social campaigns and enhancing educational initiatives in obesity management for healthcare professionals. Further studies will be instrumental in addressing patient and practitioner needs effectively.
Mathematical modeling of radiotherapy: impact of model selection on estimating minimum radiation dose for tumor control
Authors: Kutuva Achyudhan R. , Caudell Jimmy J. , Yamoah Kosj , Enderling Heiko , Zahid Mohammad U. 
Published: October 2023

IntroductionRadiation therapy (RT) is one of the most common anticancer therapies. Yet, current radiation oncology practice does not adapt RT dose for individual patients, despite wide interpatient variability in radiosensitivity and accompanying treatment response. We have previously shown that mechanistic mathematical modeling of tumor volume dynamics can simulate volumetric response to RT for individual patients and estimation personalized RT dose for optimal tumor volume reduction. However, understanding the implications of the choice of the underlying RT response model is critical when calculating personalized RT dose.MethodsIn this study, we evaluate the mathematical implications and biological effects of 2 models of RT response on dose personalization: (1) cytotoxicity to cancer cells that lead to direct tumor volume reduction (DVR) and (2) radiation responses to the tumor microenvironment that lead to tumor carrying capacity reduction (CCR) and subsequent tumor shrinkage. Tumor growth was simulated as logistic growth with pre-treatment dynamics being described in the proliferation saturation index (PSI). The effect of RT was simulated according to each respective model for a standard schedule of fractionated RT with 2 Gy weekday fractions. Parameter sweeps were evaluated for the intrinsic tumor growth rate and the radiosensitivity parameter for both models to observe the qualitative impact of each model parameter. We then calculated the minimum RT dose required for locoregional tumor control (LRC) across all combinations of the full range of radiosensitvity and proliferation saturation values. ResultsBoth models estimate that patients with higher radiosensitivity will require a lower RT dose to achieve LRC. However, the two models make opposite estimates on the impact of PSI on the minimum RT dose for LRC: the DVR model estimates that tumors with higher PSI values will require a higher RT dose to achieve LRC, while the CCR model estimates that higher PSI values will require a lower RT dose to achieve LRC.DiscussionUltimately, these results show the importance of understanding which model best describes tumor growth and treatment response in a particular setting, before using any such model to make estimates for personalized treatment recommendations.