bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Wnt/β-catenin pathway maintains homeostasis of amniocytes in Down syndrome
Authors: Chen Xiaoying , Lin Miaochun , Chen Shan , Wang Zhengsen , Li Zhaohui , Zuo Juan 
Published: June 2024

Abstract

Background Down syndrome (DS), which is caused by partial or complete triplication of chromosome 21, may cause a range of clinical features. Although most fetuses with DS exhibit typical characteristics, the molecular pathogenesis underlying DS remains unclear. Wnt signaling is known to play a crucial role in fetal growth and development. However, the link between Wnt signaling and the abnormal development of fetuses with DS remains poorly understood. In this study, our objective was to investigate the dysregulation of Wnt signaling in the amniocytes of fetuses diagnosed with DS. To this end, we determined β-catenin protein expression, oxidative stress, cell proliferation, and apoptosis in amniocytes from fetuses diagnosed with DS. Subsequently, we upregulated the Wnt/β-catenin pathway components in amniocytes from fetuses diagnosed with DS and detected the expression of related proteins. Results We found that downregulating the Wnt/β-catenin pathway components decreased cell proliferation while increasing oxidative stress and apoptosis in the amniocytes derived from fetuses diagnosed with DS compared with those seen in normal fetal amniocytes. In contrast, upregulating the Wnt/β-catenin pathway components in DS amniocytes increased cell proliferation and decreased oxidative stress and apoptosis, resulting in improved cell growth. Conclusions The Wnt/β-catenin pathway may maintain homeostasis in DS amniocytes and normalize cell growth to levels similar to those in normal cells. These findings reveal a novel molecular mechanism underlying the abnormal regulation of Wnt/β-catenin signaling during the development of fetuses with DS, thereby suggesting potential targeted therapies for DS.
Assessment of heatwave vulnerability index and its spatial distribution over Uttar Pradesh, India
Authors: Pandey Shashank , Singh Asit , Singh Amarendra , Patel Prabhat Kumar 
Published: June 2024

Abstract

The recurring extreme events are garnering a lot of attention these days, understanding heatwave vulnerability has been a hot topic among researchers due to its parameters which solely depend upon the local climate, socio-economic conditions, physiological conditions, and also on its local environmental conditions. This study looks into the spatial distribution of heatwave vulnerability over the Uttar Pradesh (UP) region divided into 75 districts. An index has been developed called the Heatwave Vulnerability Index (HVI) employing three variables namely Exposure, Sensitivity, and Adaptive capacity. In these variables, various environmental and socio-economic factors were considered. Spatial distribution for Land Surface Temperature (LST) and Normalized difference vegetation index (NDVI) have also been analyzed in this study. Furthermore, this study evaluated that a total of 11 districts have been found to be in the extremely vulnerable category. Uttar Pradesh is the most populous state in the country, and this study can provide valuable insights into planning various mitigation strategies and formulating various policies for coping with heat waves.
Treatment of E-Cigarette Use Among Hospitalized Adolescents and Young Adults: A protocol for intervention development and evaluation of preliminary efficacy and implementation outcomes in a randomized controlled trial
Authors: Wooten Shelbie , Catley Delwyn , Miller Melissa , Wilson Karen , Richter Kimber , Masonbrink Abbey R. 
Published: June 2024

Abstract

Background
Pediatric hospitalization represents a valuable opportunity to identify and treat e-cigarette use among adolescents and young adults (AYAs). Knowledge on how best to provide this care is lacking. We aim to fill this gap by developing an e-cigarette use intervention and evaluating preliminary efficacy and implementation outcomes among hospitalized AYAs.
Methods
We will enroll 144 AYAs (14-21 years) admitted to a pediatric hospital who report past 30-day e-cigarette use and randomize 2:1 to intervention or control arms. We will develop and iteratively refine an evidence-based intervention that includes education, motivational interviewing, and quit planning by a health educator trained in tobacco and e-cigarette cessation and nicotine replacement therapy prescription if indicated. Control arm participants will receive brief advice and a quit program resource handout. We will assess demographics, e-cigarette use behaviors, nicotine dependence, motivation and confidence to quit using a self-report survey at baseline and post-intervention. Our primary outcome is self-reported 30-day point prevalence e-cigarette abstinence at 3-month follow-up. Our secondary implementation outcomes are feasibility (intervention duration, interruptions), acceptability (Likert scale items, participant enrollment, intervention completion rates) and fidelity (review and fidelity scoring of intervention audio-recordings). We will use a generalized linear model assuming an underlying binomial distribution and logit link function to assess our primary outcome (past 30-day abstinence). Motivation and confidence to quit will be analyzed using a repeated measures analysis of variance. Chi-square (categorical variables) and Wilcoxon Rank Sum (continuous variables) tests will be used to assess for differences between groups.
Discussion
Given the increasing prevalence of e-cigarette use and related adverse health outcomes, proven e-cigarette use interventions for youth are critically needed. Our study will be among the first to develop and evaluate an e-cigarette use intervention for youth in the pediatric hospital. We will assess preliminary efficacy (i.e., e-cigarette abstinence at 3 month follow-up) and secondary implementation outcomes (i.e., feasibility, acceptability, fidelity). These findings will inform a larger randomized controlled trial to further assess efficacy and implementation with the potential to reach a population at increased risk for poor outcomes.
Trial Registration NCT05936099; registered on June 30th, 2023
Prevalence of accessory mental foramen and lateral lingual foramen using cone beam computed tomography: A single-center cross-sectional study.
Authors: Mostafavi Maryam , Zarch Seyed Hosein Hoseini , Eshghpour Majid , Khodadadzadeh Pedram 
Published: June 2024

Abstract

Purpose
This study aimed to assess the prevalence, dimensions, and positions of AMF and LLF in an Iranian population using CBCT imaging.
Methods and materials:
In this cross-sectional study, CBCT images of 2082 patients were retrospectively reviewed based on inclusion criteria, including images from the mandibular region taken in the past five years with accurate demographic data. Exclusion criteria included images with significant pathologies, fractures, or poor quality. CBCT images were captured, and AMF and LLF presence, dimensions, and positions were recorded relative to the mental foramen and adjacent teeth. Data analysis was performed using the Chi-square test with a 5% significance level.
Results
A total of 2082 CBCT samples (46.54% females and 53.46% males) with a mean age of 48.30 ± 12.7 years were examined. Among these, 246 AMFs were observed in 222 individuals, with 24 having two AMFs. AMF was mostly observed unilaterally, with bilateral occurrence noted in 10.81% of patients with AMF. There were no significant differences between genders in AMF and LLF prevalence. Additionally, 68 patients were found to have lateral lingual foramina (LLFs).
Conclusion
AMF and LLF were detectable using CBCT, with a prevalence of 11.81% for AMF and 5.91% for LLF in the selected Iranian population. AMF was commonly situated posterior and superior to the mental foramen, while LLF was often found near the first premolar. This knowledge is crucial for preventing nerve injury during surgery and ensuring effective nerve block procedures.
Single cell multiomic analyses reveal divergent effects of DNMT3A and TET2 mutant clonal hematopoiesis in inflammatory response
Authors: Mohammed Wazim Ismail , Fernandez Jenna , Binder Moritz , Lasho Terra , Kim Minsuk , Geyer Susan , Mazzone Amelia , Finke Christy , Mangaonkar Abhishek , Lee Jeong-Heon , Wang Liguo , Kim Kwan Hyun , Simon Vernadette , Rohakthar Fariborz Rakhshan , Munankarmy Amik , Byeon Seul Kee , Schwager Susan , Harrington Jonathan , Snyder Melissa , Robertson Keith , Pandey Akhilesh , Wieben Eric , Chia Nicholas , Gaspar-Maia Alexandre , Patnaik Mrinal 
Published: June 2024

Abstract

Background
DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposing epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematological neoplasms. While individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated.
Results
Here we make use of a natural inflammatory response occurring during coronavirus disease 2019 (COVID-19), to understand the association of these mutations with inflammatory morbidity and mortality. We demonstrate the age-independent, negative impact of DNMT3A mutant CH on COVID-19-related cytokine release severity and mortality. Using single cell proteogenomics we show that DNMT3A mutations involve myeloid and lymphoid cells. Using single cell multiomics sequencing, we identify cell-specific gene expression changes associated with DNMT3A mutations, along with significant epigenomic deregulation affecting enhancer accessibility, resulting in overexpression of IL32, a proinflammatory cytokine that can result in inflammasome activation in monocytes and macrophages. Finally, we show with single cell resolution that the loss of function of DNMT3A is directly associated with increased chromatin accessibility in mutant cells.
Conclusions
We demonstrate the negative prognostic impact of DNMT3Amt CH on COVID-19 related inflammatory morbidity and mortality. DNMT3Amt CH involves myeloid and lymphoid cells and in the context of COVID-19, was associated with inflammatory transcriptional priming, resulting in overexpression of IL32. This overexpression was secondary to increased chromatic accessibility, specific to DNMT3Amt CH cells. DNMT3Amt CH can serve as a potential biomarker for adverse inflammatory outcomes.
Anti-SARS-CoV-2 activity of steroids from traditional Chinese medicines in vitro
Authors: Yang Shiwei , Hu Xinming , Zheng Bin , Zhang Jifeng , Wang Xiaohong , Bi Wenjie , Zhu Jinmiao 
Published: June 2024

Abstract

Five steroids isolated from extracts of the skin of the herbal medicine toad, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), and bufotalin (BFTi), were subjected to molecular docking calculations with the SARS-CoV-2 main protease (PDB 6LU7 and 7BTF). The results showed that the binding energy of ABFi to the 3CL protein was − 17.044 kcal/mol, which was greater than that of CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was − 23.250 kcal/mol, which was much lower than that of CBFi and TBFi, and that of EVEN was lower than that of ABFi to the 3CL protein. ABFi more stably bound to the substrate NTP binding pocket of RNA synthesized by the RdRp protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of the RdRp enzyme. BetaCoVIJS02/human/2019 strains of SARS-CoV-2 and Vero-E6 cells were used to inhibit cell proliferation in vitro. The results revealed that ABFi had a moderate inhibitory effect on the proliferation of SARS-CoV-2 cells in vitro, with an inhibition rate of 61.12%, which was even weaker than that of remdesivir.
Imbalance of fetal growth factor levels in congenital heart disease pathology: a systematic review to investigate therapeutic potential
Authors: Ghandi Yazdan , Shahvari Samira Zakeri , Ahmadian Negar Poor , Soltani Mahbod , Musavi Seyed Amir Hossein , Satarzadeh Mohammad 
Published: June 2024

Abstract

Background
Vascular endothelial growth factor (VEGF) is a factor that is responsible for cell proliferation, vascular endothelial cell growth, and angiogenesis. Changes in the level of this factor are associated with the pathology of structural disorders such as CHD. This systematic study assessed previous studies to determine the therapeutic potential of VEGF in congenital heart disorders.
Method
This systematic review was written based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and the principle of nonbias was respected. All the articles from 2014–2024 were extracted from the Web of Science, PubMed and Scopus databases. We investigated the role of VEGF in the pathology of cardiovascular structural disorders, the therapeutic and diagnostic effects of VEGF and related factors that are influenced by this factor.
Results
The studies were assessed based on PRISMA search steps, and 22 were included in our study. Any disturbance in the production and function of VEGF is known as a genetic disorder in TOF. VEGF caused abnormal elongation of the heart tubes, as well as disproportionate growth of cardiovascular tissue just before full formation. An increase in HIF with increasing VEGF function precedes fetal heart development. HIF also mediates endothelial formation through eNOS. HIF in children with CCHD and ACHD was significantly greater than that in the control group, and its value was greater in complex CHD children than in the other groups. EGFR, iNOS and ET-1 were more abundant in ACHD than in ACHD, and their levels were positively correlated with HIF.
Conclusion
An increase in the levels of VEGF and HIF before the completion of CHD pathology is the main cause of CHD pathology, and after the completion of CHD pathology, these factors help in the regeneration of heart tissue. The regulation of VEGF and HIF levels during the fetal period is highly important for the diagnosis and treatment of CHD.
CXCL7 plays a crucial role in facilitating extramedullary invasion and osteolytic damage in multiple myeloma
Authors: Liu Peng , Wang Yue , Lan Tianwei , Zhou Chi 
Published: June 2024

Abstract

The primary distinction between multiple myeloma (MM) and its precursor conditions lies in the deterioration of the biological behavior of tumor cells. In MM, a type of mature B-cell tumor, chemokines may serve as pivotal regulatory genes. Through exploration of GEO database and single-cell RNA-seq data from our laboratory, we have identified chemokines CXCL7 as a potential key regulator of the cellular biological behavior in MM. Subsets of MM cells with high CXCL7 exhibit heightened malignant potential. Elevated CXCL7 is associated with extramedullary invasion and pathological fractures in patients. In vitro, CXCL7 promoted the proliferation, invasion and migration of MM cells. Leveraging the homing ability of plasma cell, we established a mouse xenograft tumor model through vein injection of a CXCL7-overexpressing cell line. We found that MM cells with elevated CXCL7 exhibited enhanced engraftment in bone marrow, induced extramedullary lesions and increased susceptibility to leg fractures. Through exploration of intracellular signaling pathways and subsequent experiments, we observed that CXCL7 can modulate the biological behavior of MM cells by activating the IL-2-STAT5 pathway in the absence of exogenous IL-2. Our findings provide new insights into understanding the pathogenesis mechanisms underlying MM, suggesting that targeting CXCL7 may offer promising therapeutic opportunities.
The Preparation of a novel moisture-curing silicone conformal coating
Authors: Pan Zhaoqun , Zhong Min , Lin Liangwei 
Published: June 2024

Abstract

In this research, high molecular weight hydroxyl-terminated polydimethylsiloxane (PDMS-OH) was successfully synthesized through a hydroxyl condensation reaction. The optimal reaction conditions included a temperature of 110°C, a reaction time of 4 hours, and a catalyst TMAH amount of 0.08 phr. The structure of PDMS-OH was characterized using nuclear magnetic resonance (1H-NMR) spectroscopy. Subsequently, the PDMS-OH was end-capped with methyl orthosilicate (TMOS) to produce PDMS-TMOS, with a capping agent to hydroxyl group molar ratio of 2:1. The structural analysis of PDMS-TMOS was conducted using Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The surface drying time for the moisture-curing coating of PDMS-TMOS was found to be 2 hours at room temperature and 25 minutes at 80 ℃, respectively. The addition of MQ resins to the conformal coatings resulted in a tensile strength of 0.0742 MPa and an elongation at break of 212.7% for the formed film. The coating offers advantages such as a straightforward synthesis process, cost-effectiveness, and high reproducibility, thereby potentially broadening its industrial applications.
Eculizumab as first line treatment for patients with severe presentation of Complement Factor H antibodies mediated Hemolytic Uremic Syndrome
Authors: Coccia Paula Alejandra , Alconcher Laura Fernanda , Ferraris Veronica , Lucarelli Lucas Ivan , Grillo Maria Agostina , Arias Andrea , Saurit Mariana , Ratto Viviana Marcela , Raddavero Caludia Andrea , Santos Celia Dos , Lucero Analía Sanchez 
Published: June 2024

Abstract

Background: Complement Factor H (CFH) antibodies mediated Hemolytic Uremic Syndrome (HUS) has varying prevalence globally. Plasmapheresis and Immunosuppressive drugs are the standard treatment. Recently, Eculizumab has been reported as an effective alternative. The aim of this study is to report four children with CFH antibodies mediated HUS managed with Eculizumab plus immunosuppression as first line therapy.Methods: A retrospective chart review was conducted for children aged ≤ 18 years old with complement-mediated HUS in two referral centers. Patients with CFH antibodies mediated HUS treated with Eculizumab as first-line therapy were included.Results: Four children (aged 6–11 years old) were included. Dialysis was necessary in three patients. Eculizumab was administered 5–23 days after onset. None of them received plasmapheresis. Prednisone and mycophenolate mofetil were added after receiving positive CFH antibody results. Hematological signs and kidney function improved after the second Eculizumab dose. Eculizumab was discontinued in three patients after six months. One patient required rituximab due to persistent high CFH antibody titers, discontinuation of Eculizumab occurred after 15 months without recurrence. No treatment-related complications were observed. During a mean 12-month follow-up (range 6–24 months), no relapses were recorded and all patients ended with normal GFR.Conclusion Our data suggest that a short course of 6 months of C5 inhibitor might be sufficient to reverse TMA symptoms and improve kidney function in severe patients with CFH antibody mediated HUS. Simultaneously, adding immunosuppressive agents might reduce the risk of relapse and allow cessation of C5 inhibition in a shorter period of time.
Evaluation of alternative prognostic thresholds for SP142 and 22C3 immunohistochemical PD-L1 expression in triple-negative breast cancer: results from a population-based cohort
Authors: Sigurjonsdottir Gudbjörg , De Marchi Tommaso , Ehinger Anna , Hartman Johan , Ullén Susann , Leandersson Karin , Bosch Ana , Staaf Johan , Killander Fredrika , Niméus Emma 
Published: June 2024

Abstract

Background
Immune checkpoint inhibitors are now a part of the treatment arsenal for triple-negative breast cancer (TNBC) but refinement of PD-L1 as a prognostic and predictive biomarker is a clinical priority. We aimed to evaluate the relevance of novel PD-L1 immunohistochemical (IHC) thresholds in TNBC with regards to PD-L1 gene expression, prognostic value, tumor infiltrating lymphocytes (TILs) and TNBC molecular subtypes.
Material & Methods
We evaluated PD-L1 on a tissue microarray with the SP142 (immune cell (IC) score) and the 22C3 (combined positive score; CPS) IHC assays and evaluated abundance of TILs in a population-based cohort of 237 early-stage TNBC patients. Survival analysis was performed and RNA sequencing data employed for molecular profiling.
Results
As expected, PD-L1 positivity (IC ≥1% and/or CPS ≥1) was significantly associated with better prognosis compared to zero PD-L1 expression. Importantly however, also patients with intermediate expression (IC >0%, <1%; CPS >0, <1) showed a trend towards improved outcome. Tumors with intermediate PD-L1 IHC expression also had intermediate PD-L1 (CD274) gene expression (mRNA). Patients that were both low in TILs (<30%) and PD-L1 (IC <1%; CPS <1), tended to have the poorest prognosis.
PD-L1 positive tumors clustered significantly more often as Immunomodulatory-high and Basal-Like 1-high TNBC molecular subtypes and were enriched in immune response and cell cycle/proliferation signaling pathways. PD-L1-zero tumors on the other hand were enriched in cell growth, differentiation and metastatic potential pathways and clustered more prevalently as Luminal-Androgen-Receptor-high and Mesenchymal-high. PD-L1-intermediate tumors categorized with neither PD-L1-positive nor PD-L1-zero tumors on the hierarchical clustering level, consigning them as a unique subgroup.
Conclusion
With both SP142 and 22C3, we identified an intermediate IHC PD-L1 group within TNBCs that was supported on the molecular level. Any PD-L1 IHC expression, even though it is <1, tended to have positive prognostic impact. We suggest that the generally accepted threshold of PD-L1 IHC positivity in TNBC should be investigated further.
Trial Registration The Swedish Cancerome Analysis Network – Breast (SCAN-B) study was retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.
A rare cause of echogenic kidneys with oligohydramnios in the fetus: report of two different cases
Authors: Phetthong Tim , Achaloetvaranon Krit , Diawtipsukon Sanpon 
Published: June 2024

Abstract

Background
Prenatal ultrasound findings of fetal bilateral echogenic kidneys accompanied by oligohydramnios can be highly stressful for both pregnant women and physicians. The diversity of underlying causes makes it challenging to confirm a prenatal diagnosis, predict postnatal outcomes, and counsel regarding recurrence risks in future pregnancies.
Case Presentation
We report two cases of abnormal fetal echogenic kidneys with oligohydramnios detected in the early third trimester. Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic syndrome, was initially suspected in both cases. However, postnatal diagnoses differed: the first case was confirmed as glomerulocystic kidney disease (GCKD) through renal pathology, while the second case was diagnosed as ARPKD with a compound heterozygous likely pathogenic PKHD1 mutation.
Conclusion
Prenatal diagnosis of fetal echogenic kidneys with oligohydramnios should prioritize accurate diagnosis. Given the differences in the clinical spectrum, GCKD should be considered a differential diagnosis for this condition, particularly ARPKD. This study highlights the importance and benefits of postnatal renal pathology and molecular diagnosis for precise diagnosis and effective counseling.