bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine modification—a key player in viral infection
Authors: Zhang Xiaoyue , Peng Qiu , Wang Lujuan 
Published: October 2023

AbstractN6-methyladenosine (m6A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases (“writers”), demethylases (“erasers”), and m6A-binding proteins (“readers”). m6A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m6A lead to aberrant expression of important viral genes. Here, we review the role of m6A modifications in viral replication and virus–host interactions. In particular, we focus on DNA and RNA viruses associated with human diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV)-1, Epstein–Barr virus (EBV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). These findings will contribute to the understanding of the mechanisms of virus–host interactions and the design of future therapeutic targets for treatment of tumors associated with viral infections.
Redefining serological diagnostics with immunoaffinity proteomics
Authors: Walter Jonathan , Eludin Zicki , Drabovich Andrei P. 
Published: October 2023

AbstractSerological diagnostics is generally defined as the detection of specific human immunoglobulins developed against viral, bacterial, or parasitic diseases. Serological tests facilitate the detection of past infections, evaluate immune status, and provide prognostic information. Serological assays were traditionally implemented as indirect immunoassays, and their design has not changed for decades. The advantages of straightforward setup and manufacturing, analytical sensitivity and specificity, affordability, and high-throughput measurements were accompanied by limitations such as semi-quantitative measurements, lack of universal reference standards, potential cross-reactivity, and challenges with multiplexing the complete panel of human immunoglobulin isotypes and subclasses. Redesign of conventional serological tests to include multiplex quantification of immunoglobulin isotypes and subclasses, utilize universal reference standards, and minimize cross-reactivity and non-specific binding will facilitate the development of assays with higher diagnostic specificity. Improved serological assays with higher diagnostic specificity will enable screenings of asymptomatic populations and may provide earlier detection of infectious diseases, autoimmune disorders, and cancer. In this review, we present the major clinical needs for serological diagnostics, overview conventional immunoassay detection techniques, present the emerging immunoassay detection technologies, and discuss in detail the advantages and limitations of mass spectrometry and immunoaffinity proteomics for serological diagnostics. Finally, we explore the design of novel immunoaffinity-proteomic assays to evaluate cell-mediated immunity and advance the sequencing of clinically relevant immunoglobulins.
Developmental validation of a high-resolution panel genotyping 639 Y-chromosome SNP and InDel markers and its evolutionary features in Chinese populations
Authors: Zhao Guang-Bin , Miao Lei , Wang Mengge , Yuan Jia-Hui , Wei Lan-Hai , Feng Yao-Sen , Zhao Jie , Kang Ke-Lai , Zhang Chi , Ji An-Quan , He Guanglin , Wang Le 
Published: October 2023

AbstractUniparental-inherited haploid genetic marker of Y­chromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741×. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/μL tannic acid, 20 ng/μL humic acid, or 37.5 μM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.
Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma—randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol
Authors: Modesto Anouchka , Tougeron David , Tremolières Pierre , Ronchin Philippe , Jouve Ariane Darut , Leignel Delphine Argo , Vendrely Véronique , Riou Olivier , Martin-Babau Jérôme , Le Sourd Samuel , Mirabel Xavier , Leroy Thomas , Huguet Florence , Montaigne Lucile , Baumgaertner Isabelle , Deslandres Marion , Moyal Elizabeth , Seva Catherine , Selves Janick , Otal Philippe , Pezzella Veronica , Guimbaud Rosine , Filleron Thomas , Quéro Laurent 
Published: October 2023

Abstract
Background
In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67).

Methods
ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory.
The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging.

Ancillary studies are planned
PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers.

Conclusion
Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation.

Trial registration
ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.
MEX3C as a potential target for hepatocellular carcinoma drug and immunity: combined therapy with Lenvatinib
Authors: Guo Jinhui , Zhao Jie , Xu Qiuran , Huang Dongsheng 
Published: October 2023

Abstract
Background
The immune microenvironment within hepatocellular carcinoma (HCC) is remarkably intricate. Although the combination of an immune checkpoint inhibitor and Lenvatinib can extend the overall survival of HCC patients, the outcome remains suboptimal.

Methods
We assessed alterations in MEX3C expression during hepatocarcinogenesis by validating multiple databases and subsequently developed a predictive model. Subsequently, we enriched the associated genes of MEX3C to investigate its functional role. We examined the correlation between MEX3C expression levels and immune infiltrating cells. The effects of MEX3C knockdown and Lenvatinib on hepatoma cells were observed by cell function experiments.

Results
MEX3C expression is elevated in HCC compared to normal tissues, and its high expression correlates with poor prognosis. Immune checkpoint expression was elevated in the high MEX3C expression group, concomitant with heightened myeloid-derived suppressor cell (MDSC) expression. The combination of MEX3C knockdown and Lenvatinib demonstrated a stronger inhibitory effect on HCC cells compared to Lenvatinib alone.

Conclusion
MEX3C shows promise as a potential therapeutic target for treating HCC. Furthermore, the combination of MEX3C knockdown and Lenvatinib could offer a novel therapeutic avenue for HCC treatment.
Prevalence and associated risk factors for chronic kidney disease in the elderly physically disabled population in Shanghai, China: a cross-sectional study
Authors: Wu Hengjing , Li Yao , Ren Longbing , Li Jue , Wang Yiyan , Jiang Chenghua , Wu Jing 
Published: October 2023

Abstract
Background
The global prevalence of chronic kidney disease (CKD) in the general population is relatively clear. Our previous study showed that elderly individuals who are physically disabled are more likely to experience kidney function impairment, and the main purpose of this study was to determine the prevalence and risk factors associated with CKD in elderly patients with physical disabilities.

Methods
A total of 2679 elderly individuals with physical disabilities from the 2018 Shanghai Disability Health Survey were screened to calculate the prevalence of CKD. Multiple logistic regression was performed to identify the factors associated with CKD. Detailed subgroup analyses of disability level were also conducted.

Results
We confirmed CKD in 287 of 2679 (10.7%) participants. Female sex, age, history of hypertension, red blood cell count, albumin, urea, and uric acid (UA) were independently correlated with CKD. Age and UA abnormalities were common risk factors for different levels of disabilities.

Conclusion
The prevalence of CKD is higher in the mild level of older physically handicapped individuals. Age and the level of UA should also be considered in this population. The preventive strategies for patients with two levels of elderly disability should have different focuses.
Validation of the Swedish version of the safe environment for every kid (SEEK) parent screening questionnaire
Authors: Engström Maria , Lindqvist Sara , Janson Staffan , Feldman Inna , Dubowitz Howard , Lucas Steven 
Published: October 2023

Abstract
Background
Psychosocial risk factors in the home may impair children’s health and development and increase the risk of maltreatment. The Safe Environment for Every Kid (SEEK) model was developed to provide pediatric primary care professionals with a structured way to identify common psychosocial problems. The SEEK model includes use of the Parent Screening Questionnaire (SEEK-PSQ) at routine preventive child health visits, discussion with parents about their responses and, when indicated, referral to relevant services. The SEEK-PSQ has not previously been available in Swedish. The aim of the present study was to evaluate the psychometric properties of an adapted Swedish version of the SEEK-PSQ (PSQ-S).

Methods
This study is part of a cluster-randomised controlled trial of SEEK in the Swedish child health services. To validate the PSQ-S, parents (n = 852) with children 0–18 months of age were invited to complete a survey including the PSQ-S as well as evidence-based standardized instruments for the targeted psychosocial risk factors: economic worries, depressive symptoms, parental stress, alcohol misuse and intimate partner violence (IPV). Baseline data from 611 (72%) parents were analysed regarding sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each risk factor.

Results
As a whole, the PSQ-S had a sensitivity of 93%, specificity of 52%, PPV of 67% and NPV of 87%. For mothers and fathers combined, sensitivity was 80% for economic worries, 89% for depressive symptoms, 78% for parental stress, 47% for intimate partner violence (IPV) and 70% for alcohol misuse. Specificity was highest for IPV and alcohol misuse (91%) and lowest for depressive symptoms (64%). NPV values were high (81–99%) and PPV values were low to moderate (22–69%) for the targeted problems. Sensitivity was higher for mothers compared to fathers for economic worries, depressive symptoms and IPV. This difference was particularly evident for IPV (52% for mothers, 27% for fathers).

Conclusion
The SEEK-PSQ-S demonstrated good psychometric properties for identifying economic worries, depressive symptoms, parental stress and alcohol misuse but low sensitivity for IPV. The PSQ-S as a whole showed high sensitivity and NPV, indicating that most parents with or without the targeted psychosocial risk factors were correctly identified.

Trial registration
ISRCTN registry, study record 14,429,952 (https://doi.org/10.1186/ISRCTN14429952) Registration date 27/05/2020.
Parents, but not their children, demonstrate greater delay discounting with resource scarcity
Authors: Button Alyssa M. , Paluch Rocco A. , Schechtman Kenneth B. , Wilfley Denise E. , Geller Nancy , Quattrin Teresa , Cook Stephen R. , Eneli Ihouma U. , Epstein Leonard H. 
Published: October 2023

AbstractBackgroundIndividuals with obesity tend to discount the future (delay discounting), focusing on immediate gratification. Delay discounting is reliably related to indicators of economic scarcity (i.e., insufficient resources), including lower income and decreased educational attainment in adults. It is unclear whether the impact of these factors experienced by parents also influence child delay discounting between the ages of 8 and 12-years in families with obesity.MethodsThe relationship between indices of family income and delay discounting was studied in 452 families with parents and 6–12-year-old children with obesity. Differences in the relationships between parent economic, educational and Medicaid status, and parent and child delay discounting were tested.ResultsResults showed lower parent income (p = 0.019) and Medicaid status (p = 0.021) were differentially related to greater parent but not child delay discounting among systematic responders.ConclusionsThese data suggest differences in how indicators of scarcity influence delay discounting for parents and children, indicating that adults with scarce resources may be shaped to focus on immediate needs instead of long-term goals. It is possible that parents can reduce the impact of economic scarcity on their children during preadolescent years. These findings suggest a need for policy change to alleviate the burden of scarce conditions and intervention to modify delay discounting rate and to improve health-related choices and to address weight disparities.
Determinants of COVID-19-related knowledge and disrupted habits during epidemic waves among women of childbearing age in urban and rural areas of the Malagasy Middle East
Authors: Rakotosamimanana Sitraka , Mangahasimbola Reziky Tiandraza , Ratovoson Rila , Randremanana Rindra Vatosoa 
Published: October 2023

Abstract
Background
With regard to the coronavirus disease (COVID-19) pandemic in Madagascar, little is known about the knowledge, the perceptions and the impacts of this disease on women of childbearing age. People’s knowledge of COVID-19 can have an impact on their attitudes towards seeking care. The aim of the current study is to determine the knowledge of COVID-19 and associated determinants among women of childbearing age in Moramanga.

Methods
A cross-sectional study based on questionnaire administration was used among women of childbearing age. Data collection was conducted from August to October 2021. A scoring method was applied to evaluate their knowledge level and perceptions about COVID-19 and its impacts on their lives. A binary stepwise logistic regression was performed to determine the sociodemographic determinants of their knowledge level about COVID-19.

Results
A total of 885 women of childbearing age from urban and rural Moramanga areas were interviewed. Approximately 49.8% (441/885) lived in urban areas, and 50.2% (444/885) lived in rural areas. Approximately 35.3% (322/885) of the participants had a good level of knowledge of COVID-19. Multivariate analysis showed that the probability of having a good level of knowledge of COVID-19 had a significant statistical association (p value < 0.05) with living in an urban area [AOR: 2.89; 95% CI (1.89–4.42)], telephone ownership [AOR: 1.71; 95% CI (1.16–2.53)], radio ownership [AOR 2.2; 95% CI (1.43–3.38)], watching TV [AOR = 1.95; 95% CI (1.34–2.83)] and reading journal papers [AOR = 3.74 95% CI (1.69–8.27)].

Conclusions
Almost a third of the sampled women of childbearing age had a good level of knowledge of COVID-19. Access to information through telecommunications technologies increases the chances of being better informed about the disease. To avoid the negative repercussions of infectious disease epidemics, it is necessary to improve the awareness of childbearing women about these diseases by taking demographic features of the population into account.
Causal effects of inflammatory bowel diseases on the risk of kidney stone disease: a two-sample bidirectional mendelian randomization
Authors: Zhang Huayang , Huang Yong , Zhang Junyong , Su Huiyi , Ge Chengguo 
Published: October 2023

Abstract
Background
Existing epidemiological observational studies have suggested interesting but inconsistent clinical correlations between inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and kidney stone disease (KSD). Herein, we implemented a two-sample bidirectional Mendelian randomization (MR) to investigate the causal relationship between IBD and KSD.

Methods
Data on IBD and KSD were obtained from Genome-Wide Association Studies (GWAS) summary statistics and the FinnGen consortium, respectively. Strict selection steps were used to screen for eligible instrumental SNPs. We applied inverse variance weighting (IVW) with the fix-effects model as the major method. Several sensitivity analyses were used to evaluate pleiotropy and heterogeneity. Causal relationships between IBD and KSD were explored in two opposite directions. Furthermore, we carried out multivariable MR (MVMR) to obtain the direct causal effects of IBD on KSD.

Results
Our results demonstrated that CD could increase the risk of KSD (IVW: OR = 1.06, 95% CI = 1.03–1.10, p < 0.001). Similar results were found in the validation group (IVW: OR = 1.05, 95% CI = 1.01–1.08, p = 0.013) and in the MVMR analysis. Meanwhile, no evidence of a causal association between UC and KSD was identified. The reverse MR analysis detected no causal association.

Conclusions
This MR study verified that CD plays a critical role in developing kidney stones and that the effect of UC on KSD needs to be further explored.
Inadequate care and excessive overprotection during childhood are associated with the presence of diabetes mellitus in adulthood in a general Japanese population: a cross-sectional analysis from the Hisayama Study
Authors: Shibata Mao , Hosoi Masako , Anno Kozo , Hirabayashi Naoki , Hirakawa Yoichiro , Kawata Hiroshi , Iwaki Rie , Sawamoto Ryoko , Sudo Nobuyuki , Ninomiya Toshiharu 
Published: October 2023

Abstract
Objective
To investigate associations between parenting styles during childhood and diabetes in adulthood in a Japanese community.

Methods
In 2011, 710 community-dwelling Japanese residents aged ≥ 40 years were assessed for the presence of diabetes and for their perceptions of the parenting style of their parents, as measured using the “care” and “overprotection” scales of the Parental Bonding Instrument. Care and overprotection scores for each parent were dichotomized by age-specific median values. Diabetes mellitus was defined as a fasting plasma glucose level of ≥ 7.0 mmol/L, a 2-h post-loaded glucose level of ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, and/or the current use of insulin or oral glucose-lowering agents. The odds ratios (ORs) for prevalent diabetes were calculated using a logistic regression model.

Results
The prevalence of diabetes was 14.9%. Subjects with a high paternal overprotection score had a significantly greater likelihood of prevalent diabetes than those with a low paternal overprotection score after adjusting for confounders (OR 1.71, 95% confidence interval [CI] 1.06–2.77), while there was no significant association between paternal care and diabetes. Additionally, the multivariable-adjusted ORs for the presence of diabetes were significantly higher in subjects with a low maternal care score (OR 1.61, 95%CI 1.00–2.60) or in subjects with a high maternal overprotection score (OR 1.73, 95%CI 1.08–2.80). Moreover, the subjects with a low care score and high overprotection score for both their father and mother had a significantly higher multivariable-adjusted OR of diabetes than those with a high care score and low overprotection score for both parents (OR 2,12, 95%CI 1.14–3.95).

Conclusions
This study suggests that inadequate care and excessive overprotection during childhood may contribute to the development of diabetes in adulthood.