bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in placental markers and later autistic traits
Authors: Tiemeier Henning , Tsompanidis Alex , Blanken Laura , Broere-Brown Zoe , Rijn Bas van , Baron-Cohen Simon 
Published: July 2022

Abstract
Autism and related neurodevelopmental traits are more prevalent in males. Placental complications are also more frequent in male pregnancies. It is unclear if sex differences in placental function can predict sex differences in autistic traits. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1st (mean = 13.5[SD = 2.0] weeks gestation) and 2nd trimesters (mean = 20.6[SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models, controlling for various confounders including placental weight. Mediation analysis was conducted to study if placental proteins mediated the effects of biological sex on autistic traits in childhood. sFlt-1 levels were significantly lower in males in both time-points but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1st trimester, and significantly higher in the 2nd trimester, thus levels increased faster in males during gestation. Higher PlGF levels in the 2nd trimester and the rate of PlGF increase were associated with higher autistic traits in linear regression models (PlGF-2nd : n = 3469,b = 0.24[SE = 0.11], p = 0.03). In sex-stratified analyses, these associations were significant in females but not males. Mediation analyses showed that higher autistic traits in males were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2nd : n = 3469, ACME: b = 0.006, [SE = 0.002], p = 0.004). In conclusion, placental sex differences in PlGF levels are linked to sex differences in autistic traits.
Development and Validation of the Thirst Distress Scale for Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Ozcan Seyda Gul , Bek Sibel Gokcay , Eren Necmi , Atli Zeynep , Yildiz Abdülmecit , Kocyigit İsmail , Cavdar Caner , Tunc Sertac , Waldréus Nana , Ecder Tevfik , Seyahi Nurhan 
Published: July 2022

Abstract
Background and Aims:
Thirst, is the main driver for fluid consumption. Abundant water intake is advised for patients with autosomal dominant polycystic kidney disease (ADPKD). However, daily routines may limit water intake. There is no established tool to quantify the drivers of water intake in ADPKD patients. The aim of this study was to modify and validate a thirst distress scale (TDS) to identify the factors that influence water intake in ADPKD patients.
Methods
The TDS-heart failure questionnaire was first modified to TDS-PKD to adapt to patients with ADPKD to assess (a) the intensity of thirst, (b) the consequences if the quench for thirst is not satisfied enough and (c) the disturbing effects of thirst on quality of life. Then, the TDS-PKD questionnaire was translated to Turkish using the guidelines of the World Health Organization. An electronic survey with the SurveyMonkey platform was used to collect data. Thirst intensity was evaluated using a visual analog scale (VAS).
Results
The questionnaire was filled in by 186 ADPKD patients, of which 126 were on tolvaptan therapy. The TDS-PKD questionnaire showed good internal consistency, with a Cronbach's alpha value of 0.859. According to the exploratory factor analysis, a three-factor structure was obtained. Three factors explained 60.7% of the total variance. There was a positive and statistically significant correlation between the total TDS and VAS scores (r = 0.589, p < 0.001). The average TDS-PDK score was 39.0 ± 1.4.
Conclusion
The TDS-PKD questionnaire is a valid and reliable tool for evaluating the thirst distress in ADPKD patients.
Dapagliflozin alleviates diabetic kidney disease via HIF‐1α/HO1 mediated ferroptosis
Authors: Wang yihui , Chang Dongyuan , Zhao Ming-hui , Chen Min 
Published: July 2022

Abstract
Background: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. In recent clinical trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed excellent renoprotection effects, but the underlying mechanism remains to be investigated. Previous studies have revealed an important role of ferroptosis, which is mediated by iron overload and lipid peroxidation, in the progression of DKD. Therefore, it is of interest to explore the effects of SGLT2i on ferroptosis in DKD due to its role in alleviating oxidative stress.Methods: Diabetic (db/db) mice were administered with dapagliflozin or solvent treatment from 9 to 22 weeks of age, and were compared with non-diabetic (m/m) mice. High glucose/high fat (HG/HF) was applied to HK-2 cells, and effects of dapagliflozin on ferroptosis in HK-2 cells as well as the underlying mechanism were investigated.Results: Typical changes of ferroptosis including massive lipid peroxidation, reduced antioxidant capability, and iron overload were found in db/db mice and HG/HF treated HK-2 cells. Furthermore, increased expression of hypoxia‐inducible factor‐1α (HIF‐1α) and heme oxygenase-1 (HO1) was observed in db/db mice and HG/HF cultured cells as well. Dapagliflozin treatment significantly ameliorated the ferroptosis-related changes via inhibiting HIF‐1α/HO1 axis in vivo and in vitro. Besides, downregulation of HIF‐1α/HO1 axis rescued ferroptosis, while overexpression of HO1 aggravated ferroptosis induced by HG/HF in HK-2 cells. In DKD patients, the expression level of GPX4 in the kidney was significantly lower than that in healthy controls.Conclusion: SGLT2i play a renal protective effect, at least in parts, via inhibiting HIF‐1α/HO1 axis mediated ferroptosis.
Clustering of Juvenile Canavan disease in an Indian community due to population bottleneck and isolation: Genomic signatures of a founder event
Authors: Arunachal Gautham , Kotambail Ananthapadmanabha , Selvam Pavalan , Muthusamy Karthik , Thomas Maya , Sudhakar Sniya , Ghati Chetan , Danda Sumita 
Published: July 2022

Abstract
Mild/juvenile Canavan disease (M/JCD) is less frequently reported in literature and little is known about its pathogenetic mechanisms. We report a comprehensive investigation into the pathogenetic mechanism of a novel ASPA(NM_000049.4):c.526G > A(p.Gly176Ser) variant in two families. The families belong to Telugu Devanga Chettiar community (TDC) from southern India. TDC has a complex history of migration from their historical origin centuries ago with high endogamy. TDC probably has the highest clustering M/JCD recorded historically (around 24 cases). The pathogenic variant was shown to cause non-classical splicing defect resulting in two different transcripts. The splicing aberration, a loss of function mechanism coupled with a milder missense effect can explain the milder phenotype compared to the infantile onset CD. The high clustering of an extremely rare form of neurodegenerative disorder with reduced fitness, indicated to a possibility of founder event. Genotyping array of TDC and multiple distinct populations of Indian origin for several population genetic parameters was performed. It yielded robust signatures of a founder event, such as a high fixation index, increased runs of homozygosity and identity-by-descent estimation in TDC in the absence of consanguinity; large haplotype with high linkage disequilibrium comprising the pathogenic variant; presence of a robust population structure; mutation dating, estimating the age of the potential founder of TDC at around 375 years; possibly a high carrier rate in TDC. This study has not only focused its attention on natural history and pathogenetics but also paves way for carrier screening programs in TDC and future therapeutic studies.
Genetic Trajectory and Clonal Evolution of Multiple Primary Lung Cancer with Lymph Node Metastasis
Authors: Li Chunxiang , Tian He , Wang Yalong , Yang Zhenlin , Chen Ping , Fan Tao , Xiao Chu , Bai Guangyu , Li Lin , Zheng Bo , He Jie 
Published: July 2022

Abstract
Multiple primary lung cancer (MPLC) with lymph node metastasis (LNM) is a rare phenomenon of multifocal lung cancer. The genomic landscapes of MPLC and the clonal evolution pattern between primary lung lesions and lymph node metastasis haven’t been fully illustrated. We performed whole-exome sequencing (WES) on 52 FFPE (Formalin-fixed Paraffin-Embedded) samples from 11 patients diagnosed with MPLC with LNM. Genomic profiling and phylogenetic analysis were conducted to infer the evolutional trajectory within each patient. The top 5 most frequently mutated genes in our study were TTN (76.74%), MUC16 (62.79%), MUC19 (55.81%), FRG1 (46.51%), and NBPF20 (46.51%). For 81.82% of patients (9/11), most genetic alterations harbored by pulmonary tumors were mutually exclusive, suggesting their heterogenous origins. Individually, the genetic profile of lymph node metastatic lesions overlapped with that of multiple lung cancers in different degrees but are more genetically related to specific pulmonary lesions. SETD2 was a potential metastasis biomarker of MPLC. The mean putative neo-antigen number of the primary tumor (646.5) is higher than that of lymph node metastases (300, p = 0.2416). Primary lung tumors and lymph node metastases are highly heterogenous in immune repertoires. Our findings portrayed the comprehensive genomic landscape of MPLC with LNM. We characterized the genomic heterogeneity among different tumors and offered novel clues of the clonal evolution between MPLC and their lymphatic metastases, thus advancing the treatment strategies and preventions of MPLC with LNM.
Self-rated Health Status and Associated Factors in Rural Workers
Authors: Martins Cleodice Alves , Prado Camila Bruneli do , Ferreira Júlia Rabelo Santos , Zandonade Eliana , Bezerra Olívia Maria de Paula Alves , Salaroli Luciane Bresciani 
Published: July 2022

Abstract
Background: Self-rated health status can be considered a good predictor of morbidity and mortality and has been used because of its easy assessment and applicability. The instrument is efficient for understanding sociodemographic, environmental and clinical conditions that may be related to the self-rated health status. Thus, this study aims to analyze the self-assessment of health status in rural workers and its association with socioeconomic characteristics, lifestyle, clinical condition and work characteristics.Methods: This is a cross-sectional study carried out with farmers of both sexes who had agriculture as their main source of income, in the municipality of Santa Maria de Jetibá. A simple and direct question was used: “In general, compared to people your age, how do you rate your own state of health?” to see how they rate their current health status. The independent variables analyzed were socioeconomic, clinical, health and work conditions. The magnitude of the associations was evaluated by means of hierarchical logistic regression in levels. Results: It was found that 42.1% of farmers self-rated their health status as regular or poor. Females had a risk of worse self-rated health (OR=0,705; 95% CI: 0,522 - 0,951), socioeconomic classes C (OR=1,937; 95% CI: 1,009-3,720), D/E (OR= 2,280; 95% CI: 1,178-4,415), the body mass index (OR=1,477; 95% CI: 1,086-2,008), multimorbidity (OR=1,715; 95% CI: 1,201-2,447) and complex multimorbidity (OR=1,738;95% CI: 1,097-2,751). Conclusion: It was concluded that the presence of chronic diseases, socioeconomic status, female gender and overweight were risk factors for a negative self-rated health. The identification of these determinants through self-rated can support the planning of actions aimed at the health of the rural population.Register: This study was approved by the Research Ethics Committee of the Health Sciences Center of the Federal University of Espírito Santo, under protocol number nº. 2091172 (CAAE 52839116.3.0000.5060). All research participants signed the Informed Consent Term.
Assessment of data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries through key informant’s interviews
Authors: Belizán Maria , Cairoli Federico Rodriguez , Mazzoni Agustina , Goucher Erin , Zaraa Sabra , Matthews Sarah , Pingray Verónica , Stergachis Andy , Xiong Xu , Berrueta Mabel , Buekens Pierre 
Published: July 2022

Abstract
Background: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to use this tool in sites using MNCH data collection systems through informant interviews.Methods: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to complete the domains included in the assessment tool. Results: We interviewed a total of 9 stakeholders including: central-level systems key informants and/or site level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (​​India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). Similarities among sites were found regarding some domains such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy such as routine collection of MNCH individual data, and capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR)Conclusion: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by integrating the currently used individual MNCH data collection systems in some sites in LMICs.
Direct association of Mg1 with a protease inhibitor confers resistance to rice root-knot nematode
Authors: Wang Xiaomin , Cheng Rui , Xu Daochao , Huang Renliang , Li Haoxing , Jin Liang , Wu Yufeng , Tang Jiuyou , Sun Changhui , Peng Deliang , Chu Chengcai , Guo Xiaoli 
Published: July 2022

Abstract
The rice root-knot nematode (Meloidogyne graminicola) is one of the most destructive pests threatening rice (Oryza sativa L.) production in Asia; however, no rice resistance genes have been cloned. Here, we demonstrate that M. graminicola-resistance gene 1 (Mg1), an R gene highly expressed at the site of nematode invasion, determines resistance against the nematode in several rice varieties. Introgressing Mg1 into susceptible varieties dramatically increases resistance, for which the leucine-rich repeat domain is critical for recognizing root-knot nematode invasion. We also establish the transcriptome and cytological changes that allow a rapid and robust response during the incompatible interaction that occurs in resistant rice upon nematode invasion. Furthermore, we identified a putative protease inhibitor that directly interacts with Mg1 during Mg1-mediated resistance. Our findings provide insight into the molecular basis of nematode resistance as well as valuable resources for developing rice varieties with improved nematode resistance.
Fluid-structure interaction simulation of visceral perfusion and impact of different cannulation methods on aortic dissection
Authors: Lee Gyu-Han , Heo Woon , Lee Youngjin , Kim Tae-Hoon , Huh Hyungkyu , Song Suk-Won , Ha Hojin 
Published: July 2022

Abstract
Hemodynamics in aortic dissection (AD) is closely associated with the risk of aortic aneurysm, coarctation, rupture, hypertension, and malperfusion. Altered blood flow in patients with AD can lead to severe complications such as visceral malperfusion. In this study, we aimed to investigate the effect of cannulation flow on hemodynamics in patients with AD using a fluid-structure interaction simulation. We developed a specific-idealized AD model including intimal tear on descending thoracic aorta. Two different cannulation methods were tested: 1) Axillary cannulation (AC) only through the brachiocephalic trunk, and 2) combined axillary and femoral cannulation (AFC) through the brachiocephalic trunk and the right common iliac artery. The AC was found to develop the pressure difference between the true and false lumens due to the difference of the flow rate through each lumen. This pressure difference collapses the true lumen, disturbing blood flow to the celiac and superior mesenteric arteries. However, in the AFC, the pressure levels between the two lumens were similar, no collapse occurred, and the visceral flow was increased compared to that in the AC. Lastly, the collapse of true lumen was affected by the cannulation flow rate and also stiffness of the intimal flap.
Evaluating heavy metal pollution risks and enzyme activity in areas with intensive hazelnut cultivation under humid ecological conditions
Authors: BAYRAKLI Betül 
Published: July 2022

Abstract
Unlike organic pollutants, heavy metals are often unchanging, non-degradable, and persistent in soil and water. So, they negatively impact the surrounding ecosystems and human health. In this context, the main objectives of this study were to i-) determine some physical, chemical, and biological properties and heavy metal concentrations of different soils in intensive hazelnut cultivation areas under humid ecological conditions; ii-) reveal the heavy metal pollution risks of these areas by their enrichment factor (EF), contamination factor (CF), geo-accumulation index (Igeo), degree of contamination (DC), pollution load index (PLI), and potential ecological risk index (PERI); iii-) analyze the quality of soils contaminated with heavy metals by their total enzyme activity index (TEI) and the geometric mean of enzymatic activities (GMea); iv) explore the correlation between heavy metals and soil enzyme activity indices. According to our results, the average concentrations of heavy metals in the study area ranked as Fe > Mn > Zn > Cr > Ni > Cu > Co > Pb > Cd. Based on EF, the area was evaluated as between deficiency to low enrichment and moderate enrichment for all elements except for Cd. 92.5% of Cd was in the significant enrichment class. Based on CF, the area was in the low to moderate contamination class for all elements except for Cd, with a significant, high contamination risk for Cd. According to Igeo, the area was uncontaminated to moderately contaminated for all elements except Cd, but it was at risk of moderate to strong contamination for Cd. According to DC, 12.5% of the area had a low degree of contamination, 77.5% a moderate degree, and 10% a considerable degree. Besides, for PLI, 12.5% of the area was in the perfection class, 77.5% in the baseline of pollution class, and 10% in the deterioration of site quality class. Nearly 70% of the soils had a low risk for the analyzed ecosystem and the remaining soils (30%) had moderate risk. Moreover, the area had a GMea of 69.97–208 and a TEI of 2.111–5.859. Finally, analyzing the heavy metals and soil enzyme activity indices, show that there is a negative correlation between Ni and GMea (p < 0.01) and TEI (p < 0.05).
Multi-omics reveals the key and specific miRNA-mRNA modules underlying salt tolerance in wild emmer wheat (Triticum dicoccoides L.)
Authors: Yang Guang , Pan Wenqiu , Cao Rui , Guo Qifan , Cheng Yue , Zhao Qinlong , Cui Licao , Nie Xiaojun 
Published: July 2022

Abstract
Background
Salt stress is one of the most destructive environmental factors limiting crop growth and development. MicroRNAs (miRNAs) are a class of conserved endogenous small non-coding RNAs, playing the crucial role in regulating salt response and tolerance in plant. However, the miRNAs in wild emmer wheat, especially the key and specific salt-responsive miRNAs are not well studied.
Results
Here, we performed small RNA, transcriptome, and degradome sequencing of both of salt-tolerance (ST) and salt-sensitive (SS) wild emmer genotypes to identify the miRNA-mRNA modules associating with salt tolerance. Totally, 775 miRNAs, including 361 conserved known miRNAs and 414 novel miRNAs were detected. Differential expression analysis identified 93 salt-responsive miRNAs under salt stress. Combined with RNA-seq and degradome sequencing analysis, 224 miRNA-mRNA modules displayed the complete opposite expression trends between ST and SS genotypes, most of which functionally enriched into ROS homeostasis maintaining, osmotic pressure modulating, and root growth and development. Finally, the qRT-PCR and a large-scale yeast functional screening were also performed to initially validate the expression pattern and function of candidate genes.
Conclusions
This study reported the key and specific miRNA-mRNA modules associated with salt tolerance in wild emmer, which lay the foundation for improving the salt tolerance in cultivated emmer and bread wheat through miRNA engineering approach.
Achieving CD8+ T cell-dependent lethality by targeting cancer USP14 in hepatocellular carcinoma
Authors: Li Binkui , Yuan Yichuan , Niu Yi , Huang Zhenkun , Shi Yunxing , Lin Zhu , Zuo Dinglan , Zhong Chengrui , Li Kai , Yuan Yun-Fei , Guan Xin-Yuan 
Published: July 2022

Abstract
The application of immunotherapies in hepatocellular carcinoma (HCC) have been hindered by resistance to therapeutics. Cancer cell-induced CD8 + T cell dysfunction may account for the failure of tumor immunotherapies. Here, we identified USP14 as an essential driver of cancer cells tolerance to CD8 + T cells through genome-wide screening. scRNA-seq showed that cancer USP14 was frequently upregulated in tumor tissues from patients with HCC. The elevated USP14 was positively correlated with resistance to immunotherapy and poor prognoses. Inhibition of cancer USP14 arrested the growth of HCC with the existence of CD8 + T cells in vivo and in vitro. Furtherly, targeting cancer USP14 boosted immunotherapy efficacy. Mechanistically, the USP14 highly-expressed HCC cells were avidly consumed and outcompeted CD8 + T cells for glucose by stabilizing GLUT1 expression, resulting in CD8 + T cells starving and dysfunction. Collectively, our data defined USP14 as a potential immunotherapy target in HCC.