bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes and mechanisms of apparent resistivity before earthquakes of MS6.0–6.9 on the Chinese mainland
Authors: Xie Tao , Han Ying , Ye Qing , Xue Yan 
Published: June 2023

China has been conducting fixed continuous apparent resistivity observations since 1967. Up to June 2022, 45 earthquakes with magnitudes of MS6.0–6.9 have occurred within a range of approximately 250 km from normal operating stations. Through literature investigation and data analysis, monitoring stations counted 61 short-medium-term apparent resistivity anomalous changes (i.e., 44 decrease changes, 15 increase changes, and 2 perturbance changes) appearing before 39 of these earthquakes. In this study, we utilize a fault virtual dislocation model to understand the relative deformations around the epicenters before these earthquakes. The comparison results showed that 36 of the 44 decrease changes were in areas with compression enhancement and that 9 of the 15 increase changes were in areas with relative dilatancy. The results from rock petrophysical experiments and the resistivity model of the cracked medium showed decreased changes in the resistivity of water-bearing geomaterials during the successive loading of compressive stress, while the resistivity showed increased changes during the stress unloading process. Moreover, 45 of the 61 apparent resistivity anomalies were consistent with the mechanism of resistivity change under stress. These apparent resistivity anomalous changes before earthquakes may be related to the seismogenic processes such that the resistivity change is caused by medium deformation.
Impact of progesterone concentration on human chorionic gonadotropin trigger day on clinical outcomes with one top-quality cleavage-stage embryo or blastocyst transfer in fresh in vitro fertilization cycles
Authors: Xu Jianing , Zhang Cuilian , Wang Shuna , Zhang Shaodi 
Published: June 2023

ObjectiveTo investigate the impact of the progesterone concentration on the human chorionic gonadotropin (hCG) trigger day on clinical outcomes with an antagonist protocol.MethodsThe retrospective cohort study included a total of 1,550 fresh autologous ART cycles with one top-quality embryo transfer. Multivariate regression analysis, curve fitting, and threshold effect analysis were performed.ResultsA significant association was found between the progesterone concentration and clinical pregnancy rate (adjusted OR, 0.77; 95% CI, 0.62–0.97; P = 0.0234), especially in blastocyst transfer (adjusted OR, 0.56; 95% CI, 0.39–0.78; P = 0.0008). The association between the progesterone concentration and the ongoing pregnancy rate was insignificant. The clinical pregnancy rate showed a linear relationship with an increased progesterone concentration in cleavage-stage embryo transfer. In blastocyst transfer, as the progesterone concentration increased, the clinical and ongoing pregnancy rates showed a parabolic reverse-U curve; the curve initially increased before declining at high progesterone concentrations. The clinical pregnancy rate increased with a progesterone concentration up to 0.80 ng/mL rather than tended to be stable. The clinical pregnancy rate significantly decreased when the progesterone concentration was ≥0.80 ng/mL.ConclusionThe progesterone concentration on the hCG trigger day exhibits a curvilinear relationship with pregnancy outcomes in blastocyst transfer cycles, and the optimal threshold of the progesterone concentration is 0.80 ng/mL.
Prevalence and associated factors of metabolic-associated fatty liver disease in overweight Finnish children and adolescents
Authors: Riekki Hanna , Aitokari Linnea , Kivelä Laura , Lahti Siiri , Hiltunen Pauliina , Vuorela Nina , Huhtala Heini , Lakka Timo A. , Kurppa Kalle 
Published: June 2023

IntroductionData on the prevalence of pediatric fatty liver disease remain limited, partly due to challenges in diagnosis. A novel concept of metabolic-associated fatty liver disease (MAFLD) makes it possible to establish the diagnosis in overweight children with sufficiently elevated alanine aminotransferase (ALT). We investigated the prevalence, risk factors, and metabolic co-morbidities of MAFLD in a large group of overweight children.MethodsData on 703 patients aged 2-16 years examined due to overweight in different levels of healthcare in 2002-2020 were collected retrospectively from patient records. MAFLD was here defined as ALT &gt;2x reference (&gt;44 U/l in girls and &gt;50 U/l in boys) in overweight children according to recently updated definition. Patients with MAFLD and without it were compared, and subgroup analyses were conducted among boys and girls.ResultsMedian age was 11.5 years, and 43% were girls. Altogether 11% were overweight, 42% obese and 47% severely obese. Abnormal glucose metabolism was present in 44%, dyslipidemia in 51%, hypertension in 48% and type 2 diabetes (T2D) in 2%. MAFLD prevalence varied between 14-20% in examined years without significant change (p=0.878). The pooled prevalence over the years was 15% (boys 18%, girls 11%; p=0.018), peaking in girls at early puberty and increasing in boys with age and puberty. Associated factors in boys were T2D (OR 7.55, 95% CI 1.23-46.2), postpubertal stage (5.39, 2.26-12.8), increased fasting insulin (3.20, 1.44-7.10), hypertriglyceridemia (2.97, 1.67-5.30), hyperglycemia (2.88, 1.64-5.07), decreased high-density lipoprotein (HDL) cholesterol (2.16, 1.18-3.99), older age (1.28, 1.15-1.42) and higher body-mass-index (1.01, 1.05-1.15), and in girls T2D (18.1, 3.16-103), hypertriglyceridemia (4.28, 1.99-9.21), and decreased HDL (4.06, 1.87-8.79).ConclusionPrevalence of MAFLD was 15%, with no statistically significant increase in the 2000s. The condition was associated in general with male gender, puberty stage and disturbances in glucose and lipid metabolism, and higher age and BMI in boys.
Case Report: Longitudinal follow-up and testicular sperm extraction in a patient with a pathogenic NR5A1 (SF-1) frameshift variant: p.(Phe70Serfs*5)
Authors: Teoli Jordan , Mallet Delphine , Renault Lucie , Gay Claire-Lise , Labrune Elsa , Bretones Patricia , Giscard D’Estaing Sandrine , Cuzin Béatrice , Dijoud Frédérique , Roucher-Boulez Florence , Plotton Ingrid 
Published: June 2023

BackgroundSteroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene, is a transcriptional factor crucial for adrenal and gonadal organogenesis. Pathogenic variants of NR5A1 are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance including disorders of sex development and oligospermia–azoospermia in 46,XY adults. Preservation of fertility remains challenging in these patients.ObjectiveThe aim was to offer fertility preservation at the end of puberty in an NR5A1 mutated patient.Case reportThe patient was born of non-consanguineous parents, with a disorder of sex development, a small genital bud, perineal hypospadias, and gonads in the left labioscrotal fold and the right inguinal region. Neither uterus nor vagina was detected. The karyotype was 46,XY. Anti-Müllerian hormone (AMH) and testosterone levels were low, indicating testicular dysgenesis. The child was raised as a boy. At 9 years old, he presented with precocious puberty treated by triptorelin. At puberty, follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone levels increased, whereas AMH, inhibin B, and testicular volume were low, suggesting an impaired Sertoli cell function and a partially preserved Leydig cell function. A genetic study performed at almost 15 years old identified the new frameshift variant NM_004959.5: c.207del p.(Phe70Serfs*5) at a heterozygous state. He was thus addressed for fertility preservation. No sperm cells could be retrieved from three semen collections between the ages of 16 years 4 months and 16 years 10 months. A conventional bilateral testicular biopsy and testicular sperm extraction were performed at 17 years 10 months of age, but no sperm cells were found. Histological analysis revealed an aspect of mosaicism with seminiferous tubules that were either atrophic, with Sertoli cells only, or presenting an arrest of spermatogenesis at the spermatocyte stage.ConclusionWe report a case with a new NR5A1 variant. The fertility preservation protocol proposed at the end of puberty did not allow any sperm retrieval for future parenthood.
Responses of carbon exchange characteristics to meteorological factors, phenology, and extreme events in a rubber plantation of Danzhou, Hainan: evidence based on multi-year data
Authors: Yang Siqi , Wu Zhixiang , Yang Chuan , Song Bo , Liu Junyi , Chen Bangqian , Lan Guoyu , Sun Rui , Zhang Jie 
Published: June 2023

IntroductionOn Hainan Island, a rubber plantation that occupies a large swath of land plays an important role in the regional carbon budget. However, the carbon exchange of the rubber plantation is poorly understood.MethodsIn this study, using the eddy covariance methods we measured carbon metrics in the rubber plantation for 13 years from 2010 to 2022.ResultsWe clarified that the rubber plantation is a carbon sink and the annual net ecosystem exchange (NEE), ecosystem respiration, and gross primary production were −911.89 ± 135.37, 1,528.04 ± 253.50, and 2,439.93 ± 259.63 gC·m−2·a−1, respectively. Carbon fluxes differed between interannual years; specifically, rainy season fluxes were nearly double dry season fluxes. Radiation explained 46% of the variation for NEE in rainy season, and temperature explained 36% of the variation for NEE in the dry season. LAI explained the highest proportion of the monthly variation in NEE (R2 = 0.72, p &lt; 0.001), indicating that when hydrothermal conditions are sufficient phenology may be the primary factor controlling carbon sequestration of rubber plantation. Due to climate change, there is an increasing probability of extreme climate events, such as typhoons, heat waves, and drought. Thus, we compared NEE before and after such events and results show extreme climate events reduce carbon uptake in the rubber plantation. We found that typhoons reduced NEE to varying degrees on different timescales. Heat waves generally decreased NEE during the day but recovered quickly and increased carbon uptake if there was sufficient precipitation. Drought reduced carbon uptake and continued to decrease even after precipitation.DiscussionEstimating the carbon sink capacity of the rubber plantation and studying the response to regional environmental changes are important for both applied research (carbon sink research and market trading, sink enhancement, and emission reduction, etc.) and basic research (land use change, phenology change, etc.).
Implications of inflammatory cell death-related IFNG and co-expressed RNAs (AC006369.1 and CCR7) in breast carcinoma prognosis, and anti-tumor immunity
Authors: Deng Yongran , Li Zhenlong , Pan Mingmei , Wu Huayun , Ni Bingqiang , Han Xueqiong 
Published: June 2023

Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA).Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed.Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels.Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy.
Genotypic capacity of post-anthesis stem reserve mobilization in wheat for yield sustainability under drought and heat stress in the subtropical region
Authors: Gurumurthy S. , Arora A. , Krishna Hari , Chinnusamy V. , Hazra K. K. 
Published: June 2023

Wheat productivity is severely affected by drought and heat stress conditions worldwide. Currently, stem reserve mobilization (SRM) is receiving increased attention as a trait that can sustain wheat yields under adverse environments. However, the significance of SRM in sustaining wheat yields under drought and heat stress conditions remains uncertain in the tropical climate of Indo-Gangetic Plain region. Therefore, this study aimed to investigate genotypic variations in SRM in wheat and their influence on yield sustainability under drought and heat stress environments. The experiment was designed in an alpha-lattice layout, accommodating 43 genotypes under four simulated environments [timely sown and well irrigated (non-stress); timely sown and water-deficit/drought stress; late-sown and well-irrigated crop facing terminally high temperature; and late-sown and water-deficit stress (both water-deficit and heat stress)]. The water-deficit stress significantly increased SRM (16%–68%, p &lt; 0.01) compared to the non-stress environment, while the heat stress conditions reduced SRM (12%–18%). Both SRM and stem reserve mobilization efficiency exhibited positive correlations with grain weight (grain weight spike−1) under all three different stress treatments (p &lt; 0.05). Strong positive correlations between stem weight (at 12 days after anthesis) and grain weight were observed across the environments (p &lt; 0.001); however, a significant positive correlation between stem weight and SRM was observed only with stress treatments. Results revealed that the SRM trait could effectively alleviate the impacts of water-deficit stress on yields. However, the SRM-mediated yield protection was uncertain under heat stress and combined water-deficit and heat stress treatments, possibly due to sink inefficiencies caused by high temperature during the reproductive period. Defoliated plants exhibited higher SRM than non-defoliated plants, with the highest increment observed in the non-stress treatment compared to all the stress treatments. Results revealed that wider genetic variability exists for the SRM trait, which could be used to improve wheat yield under drought stress conditions.
Identification, characterization, and validation of NBS-encoding genes in grass pea
Authors: Alsamman Alsamman M. , Mousa Khaled H. , Nassar Ahmed E. , Faheem Mostafa M. , Radwan Khaled H. , Adly Monica H. , Hussein Ahmed , Istanbuli Tawffiq , Mokhtar Morad M. , Elakkad Tamer Ahmed , Kehel Zakaria , Hamwieh Aladdin , Abdelsattar Mohamed , El Allali Achraf 
Published: June 2023

Grass pea is a promising crop with the potential to provide food and fodder, but its genomics has not been adequately explored. Identifying genes for desirable traits, such as drought tolerance and disease resistance, is critical for improving the plant. Grass pea currently lacks known R-genes, including the nucleotide-binding site-leucine-rich repeat (NBS-LRR) gene family, which plays a key role in protecting the plant from biotic and abiotic stresses. In our study, we used the recently published grass pea genome and available transcriptomic data to identify 274 NBS-LRR genes. The evolutionary relationships between the classified genes on the reported plants and LsNBS revealed that 124 genes have TNL domains, while 150 genes have CNL domains. All genes contained exons, ranging from 1 to 7. Ten conserved motifs with lengths ranging from 16 to 30 amino acids were identified. We found TIR-domain-containing genes in 132 LsNBSs, with 63 TIR-1 and 69 TIR-2, and RX-CCLike in 84 LsNBSs. We also identified several popular motifs, including P-loop, Uup, kinase-GTPase, ABC, ChvD, CDC6, Rnase_H, Smc, CDC48, and SpoVK. According to the gene enrichment analysis, the identified genes undergo several biological processes such as plant defense, innate immunity, hydrolase activity, and DNA binding. In the upstream regions, 103 transcription factors were identified that govern the transcription of nearby genes affecting the plant excretion of salicylic acid, methyl jasmonate, ethylene, and abscisic acid. According to RNA-Seq expression analysis, 85% of the encoded genes have high expression levels. Nine LsNBS genes were selected for qPCR under salt stress conditions. The majority of the genes showed upregulation at 50 and 200 μM NaCl. However, LsNBS-D18, LsNBS-D204, and LsNBS-D180 showed reduced or drastic downregulation compared to their respective expression levels, providing further insights into the potential functions of LsNBSs under salt stress conditions. They provide valuable insights into the potential functions of LsNBSs under salt stress conditions. Our findings also shed light on the evolution and classification of NBS-LRR genes in legumes, highlighting the potential of grass pea. Further research could focus on the functional analysis of these genes, and their potential use in breeding programs to improve the salinity, drought, and disease resistance of this important crop.
KL-6 levels in the connective tissue disease population: typical values and potential confounders–a retrospective, real-world study
Authors: Zhou Aiyuan , Tang Haiyun , Peng Wenzhong , Wang Yanan , Tang Xiaoping , Yang Hang , Lu Rongli , Pan Pinhua 
Published: June 2023

BackgroundKrebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation.MethodsFrom the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD.ResultsUnivariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the β were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P &lt; 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients.ConclusionKL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.
Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis
Authors: Cheng Wen , Liao Yang , Mou Ruiyu , Xiao Xian , Jia Yingjie 
Published: June 2023

BackgroundPrevious epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis.MethodsWe performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.ResultsGenetically determined IBD did not have a causal effect on PCa (IVW P &gt; 0.05). Additionally, there was no causal effect of Crohn’s disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P &gt; 0.05). Results of complementary methods were consistent with those of the IVW method.ConclusionsThis study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.
Imidazoquinolines with improved pharmacokinetic properties induce a high IFNα to TNFα ratio in vitro and in vivo
Authors: Keppler Manuel , Straß Simon , Geiger Sophia , Fischer Tina , Späth Nadja , Weinstein Thilo , Schwamborn Anna , Guezguez Jamil , Guse Jan-Hinrich , Laufer Stefan , Burnet Michael 
Published: June 2023

TLR Agonists have promising activity in preclinical models of viral infection and cancer. However, clinical use is only in topical application. Systemic uses of TLR-ligands such as Resiquimod, have failed due to adverse effects that limited dose and thus, efficacy. This issue could be related to pharmacokinetic properties that include fast elimination leading to low AUC with simultaneously high cmax at relevant doses. The high cmax is associated with a sharp, poorly tolerated cytokine pulse, suggesting that a compound with a higher AUC/cmax-ratio could provide a more sustained and tolerable immune activation. Our approach was to design TLR7/8-agonist Imidazoquinolines intended to partition to endosomes via acid trapping using a macrolide-carrier. This can potentially extend pharmacokinetics and simultaneously direct the compounds to the target compartment. The compounds have hTLR7/8-agonist activity (EC50 of the most active compound in cellular assays: 75-120 nM hTLR7, 2.8-3.1 µM hTLR8) and maximal hTLR7 activation between 40 and 80% of Resiquimod. The lead candidates induce secretion of IFNα from human Leukocytes in the same range as Resiquimod but induce at least 10-fold less TNFα in this system, consistent with a higher specificity for human TLR7. This pattern was reproduced in vivo in a murine system, where small molecules are thought not to activate TLR8. We found that Imidazoquinolines conjugated to a macrolide or, substances carrying an unlinked terminal secondary amine, had longer exposure compared with Resiquimod. The kinetics of pro-inflammatory cytokine release for these substances in vivo were slower and more extended (for comparable AUCs, approximately half-maximal plasma concentrations). Maximal IFNα plasma levels were reached 4 h post application. Resiquimod-treated groups had by then returned to baseline from a peak at 1 h. We propose that the characteristic cytokine profile is likely a consequence of altered pharmacokinetics and, potentially, enhanced endosomal tropism of the novel substances. In particular, our substances are designed to partition to cellular compartments where the target receptor and a distinct combination of signaling molecules relevant to IFNα-release are located. These properties could address the tolerability issues of TLR7/8 ligands and provide insight into approaches to fine-tune the outcomes of TLR7/8 activation by small molecules.