bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring
Authors: Rivera Juan Carlos , Opazo Ma. Cecilia , Hernández-Armengol Rosario , Álvarez Oscar , Mendoza-León María José , Caamaño Esteban , Gatica Sebastian , Bohmwald Karen , Bueno Susan M. , González Pablo A. , Neunlist Michel , Boudin Helene , Kalergis Alexis M. , Riedel Claudia A. 
Published: January 2024

IntroductionGestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring).MethodsGestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10–E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment.ResultsThe HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring.DiscussionGestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.
Effects of simulated winter short photoperiods on the microbiome and intestinal metabolism in Huanghe carp (Cyprinus carpio haematopterus)
Authors: Wang Wenqian , Su Shengyan , Dong Ping , Feng Wenrong , Li Jianlin , Zhang Chengfeng , Tang Yongkai 
Published: January 2024

ObjectiveAs one of the most important environmental signals, photoperiod plays a crucial role in regulating the growth, metabolism, and survival of organisms. The photoperiod shifts with the transition of the seasons. The difference in photoperiod between summer and winter is the greatest under natural conditions. However, the effect of photoperiod on Huanghe carp (Cyprinus carpio haematopterus) was paid little attention. We investigated the impact of artificial manipulation of seasonal photoperiod on Huanghe carp by integrating growth performance, intestinal flora, and intestinal metabolome.MethodWe conducted an 8-week culture experiment with summer photoperiod (14 h light:10 h dark, n = 60) as the control group and winter photoperiod (10 h light:14 h dark, n = 60) based on the natural laws.ResultsWinter photoperiod provokes significant weight increases in Huanghe carp. The altered photoperiod contributed to a significant increase in triglyceride and low-density lipoprotein cholesterol levels and the gene expressions of lipid metabolism in the intestine of Huanghe carp. 16s rDNA sequencing revealed that winter photoperiod diminished intestinal flora diversity and altered the abundance. Specifically, the relative abundances of Fusobacteria and Acidobacteriota phyla were higher but Proteobacteria, Firmicutes, and Bacteroidetes phyla were reduced. Analogously, photoperiodic changes induced a significant reduction in the Pseudomonas, Vibrio, Ralstonia, Acinetobacter, and Pseudoalteromonas at the genus level. Additionally, metabolomics analysis showed more than 50% of differential metabolites were associated with phospholipids and inflammation. Microbiome and metabolome correlation analyses revealed that intestinal microbe mediated lipid metabolism alteration.ConclusionThe winter photoperiod induced intestinal flora imbalance and lipid metabolism modification, ultimately affecting the growth of Huanghe carp. This study provides new insights into the effects of seasonal photoperiodic alteration on the well-being of fish.
Early rescue oocyte activation at 5 h post-ICSI is a useful strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles
Authors: Xue Lintao , Wang Shikai , Wei Pingpin , Liu Haifang , Mao Xianbao , Qin Jie , Li Yaoxuan , Zhang Xiaohui , Li Zhengda , Huang Yueyue , Chen Liangshi , Shi Wen , Liu Liling 
Published: January 2024

IntroductionAttempts to artificially activate unfertilized oocytes at 24 h post intracytoplasmic sperm injection (ICSI) have generally resulted in poor outcomes. This study aims to explore a new strategy for early judgement and rescue activation of unfertilized oocytes at 5 h post ICSI to avoid unexpected fertilization failure (UFF) or unexpected low fertilization (ULF) in ICSI cycles.MethodsFirstly, time-lapse data from 278 ICSI cycles were retrospectively analyzed to establish an indicator for fertilization failure prediction. Secondly, 14 UFF and 20 ULF cycles were enrolled for an observational study, early rescue oocyte activation (EROA) was performed on oocytes without post-ICSI Pb2 extrusion to investigate fertilization efficiency, embryo development and clinical outcomes.ResultsThe average time to Pb2 extrusion post-ICSI was 3.03±1.21 h, 95.54% of oocytes had extruded Pb2 before 5 h, and the sensitivity and specificity for monitoring Pb2 extrusion at 5 h by time-lapse imaging to predict fertilization were 99.59% and 99.78%, respectively. Early rescue activation of oocytes with no Pb2 extrusion resulted in acceptable fertilization and embryo developmental outcomes, in terms of the fertilization rate (75.00, 72.99%), 2PN fertilization rate (61.36, 56.93%), good-quality embryo rate (42.59, 50.00%), blastocyst formation rate (48.28, 46.03%), good-quality blastocyst rate (34.48, 33.33%), and oocyte utilization rate (36.36, 27.74%), for both UFF and ULF cycles. The clinical pregnancy, embryo implantation, and early miscarriage rates in the rescue oocyte activation group did not significantly differ from those in the Pb2 extrusion group. Fourteen unexpected fertilization failures and 20 low fertilization ICSI cycles were rescued and resulted in clinical pregnancy rates of 40.00% (4/10) and 57.14% (8/14), respectively. ConclusionsThis study demonstrates that monitoring Pb2 extrusion by time-lapse imaging can accurately predict fertilization outcomes, suggesting that early rescue oocyte activation at 5 h post ICSI is an effective strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles.
Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population
Authors: Yan Pijun , Yang Yuxia , Zhang Xing , Zhang Yi , Li Jia , Wu Zujiao , Dan Xiaofang , Wu Xian , Chen Xiping , Li Shengxi , Xu Yong , Wan Qin 
Published: January 2024

ObjectiveSystemic immune-inflammation index (SII), a novel inflammatory marker, has been reported to be associated with diabetic kidney disease (DKD) in the U.S., however, such a close relationship with DKD in other countries, including China, has not been never determined. We aimed to explore the association between SII and DKD in Chinese population.MethodsA total of 1922 hospitalized patients with type 2 diabetes mellitus (T2DM) included in this cross-sectional study were divided into three groups based on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR): non-DKD group, DKD stages 1–2 Alb group, and DKD-non-Alb+DKD stage 3 Alb group. The possible association of SII with DKD was investigated by correlation and multivariate logistic regression analysis, and receiver-operating characteristic (ROC) curves analysis.ResultsMoving from the non-DKD group to the DKD-non-Alb+DKD stage 3 Alb group, SII level was gradually increased (P for trend &lt;0.01). Partial correlation analysis revealed that SII was positively associated with urinary ACR and prevalence of DKD, and negatively with eGFR (all P&lt;0.01). Multivariate logistic regression analysis showed that SII remained independently significantly associated with the presence of DKD after adjustment for all confounding factors [(odds ratio (OR), 2.735; 95% confidence interval (CI), 1.840-4.063; P &lt; 0.01)]. Moreover, compared with subjects in the lowest quartile of SII (Q1), the fully adjusted OR for presence of DKD was 1.060 (95% CI 0.773-1.455) in Q2, 1.167 (95% CI 0.995-1.368) in Q3, 1.266 (95% CI 1.129-1.420) in the highest quartile (Q4) (P for trend &lt;0.01). Similar results were observed in presence of DKD stages 1–2 Alb or presence of DKD-non- Alb+DKD stage 3 Alb among SII quartiles. Last, the analysis of ROC curves revealed that the best cutoff values for SII to predict DKD, Alb DKD stages 1- 2, and DKD-non-Alb+ DKD stage 3 Alb were 609.85 (sensitivity: 48.3%; specificity: 72.8%), 601.71 (sensitivity: 43.9%; specificity: 72.3%), and 589.27 (sensitivity: 61.1%; specificity: 71.1%), respectively.ConclusionHigher SII is independently associated with an increased risk of the presence and severity of DKD, and SII might be a promising biomarker for DKD and its distinct phenotypes in Chinese population.
Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies
Authors: Zhou Zun-Qiang , Zhang Yi , Xu Zi-Yang , Tang Xiao-Li , Chen Xiao-Hua , Guan Jiao , Zhang Zheng-Yun 
Published: January 2024

Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments.Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts.Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling.Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies.
Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons
Authors: Radhakrishna Uppala , Sadhasivam Senthilkumar , Radhakrishnan Rupa , Forray Ariadna , Muvvala Srinivas B. , Metpally Raghu P. , Patel Saumya , Rawal Rakesh M. , Vishweswaraiah Sangeetha , Bahado-Singh Ray O. , Nath Swapan K. 
Published: January 2024

Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights.Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications.Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers.Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances.Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.
Association between gut microbiota and glioblastoma: a Mendelian randomization study
Authors: Wang Song , Yin Fangxu , Guo Zheng , Li Rui , Sun Wei , Wang Yuchao , Geng Yichen , Sun Chao , Sun Daqing 
Published: January 2024

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM.Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane’s Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota.Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01–0.19, FDR = 0.003) was identified as playing a protective role against GBM.Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.
Immunophenotype associated with high sustained antibody titers against enzyme replacement therapy in infantile-onset Pompe disease
Authors: Desai Ankit K. , Smith P. Brian , Yi John S. , Rosenberg Amy S. , Burt Trevor D. , Kishnani Priya S. 
Published: January 2024

IntroductionThe efficacy of enzyme replacement therapy (ERT) with alglucosidase alfa for infantile-onset Pompe disease (IOPD) is limited in some patients due to the development of high and sustained antibody titers (HSAT; ≥12,800).MethodsWe carried out detailed immunophenotyping of IOPD patients (n=40), including analysis of circulating cell populations by flow cytometry and plasma cytokines by multiplex array, to determine whether patients with HSAT have unique immunological characteristics compared to those with low titers (LT; &lt;12,800).ResultsCompared to patients with LT, patients who develop HSAT were skewed toward a type 2 immune profile, with an increased frequency of Th2 cells that was positively correlated with levels of Th2 (IL-4, IL-5, IL-13) and pro-inflammatory (IL-6, TNF-α, MIP-1α, MIP-1β) cytokines. B cells were increased in HSAT patients with a decreased fraction of unswitched memory B cells. Plasma GM-CSF concentrations were lower on average in HSAT patients, while CXCL11 was elevated. Finally, using principal components analysis, we derived an HSAT Signature Score that successfully stratified patients according to their antibody titers.DiscussionThe immune profiles revealed in this study not only identify potential biomarkers of patients that developed HSAT but also provide insights into the pathophysiology of HSAT that will ultimately lead to improved immunotherapy strategies.
Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study
Authors: Wolszczak-Biedrzycka Blanka , Dorf Justyna , Wojewódzka-Żelezniakowicz Marzena , Żendzian-Piotrowska Małgorzata , Dymicka-Piekarska Violetta , Matowicka-Karna Joanna , Maciejczyk Mateusz 
Published: January 2024

AimThe aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients’ MEWS scores was also assessed.Materials and methodsThe serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system.ResultsThe study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity.ConclusionsMIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.
Clinical outcomes after implantation of a new monofocal intraocular lens with enhanced intermediate function in patients with preperimetric glaucoma
Authors: Chung Ho Seok , Jang Joon Hyuck , Lee Hun , Kim Jae Yong , Tchah Hungwon 
Published: January 2024

PurposeWe evaluated the clinical outcomes after implantation of a new monofocal intraocular lens (IOL) with enhanced intermediate function in patients with preperimetric glaucoma and compared those with patients without retinal nerve fiber layer (RNFL) defects.MethodsAll patients were implanted bilaterally a new monofocal IOL with enhanced intermediate function. Patients with bilateral RNFL defects and no glaucomatous visual field defects were classified as the preperimetric glaucoma group. A total of 60 eyes of 30 patients with preperimetric glaucoma were compared with 60 eyes of 30 patients without RNFL defects. Uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus curve, contrast sensitivity, and questionnaire were evaluated 1 month and 3 months after surgery.ResultsNo difference in binocular UDVA, UIVA, and UNVA was evident between the two groups at 1 and 3 months postoperatively. Additionally, there were no significant differences between the two groups regarding the proportion of severe or very severe photic phenomena, such as glare and halos, or the overall satisfaction.ConclusionBilateral implantation of a new monofocal IOL with enhanced intermediate function in patients with preperimetric glaucoma demonstrated commensurate clinical outcomes and could be considered a feasible alternative.
Evaluation of the corneal topography based on deep learning
Authors: Xu Shuai , Yang Xiaoyan , Zhang Shuxian , Zheng Xuan , Zheng Fang , Liu Yin , Zhang Hanyu , Li Lihua , Ye Qing 
Published: January 2024

PurposeThe current study designed a unique type of corneal topography evaluation method based on deep learning and traditional image processing algorithms. The type of corneal topography of patients was evaluated through the segmentation of important medical zones and the calculation of relevant medical indicators of orthokeratology (OK) lenses.MethodsThe clinical data of 1,302 myopic subjects was collected retrospectively. A series of neural network-based U-Net was used to segment the pupil and the treatment zone in the corneal topography, and the decentration, effective defocusing contact range, and other indicators were calculated according to the image processing algorithm. The type of corneal topography was evaluated according to the evaluation criteria given by the optometrist. Finally, the method described in this article was used to evaluate the type of corneal topography and compare it with the type classified by the optometrist.ResultsWhen the important medical zones in the corneal topography were segmented, the precision and recall of the treatment zone reached 0.9587 and 0.9459, respectively, and the precision and recall of the pupil reached 0.9771 and 0.9712. Finally, the method described in this article was used to evaluate the type of corneal topography. When the reviewed findings based on deep learning and image processing algorithms were compared to the type of corneal topography marked by the professional optometrist, they demonstrated high accuracy with more than 98%.ConclusionThe current study provided an effective and accurate deep learning algorithm to evaluate the type of corneal topography. The deep learning algorithm played an auxiliary role in the OK lens fitting, which could help optometrists select the parameters of OK lenses effectively.