bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive association between nonalcoholic fatty liver disease and growth hormone deficiency in patients with nonfunctioning pituitary adenoma
Authors: Hwang Yoon-a , Lee Hye Won , Ahn Sang Hoon , Lee Eun Jig , Ku Cheol Ryong , Kim Seung Up 
Published: January 2023

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is characterized by growth hormone deficiency (GHd). We investigated the association between NAFLD and GHd in patients with nonfunctioning pituitary adenomas (NFPA).Design and methodsWe recruited patients with NFPA who underwent transsphenoidal adenectomy between January 2005 and December 2018. Pituitary function was determined by the insulin tolerance test, thyroid hormone assay, and gonadal hormone levels. NAFLD was defined as a hepatic steatosis index greater than 36.ResultsAmong 278 patients (mean age, 44.2 years; 58.6% [n=163] female), 103 (37.0%) had GHd, 139 (50.0%) had hypogonadism, and 75 (27.0%) had NAFLD. The prevalence of NAFLD was significantly higher in patients with GHd than in those without (36.9% vs. 21.1%, p=0.01). Even after adjusting for age, total cholesterol level, gonadal function, and prolactin level, patients with GHd had approximately two-fold higher prevalence of NALFD than those without GHd (adjusted odds ratio [OR]=1.85, 95% confidence interval [CI]=1.05–3.28, p=0.03). Among female patients, the prevalence of NALFD was significantly higher in those with GHd than in those without (adjusted OR=2.39, 95% CI=1.03–5.55, p=0.04); whereas, among male patients, the prevalence of NAFLD was statistically similar between those with and without GHd (p&gt;0.05). In addition, gonadal function did not affect the prevalence of NAFLD in patients with NFPA (29.3% with eugonadism vs. 47.8% with hypogonadism, p=0.14).ConclusionAmong patients with NFPA, the prevalence of NAFLD was two-fold higher in patients with GHd than that in those without GHd. Thus, screening for NAFLD might be required in NFPA patients with GHd.
Pre-pregnancy BMI was associated with gestational depressive phenotypes in a population of 12,099 women in Chongqing, China
Authors: Chen Yi , Gu Huayan , Zhou Niya , Zhou Wenzheng , Cao Jia , Chen Qing , Zhang Haiyan 
Published: January 2023

ObjectiveTo investigate the association between pre-pregnancy body mass index (BMI) and gestational depressive phenotypes.MethodsThe pregnant women receiving the first prenatal examination (4th –13th week of gestation) in Chongqing Health Center for Women and Children were recruited between February 2020 and September 2021. Depressive phenotypes was assessed by the Patient Health Questionnaire (PHQ-9) and the Symptom Checklist 90 (SCL-90) scale at recruitment. Pre-pregnancy weight and height were self-reported by the participants. Demographic and obstetric characteristics were obtained from the hospital information system. The association between pre-pregnancy BMI and the scores of PHQ-9 or SCL-90 scale was investigated by uni-variate analysis with Kruskal-Wallis test and by multi-variate analysis with linear regression model with adjustment of age, parity, smoking, alcohol consumption, and assisted reproduction. The association between pre-pregnancy BMI and PHQ-9 or SCL-90 diagnosed depressive phenotypes was analyzed by Chi-square test and logistic regression respectively.ResultsA total of 12,099 pregnant women were included, where 100% of them filled out the PHQ-9 scale and 99.6% filled out the SCL-90 scale, and 47.26% and 4.62% of the pregnant women had depressive phenotypes, respectively. Women with higher pre-pregnancy BMI had lower depressive phenotypes scores during pregnancy. Multivariable analysis of the PHQ-9 scale showed that overweight/obese subjects had a higher incidence of depressive phenotypes compared with subjects with normal BMI (OR=0.803, 95% CI [0.723, 0.892]). In a stratified analysis assessed by the PHQ-9, women who were overweight/obese prior to pregnancy were less likely to develop depressive phenotypes during pregnancy than women who were normal weight prior to pregnancy, regardless of whether they were nulliparous (OR=0.795, 95%CI[0.696,0.908]) or multiparous (OR=0.809, 95%CI[0.0.681,0.962]), while in the three age groups of 25-29 years, 30-34 years and ≥35 years, pre-pregnancy overweight/obesity were associated with lower risk of gestational depressive phenotypes. However, analysis of the SCL-90 scale showed no statistical association between depressive symptom and BMI. No substantial interaction was observed between BMI and parity or age.ConclusionsIncreased pre-pregnancy BMI may be associated with reduced risk of gestational depressive phenotypes in Chinese women. Independent studies are warranted to validate the findings of the present study.
Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial
Authors: Brandon Rebecca , Jiang Yannan , Yeu Rui Qian , Tweedie-Cullen Ry , Smallman Kate , Doherty Glenn , Macaskill-Smith Kerry A. , Doran Rebekah J. , Clark Penny , Moffitt Allan , Merry Troy , Nehren Norma , King Frances , Hindmarsh Jennie Harré , Leask Megan Patricia , Merriman Tony R. , Orr-Walker Brandon , Shepherd Peter R. , Paul Ryan , Murphy Rinki 
Published: January 2023

BackgroundUnderstanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine.AimsWe hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of Māori/Pacific ethnicity, and those with obesity and/or hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue).MethodsA randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c&gt;58mmol/mol (&gt;7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction.Results346 participants were randomised (55% Māori/Pacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmol/mol [0.5%]; 95% CI -6.3, -3.5; p&lt;0.0001). Primary intention-to-treat analysis showed no significant interaction effect by Māori/Pacific vs other ethnicity (1.5mmol/mol [0.1%], 95% CI -0.8, 3.7), and per-protocol analysis (-1.2mmol/mol [0.1%], 95% CI -4.1, 1.7). An interaction effect (-4.7mmol/mol [0.5%], 95% CI -8.1, -1.4) was found by OHTG status. Both treatments generated similar treatment satisfaction scores, although there was greater weight gain and greater improvement in lipids and liver enzymes after pioglitazone than vildagliptin.ConclusionsComparative glucose-lowering by pioglitazone and vildagliptin is not different between Māori/Pacific people compared with other New Zealand ethnic groups. Presence of OHTG predicts greater glucose lowering by pioglitazone than vildagliptin.Clinical trial registrationwww.anzctr.org.au, identifier (ACTRN12618001907235).
Triggering receptor expressed on myeloid cells-1 deletion in mice attenuates high-fat diet-induced obesity
Authors: Brustolin Benjamin , Touly Nina , Maillefer Marine , Parisot Lola , Di Pillo Elisa , Derive Marc , Gibot Sébastien 
Published: January 2023

IntroductionThe low-grade inflammatory state present in obesity leads to the development and perpetuation of comorbidities associated with obesity. Our laboratory has been working for several years on an amplification loop of the inflammatory response mediated by TREM-1 (Triggering Receptor of Expressed on Myeloid Cells-1). It is implicated in many acute (septic shock) and chronic (IBD) inflammatory diseases. Previously, TREM-1 has been shown to be overexpressed in adipose and liver tissue in obese and diabetic patients, but its impact has never been characterized in these pathologies.MethodsOur hypothesis is that TREM-1 plays a major role in the generation and perpetuation of inflammation during obesity and its associated complication (Insulin resistance and cardiac dysfunction). We assessed TREM-1 protein expression by western blot and immunofluorescence in omental and subcutaneous (pre-)adipocyte. Moreover, we submitted mice to a high-fat diet and investigated the effects of the genetic Trem1 deletion (trem1 KO mice).ResultsWe showed, for the first time, that TREM-1 is expressed and is functional in subcutaneous and omental (pre-)adipocytes. In the mouse model of high-fat diet-induced obesity, we found that Trem1 suppression limited weight gain, insulin resistance and inflammation in white adipose tissue and liver. Discussion/conclusionOur results reveal the trem1 KO model can be viewed as a preventive model and that TREM-1 seems to play an important role in the development of obesity and its associated complication. It could therefore be a new therapeutic target in this context.
Case report: 7p22.3 deletion and 8q24.3 duplication in a patient with epilepsy and psychomotor delay—Does both possibly act to modulate a candidate gene region for the patient’s phenotype?
Authors: Touhami Rahma , Foddha Hajer , Alix Eudeline , Jalloul Afef , Mougou-Zerelli Soumaya , Saad Ali , Sanlaville Damien , Haj Khelil Amel 
Published: January 2023

Background: Psychomotor delay, epilepsy and dysmorphic features are clinical signs which are described in multiple syndromes due to chromosomal imbalances or mutations involving key genes implicated in the stages of Early Embryonic Development. In this context, we report a 10 years old Tunisian patient with these three signs. Our objective is to determine the cause of developmental, behavioral and facial abnormalities in this patient.Methods: We used banding cytogenetics (karyotype) and Array Comparative Genomic Hybridization (Array CGH) to this purpose.Results: The karyotype was in favor of a derivative of chromosome 7 in the patient and Array CGH analysis revealed a loss of genetic material in 7p22.3-p22.1 (4,56 Mb) with a gain at 8q24.23-q24 (9.20 Mb) resulting from maternal 7/8 reciprocal translocation. An in silico analysis of the unbalanced region was carried out and showed that the 7p22.3-p22.1 deletion contains eight genes. Among them, BRAT1 gene, previously described in several neurodevelopmental diseases, may be a candidate gene which absence could be correlated to the patient’s phenotype. However, the 8q24.23-q24 duplication could be involved in the phenotype of this patient.Conclusion: In this study, we report for the first time a 7p deletion/8q duplication in a patient with psychomoteur delay, epilepsy and facial dysmorphism. Our study showed that Array CGH still useful for delivering a conclusive genetic diagnosis for patients having neurodevelopmental abnormalities in the era of next-generation sequencing.
A novel non-sense variant in the OFD1 gene caused Joubert syndrome
Authors: Li Chen , Wang Xingwang , Li Fake , Ding Hongke , Liu Ling , Xiong Ying , Yang Chaoxiang , Zhang Yan , Wu Jing , Yin Aihua 
Published: January 2023

Background: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis.Methods: Whole-exome sequencing and Sanger sequencing were performed to screen the causative gene variants in a suspected JBS family. RNA-seq and protein model prediction were performed to clarify the potential pathogenic mechanism. A more comprehensive review of previously reported cases with OFD1 variants is presented and may help to establish a genotype–phenotype.Results: We identified a novel non-sense variant in the OFD1 gene, OFD1 (NM_003611.3): c.2848A&gt;T (p.Lys950Ter). Sanger sequencing confirmed cosegregation among this family. RNA-seq confirmed that partial degradation of mutant transcripts, which was predicted to be caused by the non-sense-mediated mRNA decay (NMD) mechanism, may explain the reduction in the proportion of mutant transcripts. Protein structure prediction of the non-sense variant transcript revealed that this variant may lead to a change in the OFD1 protein structure.Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease.
The position of the longest intron is related to biological functions in some human genes
Authors: Dvorak Pavel , Hanicinec Vojtech , Soucek Pavel 
Published: January 2023

The evidence that introns can influence different levels of transfer of genetic information between DNA and the final product is increasing. Longer first introns were found to be a general property of eukaryotic gene structure and shown to contain a higher fraction of conserved sequence and different functional elements. Our work brings more precise information about the position of the longest introns in human protein-coding genes and possible connection with biological function and gene expression. According to our results, the position of the longest intron can be localized to the first third of introns in 64%, the second third in 19%, and the third in 17%, with notable peaks at the middle and last introns of approximately 5% and 6%, respectively. The median lengths of the longest introns decrease with increasing distance from the start of the gene from approximately 15,000 to 5,000 bp. We have shown that the position of the longest intron is in some cases linked to the biological function of the given gene. For example, DNA repair genes have the longest intron more often in the second or third. In the distribution of gene expression according to the position of the longest intron, tissue-specific profiles can be traced with the highest expression usually at the absolute positions of intron 1 and 2. In this work, we present arguments supporting the hypothesis that the position of the longest intron in a gene is another biological factor modulating the transmission of genetic information. The position of the longest intron is related to biological functions in some human genes.
A novel 9-gene signature for the prediction of postoperative recurrence in stage II/III colorectal cancer
Authors: Xin Cheng , Lai Yi , Ji Liqiang , Wang Ye , Li Shihao , Hao Liqiang , Zhang Wei , Meng Ronggui , Xu Jun , Hong Yonggang , Lou Zheng 
Published: January 2023

Background: Individualized recurrence risk prediction in patients with stage II/III colorectal cancer (CRC) is crucial for making postoperative treatment decisions. However, there is still a lack of effective approaches for identifying patients with stage II and III CRC at a high risk of recurrence. In this study, we aimed to establish a credible gene model for improving the risk assessment of patients with stage II/III CRC.Methods: Recurrence-free survival (RFS)-related genes were screened using Univariate Cox regression analysis in GSE17538, GSE39582, and GSE161158 cohorts. Common prognostic genes were identified by Venn diagram and subsequently subjected to least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis for signature construction. Kaplan-Meier (K-M), calibration, and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy and superiority of our risk model. Single-sample gene set enrichment analysis (ssGSEA) was employed to investigate the relationship between the infiltrative abundances of immune cells and risk scores. Genes significantly associated with the risk scores were identified to explore the biological implications of the 9-gene signature.Results: Survival analysis identified 347 RFS-related genes. Using these genes, a 9-gene signature was constructed, which was composed of MRPL41, FGD3, RBM38, SPINK1, DKK1, GAL3ST4, INHBB, CTB-113P19.1, and FAM214B. K-M curves verified the survival differences between the low- and high-risk groups classified by the 9-gene signature. The area under the curve (AUC) values of this signature were close to or no less than the previously reported prognostic signatures and clinical factors, suggesting that this model could provide improved RFS prediction. The ssGSEA algorithm estimated that eight immune cells, including regulatory T cells, were aberrantly infiltrated in the high-risk group. Furthermore, the signature was associated with multiple oncogenic pathways, including cell adhesion and angiogenesis.Conclusion: A novel RFS prediction model for patients with stage II/III CRC was constructed using multicohort validation. The proposed signature may help clinicians better manage patients with stage II/III CRC.
Characterizing T cell responses to enzymatically modified beta cell neo-epitopes
Authors: Nguyen Hai , Arribas-Layton David , Chow I-Ting , Speake Cate , Kwok William W. , Hessner Martin J. , Greenbaum Carla J. , James Eddie A. 
Published: January 2023

IntroductionPrevious studies verify the formation of enzymatically post-translationally modified (PTM) self-peptides and their preferred recognition by T cells in subjects with type 1 diabetes (T1D). However, questions remain about the relative prevalence of T cells that recognize PTM self-peptides derived from different antigens, their functional phenotypes, and whether their presence correlates with a specific disease endotype.MethodsTo address this question, we identified a cohort of subjects with T1D who had diverse levels of residual beta cell function. Using previously developed HLA class II tetramer reagents, we enumerated T cells that recognize PTM GAD epitopes in the context of DRB1*04:01 or PTM IA2 epitopes in the context of DQB1*03:02 (DQ8).ResultsConsistent with prior studies, we observed higher overall frequencies and a greater proportion of memory T cells in subjects with T1D than in HLA matched controls. There were significantly higher numbers of GAD specific T cells than IA2 specific T cells in subjects with T1D. T cells specific for both groups of epitopes could be expanded from the peripheral blood of subjects with established T1D and at-risk subjects. Expanded neo-epitope specific T cells primarily produced interferon gamma in both groups, but a greater proportion of T cells were interferon gamma positive in subjects with T1D, including some poly-functional cells that also produced IL-4. Based on direct surface phenotyping, neo-epitope specific T cells exhibited diverse combinations of chemokine receptors. However, the largest proportion had markers associated with a Th1-like phenotype. Notably, DQ8 restricted responses to PTM IA2 were over-represented in subjects with lower residual beta cell function. Neo-epitope specific T cells were present in at-risk subjects, and those with multiple autoantibodies have higher interferon gamma to IL-4 ratios than those with single autoantibodies, suggesting a shift in polarization during progression.DiscussionThese results reinforce the relevance of PTM neo-epitopes in human disease and suggest that distinct responses to neo-antigens promote a more rapid decline in beta cell function.
Six-month longitudinal immune kinetics after mRNA-1273 vaccination: Correlation of peak antibody response with long-term, cross-reactive immunity
Authors: Choi Min Joo , Heo Jung Yeon , Seo Yu Bin , Yoon Young Kyung , Sohn Jang Wook , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Choi Ju-yeon , Kim Hwa Jung , Lee Young Jae , Lee Hye Won , Kim Sung Soon , Kim Byoungguk , Song Joon Young 
Published: January 2023

BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort.MethodsWe recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated.ResultsThe two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed).ConclusionThis study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants.
Patient genetics shape the autoimmune response in the blistering skin disease pemphigus vulgaris
Authors: Baker John , Seiffert-Sinha Kristina , Sinha Animesh A. 
Published: January 2023

Background and aimPemphigus vulgaris (PV) is known to have one of the strongest HLA associations among autoimmune diseases. DRB1*0402 and DQB1*0503 in particular are significantly overrepresented in PV patients in certain worldwide populations. Yet, there remain significant gaps in our understanding regarding the precise link between PV-associated HLA molecules, the specificity of the autoimmune response, and clinical expression. In this study we assessed correlations between factors including HLA genotype, ethnicity, autoantibody levels, and lesion distribution in a cohort of 293 patients.Methods and populationParticipants were recruited from multiple outpatient dermatology clinic settings and patient support meetings in the USA. On intake, patients provided venous blood samples and answered questionnaires regarding their current disease activity.ResultsEighty-one percent of patients typed as either DRB1*0402 or DQB1*0503 with a high prevalence of DRB1*0402 in patients of Ashkenazi Jewish or Caucasian (non-Jewish) descent (86% and 42%, respectively) and DQB1*0503 in patients of Southeast Asian descent (78%). Patients typing as HLA DRB1*0402 had higher levels of anti-desmoglein (Dsg)3 antibodies (204.6 +/- 340.5 IU/ml) than patients without DRB1*0402 (138.5 +/- 236.4 IU/ml) (p=0.03) and had mucosal only lesions more often than cutaneous only or mucocutaneous lesions. Patients typing as DQB1*0503 had higher levels of anti-Dsg1 antibodies (47.3 +/- 59.8 IU/ml) compared to other groups (27.8 +/- 43.7 IU/ml) (p=0.06) and higher rates of mucocutaneous disease than other lesion types. We also report an unexpected HLA association of DRB1*0804 in PV patients of African descent. Sixty-four percent of this population carried the DRB1*0804 allele, and presented with highly elevated levels of anti-Dsg3 (p=0.02). However, neither African heritage nor the presence of DRB1*0804 correlated with a predilection to any specific lesion morphology. Patients that carried neither DRB1*0402, nor DQB1*0503 or DRB1*0804 had the lowest levels of anti-Dsg3 antibodies (60.0 +/- 80.0 IU/ml) and the highest rate of solely cutaneous disease compared to carriers of these alleles.ConclusionOur data illuminate the broader impact of genetic factors on disease development by showing that differences in HLA expression among patients and ethnicities play a large role in driving distinct patterns of antibody selection and disease phenotype in PV. These findings provide insights regarding clinical heterogeneity, and are relevant to developing improved, patient tailored management strategies.