bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated pulse wave velocity is associated with all-cause and cardio-cerebrovascular disease mortality in stroke population: Results from NHANES (2003–2014)
Authors: Huang Huoming , Bu Xiancong , Pan Huachun , Yang Shumin , Cheng Wenke , Shubhra Quazi T. H. , Ma Niya 
Published: April 2023

BackgroundArterial stiffness is a significant determinant and evaluation of cardio-cerebrovascular disease and all-cause mortality risk in the stroke population. Estimated pulse wave velocity (ePWV) is a well-established indirect measure of arterial stiffness. We examined the association of ePWV with all-cause and cardio-cerebrovascular disease (CCD) mortality in the stroke population in a large sample of US adults.MethodsThe study design was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014, between the ages of 18–85 years, with follow-up through December 31, 2019. 1,316 individuals with stroke among 58,759 participants were identified and ultimately, 879 stroke patients were included in the analysis. ePWV was calculated from a regression equation using age and mean blood pressure according to the following formula: ePWV = 9.587 − (0.402 × age) + [4.560 × 0.001 × (age2)] − [2.621 × 0.00001 × (age2) × MBP] + (3.176 × 0.001 × age × MBP) − (1.832 × 0.01 × MBP). Survey-weighted Cox regression models were used to assess the association between ePWV and all-cause and CCD mortality risk.ResultsThe high ePWV level group had a higher increased risk of all-cause mortality and CCD mortality compared to the low ePWV level group after fully adjusting for covariates. With an increase in ePWV of 1 m/s, the risk of all-cause and CCD mortality increased by 44%–57% and 47%–72% respectively. ePWV levels were linearly correlated with the risk of all-cause mortality (P for nonlinear = 0.187). With each 1 m/s increase in ePWV, the risk of all-cause mortality increased by 44% (HR 1.44, 95% CI: 1.22–1.69; P &lt; 0.001). When ePWV was &lt;12.1 m/s, an increase in ePWV per 1 m/s was associated with a 119% (HR 2.19, 95% CI: 1.43–3.36; P &lt; 0.001) increase in CCD mortality risk; when ePWV was ≥12.1 m/s, an increase in ePWV per 1 m/s was not associated with in CCD mortality risk.ConclusionePWV is an independent risk factor for all-cause and CCD mortality in stroke patients. Higher levels of ePWV are associated with higher all-cause mortality and CCD mortality in stroke patients.
Insulinoma in childhood: a retrospective review of 22 patients from one referral centre
Authors: Melikyan Maria , Gubaeva Diliara , Shadrina Anna , Bolmasova Anna , Kareva Maria , Tiulpakov Anatoly , Efremenkov Artem , Sokolov Yuri , Brusgaard Klaus , Christesen Henrik T. , Andersen Kirstine , Stepanov Alexey , Averyanova Julia , Makarov Sergey , Gurevich Larisa 
Published: April 2023

BackgroundInsulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).MethodsWe conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.ResultsA total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1–46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.ConclusionsIn this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.
Sperm morphological abnormalities in autosomal dominant polycystic kidney disease are associated with the Hippo signaling pathway via PC1
Authors: Shi Wei-Hui , Zhou Zhi-Yang , Ye Mu-Jin , Qin Ning-Xin , Jiang Zi-Ru , Zhou Xuan-You , Xu Nai-Xin , Cao Xian-Lin , Chen Song-Chang , Huang He-Feng , Xu Chen-Ming 
Published: April 2023

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder mostly caused by mutations in PKD1 or PKD2 genes. Here, we report thirteen ADPKD males with infertility and investigated the sperm morphological defects associated with PC1 disruption.MethodsTargeted next-generation sequencing was performed to detect PKD1 variants in patients. Sperm morphology was observed by immunostaining and transmission electron microscopy, and the sperm motility was assessed using the computer-assisted sperm analysis system. The Hippo signaling pathway was analyzed with by quantitative reverse transcription polymerase chain reaction (qPCR) and western blotting in vitro.ResultsThe ADPKD patients were infertile and their sperm tails showed morphological abnormalities, including coiled flagella, absent central microtubules, and irregular peripheral doublets. In addition, the length of sperm flagella was shorter in patients than in controls of in in. In vitro, ciliogenesis was impaired in Pkd1-depleted mouse kidney tubule cells. The absence of PC1 resulted in a reduction of MST1 and LATS1, leading to nuclear accumulation of YAP/TAZ and consequently increased transcription of Aurka. which might promote HDAC6-mediated ciliary disassembly.ConclusionOur results suggest the dysregulated Hippo signaling significantly contributes to ciliary abnormalities in and may be associated with flagellar defects in spermatozoa from ADPKD patients.
Is routine drainage necessary after thyroid surgery? A randomized controlled trial study
Authors: Wang Ziming , Qi Peng , Zhang Lixi , Zhang Ben , Liu Xuyao , Shi Qi , Zhang Qiang 
Published: April 2023

ObjectiveTo evaluate whether no drainage has an advantage over routine drainage in patients with thyroid carcinoma after unilateral thyroid lobectomy and central neck dissection.MethodsA total of 104 patients with thyroid cancer who underwent unilateral thyroid lobectomy and central lymph node dissection were randomly assigned into no drainage tube (n=52) and routine drainage tube (n=52) placement groups. General information of each patient was recorded, including the postoperative drainage volume/residual cavity fluid volume, postoperative complications, incision area comfort, and other data, and the thyroid cancer-specific quality of life questionnaire (THYCA-QoL) and patient and observer scar assessment scale (POSAS) were evaluated after surgery. At the 3–6 month follow-up exam, the differences between the two groups were compared based on univariate analysis.ResultsSignificant differences were not observed in the general and pathological information (including sex, age, body weight, body mass index (BMI), incision length, specimen volume, Hashimoto’s thyroiditis, and number of lymph nodes dissected), operation time, and postoperative complications (postoperative bleeding, incision infection, lymphatic leakage, and temporary hypoparathyroidism) between the two groups. The patients in the non-drainage group had a shorter hospital stay (2.11 ± 0.33 d) than the patients in the drainage group (3.38 ± 0.90 d) (P&lt;0.001). The amount of cervical effusion in patients in the non-drainage group (postoperative 24h: 2.20 ± 1.24 ml/48 h: 1.53 ± 1.07 ml) was significantly less than that in the drainage group (postoperative 24 hours: 22.58 ± 5.81 ml/48 h: 36.15 ± 7.61 ml) (all P&lt;0.001). The proportion of incision exudation and incision numbness in the non-drainage group was lower than that in the drainage group (all P&lt;0.05), and the pain score (VAS) and neck foreign body sensation score (FBST) decreased significantly (P&lt;0.05). During the 3- and 6-month follow-up exams, significant differences were not observed between the THYCA-QoL and drainage groups and the non-drainage group, although the scarring and POSAS values were lower than those in the drainage group. In addition, the length of stay and cost of hospitalization in the non-drainage group were lower than those in the drainage group (P&lt;0.05).ConclusionRoutine drainage tube insertion is not needed in patients with unilateral thyroid lobectomy and central neck dissection.
Permanent hypothyroidism following immune checkpoint inhibitors induced thyroiditis may be associated with improved survival: results of an exploratory study
Authors: Lee Hanna J. , Manavalan Anjali , Stefan-Lifshitz Mihaela , Schechter Clyde , Maity Aloke , Tomer Yaron 
Published: April 2023

BackgroundImmune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT.MethodsThis retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed.ResultsOf the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group.ConclusionOur results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival.
Effect of continuous glucose monitoring compared with self-monitoring of blood glucose in gestational diabetes patients with HbA1c<6%: a randomized controlled trial
Authors: Lai Mengyu , Weng Jianrong , Yang Jiaying , Gong Yujia , Fang Fang , Li Na , Kang Mei , Xu Xianming , Wang Yufan 
Published: April 2023

ObjectiveThis study evaluated the effect of continuous glucose monitoring (CGM) versus self-monitored blood glucose (SMGB) in gestational diabetes mellitus (GDM) with hemoglobin A1c (HbA1c) &lt;6%.MethodsFrom January 2019 to February 2021, 154 GDM patients with HbA1c&lt;6% at 24–28 gestational weeks were recruited and assigned randomly to either SMBG only or CGM in addition to SMBG, with 77 participants in each group. CGM was used in combination with fingertip blood glucose monitoring every four weeks until antepartum in the CGM group, while in the SMBG group, fingertip blood glucose monitoring was applied. The CGM metrics were evaluated after 8 weeks, HbA1c levels before delivery, gestational weight gain (GWG), adverse pregnancy outcomes and CGM medical costs were compared between the two groups.ResultsCompared with patients in the SMBG group, the CGM group patients had similar times in range (TIRs) after 8 weeks (100.00% (93.75-100.00%) versus 99.14% (90.97-100.00%), p=0.183) and HbA1c levels before delivery (5.31 ± 0.06% versus 5.35 ± 0.06%, p=0.599). The proportion with GWG within recommendations was higher in the CGM group (59.7% versus 40.3%, p=0.046), and the newborn birth weight was lower (3123.79 ± 369.58 g versus 3291.56 ± 386.59 g, p=0.015). There were no significant differences in prenatal or obstetric outcomes, e.g., cesarean delivery rate, hypertensive disorders, preterm births, macrosomia, hyperbilirubinemia, neonatal hypoglycemia, respiratory distress, and neonatal intensive care unit admission &gt;24 h, between the two groups. Considering glucose monitoring, SMBG group patients showed a lower cost than CGM group patients.ConclusionsFor GDM patients with HbA1c&lt;6%, regular SMBG is a more economical blood glucose monitoring method and can achieve a similar performance in glycemic control as CGM, while CGM is beneficial for ideal GWG.
Crosstalk of disulfidptosis-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in bladder cancer based on a machine learning survival framework
Authors: Zhao Songyun , Wang Lanyu , Ding Wei , Ye Bicheng , Cheng Chao , Shao Jianfeng , Liu Jinhui , Zhou Hongyi 
Published: April 2023

BackgroundBladder cancer (BLCA) is the most common malignancy of the urinary tract. On the other hand, disulfidptosis, a mechanism of disulfide stress-induced cell death, is closely associated with tumorigenesis and progression. Here, we investigated the impact of disulfidptosis-related genes (DRGs) on the prognosis of BLCA, identified various DRG clusters, and developed a risk model to assess patient prognosis, immunological profile, and treatment response.MethodsThe expression and mutational characteristics of four DRGs were first analyzed in bulk RNA-Seq and single-cell RNA sequencing data, IHC staining identified the role of DRGs in BLCA progression, and two DRG clusters were identified by consensus clustering. Using the differentially expressed genes (DEGs) from these two clusters, we transformed ten machine learning algorithms into more than 80 combinations and finally selected the best algorithm to construct a disulfidptosis-related prognostic signature (DRPS). We based this selection on the mean C-index of three BLCA cohorts. Furthermore, we explored the differences in clinical characteristics, mutational landscape, immune cell infiltration, and predicted efficacy of immunotherapy between high and low-risk groups. To visually depict the clinical value of DRPS, we employed nomograms. Additionally, we verified whether DRPS predicts response to immunotherapy in BLCA patients by utilizing the Tumour Immune Dysfunction and Rejection (TIDE) and IMvigor 210 cohorts.ResultsIn the integrated cohort, we identified several DRG clusters and DRG gene clusters that differed significantly in overall survival (OS) and tumor microenvironment. After the integration of clinicopathological features, DRPS showed robust predictive power. Based on the median risk score associated with disulfidptosis, BLCA patients were divided into low-risk (LR) and high-risk (HR) groups, with patients in the LR group having a better prognosis, a higher tumor mutational load and being more sensitive to immunotherapy and chemotherapy.ConclusionOur study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of BLCA patients, offering new insights into individualized treatment.
Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice
Authors: Krysko Olga , Korsakova Darya , Teufelberger Andrea , De Meyer Amse , Steels Jill , De Ruyck Natalie , van Ovost Judith , Van Nevel Sharon , Holtappels Gabriele , Coppieters Frauke , Ivanchenko Mikhail , Braun Harald , Vedunova Maria , Krysko Dmitri V. , Bachert Claus 
Published: April 2023

BackgroundRecent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation.ResultsIn vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice. In Alternaria alternata (Alt) - treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice.ConclusionOur study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains and could affect the processing of IL-33 and inflammatory outcome of Alt -induced airway inflammation. We suggest that mast cells and their proteases play a regulatory role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway.
Dissecting order amidst chaos of programmed cell deaths: construction of a diagnostic model for KIRC using transcriptomic information in blood-derived exosomes and single-cell multi-omics data in tumor microenvironment
Authors: Wang Chengbang , He Yuan , Zheng Jie , Wang Xiang , Chen Shaohua 
Published: April 2023

BackgroundKidney renal clear cell carcinoma (KIRC) is the most frequently diagnosed subtype of renal cell carcinoma (RCC); however, the pathogenesis and diagnostic approaches for KIRC remain elusive. Using single-cell transcriptomic information of KIRC, we constructed a diagnostic model depicting the landscape of programmed cell death (PCD)-associated genes, namely cell death-related genes (CDRGs).MethodsIn this study, six CDRG categories, including apoptosis, necroptosis, autophagy, pyroptosis, ferroptosis, and cuproptosis, were collected. RNA sequencing (RNA-seq) data of blood-derived exosomes from the exoRBase database, RNA-seq data of tissues from The Cancer Genome Atlas (TCGA) combined with control samples from the GTEx databases, and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database were downloaded. Next, we intersected the differentially expressed genes (DEGs) of the KIRC cohort from exoRBase and the TCGA databases with CDRGs and DEGs obtained from single-cell datasets, further screening out the candidate biomarker genes using clinical indicators and machine learning methods and thus constructing a diagnostic model for KIRC. Finally, we investigated the underlying mechanisms of key genes and their roles in the tumor microenvironment using scRNA-seq, single-cell assays for transposase-accessible chromatin sequencing (scATAC-seq), and the spatial transcriptomics sequencing (stRNA-seq) data of KIRC provided by the GEO database.ResultWe obtained 1,428 samples and 216,155 single cells. After the rational screening, we constructed a 13-gene diagnostic model for KIRC, which had high diagnostic efficacy in the exoRBase KIRC cohort (training set: AUC = 1; testing set: AUC = 0.965) and TCGA KIRC cohort (training set: AUC = 1; testing set: AUC = 0.982), with an additional validation cohort from GEO databases presenting an AUC value of 0.914. The results of a subsequent analysis revealed a specific tumor epithelial cell of TRIB3high subset. Moreover, the results of a mechanical analysis showed the relatively elevated chromatin accessibility of TRIB3 in tumor epithelial cells in the scATAC data, while stRNA-seq verified that TRIB3 was predominantly expressed in cancer tissues.ConclusionsThe 13-gene diagnostic model yielded high accuracy in KIRC screening, and TRIB3high tumor epithelial cells could be a promising therapeutic target for KIRC.
Syngeneic mouse model of human HER2+ metastatic breast cancer for the evaluation of trastuzumab emtansine combined with oncolytic rhabdovirus
Authors: Taha Zaid , Crupi Mathieu J.F. , Alluqmani Nouf , Fareez Faiha , Ng Kristy , Sobh Judy , Lee Emily , Chen Andrew , Thomson Max , Spinelli Marcus M. , Ilkow Carolina S. , Bell John C. , Arulanandam Rozanne , Diallo Jean-Simon 
Published: April 2023

BackgroundEstablished mouse models of HER2+ cancer are based on the over-expression of rodent Neu/Erbb2 homologues, which are incompatible with human HER2 (huHER2) targeted therapeutics. Additionally, the use of immune-deficient xenograft or transgenic models precludes assessment of native anti-tumour immune responses. These hurdles have been a challenge for our understanding of the immune mechanisms behind huHER2-targeting immunotherapies.MethodsTo assess the immune impacts of our huHER2-targeted combination strategy, we generated a syngeneic mouse model of huHER2+ breast cancer, using a truncated form of huHER2, HER2T. Following validation of this model, we next treated tumour-bearing with our immunotherapy strategy: oncolytic vesicular stomatitis virus (VSVΔ51) with clinically approved antibody-drug conjugate targeting huHER2, trastuzumab emtansine (T-DM1). We assessed efficacy through tumour control, survival, and immune analyses.ResultsThe generated truncated HER2T construct was non-immunogenic in wildtype BALB/c mice upon expression in murine mammary carcinoma 4T1.2 cells. Treatment of 4T1.2-HER2T tumours with VSVΔ51+T-DM1 yielded robust curative efficacy compared to controls, and broad immunologic memory. Interrogation of anti-tumour immunity revealed tumour infiltration by CD4+ T cells, and activation of B, NK, and dendritic cell responses, as well as tumour-reactive serum IgG.ConclusionsThe 4T1.2-HER2T model was used to evaluate the anti-tumour immune responses following our complex pharmacoviral treatment strategy. These data demonstrate utility of the syngeneic HER2T model for assessment of huHER2-targeted therapies in an immune-competent in vivo setting. We further demonstrated that HER2T can be implemented in multiple other syngeneic tumour models, including but not limited to colorectal and ovarian models. These data also suggest that the HER2T platform may be used to assess a range of surface-HER2T targeting approaches, such as CAR-T, T-cell engagers, antibodies, or even retargeted oncolytic viruses.