bluuebunny/crossref_metadata_2025_split huggingface dataset:
ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population
Authors: Liu Jie , Yuan Piaoliu , Pang Yusheng , Su Danyan 
Published: June 2023

ObjectivesKawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear.MethodsWe enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated.ResultsWhile the ITPKC rs7251246 T&gt;C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085–4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068–0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035).ConclusionThe ITPKC rs7251246 T&gt;C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.
Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis
Authors: Feng Yao-Ning , Xie Guang-Yu , Xiao Li , Mo Dun-Chang , Huang Jian-Feng , Luo Peng-Hui , Liang Xiu-Juan 
Published: June 2023

IntroductionImmune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC.MethodWe searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software.ResultsEight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58−1.19, p=0.300 and OR, 1.54; 95%CI 0.89−2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15–0.38, p&lt;0.001), neutropenia (OR, 0.07, 95%CI 0.03–0.14, p&lt;0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02−0.12, p&lt;0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39–4.81, p&lt;0.001] and AST increase [OR, 2.71, 95%CI 1.81−4.07, p&lt;0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33–4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08–2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55–81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06−4.61, p=0.030).ConclusionsCompared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.
Discordance of global assessment between the patients and physicians predicts 9-year pain-related outcomes in rheumatoid arthritis patients
Authors: Hayashi Kazuhiro , Miki Kenji , Shi Kenrin , Yukioka Masao , Hirayama Takehiro , Tsujimoto Kohei , Takeuchi Takao , Hayaishi Yasuhisa , Hayaishi Masahiro 
Published: June 2023

IntroductionPerspectives regarding the disease state often differ between patients with rheumatoid arthritis (RA) and physicians. The aim of the present longitudinal cohort study was to investigate the impact of the discordance in global assessments between patients and physicians on 9-year pain-related outcomes in patients with rheumatoid arthritis.MethodSixty-eight consecutive outpatients with rheumatoid arthritis on their first visit to a tertiary center were included. Baseline measurements included demographic data, drugs used, disease activity, and a modified Health Assessment Questionnaire (mHAQ). Discordance in global assessment between patients and physicians at baseline was defined as 10 mm higher in the patient global assessment (PGA) than in the physician global assessment. A 9-year follow-up assessment included pain intensity, the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) scale, Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Pain Disability Assessment Scale (PDAS), and Pain Self-Efficacy Questionnaire (PSEQ).ResultsThe number of patients with discordance was 26 (38%) in 68 patients. Patients with a 10 mm higher PGA than the physician global assessment at baseline measurements had significantly worse pain intensity, PCS score, PSEQ score, and EQ-5D-3L score measurements at the 9-year follow-up than those with concordance. A higher mHAQ score and 10 mm higher PGA at baseline were significantly independently associated with the EQ-5D-3L scale score and pain intensity at the 9-year follow-up.ConclusionThis longitudinal cohort study suggested that discordance in global assessment between patients and physicians modestly predicted worse 9-year pain-related outcomes in patients with rheumatoid arthritis.
Altered resting-state functional connectivity patterns in late middle-aged and older adults with obstructive sleep apnea
Authors: Martinez Villar Guillermo , Daneault Véronique , Martineau-Dussault Marie-Ève , Baril Andrée-Ann , Gagnon Katia , Lafond Chantal , Gilbert Danielle , Thompson Cynthia , Marchi Nicola Andrea , Lina Jean-Marc , Montplaisir Jacques , Carrier Julie , Gosselin Nadia , André Claire 
Published: June 2023

IntroductionObstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline, and has been associated with structural brain alterations in regions relevant to memory processes and Alzheimer’s disease. However, it is unclear whether OSA is associated with disrupted functional connectivity (FC) patterns between these regions in late middle-aged and older populations. Thus, we characterized the associations between OSA severity and resting-state FC between the default mode network (DMN) and medial temporal lobe (MTL) regions. Second, we explored whether significant FC changes differed depending on cognitive status and were associated with cognitive performance.MethodsNinety-four participants [24 women, 65.7 ± 6.9 years old, 41% with Mild Cognitive Impairment (MCI)] underwent a polysomnography, a comprehensive neuropsychological assessment and a resting-state functional magnetic resonance imaging (MRI). General linear models were conducted between OSA severity markers (i.e., the apnea-hypopnea, oxygen desaturation and microarousal indices) and FC values between DMN and MTL regions using CONN toolbox. Partial correlations were then performed between OSA-related FC patterns and (i) OSA severity markers in subgroups stratified by cognitive status (i.e., cognitively unimpaired versus MCI) and (ii) cognitive scores in the whole sample. All analyzes were controlled for age, sex and education, and considered significant at a p &lt; 0.05 threshold corrected for false discovery rate.ResultsIn the whole sample, a higher apnea-hypopnea index was significantly associated with lower FC between (i) the medial prefrontal cortex and bilateral hippocampi, and (ii) the left hippocampus and both the posterior cingulate cortex and precuneus. FC patterns were not associated with the oxygen desaturation index, or micro-arousal index. When stratifying the sample according to cognitive status, all associations remained significant in cognitively unimpaired individuals but not in the MCI group. No significant associations were observed between cognition and OSA severity or OSA-related FC patterns.DiscussionOSA severity was associated with patterns of lower FC in regions relevant to memory processes and Alzheimer’s disease. Since no associations were found with cognitive performance, these FC changes could precede detectable cognitive deficits. Whether these FC patterns predict future cognitive decline over the long-term needs to be investigated.
Hierarchical deconvolution for extensive cell type resolution in the human brain using DNA methylation
Authors: Zhang Ze , Wiencke John K. , Kelsey Karl T. , Koestler Devin C. , Molinaro Annette M. , Pike Steven C. , Karra Prasoona , Christensen Brock C. , Salas Lucas A. 
Published: June 2023

IntroductionThe human brain comprises heterogeneous cell types whose composition can be altered with physiological and pathological conditions. New approaches to discern the diversity and distribution of brain cells associated with neurological conditions would significantly advance the study of brain-related pathophysiology and neuroscience. Unlike single-nuclei approaches, DNA methylation-based deconvolution does not require special sample handling or processing, is cost-effective, and easily scales to large study designs. Existing DNA methylation-based methods for brain cell deconvolution are limited in the number of cell types deconvolvedMethodsUsing DNA methylation profiles of the top cell-type-specific differentially methylated CpGs, we employed a hierarchical modeling approach to deconvolve GABAergic neurons, glutamatergic neurons, astrocytes, microglial cells, oligodendrocytes, endothelial cells, and stromal cells.ResultsWe demonstrate the utility of our method by applying it to data on normal tissues from various brain regions and in aging and diseased tissues, including Alzheimer’s disease, autism, Huntington’s disease, epilepsy, and schizophrenia.DiscussionWe expect that the ability to determine the cellular composition in the brain using only DNA from bulk samples will accelerate understanding brain cell type composition and cell-type-specific epigenetic states in normal and diseased brain tissues.
Characterization, antioxidant activity, and mineral profiling of Auricularia cornea mushroom strains
Authors: Khan Asif Ali , Lu Li-Xin , Yao Fang-Jie , Fang Ming , Wang Peng , Zhang You-Min , Meng Jing-Jing , Ma Xiao-Xu , He Qi , Shao Kai-Sheng , Wei Yun-hui , Xu Baojun 
Published: June 2023

BackgroundMushrooms are considered as next-generation healthy food components. Owing to their low-fat content, high-quality proteins, dietary fiber, and rich source of nutraceuticals. They are ideally preferred in formulation of low-caloric functional foods. In this view, the breeding strategies of mushroom Auricularia cornea (A. cornea) focusing on high yield and higher quality with rich nutritional values and health benefits are still needed.Materials and methodsA total of 50 strains of A. cornea were used to analyze the bio efficiency and the time required for fruiting body formation following the cultivation experiment. The calorimetric method was used to evaluate the antioxidant activity and quantify the crude polysaccharides and minerals content thereafter.ResultsThe results showed that the time required for fruiting body formation and biological efficiency varied significantly among the selected strains. Noticeably, the wild domesticated strain Ac13 of A. cornea mushroom showed the shortest fruit development time (80 days). Similarly, the hybrid strains including Ac3 and Ac15 possessed the highest biological efficiency (82.40 and 94.84%). Hybrid strains Ac18 (15.2%) and cultivated strains Ac33 (15.6%) showed the highest content of crude polysaccharides, while cultivated strains Ac1 and Ac33, demonstrated the highest content of total polysaccharides in the fruiting body (216 mg. g−1 and 200 mg. g−1). In the case of mineral content, the highest zinc contents were observed from the cultivated strain Ac46 (486.33 mg·kg−1). The maximum iron content was detected from the hybrid strain Ac3 (788 mg·kg−1), and the wild domesticated strain Ac28 (350 mg·kg−1). The crude polysaccharides of the A. cornea strain showed significant antioxidant potential, and the ability of Ac33 and Ac24 to scavenge DPPH radicals and ABTS, which was significantly improved compared to other strains, respectively. Principal component analysis was applied to examine the agronomic traits and chemical compounds of various strains of A. cornea mushrooms. The results revealed that cultivated, wild domesticated, and hybrid strains of A. cornea exhibited distinct characteristics in terms of growth, yield, and nutritional properties.ConclusionThe crude polysaccharides from A. cornea mushroom strains act as natural antioxidants, the wild, hybrid, and commercial A. cornea mushroom strains can achieve rapid growth, early maturation, and high yields. The evaluation of biochemical indexes and nutritional characteristics of strains with excellent traits provided a scientific basis for initiating high-quality breeding, provided germplasm resources for the production of “functional food” with real nutritional and health value.
Preoperative staging of uterine cancer: can transvaginal ultrasonography play a role?
Authors: Rei Mariana , Costa-Santos Cristina , Bernardes João , Costa Antónia 
Published: June 2023

IntroductionPreoperative staging of uterine cancer has recently been implied as an important contribution to an accurate selection of low-risk cases, ultimately avoiding unnecessary lymph node debulking. The aim of this study was to evaluate the validity of transvaginal ultrasonography (TVS) in preoperative staging of uterine cancer in comparison to pelvic magnetic resonance imaging (MRI) and permanent section.MethodsWe conducted a prospective longitudinal multicenter trial between 2017 and 2018. Inclusion criteria comprised cases of endometrial neoplasia histologically confirmed or strong imaging suspicion, candidates for elective surgery as primary treatment. Proportions of Agreement (PA), kappa statistic (K), sensitivity, specificity and accuracy were calculated with 95% confidence intervals (95%CI).ResultsEighty-two patients were eligible for the study, presenting a mean age of 68 years (standard deviation 11). In what concerns the TVS evaluation of myometrial invasion, the subjective and objective methods of Gordon and Karlsson presented a sensitivity of 79%, 79% and 67% [95%CI 63-91; 63-91; 50-81], a specificity of 65%, 58% and 79% [95%CI 49-79; 42-73; 64-89] and an overall accuracy of 72%, 68% and 73% [95%CI 61-81; 57-78; 63-82]. MRI presented respectively a sensitivity, specificity and overall accuracy of 92%, 70% and 82% [95%CI 77-98; 52-85; 71-90]. Regarding cervical involvement, the sensitivity was respectively 31%, 50% and 67% [95%CI 9-61; 21-79; 35-90] for the subjective method, objective TVS and MRI, and the specificity was 98%, 90% and 100% [95%CI 92-100; 77-97; 94;100]. Agreement between TVS and MRI was superior in the assessment of cervical invasion, with PA ranging from 0.82 to 0.93 and K from 0.45 to 0.58, in comparison to myometrial invasion with PA ranging from 0.68 to 0.73 and K from 0.31 to 0.50. Considering the assessment of cervical involvement, as MRI showed a specificity of 100% it is not possible to increase the specificity. However, it was possible to increase the sensitivity, considering the combination of TVS with objective approach and MRI.ConclusionTVS may have a promising role as a tool for preoperative staging of endometrial carcinoma, presenting a performance that approximates to MRI, with a higher agreement in the assessment of cervical invasion.
Application of a three-dimensional printed pelvic model in laparoscopic radical resection of rectal cancer
Authors: Lu Feng , Qiu Lei , Yu Peng , Xu Da-Lai , Miao Yong-Chang , Wang Gang 
Published: June 2023

IntroductionTo investigate the application value of a three-dimensional (3D) printed pelvic model in laparoscopic radical resection of rectal cancer.MethodsClinical data of patients undergoing laparoscopic radical rectal cancer surgery in The Second People's Hospital of Lianyungang City from May 2020 to April 2022 were selected. Patients were randomly divided into general imaging examination group (control group, n=25) and 3D printing group (observation group, n=25) by random number table method, and the perioperative situation of patients in the two groups was compared.ResultsThere was no significant difference in general data between the two groups (p&gt;0.05). Operation time, intraoperative blood loss, intraoperative time to locate inferior mesenteric artery, intraoperative time to locate left colic artery, first postoperative exhaust time and length of hospital stay in the observation group were all lower than those in the control group (P &lt; 0.05); There were no significant differences in the total number of lymph nodes and complications between the two groups (P &gt; 0.05).DiscussionThe application of 3D printed pelvic model in laparoscopic radical resection of rectal cancer is conducive to understanding pelvic structure and mesenteric vascular anatomy, reducing intraoperative bleeding and shortening operation time, which is worthy of further clinical application.
Lestaurtinib inhibits Citron kinase activity and medulloblastoma growth through induction of DNA damage, apoptosis and cytokinesis failure
Authors: Pallavicini Gianmarco , Iegiani Giorgia , Parolisi Roberta , Ferraro Alessia , Garello Francesca , Bitonto Valeria , Terreno Enzo , Gai Marta , Di Cunto Ferdinando 
Published: June 2023

IntroductionMedulloblastoma (MB), the most common malignant pediatric brain tumor, is currently treated with surgery followed by radiation and chemotherapy, which is accompanied by severe side effects, raising the need for innovative therapies. Disruption of the microcephaly-related gene Citron kinase (CITK) impairs the expansion of xenograft models as well as spontaneous MB arising in transgenic mice. No specific CITK inhibitors are available.MethodsLestaurtinib, a Staurosporine derivative also known as CEP-701, inhibits CITK with IC50 of 90 nM. We therefore tested the biological effects of this molecule on different MB cell lines, as well as in vivo, injecting the drug in MBs arising in SmoA1 transgenic mice.ResultsSimilar to CITK knockdown, treatment of MB cells with 100 nM Lestaurtinib reduces phospho-INCENP levels at the midbody and leads to late cytokinesis failure. Moreover, Lestaurtinib impairs cell proliferation through CITK-sensitive mechanisms. These phenotypes are accompanied by accumulation of DNA double strand breaks, cell cycle block and TP53 superfamily activation in vitro and in vivo. Lestaurtinib treatment reduces tumor growth and increases mice survival.DiscussionOur data indicate that Lestaurtinib produces in MB cells poly-pharmacological effects extending beyond the inhibition of its validated targets, supporting the possibility of repositioning this drug for MB treatment.
Identification of a six-gene signature to predict survival and immunotherapy effectiveness of gastric cancer
Authors: Wang Qi , Zhang Biyuan , Wang Haiji , Hu Mingming , Feng Hui , Gao Wen , Lu Haijun , Tan Ye , Dong Yinying , Xu Mingjin , Guo Tianhui , Ji Xiaomeng 
Published: June 2023

BackgroundGastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients.MethodsWe studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature’s performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ResultsThere were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ConclusionIn conclusion, we discovered a 6 gene signature to forecast GC patients’ OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.
Assisted reproductive techniques do not impact late neurodevelopmental outcomes of preterm children
Authors: Lefebvre Tiphaine , Flamant Cyril , Olivier Marion , Gascoin Géraldine , Bouet Pierre-Emmanuel , Roze Jean-Christophe , Barrière Paul , Fréour Thomas , Muller Jean-Baptiste 
Published: June 2023

ObjectiveAssisted reproductive technology (ART) increases the rate of preterm births, though few studies have analyzed outcomes for these infants. No data are available on 4-year-old children born prematurely after ART. The objective was to investigate whether ART affect the neurodevelopmental outcomes at 4 years in preterm infants born before 34 weeks of gestational age (GA).Methods and resultsA total of 166 ART and 679 naturally conceived preterm infants born before 34 weeks GA between 2013 and 2015 enrolled in the Loire Infant Follow-up Team were included. Neurodevelopment was assessed at 4 years using the age and stage questionnaire (ASQ) and the need for therapy services. The association between the socio-economic and perinatal characteristics and non-optimal neurodevelopment at 4 years was estimated. After adjustment, the ART preterm group remained significantly associated with a lower risk of having at least two domains in difficulty at ASQ: adjusted odds ratio (aOR) 0.34, 95% confidence interval (CI) (0.13–0.88), p = 0.027. The factors independently associated with non-optimal neurodevelopment at 4 years were male gender, low socio-economic level, and 25–30 weeks of GA at birth. The need for therapy services was similar between groups (p = 0.079). The long-term neurodevelopmental outcomes of preterm children born after ART are very similar, or even better than that of the spontaneously conceived children.