bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review
Authors: Fu Youqing , Xu Wanfang , Wang Qingming , Lin Yangyang , He Peiqing , Liu Yanhui , Yuan Haiming 
Published: May 2022

Background:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenital anomalies. Currently, more than 300 MWS patients have been described in the literature, and nearly 280 variants in ZEB2 have been identified.Methods: In this study, we report three unrelated Chinese patients presenting multiple congenital anomalies that were consistent with those of MWS. Whole-exome sequencing (WES) was used to identify the causative variants.Results: WES identified two novel de novo frameshift variants in ZEB2 (NM_014795.4:c.2136delC, p. Lys713Serfs*3 and c.2740delG, p. Gln914Argfs*16) in patients 1 and 2, respectively, and a novel de novo splicing variant in ZEB2 (NM_014795.4:c.808-2delA) in patient 3, all of which were confirmed by Sanger sequencing. Next, we systematically reviewed the clinical characteristics of Chinese and Caucasian MWS patients. We revealed a higher incidence of constipation in Chinese MWS patients compared to that previously reported in Caucasian cohorts, while the incidence of Hirschsprung disease and happy demeanor was lower in Chinese MWS patients and that epilepsy in Chinese MWS patients could be well-controlled compared to that in Caucasian MWS individuals.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical characteristics of MWS. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with MWS.
High-Throughput Sequencing to Investigate lncRNA-circRNA-miRNA-mRNA Networks Underlying the Effects of Beta-Amyloid Peptide and Senescence on Astrocytes
Authors: Deng Yuxin , Song Hui , Xiao Yan , Zhao Yi , Chu Liangzao , Ding Jiuyang , Shen Xiangchun , Qi Xiaolan 
Published: May 2022

Astrocytes are widely distributed in the central nervous system and play an essential role in the function of neuronal cells. Associations between astrocytes and Alzheimer’s disease (AD) have been noted, and recent work has implicated circular RNA (circRNA) and long non-coding RNA (lncRNA) in the development of AD. However, few reports have investigated which lncRNA and circRNA are involved in the influence of amyloid beta (Aβ) and senescence on astrocytes. This study therefore examines changes at the transcriptome level to explore the effects of Aβ and senescence on astrocytes. Primary cultured astrocytes were treated with Aβ and cultured for 90 days in vitro, and high-throughput sequencing was performed to identify differentially expressed RNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed genes were associated with the focal adhesion signaling pathway, extracellular matrix receptor signaling pathway, and the extracellular matrix. The protein–protein interaction network was then constructed, and 103 hub genes were screened out; most of these were strongly associated with the expression of the extracellular matrix, extracellular matrix receptor signaling pathway, and focal adhesion. Two competing endogenous RNA networks were constructed based on the selected hub gene and differential RNAs, and we identified multiple competing endogenous RNA regulatory axes that were involved in the effects of Aβ and senescence on astrocytes. This is the first study to explore the molecular regulation mechanism of Aβ and senescence on primary astrocytes from the perspective of the whole transcriptome. In uncovering the signaling pathways and biological processes involved in the effects of Aβ and senescence on astrocytes, this work provides novel insights into the pathogenesis of AD at the level of competing endogenous RNA network regulation.
Identification and Verification of Feature Biomarkers Associated With Immune Cells in Dilated Cardiomyopathy by Bioinformatics Analysis
Authors: Zhu Tingfang , Wang Mingjie , Quan Jinwei , Du Zunhui , Li Qiheng , Xie Yuan , Lin Menglu , Xu Cathy , Xie Yucai 
Published: May 2022

Objective: To explore immune-related feature genes in patients with dilated cardiomyopathy (DCM).Methods: Expression profiles from three datasets (GSE1145, GSE21610 and GSE21819) of human cardiac tissues of DCM and healthy controls were downloaded from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were identified by the ‘limma’ package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to identify biological functions of the DEGs. The compositional patterns of stromal and immune cells were estimated using xCell. Hub genes and functional modules were identified based on protein-protein interaction (PPI) network analysis by STRING webtool and Cytoscape application. Correlation analysis was performed between immune cell subtypes and hub genes. Hub genes with |correlation coefficient| &gt; 0.5 and p value &lt;0.05 were selected as feature biomarkers. A logistic regression model was constructed based on the selected biomarkers and validated in datasets GSE5406 and GSE57338.Results: A total of 1,005 DEGs were identified. Functional enrichment analyses indicated that extracellular matrix remodeling and immune and inflammation disorder played important roles in the pathogenesis of DCM. Immune cells, including CD8+ T-cells, macrophages M1 and Th1 cells, were proved to be significantly changed in DCM patients by immune cell infiltration analysis. In the PPI network analysis, STAT3, IL6, CCL2, PIK3R1, ESR1, CCL5, IL17A, TLR2, BUB1B and MYC were identified as hub genes, among which CCL2, CCL5 and TLR2 were further screened as feature biomarkers by using hub genes and immune cells correlation analysis. A diagnosis model was successfully constructed by using the three biomarkers with area under the curve (AUC) scores 0.981, 0.867 and 0.946 in merged dataset, GSE5406 and GSE57338, respectively.Conclusion: The present study identified three immune-related genes as diagnostic biomarkers for DCM, providing a novel perspective of immune and inflammatory response for the exploration of DCM molecular mechanisms.
Systemic Inflammation Evaluated by Interleukin-6 or C-Reactive Protein in Critically Ill Patients: Results From the FROG-ICU Study
Authors: Picod Adrien , Morisson Louis , de Roquetaillade Charles , Sadoune Malha , Mebazaa Alexandre , Gayat Etienne , Davison Beth A. , Cotter Gad , Chousterman Benjamin Glenn 
Published: May 2022

BackgroundThe prognostic impact of high concentration of interleukin-6 (IL-6) or C-reactive protein (CRP), two routinely available markers of systemic inflammation in the general population of critically ill patients, remains unclear. In a large cohort of critically ill patients including septic and non-septic patients, we assessed the relationship between baseline IL-6 or CRP and mortality, organ dysfunction, and the need for organ support.MethodsThis was an ancillary analysis of the prospective French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study including patients with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following intensive care unit (ICU) admission. The primary objective was to determine the association between baseline IL-6 or CRP concentration and survival until day 90. Secondary outcomes included organ dysfunction as evaluated by the Sequential Organ Failure Assessment (SOFA) score, and the need for organ support, including vasopressors/inotropes and/or renal replacement therapy (RRT).ResultsMedian IL-6 and CRP concentrations (n = 2,076) at baseline were 100.9 pg/ml (IQR 43.5–261.7) and 143.7 mg/L (IQR 78.6–219.8), respectively. Day-90 mortality was 30%. High IL-6 or CRP was associated with worse 90-day survival (hazard ratios 1.92 [1.63–2.26] and 1.21 [1.03–1.41], respectively), after adjustment on the Simplified Acute Physiology Score II (SAPS-II). High IL-6 was also associated with the need for organ-support therapies, such as vasopressors/inotropes (OR 2.67 [2.15–3.31]) and RRT (OR 1.55 [1.26–1.91]), including when considering only patients independent from those supports at the time of IL-6 measurement. Associations between high CRP and organ support were inconsistent.ConclusionIL-6 appears to be preferred over CRP to evaluate critically ill patients’ prognoses.
Case Report: Combining Molar Interradicular Osteotomy With Immediate Implant Placement: A Three-Year Case-Series Study
Authors: Alagl Adel S. , Madi Marwa 
Published: May 2022

Background: Immediate implant placement in the area of multirooted molars includes many anatomical challenges, particularly with osteotomy preparation in the interradicular bone.Methods: In this article, we are reporting ten cases in which implant beds were prepared before root extraction. After coronectomy, pre-extractive interradicular implant bed preparations were performed through the retained root complexes. A dimple in the roof of the furcation was created using a no. 8 round surgical bur. The osteotomies were then completed through the tooth’s initially retained root complex in the regular sequence of drilling. Before implant placement, the remaining root segments were removed. The retained root parts guided the osteotomy drills and allowed for precise positioning and angulation of the implant bed preparation with respect to the emergence profile of the tooth.Results: Data from a 3-year follow-up of the crestal bone showed good bone levels in relation to the implant platform.Conclusion: The technique described permitted accurate implant placement in the prepared osteotomy, thus enabling immediate implant positioning in multirooted extraction sites.
The Impact of Initial COVID-19 Episode Inflammation Among Adults on Mortality Within 12 Months Post-hospital Discharge
Authors: Mainous Arch G. , Rooks Benjamin J. , Orlando Frank A. 
Published: May 2022

BackgroundInflammation in the initial COVID-19 episode may be associated with post-recovery mortality. The goal of this study was to determine the relationship between systemic inflammation in COVID-19 hospitalized adults and mortality after recovery from COVID-19.MethodsAn analysis of electronic health records (EHR) for patients from 1 January, 2020 through 31 December, 2021 was performed for a cohort of COVID-19 positive hospitalized adult patients. 1,207 patients were followed for 12 months post COVID-19 episode at one health system. 12-month risk of mortality associated with inflammation, C-reactive protein (CRP), was assessed in Cox regressions adjusted for age, sex, race and comorbidities. Analyses evaluated whether steroids prescribed upon discharge were associated with later mortality.ResultsElevated CRP was associated other indicators of severity of the COVID-19 hospitalization including, supplemental oxygen and intravenous dexamethasone. Elevated CRP was associated with an increased mortality risk after recovery from COVID-19. This effect was present for both unadjusted (HR = 1.60; 95% CI 1.18, 2.17) and adjusted analyses (HR = 1.61; 95% CI 1.19, 2.20) when CRP was split into high and low groups at the median. Oral steroid prescriptions at discharge were found to be associated with a lower risk of death post-discharge (adjusted HR = 0.49; 95% CI 0.33, 0.74).DiscussionHyperinflammation present with severe COVID-19 is associated with an increased mortality risk after hospital discharge. Although suggestive, treatment with anti-inflammatory medications like steroids upon hospital discharge is associated with a decreased post-acute COVID-19 mortality risk.
The Effects of Alda-1 Treatment on Renal and Intestinal Injuries After Cardiopulmonary Resuscitation in Pigs
Authors: Yu Qian , Gao Jianbo , Shao Xuebo , Lu Wei , Chen Linling , Jin Lili 
Published: May 2022

AimAfter successful cardiopulmonary resuscitation (CPR), most survivors will develop acute kidney injury and intestinal barrier dysfunction, both of which contribute to the poor outcomes of cardiac arrest (CA) victims. Recently, the aldehyde dehydrogenase 2 (ALDH2) agonist, Alda-1 was shown to effectively alleviate regional ischemia/reperfusion injury of various organs. In the present study, we investigated the effects of Alda-1 treatment on renal and intestinal injuries after CA and resuscitation in pigs.MethodsTwenty-four male domestic pigs were randomly divided into one of the three groups: sham (n = 6), CPR (n = 10), or CPR+Alda-1 (n = 8). CA was induced and untreated for 8 min, and then CPR was performed for 8 min in the CPR and CPR+Alda-1 groups. At 5 min after resuscitation, a dose of 0.88 mg/kg of Alda-1 was intravenously administered in the CPR+Alda-1 group. The biomarkers of renal and intestinal injuries after resuscitation were regularly measured for a total of 24 h. Subsequently, the animals were euthanized, and then renal and intestinal tissues were obtained for the measurements of ALDH2 activity and expression, and cell apoptosis and ferroptosis.ResultsFive of the 10 animals in the CPR group and six of the eight animals in the CPR+Alda-1 group were successfully resuscitated. After resuscitation, the levels of biomarkers of renal and intestinal injuries were significantly increased in all animals experiencing CA and resuscitation compared with the sham group; however, Alda-1 treatment significantly alleviated renal and intestinal injuries compared to the CPR group. Post-resuscitation ALDH2 activity was significantly decreased and its expression was markedly reduced in the kidney and intestine in those resuscitated animals compared with the sham group; nevertheless, both of them were significantly greater in those animals receiving Alda-1 treatment compared to the CPR group. In addition, renal, intestinal apoptosis and ferroptosis after resuscitation were observed in the CPR and CPR+Alda-1 groups, in which both of them were significantly milder in the CPR+Alda1 group than in the CPR group.ConclusionsThe activation of ALDH2 by Alda-1 treatment significantly alleviated post-resuscitation renal and intestinal injuries through the inhibition of cell apoptosis and ferroptosis in a pig model of CA and resuscitation.
Newly Diagnosed Hepatic Encephalopathy Presenting as Non-convulsive Status Epilepticus: A Case Report and Literature Review
Authors: Olivero Marco , Gagliardi Delia , Costamagna Gianluca , Velardo Daniele , Magri Francesca , Triulzi Fabio , Conte Giorgio , Comi Giacomo P. , Corti Stefania , Meneri Megi 
Published: May 2022

BackgroundHepatic encephalopathy is characterized by psychiatric and neurological abnormalities, including epileptic seizure and non-convulsive and convulsive status epilepticus. Conventional brain magnetic resonance imaging is useful in supporting diagnosis since it can reveal specific radiological findings. In the literature, there is no description of hepatic encephalopathy onset as non-convulsive status epilepticus; we provide the first report.Case SummaryWe report a case of a 67-year-old woman, without history of cirrhosis, presenting altered mental state, normal brain computed tomography imaging, and electroencephalography suggestive of epileptic activity. We suspected non-convulsive status epilepticus, and we administered diazepam and levetiracetam with clinical improvement. Thus, we made a diagnosis of non-convulsive status epilepticus. A radiological study with brain magnetic resonance imaging showed bilateral hyperintensity on T1-weighted sequences of globus pallidus and hyperintensity of both corticospinal tracts on T2-weighted fluid-attenuated inversion recovery sequences. Blood tests revealed hyperammonemia, mild abnormality of liver function indices, and chronic Hepatitis B and D virus coinfection. Hepatic elastosonography suggested liver cirrhosis. The patient started antiviral therapy with entecavir and prevention of hepatic encephalopathy with rifaximin and lactulose; she was discharged with a normal mental state.ConclusionsHepatic encephalopathy can present as an initial manifestation with non-convulsive status epilepticus. Electroencephalography is useful for differentiating non-convulsive status epilepticus from an episode of hepatic encephalopathy, and neuroimaging aids the diagnostic process.
Joint Association of Low Vitamin K1 and D Status With First Stroke in General Hypertensive Adults: Results From the China Stroke Primary Prevention Trial (CSPPT)
Authors: Wei Yaping , Ma Hai , Xu Benjamin , Wang Zhuo , He Qiangqiang , Liu Lishun , Zhou Ziyi , Song Yun , Chen Ping , Li Jianping , Zhang Yan , Mao Guangyun , Wang Binyan , Tang Genfu , Qin Xianhui , Zhang Hao , Xu Xiping , Huo Yong , Guo Huiyuan 
Published: May 2022

BackgroundVitamin K plays a role in preventing vascular calcification and may have a synergetic influence with vitamin D on cardiovascular health. However, whether this relationship applies to stroke, especially in a high-risk population of hypertensive individuals, remains unclear. The present study aims to study the joint association of low vitamin K1 and D status with first stroke in general hypertensive adults.MethodsThis study used a nested, case–control design with data from the China Stroke Primary Prevention Trial. The analysis included 604 first total stroke patients and 604 matched controls from a Chinese population with hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.ResultsThere was a non-linear negative association between plasma vitamin K1 and the risk of first total stroke or ischemic stroke in the enalapril-only group. Compared to participants in vitamin K1 quartile 1, a significantly lower risk of total stroke (OR = 0.58, 95% CI: 0.36, 0.91, P = 0.020) or ischemic stroke (OR = 0.34, 95% CI: 0.17, 0.63, P &lt; 0.001) was found in participants in vitamin K1 quartile 2-4 in the enalapril-only group. When further divided into four subgroups by 25(OH)D and vitamin K1, a significantly higher risk of total stroke or ischemic stroke was observed in participants with both low vitamin K1 and 25(OH)D compared to those with both high vitamin K1 and 25(OH)D in the enalapril-only group. No increased risk was observed in the groups low in one vitamin only.ConclusionLow concentrations of both vitamin K1 and 25(OH)D were associated with increased risk of stroke.
Predictive Efficacy of a Radiomics Random Forest Model for Identifying Pathological Subtypes of Lung Adenocarcinoma Presenting as Ground-Glass Nodules
Authors: Zhao Fen-hua , Fan Hong-jie , Shan Kang-fei , Zhou Long , Pang Zhen-zhu , Fu Chun-long , Yang Ze-bin , Wu Mei-kang , Sun Ji-hong , Yang Xiao-ming , Huang Zhao-hui 
Published: May 2022

Purpose To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs).MethodsWe retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect.ResultsThere was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P&gt;0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities.ConclusionsThe radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application.
Peripheral T-Cell Lymphomas Involving the Central Nervous System: A Report From the Czech Lymphoma Study Group Registry
Authors: Mocikova Heidi , Pytlík Robert , Benesova Katerina , Janikova Andrea , Duras Juraj , Sykorova Alice , Steinerova Katerina , Prochazka Vit , Campr Vit , Belada David , Trneny Marek 
Published: May 2022

IntroductionWe analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066).Materials and MethodsOut of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse.ResultsPatients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1).ConclusionsThe incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.