bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma
Authors: Liu Xu-Sheng , Liu Jia-Min , Chen Yi-Jia , Li Fu-Yan , Wu Rui-Min , Tan Fan , Zeng Dao-Bing , Li Wei , Zhou Hong , Gao Yan , Pei Zhi-Jun 
Published: October 2021

Background: Hexokinase 2 not only plays a role in physiological function of human normal tissues and organs, but also plays a vital role in the process of glycolysis of tumor cells. However, there are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study.Methods: Oncomine, Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to analyze the expression differences of HK2 in Pan-cancer and ESCA cohort, and to analyze the correlation between HK2 expression level and clinicopathological features of TCGA ESCA samples. GO/KEGG, GGI, and PPI analysis of HK2 was performed using R software, LinkedOmics, GeneMANIA and STRING online tools. The correlation between HK2 and ESCA immune infiltration was analyzed TIMER and TCGA ESCA cohort. The correlation between HK2 expression level and m6A modification of ESCA was analyzed by utilizing TCGA ESCA cohort.Results: HK2 is highly expressed in a variety of tumors, and its high expression level in ESCA is closely related to the weight, cancer stages, tumor histology and tumor grade of ESCA. The analysis results of GO/KEGG showed that HK2 was closely related to cell adhesion molecule binding, cell-cell junction, ameboidal-type cell migration, insulin signaling pathway, hif-1 signaling pathway, and insulin resistance. GGI showed that HK2 associated genes were mainly involved in the glycolytic pathway. PPI showed that HK2 was closely related to HK1, GPI, and HK3, all of which played an important role in tumor proliferation. The analysis results of TIMER and TCGA ESCA cohort indicated that the HK2 expression level was related to the infiltration of various immune cells. TCGA ESCA cohort analyze indicated that the HK2 expression level was correlated with m6A modification genes.Conclusion: HK2 is associated with tumor immune infiltration and m6A modification of ESCA, and can be used as a potential biological target for diagnosis and therapy of ESCA.
Familial Temperature-Sensitive Auditory Neuropathy: Distinctive Clinical Courses Caused by Variants of the OTOF Gene
Authors: Zhu Yi-Ming , Li Qi , Gao Xue , Li Yan-Fei , Liu You-Li , Dai Pu , Li Xiang-Ping 
Published: October 2021

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype–phenotype correlations in a family with TSAN.Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only.Results: Audiological tests during the patients’ febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G &gt; C (p.Glu1700Gln), and one novel variant, c.4882C &gt; A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family.Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.
Highly Efficient Phosphorescent Blue-Emitting [3+2+1] Coordinated Iridium (III) Complex for OLED Application
Authors: Liu Zijian , Zhang Si-Wei , Zhang Meng , Wu Chengcheng , Li Wansi , Wu Yuan , Yang Chen , Kang Feiyu , Meng Hong , Wei Guodan 
Published: October 2021

Cyclometalated iridium (III) complexes are indispensable in the field of phosphorescent organic light-emitting diodes (PhOLEDs), while the improvement of blue iridium (III) complexes is as yet limited and challenging. More diversified blue emitters are needed to break through the bottleneck of the industry. Hence, a novel [3+2+1] coordinated iridium (III) complex (noted as Ir-dfpMepy-CN) bearing tridentate bis-N-heterocyclic carbene (NHC) chelate (2,6-bisimidazolylidene benzene), bidentate chelates 2-(2,4-difluorophenyl)-4-methylpyridine (dfpMepy), and monodentate ligand (-CN) has been designed and synthesized. The tridentate bis-NHC ligand enhances molecular stability by forming strong bonds with the center iridium atom. The electron-withdrawing groups in the bidentate ligand (dfpMepy) and monodentate ligand (-CN) ameliorate the stability of the HOMO levels. Ir-dfpMepy-CN shows photoluminescence peaks of 440 and 466 nm with a high quantum efficiency of 84 ± 5%. Additionally, the HATCN (10 nm)/TAPC (40 nm)/TcTa (10 nm)/10 wt% Ir-dfpMepy-CN in DPEPO (10 nm)/TmPyPB (40 nm)/Liq (2.5 nm)/Al (100 nm) OLED device employing the complex shows a CIE coordinate of (0.16, 0.17), reaching a deeper blue emission. The high quantum efficiency is attributed to rapid singlet to triplet charge transfer transition of 0.9–1.2 ps. The successful synthesis of Ir-dfpMepy-CN has opened a new window to develop advanced blue emitters and dopant alternatives for future efficient blue PhOLEDs.
Clinical and Imaging Features of Patients With Encephalitic Symptoms and Myelin Oligodendrocyte Glycoprotein Antibodies
Authors: Wang Jingsi , Qiu Zhandong , Li Dawei , Yang Xixi , Ding Yan , Gao Lehong , Liu Aihua , Song Yang , Li Cunjiang , Gao Ran , Wang Lin , Wu Liyong , Jia Longfei , Guo Dongmei , Zhou Aihong , Jia Jianping , Huang Liyuan , Qu Miao , Gao Li , Dong Huiqing , Hao Junwei , Liu Zheng 
Published: October 2021

BackgroundMyelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD.MethodsWe reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis.ResultsWe identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E.ConclusionsThis study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions.
Sarcoidosis Following Hematopoietic Stem Cell Transplantation: Clinical Characteristics and HLA Associations
Authors: Wurm-Kuczera Rebecca Isabel , Buentzel Judith , Koenig Julia Felicitas Leni , Legler Tobias , Valk Jan-Jakob , Hasenkamp Justin , Jung Wolfram , Rademacher Jan-Gerd , Korsten Peter , Wulf Gerald Georg 
Published: October 2021

PurposeExtrinsic factors and genetic predisposition contribute to the etiology of sarcoidosis, converging in a phenotype of altered immune response associated with multisystemic inflammatory granulomatous tissue infiltration. Immunological reconstitution after hematopoietic stem cell transplantation (HSCT) may represent a unique window for the pathogenesis of the disease. We describe the incidence, clinicopathological features, and HLA associations of sarcoidosis after HSCT in a single-center cohort of patients, together with data from previously published cases.MethodsWe retrospectively analyzed clinical characteristics and HLA haplotypes from allogeneic (allo) or autologous (auto) HSCT patients from January 2001 through May 2021 at the University Medicine Goettingen (UMG), and data from previously published cases.ResultsA total number of 19 patients was identified. These included 4 patients from our center (3 allo HSCT and 1 auto HSCT) and 15 patients from the literature review. Thirteen patients had received an allo HSCT, and six patients had received an auto HSCT. Sarcoidosis occurred after a median interval of 20 (after allo HSCT) and 7 (after auto HSCT) months, respectively. The predominant HLA allele associated with sarcoidosis was HLA DRB1*03:01. Sarcoidosis involved the respiratory tract in 15 patients (three unknown, one without pulmonary involvement), and it was associated with graft-versus-host disease in 7 of 13 patients receiving allo HSCT. None of the donors or patients had a history of sarcoidosis before transplantation. Disease manifestations resolved with standard glucocorticoid treatment without long-term sequelae.ConclusionSarcoidosis may occur at low frequency during reconstitution of the immune system after HSCT. HLA allele associations reflect the associations observed in the general population, particularly with DRB1*03:01. Further insights into the interplay between Tcell reconstitution and the development of sarcoidosis could also provide novel approaches to an improved understanding of the pathogenesis in sarcoidosis.
Blocking of EphA2 on Endometrial Tumor Cells Reduces Susceptibility to Vδ1 Gamma-Delta T-Cell-Mediated Killing
Authors: Hudecek Robert , Kohlova Barbora , Siskova Ingrid , Piskacek Martin , Knight Andrea 
Published: October 2021

BackgroundEndometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus causing chronic inflammation, severe pain, and infertility. However, the innate immunity of gamma-delta (γδ) T lymphocytes in endometriosis has not been characterized. Women with endometriosis present numerous endocrine and immune dysfunctions and elevated risk for endometrial, ovarian, and breast cancers. The tyrosine kinase EphA2 is often overexpressed in cancer including endometrial carcinoma.MethodsWe analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (n = 19) and compared the counts with that of age- and sex-matched healthy donors (n = 33) using flow cytometry. Vδ1 and Vδ2 T cells isolated from healthy donors were used against KLE, RL-95, and Ishikawa endometrial tumor cells in 4 h flow cytometric cytotoxicity assays. The EphA2 blocking studies were performed using antibody, small-molecule inhibitor ALW-II-41-27, and the CRISPR/Cas9.ResultsWe determined Vδ1 T cells substantially reduced in patients’ peripheral blood (p &lt; 0.01) and peritoneal fluid (p &lt; 0.001). No differences were found for circulating Vδ2 T cells compared with peritoneal fluid samples. We observed inherent cytotoxic reactivity of Vδ1 and Vδ2 γδ T lymphocytes against endometrial tumor cells. Importantly, we found reduced specific lysis of EphA2-positive cell lines KLE and RL-95 by Vδ1 T cells in the EphA2 antibody blocking studies and by the EphA2 inhibitor. Furthermore, Vδ1 T-cell-mediated killing was significantly decreased in RL-95 cell EPHA2 knockout. Finally, potent cytolytic activity exerted by Vδ1 T cells was significantly reduced in EPHA2 knockouts in renal A-498 and colon HT-29 carcinoma cell lines.ConclusionsWe determined variable levels of Vδ1 and Vδ2 γδ T cells in endometriosis patients. We observed inherent cytotoxic reactivity of γδ T-cell subsets against endometrial cell lines. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of endometrial tumor killing mediated by Vδ1 γδ T cells. These results suggest that EphA2 is involved in tumor cell lysis and contributes to susceptibility to Vδ1 γδ T cells cytotoxic reactivity.
Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants
Authors: Bayarri-Olmos Rafael , Jarlhelt Ida , Johnsen Laust Bruun , Hansen Cecilie Bo , Helgstrand Charlotte , Rose Bjelke Jais , Matthiesen Finn , Nielsen Susanne Dam , Iversen Kasper Karmark , Ostrowski Sisse Rye , Bundgaard Henning , Frikke-Schmidt Ruth , Garred Peter , Skjoedt Mikkel-Ole 
Published: October 2021

The recent identification and rise to dominance of the P.1 and B.1.351 SARS-CoV-2 variants have brought international concern because they may confer fitness advantages. The same three positions in the receptor-binding domain (RBD) are affected in both variants, but where the 417 substitution differs, the E484K/N501Y have co-evolved by convergent evolution. Here we characterize the functional and immune evasive consequences of the P.1 and B.1.351 RBD mutations. E484K and N501Y result in gain-of-function with two different outcomes: The N501Y confers a ten-fold affinity increase towards ACE-2, but a modest antibody evasion potential of plasma from convalescent or vaccinated individuals, whereas the E484K displays a significant antibody evasion capacity without a major impact on affinity. On the other hand, the two different 417 substitutions severely impair the RBD/ACE-2 affinity, but in the combined P.1 and B.1.351 RBD variants, this effect is partly counterbalanced by the effect of the E484K and N501Y. Our results suggest that the combination of these three mutations is a two-step forward and one step back in terms of viral fitness.
Association Between Serum Creatinine Concentrations and Overall Survival in Patients With Colorectal Cancer: A Multi-Center Cohort Study
Authors: Yang Ming , Zhang Qi , Ruan Guo-Tian , Tang Meng , Zhang Xi , Song Meng-Meng , Zhang Xiao-Wei , Zhang Kang-Ping , Ge Yi-Zhong , Shi Han-Ping 
Published: October 2021

BackgroundColorectal cancer (CRC) is one of the most common malignancies throughout the world, with high rates of morbidity and mortality. Previous studies reported that serum creatinine (Scr) concentrations were associated with overall survival (OS) in cancer patients, but little is known about the association between Scr and OS in patients with CRC. This study investigated the relationship between Scr concentrations and OS in patients with CRC and examined possible effect modifiers.MethodsA retrospective cohort, including 1,733 patients with CRC, was established from a multi-center clinical study. Patients were divided into low (&lt;71 μmol/L in men or &lt;59 μmol/L in women), normal (71-104 μmol/L in men or 59-85 μmol/L in women) and high (&gt;104 μmol/L in men or &gt;85 μmol/L in women) Scr groups. Cox regression analysis was used to examine association between Scr concentrations and OS. Stratified (subgroup) analyses were used to examine men and women separately. Interaction tests were used to evaluate associations between each variable and OS, as well as possible interactions of these variables with Scr levels. Cross-classified analyses were used only in men.ResultsPatients with low [hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.19-1.72; P &lt; 0.001] or high (HR = 1.89, 95% CI = 1.36-2.63; P &lt; 0.001) Scr level had a significantly lower OS than patients with normal Scr levels. Significant interactions with Scr concentrations were observed for body mass index (P for interaction = 0.019) in men.ConclusionLow or high Scr concentration is associated with significantly lower OS in patients with CRC. Future study is warranted to investigate the underlying mechanism.
Conditional Intravesical Recurrence-Free Survival Rate After Radical Nephroureterectomy With Bladder Cuff Excision for Upper Tract Urothelial Carcinoma
Authors: Chung Jae Hoon , Song Wan , Kang Minyong , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong IL , Jeon Seong Soo , Lee Hyun Moo , Sung Hyun Hwan 
Published: October 2021

BackgroundTo evaluate the conditional intravesical recurrence (IVR)–free (IVRF) survival rate in patients with upper tract urothelial carcinoma (UTUC) who had no history of bladder cancer and no concomitant bladder cancer. Hence, we aimed to analyze a relatively large number of patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision (RNUx).MethodsWe retrospectively analyzed the data of 1,095 patients with UTUC who underwent RNUx. Their baseline characteristics, bladder tumor history, and UTUC features were analyzed to evaluate oncological outcomes. To determine the factors affecting IVR, surgical modality, use of preoperative ureteroscopy, TNM stage, and pathological outcomes were evaluated. Multivariable Cox regression analyses were performed to evaluate the factors affecting IVR. Conditional IVRF survival rate was analyzed using Kaplan–Meier curves.ResultsAmong the 1,095 patients, 462 patients developed IVR, and the mean time to the development of IVR was 13.08 ± 0.84 months after RNUx. A total of 30.74% of patients with IVR and 15.32% of those without IVR had a history of bladder cancer (p &lt; 0.001). Multivariable analysis showed that a history of bladder cancer, multifocal tumors, use of preoperative ureteroscopy, extravesical bladder cuffing method, lymph node involvement, positive surgical margins, and use of adjuvant chemotherapy were determined to be risk factors for IVR. The conditional IVRF rate was 74.0% at 12 months after RNUx, 87.1% at 24 months after RNUx, 93.6% at 36 months after RNUx, and 97.3% at 60 months after RNUx. The median IVRF survival period was 133.00 months for all patients. In patients with IVRF at 24 months after RNUx, only ureteroscopy was an independent risk factor for IVR [hazard ratio (HR) 1.945, p = 0.040]. In patients with IVRF at ≥36 months, there was no significant factor affecting IVR.ConclusionsActive IVR assessment is required until 36 months after RNUx. In addition, patient education and regular screening tests, such as urine analysis and cytology, are required for patients with IVRF for ≥36 months.
Distinguishing Hepatocellular Carcinoma From Hepatic Inflammatory Pseudotumor Using a Nomogram Based on Contrast-Enhanced Ultrasound
Authors: Liao Mengting , Wang Chenshan , Zhang Bo , Jiang Qin , Liu Juan , Liao Jintang 
Published: October 2021

BackgroundHepatocellular carcinoma (HCC) and hepatic iflammatory pseudotumor (IPT) share similar symptoms and imaging features, which makes it challenging to distinguish from each other in clinical practice. This study aims to develop a predictive model based on contrast-enhanced ultrasound (CEUS) and clinical features to discriminate HCC from IPT.MethodsSixty-two IPT and 146 HCC patients were enrolled in this study, where pathological diagnosis served as the reference standard for diagnosis. Clinical and ultrasound imaging data including CEUS features: enhancement degree during arterial phase, portal phase and delayed phase, enhancement pattern, early washout within 60 s, feeding artery, peritumoral vessels, peritumoral enhancement, and margin of nonenhanced area were retrospectively collected. Imaging data were reviewed by two experienced ultrasound doctors. Patients were randomly assigned to training and validation sets. Chi-squared test followed by LASSO regression was performed on ultrasonographic features in the training set to identify the most valuable features that distinguish HCC from IPT, based on which the sonographic score formula was generated. With the significant clinical and ultrasonographic indicators, a nomogram was developed. The performance of the nomogram was verified by ROC curve and decision curve analysis (DCA) with the comparison with sonographic score and the ultrasound doctor’s diagnosis.ResultsThe most valuable ultrasonographic features that distinguish between HCC and IPT were enhancement degree during arterial phase, early washout, peritumoral vessels, peritumoral enhancement, and liver background. The sonographic score based on these features was verified to be an independent factor that predicts the diagnosis (p = 0.003). Among the clinical indicators, AFP (p = 0.009) and viral hepatitis infection (p = 0.004) were significant. Sonographic score, AFP, and viral hepatitis were used to construct a predictive nomogram. The AUC of the nomogram was 0.989 and 0.984 in training and validation sets, respectively, which were higher than those of sonographic score alone (0.938 and 0.958) or the ultrasound doctor’s diagnosis (0.794 and 0.832). DCA showed the nomogram provided the greatest clinical usefulness.ConclusionA predictive nomogram based on a sonographic signature improved the diagnostic performance in distinguishing HCC and IPT, which may help with individualized diagnosis and treatment in clinical practice.