bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary hormonal alterations in short-term severe hypothyroidism; in the focus: Apelin and copeptin
Authors: Gergics Marin , Pham-Dobor Gréta , Horváth-Szalai Zoltán , Kőszegi Tamás , Mezősi Emese , Bajnok László 
Published: September 2022

ObjectiveThis study aimed to investigate the complex interactions of thyroid hormone, apelin, and copeptin in the fluid–ion homeostasis of patients with severe transitory hypothyroidism.MethodsIn this prospective observational study, 39 patients (ECOG: 0; 11 men, 28 women, mean age: 50.3 ± 14.9 years) were investigated during short-term severe hypothyroidism due to surgical removal of the thyroid gland and after adequate thyroid replacement therapy. In addition to the routinely available lab tests, copeptin and apelin levels were determined using ELISA.ResultsIn the hypothyroid state, apelin concentration was lower, while copeptin levels did not differ compared to the euthyroid condition. Apelin showed a positive correlation with copeptin (p = 0.003), sodium (p = 0.002), NT-proBNP (p &lt; 0.001), and fT4 (p &lt; 0.001) and a negative correlation with thyroid-stimulating hormone (TSH) (p &lt; 0.001). In multivariate linear regression models, copeptin and TSH proved to be significant independent predictors of apelin levels, of which TSH had an explanatory power of 48.7%. Aside from apelin, copeptin only correlated with sodium (p = 0.046). Sodium levels were negatively associated with TSH (p = 0.004) and positively with ACTH (p = 0.002) and cortisol (p = 0.047), in addition to copeptin. None of the parameters were independent predictors of serum sodium levels in a multivariate regression model.ConclusionsIn short-term severe hypothyroidism, serum apelin level is markedly decreased, which may predispose susceptible patients to hyponatremia, while the level of copeptin is unchanged. TSH and copeptin are independent predictors of apelin concentration, of which TSH is stronger.
Influence of grooved rib tip structure on tip loss and heat transfer in a gas turbine blade
Authors: Kong Zhiqi , Zhang Tianyi , Du Wei 
Published: September 2022

This study focuses on the effects of three groove tip structures (full rib groove tip, partial rib tip on the suction side, and partial rib tip on the pressure side) on tip leakage flow, aerodynamic characteristics of a cascade, and heat transfer in a gas turbine blade. The groove’s width B = 1.6 mm, while the tip clearance is τ = 1.2 mm. Results of the flow parameters, fluid flow, and heat transfer in the recessed channel are discussed. The results show that all ribbed tips obtain more uniform outlet flow angle distribution and higher aerodynamic performance than the plane tips. The total aerodynamic pressure loss of the ribbed tips on the pressure side is the same as that of complete ribbed tips. The evolution mechanisms are different, although both can improve the turbine efficiency. Although the partial rib tip on the pressure side weakens the mixing of the channel vortex and leakage vortex near the trailing edge and has the best control effect on the leakage vortex, the lack of the suction side rib will make it easier for the low-energy fluid to flow into the gap from the front of the suction side, which is not conducive to reducing the leakage flow inside the gap; the full rib tip not only minimizes the tip relative leakage flow and leakage loss but also increases the channel vortex loss. With the complex vortex system in the groove and the rib blocking effect at the leakage outlet, the suction-side rib tip becomes the tip structure with the best leakage flow control effect under the same clearance, but the leakage vortex loss is the highest.
Defining and targeting patterns of T cell dysfunction in inborn errors of immunity
Authors: Campos Jose S. , Henrickson Sarah E. 
Published: September 2022

Inborn errors of immunity (IEIs) are a group of more than 450 monogenic disorders that impair immune development and function. A subset of IEIs blend increased susceptibility to infection, autoimmunity, and malignancy and are known collectively as primary immune regulatory disorders (PIRDs). While many aspects of immune function are altered in PIRDs, one key impact is on T-cell function. By their nature, PIRDs provide unique insights into human T-cell signaling; alterations in individual signaling molecules tune downstream signaling pathways and effector function. Quantifying T-cell dysfunction in PIRDs and the underlying causative mechanisms is critical to identifying existing therapies and potential novel therapeutic targets to treat our rare patients and gain deeper insight into the basic mechanisms of T-cell function. Though there are many types of T-cell dysfunction, here we will focus on T-cell exhaustion, a key pathophysiological state. Exhaustion has been described in both human and mouse models of disease, where the chronic presence of antigen and inflammation (e.g., chronic infection or malignancy) induces a state of altered immune profile, transcriptional and epigenetic states, as well as impaired T-cell function. Since a subset of PIRDs amplify T-cell receptor (TCR) signaling and/or inflammatory cytokine signaling cascades, it is possible that they could induce T-cell exhaustion by genetically mimicking chronic infection. Here, we review the fundamentals of T-cell exhaustion and its possible role in IEIs in which genetic mutations mimic prolonged or amplified T-cell receptor and/or cytokine signaling. Given the potential insight from the many forms of PIRDs in understanding T-cell function and the challenges in obtaining primary cells from these rare disorders, we also discuss advances in CRISPR-Cas9 genome-editing technologies and potential applications to edit healthy donor T cells that could facilitate further study of mechanisms of immune dysfunctions in PIRDs. Editing T cells to match PIRD patient genetic variants will allow investigations into the mechanisms underpinning states of dysregulated T-cell function, including T-cell exhaustion.
Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg
Authors: Yu Yu , Zhang Yingqiang , Dai Yuzhu , Sun Qingyang , Jiang Chun , Xu Xujian , Mei Chuanzhong , Cheng Jun 
Published: September 2022

ObjectiveWe detected the serum HBsAg immune complex (HBsAg-CIC) and sequenced the HBV S gene in these patients to reveal the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics, protein function changes, and HBsAg immune complex formation.MethodsA total of 204 samples were collected and divided into high-level (n = 60, HBsAg level &gt;10 IU/ml) and low-level (n = 144, HBsAg level ≤ 10 IU/ml) HBsAg groups. The clinical and epidemiological data of the two groups were statistically compared. According to different serological patterns and genotypes, the HBsAg-CIC results of the high-level and low-level HBsAg groups were divided into different subgroups, and then the HBsAg-CIC positive rates among different subgroups were compared. We sequenced the S gene of HBV from the two groups and identified the relevant mutations in the MHR of the S gene. In addition, we compared the changes in HBsAg protein properties and functions after hot spot mutation in the MHR of the S gene.ResultsComparing the positive rates of HBsAg-CIC under different serological patterns and genotypes in the two groups, the HBsAg-CIC positive rate was higher in the low-level HBsAg group. Moreover, there was weak correlation between HBsAg-CIC and HBsAg or HBV DNA in both groups (r = 0.32, 0.27, 0.41, 0.48; P &lt; 0.05). Sequencing of S gene in the two groups, showed that the hot-spot mutations were T126A, M133L/T/S, and F134L/T/I in MHR of S gene of genotype B, and hot-spot mutations were Q101R and I126S/T in MHR of S gene of genotype C. Additionally, the positive rate of MHR mutation in the S gene from HBsAg-CIC positive patients was higher in the low-level HBsAg group.ConclusionThe host immune process of clearing HBV seems to have multiple site mutations in MHR, which changes the physicochemical properties and functions of HBsAg and intensifies the formation of HBsAg-CIC, thus avoiding the effective recognition of HBsAg by the host and resulting in immune tolerance between the host and HBV, which may be one of the formation mechanisms of sustained low-level expression of HBsAg in the serum of HBV-infected persons.
Diagnostic value of an algorithm for autoimmune epilepsy in a retrospective cohort
Authors: Sakamoto Mitsuhiro , Matsumoto Riki , Shimotake Akihiro , Togawa Jumpei , Takeyama Hirofumi , Kobayashi Katsuya , Leypoldt Frank , Wandinger Klaus-Peter , Kondo Takayuki , Takahashi Ryosuke , Ikeda Akio 
Published: September 2022

PurposeThis study aims to propose a diagnostic algorithm for autoimmune epilepsy in a retrospective cohort and investigate its clinical utility.MethodsWe reviewed 60 patients with focal epilepsy with a suspected autoimmune etiology according to board-certified neurologists and epileptologists. To assess the involvement of the autoimmune etiology, we used the patients' sera or cerebrospinal fluid (CSF) samples to screen for antineuronal antibodies using rat brain immunohistochemistry. Positive samples were analyzed for known antineuronal antibodies. The algorithm applied to assess the data of all patients consisted of two steps: evaluation of clinical features suggesting autoimmune epilepsy and evaluation using laboratory and imaging findings (abnormal CSF findings, hypermetabolism on fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging abnormalities, and bilateral epileptiform discharges on electroencephalography). Patients were screened during the first step and classified into five groups according to the number of abnormal laboratory findings. The significant cutoff point of the algorithm was assessed using a receiver-operating characteristic curve analysis.ResultsFourteen of the 60 patients (23.3%) were seropositive for antineuronal antibodies using rat brain immunohistochemistry. Ten patients had antibodies related to autoimmune epilepsy/encephalitis. The cutoff analysis of the number of abnormal laboratory and imaging findings showed that the best cutoff point was two abnormal findings, which yielded a sensitivity of 78.6%, a specificity of 76.1%, and an area under the curve of 0.81.ConclusionThe proposed algorithm could help predict the underlying autoimmune etiology of epilepsy before antineuronal antibody test results are available.
Continuous theta-burst stimulation over the left posterior inferior frontal gyrus induced compensatory plasticity in the language network
Authors: An HyunJung , Bashir Shahid , Cha Eunsil , Lee Jeongeun , Ohn Suk Hoon , Jung Kwang-Ik , Yoo Woo-Kyoung 
Published: September 2022

IntroductionContinuous theta-burst stimulation (cTBS) has been used as an effective tool in inducing inhibitory aftereffect within a short time periods in the motor cortex; this has been demonstrated in the language network to a limited degree with controversial effect. In this study, we aimed to delineate the offline effect of cTBS-induced changes to the left posterior inferior frontal gyrus (pIFG) in healthy subjects using functional magnetic resonance imaging (fMRI).MethodsTwenty healthy, normal subjects (mean age: 30.84 years) were recruited. They all were right-handed and had no contra-indications for fMRI or cTBS. They were randomly assigned into the treatment group or the sham control group.ResultsANOVA showed that cTBS had a significant main effect only when the sham treatment was subtracted from the real stimulation in left superior temporal, left inferior frontal gyrus, thalamus, and right insular cortex (uncorrected p &lt; 0.002). The subjects' post-cTBS condition differed significantly from their pre-cTBS condition in the left pIFG (uncorrected p &lt; 0.002). There were interactions in the pIFG, bilateral superior parietal lobules, left superior temporal, left supramarginal, and left cuneus areas. The application of cTBS induced increased BOLD signals in language-related networks by stimulating the left pIFG (BA 44). This implies that inhibiting the pIFG led to increased use of language network resources.ConclusionThis study demonstrated cTBS-induced changes in the language network caused by stimulation of the left pIFG. Based on these findings, future studies on the therapeutic effects of cTBS on the right Broca's homolog area are warranted.
Fragile X-associated tremor ataxia syndrome rating scale: Revision and content validity using a mixed method approach
Authors: Tosin Michelle H. S. , Stebbins Glenn T. , Goetz Christopher G. , Hagerman Randi J. , Hessl David , Zolecki Melissa A. , Todd Peter K. , Leehey Maureen A. , Hall Deborah A. 
Published: September 2022

BackgroundThe original Fragile X-associated Tremor Ataxia Syndrome Rating Scale (FXTAS-RS) contained 61 items, some requiring modifications to better meet recommendations for patient-focused rating scale development.PurposeProvide initial validation of a revised version of the FXTAS-RS for motor signs.MethodWe conducted a two-phase mixed-method approach. In Phase 1, revision, we implemented a Delphi technique identifying pertinent domains/subdomains and developing items through expert consensus. In Phase 2, content validation, we conducted cognitive pretesting assessing comprehensibility, comprehensiveness, and relevance of items to FXTAS motor signs.ResultsAfter five rounds of Delphi panel and two rounds of cognitive pretesting, the revised version of the FXTAS-RS was established with 18 items covering five domains and 13 subdomains of motor signs. Cognitive pretesting revealed adequate content validity for the assessment of FXTAS motor signs.ConclusionThe revised FXTAS-RS has been successfully validated for content and it is now ready for large-scale field validation.
TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy
Authors: Wang Xiao-Kun , Gao Chao , Zhong He-Quan , Kong Xiang-Yu , Qiao Rui , Zhang Hui-Chun , Chen Bai-Yun , Gao Yang , Li Bing 
Published: September 2022

Objective: Several studies have shown the significance of neuroinflammation in the pathological progress of cerebral palsy (CP). However, the etiology of CP remains poorly understood. Spastic CP is the most common form of CP, comprising 80% of all cases. Therefore, identifying the specific factors may serve to understand the etiology of spastic CP. Our research aimed to find some relevant factors through protein profiling, screening, and validation to help understand the pathogenesis of cerebral palsy.Materials and methods: In the current study, related clinical parameters were assessed in 18 children with spastic CP along with 20 healthy individuals of the same age. Blood samples of the spastic CP children and controls were analyzed with proteomics profiling to detect differentially expressed proteins. On the other hand, after hypoxic-ischemic encephalopathy (HIE) was induced in the postnatal day 7 rat pups, behavioral tests were performed followed by detection of the differentially expressed markers and inflammatory cytokines in the peripheral blood and cerebral cortex of the CP model rats by Elisa and Western blot. Independent sample t-tests, one-way analysis of variance, and the Pearson correlation were used for statistical analysis.Results: Through proteomic analysis, differentially expressed proteins were identified. Among them, tissue-nonspecific alkaline phosphatase (TNAP), the gene expression product of alkaline phosphatase (ALPL), was downregulated in spastic CP. In addition, significantly lower TNAP levels were found in the children with CP and model rats. In contrast, compared with the sham rats, the model rats demonstrated a significant increase in osteopontin and proinflammatory biomarkers in both the plasma and cerebral cortex on the ischemic side whereas serum 25 hydroxyvitamin D and IL-10 were significantly decreased. Moreover, serum TNAP level was positively correlated with serum CRP and IL-10 in model rats.Conclusion: These results suggest that TNAP is the potential molecule playing a specific and critical role in the neuroinflammation in spastic CP, which may provide a promising target for the diagnosis and treatment of spastic CP.
Incidence, mortality, and survival analyses of patients with thymic lymphoma
Authors: Wang Li , Wang Zhile , Huo Lanqing , Zhao Ailin 
Published: September 2022

ObjectivesTo explore the clinical and prognostic characteristics of thymic lymphoma and the effects of current treatments on the prognosis.MethodsPatients diagnosed as primary thymic lymphoma between 1975 and 2018 from the nine states of the US were identified, including Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle–Puget Sound, and Utah. Incidence and mortality rates were analyzed using SEER*Stat 8.3.9 software. Univariate and multivariate Cox regressions were performed to identify prognostic factors. The Kaplan–Meier curve and log-rank test were used to compare overall survival (OS) among different treatments.ResultsA total of 233 patients diagnosed as thymic lymphoma were identified, and eight of them were lost to follow-up or died upon diagnosis. The incidence of thymic lymphoma was 2.032 per ten million (95% CI: 1.777–2.312), and the mortality rate was 0.649 per ten million (95% CI: 0.508–0.817). Among the 225 patients with definite follow-up, 98 were males and 127 were females, with a median age of 33 years. The Cox regression results showed that age and pathological type were independent risk prognostic factors. The 5-, 10-, and 20-year OS were 80.0%, 77.5%, and 70.9%, respectively. For Ann Arbor stage I and II patients, there was no significant difference between the surgical group (N = 78) and the non-operative group (N = 65; P = 0.270). The radiotherapy group (N = 79) had better OS than the non-radiotherapy group (N = 64) in the first 25 years, and the prognosis in the later years was not significantly different (P = 0.051). The chemotherapy group (N = 37) had a significantly better prognosis than the non-chemotherapy group (N = 37; P = 0.020). Patients who received postoperative radiotherapy (N = 45) or who only received radiotherapy (N = 34) seemed to have better OS than that of patients who only received surgery (N = 33), although the difference was not significant (P = 0.063).ConclusionsAge and pathological type were independent prognostic factors for thymic lymphoma. Surgical treatment had limited effects on OS, while both radiotherapy and chemotherapy could significantly improve the survival outcome.
Patients with melanoma treated with immune checkpoint inhibitors who had non-thyroid endocrine and skin immune-related adverse events have better prognosis: A systematic review and meta-analysis
Authors: Sun Qian , Sun Hongyan , Wu Nan , Hu Yue , Zhang Fangqing , Cong Xianling 
Published: September 2022

BackgroundSeveral studies have reported an association between the occurrence of immune-related adverse events (irAEs) and prognosis in patients with melanoma treated with immune checkpoint inhibitors (ICIs), but the results remain controversial. We conducted a systematic review and meta-analysis to investigate the association between irAEs and survival in patients with melanoma treated with ICIs.MethodsWe searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases through May 5, 2022 for clinical studies evaluating the association between irAEs and in melanoma patients treated with ICIs. Combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using fixed- or random-effects models based on heterogeneity. ResultsA total of 60 articles were included, with 16,520 patients. In patients with melanoma treated with ICIs, the occurrence of irAEs was significantly associated with better OS (HR, 0.58; 95% confidence interval [CI], 0.51–0.66; P&lt;0.00001) and PFS (HR, 0.61; 95%CI, 0.51–0.72; P&lt;0.00001). Endocrine irAEs (OS, HR, 0.81; 95%CI, 0.72–0.92; P=0.001; PFS: HR, 0.84; 95%CI, 0.73–0.96, P=0.009), skin irAEs (OS, HR, 0.59; 95%CI, 0.41–0.85; P=0.004; PFS: HR, 0.43; 95%CI, 0.36–0.52; P&lt;0.00001), vitiligo (OS, HR, 0.22; 95%CI, 0.15–0.31; P&lt;0.00001; PFS, HR, 0.33; 95%CI, 0.25–0.44; P&lt;0.00001), and grade 1–2 irAEs (OS, HR, 0.67; 95%CI, 0.58–0.78; P&lt;0.00001; PFS, HR, 0.62; 95%CI, 0.51–0.76; P&lt;0.00001) showed similar results. However, thyroid, lung, gastrointestinal, liver, and grade 3–4 irAEs were not significantly associated with OS and PFS. The occurrence of non-thyroid endocrine irAEs was significantly associated with better OS (HR, 0.22; 95%CI, 0.15–0.31; P&lt;0.00001). In patients with melanoma treated with anti-programmed cell death protein 1 (OS, HR, 0.61; 95%CI, 0.51–0.72; P&lt;0.00001; PFS, HR, 0.59; 95%CI, 0.47–0.74; P&lt;0.00001), the association between irAEs and clinical benefit was clearer than in patients treated with anti-cytotoxic T-lymphocyte-associated protein 4 (OS, HR, 0.68; 95%CI, 0.52–0.89; P=0.005; PFS, HR, 0.93; 95%CI, 0.49–1.78; P=0.83).ConclusionAmong patients with melanoma treated with ICIs, those who developed non-thyroid endocrine irAEs and cutaneous irAEs have better prognosis. This suggests that non-thyroid endocrine irAEs and cutaneous irAEs may be a prognostic biomarker for patients with melanoma treated with ICIs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022338308.
Clinical features and prognostic factors in patients with microvascular infiltration of hepatocellular carcinoma: Development and validation of a nomogram and risk stratification based on the SEER database
Authors: Yang Dashuai , Zhu Mingqiang , Xiong Xiangyun , Su Yang , Zhao Fangrui , Hu Yong , Zhang Guo , Pei Junpeng , Ding Youming 
Published: September 2022

BackgroundThe goal is to establish and validate an innovative prognostic risk stratification and nomogram in patients of hepatocellular carcinoma (HCC) with microvascular invasion (MVI) for predicting the cancer-specific survival (CSS).Methods1487 qualified patients were selected from the Surveillance, Epidemiology and End Results (SEER) database and randomly assigned to the training cohort and validation cohort in a ratio of 7:3. Concordance index (C-index), area under curve (AUC) and calibration plots were adopted to evaluate the discrimination and calibration of the nomogram. Decision curve analysis (DCA) was used to quantify the net benefit of the nomogram at different threshold probabilities and compare it to the American Joint Committee on Cancer (AJCC) tumor staging system. C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) were applied to evaluate the improvement of the new model over the AJCC tumor staging system. The new risk stratifications based on the nomogram and the AJCC tumor staging system were compared.ResultsEight prognostic factors were used to construct the nomogram for HCC patients with MVI. The C-index for the training and validation cohorts was 0.785 and 0.776 respectively. The AUC values were higher than 0.7 both in the training cohort and validation cohort. The calibration plots showed good consistency between the actual observation and the nomogram prediction. The IDI values of 1-, 3-, 5-year CSS in the training cohort were 0.17, 0.16, 0.15, and in the validation cohort were 0.17, 0.17, 0.17 (P&lt;0.05). The NRI values of the training cohort were 0.75 at 1-year, 0.68 at 3-year and 0.67 at 5-year. The DCA curves indicated that the new model more accurately predicted 1-year, 3-year, and 5-year CSS in both training and validation cohort, because it added more net benefit than the AJCC staging system. Furthermore, the risk stratification system showed the CSS in different groups had a good regional division.ConclusionsA comprehensive risk stratification system and nomogram were established to forecast CSS for patients of HCC with MVI.