bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis
Authors: Li Ziqi , Hou Pengwei , Mu Shuwen , Wang Renzhi , Miao Hui , Feng Ming , Wang He , Zhang Wentai , Chen Yihao , Feng Tianshun , Wang Shousen , Fang Yi 
Published: February 2023

ObjectiveCOVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic.MethodsA search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients.ResultsA total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P &lt; 0.001), whereas FT4 were significantly higher (P &lt; 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P &lt; 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P &lt; 0.001), and 0.22 (P &lt; 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors.ConclusionsCompared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.
Adrenal crisis in infants and young children with adrenal insufficiency: Management and prevention
Authors: Bizzarri Carla , Capalbo Donatella , Wasniewska Malgorzata Gabriela , Baronio Federico , Grandone Anna , Cappa Marco 
Published: February 2023

BackgroundDespite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency.ObjectiveWe summarized current standards of clinical practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency.ResultsFifty-one children were investigated. Forty-one patients (32 patients &lt;4 yrs and 9 patients &gt;4 yrs) used quartered non-diluted 10 mg tablets. Two patients &lt;4 yrs used a micronized weighted formulation obtained from 10 mg tablets. Two patients &lt;4 yrs used a liquid formulation. Six patients &gt;4 yrs used crushed non-diluted 10 mg tablets. The overall number of episodes of adrenal crisis was 7.3/patient/yr in patients &lt;4yrs and 4.9/patient/yr in patients &gt;4 yrs. The mean number of hospital admissions was 0.5/patient/yr in children &lt;4 yrs and 0.53/patient/yr in children &gt;4 yrs. There was a wide variability in the individual number of events reported. Both children on therapy with a micronized weighted formulation reported no episode of suspected adrenal crisis during the 6-month observation period.ConclusionParental education on oral stress dosing and switching to parenteral hydrocortisone when necessary are the essential approaches to prevent adrenal crisis in children.
Research into the characteristic molecules significantly affecting liver cancer immunotherapy
Authors: Chen Junhong , Jin Hengwei , Zhou Hao , Hei Xufei , Liu Kai 
Published: February 2023

BackgroundThe past decade has witnessed unprecedented scientific breakthroughs, including immunotherapy, which has great potential in clinical applications for liver cancer.MethodsPublic data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and analyzed with R software.ResultsThe LASSO and SVM-RFE machine learning algorithms identified 16 differentially expressed genes (DEGs) related to immunotherapy, namely, GNG8, MYH1, CHRNA3, DPEP1, PRSS35, CKMT1B, CNKSR1, C14orf180, POU3F1, SAG, POU2AF1, IGFBPL1, CDCA7, ZNF492, ZDHHC22, and SFRP2. Moreover, a logistic model (CombinedScore) was established based on these DEGs, showing an excellent prediction performance for liver cancer immunotherapy. Patients with a low CombinedScore might respond better to immunotherapy. Gene Set Enrichment Analysis showed that many metabolism pathways were activated in patients with a high CombinedScore, including butanoate metabolism, bile acid metabolism, fatty acid metabolism, glycine serine and threonine metabolism, and propanoate metabolism. Our comprehensive analysis showed that the CombinedScore was negatively correlated with the levels of most tumor-infiltrating immune cells and the activities of key steps of cancer immunity cycles. Continually, the CombinedScore was negatively associated with the expression of most immune checkpoints and immunotherapy response-related pathways. Moreover, patients with a high and a low CombinedScore exhibited diverse genomic features. Furthermore, we found that CDCA7 was significantly correlated with patient survival. Further analysis showed that CDCA7 was positively associated with M0 macrophages and negatively associated with M2 macrophages, suggesting that CDCA7 could influence the progression of liver cancer cells by affecting macrophage polarization. Next, single-cell analysis showed that CDCA7 was mainly expressed in prolif T cells. Immunohistochemical results confirmed that the staining intensity of CDCA7 was prominently increased in the nucleus in primary liver cancer tissues compared to adjacent non-tumor tissues.ConclusionsOur results provide novel insights into the DEGs and factors affecting liver cancer immunotherapy. Meanwhile, CDCA7 was identified as a potential therapeutic target in this patient population.
Advances in preventive vaccine development against HTLV-1 infection: A systematic review of the last 35 years
Authors: Santana Carolina Souza , Andrade Felipe de Oliveira , da Silva Greice Carolina Santos , Nascimento Jéssica Oliveira de Souza , Campos Raissa Frazão , Giovanetti Marta , Santos Luciane Amorim , Gois Luana Leandro , Alcantara Luiz Carlos Júnior , Barreto Fernanda Khouri 
Published: February 2023

IntroductionThe Human T-lymphotropic virus type 1 (HTLV-1) was the first described human retrovirus. It is currently estimated that around 5 to 10 million people worldwide are infected with this virus. Despite its high prevalence, there is still no preventive vaccine against the HTLV-1 infection. It is known that vaccine development and large-scale immunization play an important role in global public health. To understand the advances in this field we performed a systematic review regarding the current progress in the development of a preventive vaccine against the HTLV-1 infection.MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA®) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO). The search for articles was performed in PubMed, Lilacs, Embase and SciELO databases. From the 2,485 articles identified, 25 were selected according to the inclusion and exclusion criteria.ResultsThe analysis of these articles indicated that potential vaccine designs in development are available, although there is still a paucity of studies in the human clinical trial phase.DiscussionAlthough HTLV-1 was discovered almost 40 years ago, it remains a great challenge and a worldwide neglected threat. The scarcity of funding contributes decisively to the inconclusiveness of the vaccine development. The data summarized here intends to highlight the necessity to improve the current knowledge of this neglected retrovirus, encouraging for more studies on vaccine development aiming the to eliminate this human threat.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42021270412).
Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis
Authors: Liang Zhou , Hu Xinrong , Lin Ruoni , Tang Ziwen , Ye Ziyin , Mao Ren , Chen Wei , Zhou Yi 
Published: February 2023

BackgroundThere is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying the coexistence of CKD and UC are unclear. This study aimed to investigate the key molecules and pathways that may mediate the co-occurrence of CKD and UC through quantitative bioinformatics analysis based on a public RNA-sequencing database.MethodsThe discovery datasets of CKD (GSE66494) and UC (GSE4183), as well as validation datasets of CKD (GSE115857) and UC (GSE10616), were downloaded from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) with GEO2R online tool, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the DEGs were performed. Next, protein-protein interaction network was constructed with Search Tool for the Retrieval of Interacting Genes (STRING) and visualized by Cytoscape. Gene modules were identified by the plug-in MCODE and hub genes were screened using the plug-in CytoHubba. Then, correlation between immune cell infiltration and hub genes was analyzed, and the receiver operating characteristic curves were used to assess the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the relevant findings.ResultsA total of 462 common DEGs were identified and selected for further analyses. GO and KEGG enrichment analyses indicated that these DEGs were primarily enriched in immune- and inflammation-related pathways. Among them, the PI3K-Akt signaling pathway ranked top in both discovery and validation cohorts, and the key signal molecule phosphorylated Akt (p-Akt) was shown to be significantly overexpressed in human CKD kidneys and UC colons, and further elevated in CKD-UC comorbidity specimens. Moreover, nine candidate hub genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, and CSF3, were identified, of which ICAM1 was validated as a common hub gene. Besides, immune infiltration analysis revealed that neutrophils, macrophages, and CD4+ T memory cells significantly accumulated in both diseases, and ICAM1 was remarkably associated with neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated neutrophil infiltration was validated to be upregulated in kidney and colon biopsies of CKD and UC patients, and further increased in patients diagnosed with both CKD and UC. Finally, ICAM1 had shown critical value as a diagnostic marker for the co-occurrence of CKD and UC.ConclusionsOur study elucidated that immune response, PI3K-Akt signaling pathway, and ICAM1-mediated neutrophil infiltration might be the common pathogenesis of CKD and UC, and identified ICAM1 as a key potential biomarker and therapeutic target for the comorbidity of these two diseases.
Hydrogen peroxide attenuates rhinovirus-induced anti-viral interferon secretion in sinonasal epithelial cells
Authors: Lee Sang Hag , Han Mun Soo , Lee Tae Hoon , Lee Da Bin , Park Jae Hyung , Lee Seung Hyeok , Kim Tae Hoon 
Published: February 2023

BackgroundAltered innate defense mechanisms, including an imbalance between oxidants and antioxidants release, have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). The aim of this study is to investigate whether oxidative stress may attenuate the secretion of anti-viral interferons in human sinonasal mucosa.MethodsThe levels of H2O2 in nasal secretion were increased in patients with CRS with nasal polyps, compared with that of CRS patients without nasal polyps and control subjects. Normal sinonasal epithelial cells derived from healthy subjects were cultured under an air-liquid interface. The cultured cells were infected with rhinovirus 16 (RV 16) or treated with poly (I: C), TLR3 agonist, after being pretreated with an oxidative stressor, H2O2 or antioxidant, N-acetylcysteine (NAC). Thereafter, the expression levels of type I (IFN-β) and type III (IFN-λ1 and λ2) interferons and interferon-stimulated genes (ISGs) were evaluated with RT-qPCR, ELISA, and western blot.ResultsThe data showed that the production of type I (IFN-β) and type III (IFN-λ1 and λ2) interferons and ISGs was upregulated in cells infected with RV 16 or treated with poly (I: C). However, their up-regulated expression was attenuated in cells pretreated with H2O2, but not inhibited in cells pretreated with NAC. In line with these data, the up-regulated expression of TLR3, RIG-1, MDA5, and IRF3 was reduced in cells pretreated with H2O2, but not attenuated in cells treated with NAC. Furthermore, cells transfected with Nrf2 siRNA showed decreased secretion of anti-viral interferons whereas sulforaphane treatment enhanced the secretory capacity of antiviral interferons.ConclusionsThese results suggest that the production of RV16-induced antiviral interferons may be attenuated by oxidative stress.
An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway
Authors: Trezise Stephanie , Kong Isabella Y. , Hawkins Edwin D. , Herold Marco J. , Willis Simon N. , Nutt Stephen L. 
Published: February 2023

BackgroundHumoral immunity depends on the differentiation of B cells into antibody secreting cells (ASCs). Excess or inappropriate ASC differentiation can lead to antibody-mediated autoimmune diseases, while impaired differentiation results in immunodeficiency.MethodsWe have used CRISPR/Cas9 technology in primary B cells to screen for regulators of terminal differentiation and antibody production.ResultsWe identified several new positive (Sec61a1, Hspa5) and negative (Arhgef18, Pold1, Pax5, Ets1) regulators that impacted on the differentiation process. Other genes limited the proliferative capacity of activated B cells (Sumo2, Vcp, Selk). The largest number of genes identified in this screen (35) were required for antibody secretion. These included genes involved in endoplasmic reticulum-associated degradation and the unfolded protein response, as well as post-translational protein modifications.DiscussionThe genes identified in this study represent weak links in the antibody-secretion pathway that are potential drug targets for antibody-mediated diseases, as well as candidates for genes whose mutation results in primary immune deficiency.
Preventive effects of Mycobacterium tuberculosis DNA vaccines on the mouse model with latent tuberculosis infection
Authors: Liang Yan , Li Xiaoping , Yang Yourong , Xiao Li , Liang Yumei , Mi Jie , Xue Yong , Gong Wenping , Wang Lan , Wang Jie , Zhang Junxian , Shi Yingchang , Peng Bizhen , Chen Xiaoyang , Zhao Weiguo , Wu Xueqiong 
Published: February 2023

BackgroundAbout a quarter of the world’s population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model.MethodsA mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation.ResultsUsing chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P&lt;0.0001, P&lt;0.05). These vaccines could induce antigen-specific cellular immune responses. The number of IFN-γ effector T cells spots secreted by spleen lymphocytes in the ag85ab DNA group was significantly increased than those in the control groups (P&lt;0.05). In the splenocyte culture supernatant, IFN-γ and IL-2 levels in the ag85ab, rv2029c, and rv2659c DNA groups significantly increased (P&lt;0.05), and IL-17A levels in ag85ab and rv2659c DNA groups also significantly increased (P&lt;0.05). Compared with the PBS and vector groups, the proportion of CD4+CD25+FOXP3+ regulatory T cells in spleen lymphocytes of ag85ab, rv2660c, rv2029c, and rv3407 DNA groups were significantly reduced (P&lt;0.05).ConclusionsMTB ag85ab and 7 kinds of latent DNA vaccines showed immune preventive efficacies on a mouse model of LTBI, especially the rv2659c, and rv1733c DNA. Our findings will provide candidates for the development of new multi-stage vaccines against TB.
Clinical spectrum and outcomes of idiopathic inflammatory myopathies in South Africans
Authors: Birch Candice , Tikly Mohammed , Govind Nimmisha 
Published: February 2023

BackgroundIdiopathic inflammatory myopathies (IIM) are rare diseases for which there is a paucity of data in Africa. We undertook a retrospective records review of clinical and laboratory features of patients with IIM attending a tertiary service in Gauteng, South Africa.Materials and methodsCase records of patients seen between January 1990 and December 2019 and fulfilling the Bohan and Peter criteria for IIM were reviewed for demographics, clinical features, special investigations and drug therapy.ResultsOf 94 patients included in the study, 65 (69.1%) had dermatomyositis (DM) and 29 (30.9%) had polymyositis (PM). Overall, the mean (SD) age at presentation and disease duration were 41.5 (13.6) and 5.9 (6.2) years, respectively. 88 (93.6%) were Black Africans. The most common cutaneous features in DM patients were Gottron’s lesions (72.3%) and abnormal cuticular overgrowth (67.7%). Dysphagia was the most common extra-muscular feature (31.9%), more so in PM than DM (p = 0.02). Creatine kinase, total leucocyte count and CRP were similarly higher in PM than DM patients (p = 0.006, 0.002, and 0.01, respectively). Anti-nuclear and anti-Jo-1 antibodies were positive in 62.2 and 20.4% of patients tested, respectively, the latter significantly more in PM than DM patients (OR = 5.1, p = 0.03) and more likely to be positive with ILD (p = 0.001). Corticosteroids were prescribed in all patients, 89.4% had additional immunosuppressive drugs and 6.4% required intensive/high care. Malignancies occurred in three patients, all of whom had DM. There were seven known deaths.ConclusionThe present study provides further insights into the spectrum of clinical features of IIM, especially cutaneous features of DM, anti-Jo-1 antibodies and associated ILD, in a cohort of predominantly black African patients.
Post-operative gamma knife radiosurgery for WHO grade I intracranial meningiomas: A single-center, retrospective study
Authors: Yu Jinxiu , Zeng Jiamin , Hu Guanye , Wang Jing , Chen Guohao , Huang Minyi , Liang Shunyao , He Yong , Deng Yinhui , Gong Ye , Fu Junyi 
Published: February 2023

ObjectiveTo explore the results of the Gamma Knife radiosurgery (GKRS) for World Health Organization (WHO) grade I intracranial meningiomas after surgical resection.MethodsA total of 130 patients who were pathologically diagnosed as having WHO grade I meningiomas and who underwent post-operative GKRS were retrospectively reviewed in a single center.ResultsOf the 130 patients, 51 patients (39.2%) presented with radiological tumor progression with a median follow-up time of 79.7 months (ranging from 24.0 to 291.3 months). The median time to radiological tumor progression was 73.4 months (ranging from 21.4 to 285.3 months), whereas 1-, 3-, 5-, and 10-year radiological progression-free survival (PFS) was 100, 90, 78, and 47%, respectively. Moreover, 36 patients (27.7%) presented with clinical tumor progression. Clinical PFS at 1, 3, 5, and 10 years was 96, 91, 84, and 67%, respectively. After GKRS, 25 patients (19.2%) developed adverse effects, including radiation-induced edema (n = 22). In a multivariate analysis, a tumor volume of ≥10 ml and falx/parasagittal/convexity/intraventricular location were significantly associated with radiological PFS [hazard ratio (HR) = 1.841, 95% confidence interval (CI) = 1.018–3.331, p = 0.044; HR = 1.761, 95% CI = 1.008–3.077, p = 0.047]. In a multivariate analysis, a tumor volume of ≥10 ml was associated with radiation-induced edema (HR = 2.418, 95% CI = 1.014–5.771, p = 0.047). Of patients who presented with radiological tumor progression, nine were diagnosed with malignant transformation. The median time to malignant transformation was 111.7 months (ranging from 35.0 to 177.2 months). Clinical PFS after repeat GKRS was 49 and 20% at 3 and 5 years, respectively. Secondary WHO grade II meningiomas were significantly associated with a shorter PFS (p = 0.026).ConclusionsPost-operative GKRS is a safe and effective treatment for WHO grade I intracranial meningiomas. Large tumor volume and falx/parasagittal/convexity/intraventricular location were associated with radiological tumor progression. Malignant transformation was one of the main cause of tumor progression in WHO grade I meningiomas after GKRS.