bluuebunny/crossref_metadata_2025_split huggingface dataset:
TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Iqbal Kaleem , Qadri Zeeshan , Ahmed Saeeda O. , Al-Rasheed Maha , AlQatie Ahmed A. , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: March 2022

BackgroundPapillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity.MethodsWe retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis.ResultsAmong the PTMC patients included in this cohort, DM was noted in 6.0% (11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and male sex were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis.ConclusionsOur study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients.
TMT-Based Quantitative Proteomics Analysis of Synovial Fluid-Derived Exosomes in Inflammatory Arthritis
Authors: Huang Yukai , Liu Yuqi , Huang Qidang , Sun Shanmiao , Ji Zhuyi , Huang Lixin , Li Zhi , Huang Xuechan , Deng Weiming , Li Tianwang 
Published: March 2022

ObjectivesTo compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients.MethodsExosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted.ResultsA total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in “neutrophil degranulation” and “prion diseases”. Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in “acute-phase response” and “citrate cycle”. One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in “serine-type endopeptidase inhibitor activity” and “complement and coagulation cascades”. Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p &lt; 0.05).ConclusionOur study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).
N6-Methyladenosine Regulator-Mediated Immue Patterns and Tumor Microenvironment Infiltration Characterization in Glioblastoma
Authors: Xiong Wu , Li Cong , Wan Bowen , Zheng Ziyang , Zhang Yingfei , Wang Siming , Fan Jin 
Published: March 2022

BackgroundEpigenetic modifications, according to emerging evidence, perform a critical role for cellular immune response and tumorigenesis. Nonetheless, the role of N6-methyladenosine modification in shaping of the glioblastoma tumor microenvironment is unknown.MethodsN6-methyladenosine(m6A) methylation patterns in GBM patients were evaluated via multiple omics analysis of 15 m6A regulators and systematically correlated with tumor immune features. For quantification of N6-methyladenosine methylation patterns of individual patients, GM-score was developed and correlated with clinical and immunological characteristics.ResultsGlioblastoma has two different m6A methylation patterns that are strongly associated with TME characteristics, tumor subtype, immunotherapy response, and patient prognosis. High-GM-score is associated with an immune tolerance phenotype dominated by the IDH1 wild molecular subtype and the Mesenchymal tissue subtype, as well as a high infiltration of immune cells and stromal cells and a poor prognosis. Furthermore, despite higher immune checkpoint expression, individuals with a high-GM-score have a poorer response to anti-CTLA4 immunotherapy regimens due to T-cells dysfunctional. Low-GM-score individuals had an immunodeficient phenotype dominated by IDH mutant molecular subtypes and Proneural tissue subtypes, with less immune cell infiltration and a better prognosis. Furthermore, patients with low-GM-scores had higher microsatellite instability (MSI) and t-cell exclusion scores, as well as a better response to anti-CTLA4 immunotherapy regimens.ConclusionThis study demonstrated that m6A modification patterns play an important role in the shaping of TME complexity and diversity. The GM-score could identify m6A modification patterns in individual patients, resulting in a more personalization and efficacious anti-tumor immunotherapy strategy.
Natural SARS-CoV-2 Infection Affects Neutralizing Activity in Saliva of Vaccinees
Authors: Garziano Micaela , Utyro Olga , Poliseno Mariacristina , Santantonio Teresa Antonia , Saulle Irma , Strizzi Sergio , Lo Caputo Sergio , Clerici Mario , Introini Andrea , Biasin Mara 
Published: March 2022

BackgroundSARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed.Material and MethodsWe fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the “wild type” SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay.ResultsNA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV.DiscussionThe difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant.ConclusionsThe administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.
Two CIDP Variants Patients With Anti-Caspr1 Antibodies in South China
Authors: Li Chong , Zheng Hui , Yuan Chao , Li Yanran , Hu Yafang , Jiang Haishan 
Published: March 2022

Background and ObjectivesChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an immune-mediated heterogeneous disease that involves both cellular and humoral immunity. The advent of the new concept of node-paranodopathy in recent years has boosted the identification of more antibody-positive CIDP variants patients. Cases of Caspr1 autoantibodies are the least common. Here, we reported two patients with Caspr1 autoantibodies and summarized their clinical features and treatment responses.MethodsDo statistical analyses on the clinical manifestations and laboratory examinations obtained from two patients identified in this study, and eight patients with anti-Caspr1 antibodies reported in previous research. And based on the developed scoring standard, draw the radar charts and line graphs.ResultsSimilar to other studies, the two patients we mentioned had a subacute and severe onset, distal phenotype, sensory ataxia, and severe pain. Differently, they had severe pain accompanying cold sense and coarse tremor in both hands, which may be a typical symptom for the anti-Caspr1 positive patient in south China. And we drew the line and radar graph for two China patients based on five aspects, muscle strength, sensory nerve, cranial nerve, laboratory tests, and NCS examinations. The two visual data charts offered new complementary means for the diagnostic assessment of CIDP variants.ConclusionPain with cold sense, coarse tremor in hands, and CSF protein levels greater than 3g/L may be the source of the distinct symptoms observed in patients with anti-Caspr1 autoantibodies in south China.
The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia
Authors: Vesce Fortunato , Battisti Chiara , Crudo Michele 
Published: March 2022

Pregnancy can be defined a vascular event upon endocrine control. In the human hemo-chorial placentation the chorionic villi penetrate the wall of the uterine spiral arteries, to provide increasing amounts of nutrients and oxygen for optimal fetal growth. In any physiological pregnancy the natural maternal response is of a Th1 inflammatory type, aimed at avoiding blood loss through the arteriolar wall openings. The control of the vascular function, during gestation as in any other condition, is achieved through the action of two main types of prostanoids: prostaglandin E2 and thromboxane on the one hand (for vasoconstriction and coagulation), prostacyclin on the other (for vasodilation and blood fluidification). The control of the maternal immune response is upon the responsibility of the fetus itself. Indeed, the chorionic villi are able to counteract the natural maternal response, thus changing the inflammatory Th1 type into the anti-inflammatory Th2. Clinical and experimental research in the past half century address to inflammation as the leading cause of abortion, pregnancy loss, premature delivery and related pulmonary, cerebral, intestinal fetal syndromes. Increased level of Interleukin 6, Interleukin 1-beta, Tumor Necrosis Factor-alfa, Interferon-gamma, are some among the well-known markers of gestational inflammation. On the other side, COVID-19 pneumonia is a result of extensive inflammation induced by viral replication within the cells of the respiratory tract. As it may happen in the uterine arteries in the absence of an effective fetal control, viral pneumonia triggers pulmonary vascular coagulation. The cytokines involved in the process are the same as those in gestational inflammation. As the fetus breathes throughout the placenta, fetal death from placental thrombosis is similar to adult death from pulmonary thrombosis. Preventing and counteracting inflammation is mandatory in both conditions. The most relevant literature dealing with the above-mentioned concepts is reviewed in the present article.
Evaluation of a Multi-Season, Community-Based Larval Source Management Program on Bioko Island, Equatorial Guinea
Authors: García Guillermo A. , Fuseini Godwin , Mba Nlang Jose Antonio , Nsue Maye Valeriano Olo , Bela Nestor Rivas , Wofford Rachel N. , Weppelmann Thomas A. , Matulis Graham , Efiri Prudencio Bibang , Smith Jordan M. , Rivas Matilde Riloha , Phiri Wonder Philip , von Fricken Michael E. 
Published: March 2022

BackgroundIn 2015 and 2016, the Bioko Island Malaria Control Project (BIMCP) introduced a pilot larvicide program, which recruited local volunteers to assess the sustainability and effectiveness of community-led larval source management. This study evaluates the effectiveness of the community-led LSM program to determine if this type of intervention could be used as a sustainable malaria control method on Bioko Island.MethodsThe pilot program was split into two phases, both taking place between February and December, with phase I in 2015 and phase II in 2016. During phase I, the BIMCP team assisted in identifying and treating Anopheles species mosquito breeding habitats. During phase II, community volunteers, with supervision from designated community leaders, identified and treated breeding habitats. Larval source management took place at thirteen locations around the Island during both phases. Human landing catches were conducted at seven sentinel sites once every month for the duration of the study period to determine average nightly biting rates.ResultsDuring phase I, 1,033 breeding sites were identified with a 100% treatment coverage rate. Only 970 breeding sites were identified in phase II with a 75% treatment coverage rate, a significant decrease from phase I (p&lt;0.001). Between phase I and phase II, larvicide usage also decreased by 45% (95% CI: 32, 59%, p=0.003). However, excluding the sentinel site Balboa, vector density showed a nonsignificant (p=0.272) relationship between phase I and phase II.ConclusionOverall, community-based larval source management can be effective with strong operational management and oversight. However, repeated training and evaluation will be necessary to monitor the effectiveness and sustainability of such interventions.
Abiotrophia Defectiva as a Rare Cause of Mitral Valve Infective Endocarditis With Mesenteric Arterial Branch Pseudoaneurysm, Splenic Infarction, and Renal Infarction: A Case Report
Authors: Li Jiayu , Zhou Li , Gong Xuhe , Wang Yuan , Yao Daokuo , Li Hongwei 
Published: March 2022

IntroductionAbiotrophia defectiva (A. defectiva) is a rare species leading to infective endocarditis (IE) with a poor prognosis. We describe a previously healthy patient with mitral valve infective endocarditis caused by A. defectiva.Case reportA young man was admitted with intermittent fever. Echocardiography confirmed vegetation on the mitral valve with evidence of valve perforation and severe mitral regurgitation. Three sets of blood cultures became positive for A. defectiva. As he presented with manifestations of mesenteric arterial branch pseudoaneurysm, splenic and renal infarction, mitral valve replacement, and embolization of superior mesenteric aneurysm were operated during 8 weeks' targeted antibiotic therapy.ConclusionThis case study emphasizes the importance of considering A. defectiva as a rare but important cause of IE and of performing blood culture to make its accurate diagnosis and timely anti-infective treatment. Early surgical management and active prevention of complications have been associated with a favorable prognosis.
Validation of the Portable Next-Generation VECTRA H2 3D Imaging System for Periocular Anthropometry
Authors: Fan Wanlin , Guo Yongwei , Hou Xiaoyi , Liu Jinhua , Li Senmao , Ju Sitong , Matos Philomena Alice Wawer , Simon Michael , Rokohl Alexander C. , Heindl Ludwig M. 
Published: March 2022

PurposePortable three-dimensional imaging systems are becoming increasingly common for facial measurement analysis. However, the reliability of portable devices may be affected by the necessity to take three pictures at three time points. The purpose of this study was to evaluate the effectiveness of portable devices for assessing the periocular region.MethodsIn 60 Caucasian volunteers (120 eyes), four facial scans (twice for each instrument) using the portable VECTRA H2 and static VECTRA M3 devices were performed; patients' heads were kept straight, looking ahead, with a neutral facial expression. One assessor set 52 periocular landmarks in the periocular area of each image and subsequently assessed intra- and inter-device reliability by comparing two within-device measurements and one between-device measurement, respectively.ResultsThe mean absolute difference (MAD) (0.13 and 0.12 units), relative error of measurement (REM) (0.61 and 0.68%), technical error of measurement (TEM)(1.02 and 0.80 units), relative TEM (rTEM) (5.51 and 4.43%), and intraclass correlation coefficient (ICC) (0.89, 0.89) showed good intra-device reliability for M3 and H2; MAD (0.63, 0.62 units), REM (2.83, 2.69%), TEM (1.31, 1.10 units), rTEM (7.62, 5.57%), and ICC (0.79, 0.83) indicated that inter-device reliability deteriorated compared to intra-device reliability and that the inter-device reliability of the first scan (moderate) was lower than that of the average of the two scans (good).ConclusionsThe portable VECTRA H2 device proved reliable in assessing most periocular linear distances, curve distances, and angles; some improvement in inter-device reliability can be achieved by using the average of two scans.
Factors Predicting COVID-19 Vaccination Uptake Among Men Who Have Sex With Men in China: An Observational Prospective Cohort Study
Authors: Zhang Kechun , Chan Paul Shing-fong , Chen Siyu , Fang Yuan , Cao He , Chen Hongbiao , Hu Tian , Chen Yaqi , Zhou Xiaofeng , Wang Zixin 
Published: March 2022

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected sexual minorities including men who have sex with men (MSM). This study investigated factors associated with the uptake of COVID-19 vaccination among MSM in China.MethodsInclusion criteria were: (1) born biologically male, (2) had oral or anal sex with men in the past year, (3) aged at least 18 years, and (4) lived in Shenzhen, China. Prospective participants were recruited through outreach in gay bars and saunas, online recruitment, and peer referrals. Participants completed a baseline online survey between August and September 2020 and a follow-up online survey between April and May 2021. Logistic regression models were fitted for data analysis.ResultsAmong 420 participants who completed the baseline survey, 303 completed the follow-up survey. Among participants being followed up, 113 (37%) received at least one dose of COVID-19 vaccination during the study period. After adjusting for significant sociodemographic characteristics, five baseline predisposing factors predicted COVID-19 vaccination uptake during the follow-up period, including asking whether their partners had COVID-19 symptoms [adjusted odds ratio (AOR): 1.17, 95% confidence interval (CI): 1.00–1.38], washing hands before and after sex (AOR: 1.23, 95% CI: 1.03–1.46), sanitizing before and after sex (AOR: 1.17, 95% CI: 1.00–1.37), perceived higher risk of COVID-19 transmission through sexual behaviors (AOR: 1.28, 95% CI: 1.04–1.58), and panic about COVID-19 (AOR: 1.48, 95% CI: 1.16–1.89). Regarding enabling factors, receiving testing for sexually transmitted infections (STI) (AOR: 2.19, 95% CI: 1.25–3.85) and other prevention measures for human immunodeficiency virus (HIV)/STI (AOR: 2.61, 95% CI: 1.56–4.37) 6 months prior to the baseline survey were associated with higher uptake of COVID-19 vaccination.ConclusionMSM’s uptake rate of COVID-19 vaccination was comparable to that of the general population in Shenzhen, China. This study offered an overview for us to identify tapping points that can encourage COVID-19 vaccination uptake among Chinese MSM.
The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of Patients With Inflammatory Arthritis: The MAINSTREAM Study
Authors: Favalli Ennio Giulio , Gobbini Andrea , Bombaci Mauro , Maioli Gabriella , Biggioggero Martina , Pesce Elisa , Favalli Andrea , Martinovic Martina , Fabbris Tanya , Marchisio Edoardo , Bandera Alessandra , Gori Andrea , Abrignani Sergio , Grifantini Renata , Caporali Roberto 
Published: March 2022

ObjectivesGiven the high occurrence of asymptomatic subsets, the true prevalence of SARS-CoV-2 infection in rheumatic patients is still underestimated. This study aims to evaluate the seroprevalence of SARS-CoV-2 antibodies in rheumatic musculoskeletal diseases (RMD) patients receiving immunomodulatory drugs.MethodsAll consecutive patients with rheumatoid arthritis or spondyloarthritis receiving disease-modifying antirheumatic drugs (DMARDs) evaluated between 4th May and 16th June 2020 were included. All participants were tested for anti-SARS-CoV-2 antibodies (IgG, IgM, IgA) by ELISA and were questioned about previous COVID-19 symptoms and clinical course. Results were compared with healthy population from the same region and with a control group of healthy subjects diagnosed with confirmed COVID-19.ResultsThe study population includes 358 patients. The overall prevalence of anti-SARS-CoV-2 antibodies (18.4%) was higher than prevalence rate based on swab-positivity (1.12%) or clinically suspected cases (10.6%), but consistent with seroprevalence observed in the healthy population. Among seropositive patients 58% were asymptomatic. Mean anti-SARS-CoV-2 titer was comparable with the control group. No differences in seroprevalence were observed according to age, sex, rheumatic disease and treatment with conventional, biologic or targeted synthetic DMARDs, whereas glucocorticoids and comorbidities resulted in higher seroprevalence rate.ConclusionsThe results of this study are reassuring about the low impact of RMDs and immunomodulatory therapies on the risk and clinical course of COVID-19 and on humoral immune response to SARS-CoV-2 infection.