bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience
Authors: Suri Deepti , Rawat Amit , Jindal Ankur Kumar , Vignesh Pandiarajan , Gupta Anju , Pilania Rakesh Kumar , Joshi Vibhu , Arora Kanika , Kumrah Rajni , Anjani Gummadi , Aggarwal Amita , Phadke Shubha , Aboobacker Fouzia N. , George Biju , Edison Eunice Sindhuvi , Desai Mukesh , Taur Prasad , Gowri Vijaya , Pandrowala Ambreen Abdulwahab , Bhattad Sagar , Kanakia Swati , Gottorno Marco , Ceccherini Isabella , Almeida de Jesus Adriana , Goldbach-Mansky Raphaela , Hershfield Michael S. , Singh Surjit 
Published: March 2021

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.
Human PD-1hiCD8+ T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis
Authors: Higashioka Kazuhiko , Yoshimura Motoki , Sakuragi Takahide , Ayano Masahiro , Kimoto Yasutaka , Mitoma Hiroki , Ono Nobuyuki , Arinobu Yojiro , Kikukawa Makoto , Yamada Hisakata , Horiuchi Takahiko , Akashi Koichi , Niiro Hiroaki 
Published: March 2021

BackgroundRheumatoid arthritis (RA) is a prototypical autoantibody-driven autoimmune disease in which T-B interactions play a critical role. Recent comprehensive analysis suggests that PD-1+CD8+T cells as well as two distinct IL-21-producing PD-1+CD4+T cell subsets, follicular helper T (Tfh) and peripheral helper T (Tph) cells, are involved in the pathogenesis of RA. Herein, we aimed to clarify a generation mechanism of IL-21-producing CD8+T cells in humans, and to characterize this novel subset in patients with RA.MethodsCD8+T cells in the peripheral blood (PB) and synovial fluid (SF) of healthy control (HC) and patients with RA were subject to the analysis of IL-21 mRNA and protein. We evaluated the surface marker, cytokine and transcription profiles of IL-21-producing CD8+T cells in HCPB, RAPB and RASF.ResultsIL-21-producing CD8+T cells were enriched in the CD45RA-(memory) PD-1+, especially PD-1hisubpopulation, and IL-12 and IL-21 synergistically induced IL-21 production by naïve CD8+T cells. Memory PD-1hiCD8+T cells in HCPB facilitated plasmablast differentiation and IgG production in an IL-21-dependent manner. In addition, PD-1hiCD8+T cells in RASF and RAPB produced large amounts of IL-21 and were characterized by high levels of CD28, ICOS, CD69, HLA-DR, and CCR2 but not CXCR5. Furthermore, PD-1hiCD8+T cells expressed high levels of transcripts ofMAFandPRDM1, a feature observed in Tph cells.ConclusionsIdentification of IL-21-producing PD-1hiCD8+T cells expands our knowledge of T cell subsets with B helper functions in RA. Selective targeting of these subsets could pave an avenue for the development of novel treatment strategies for this disease.
Novel Predictors and Risk Score of Treatment Failure in Peritoneal Dialysis-Related Peritonitis
Authors: Liu Xiang , Qin Aiya , Zhou Huan , He Xueqin , Cader Shamlin , Wang Sirui , Tang Yi , Qin Wei 
Published: March 2021

Objective: Peritonitis is a severe complication in peritoneal dialysis (PD). This study was performed to identify predictors and establish a risk score for treatment failure in peritonitis patients.Methods: A single-center, retrospective observational study was conducted. The basic demographic characteristics, clinical and laboratory data of all patients with peritonitis during the study period were documented and analyzed. Multivariate logistic regression was applied to examine independent predictors of treatment failure, and a risk prediction score was established.Results: Three hundred fourteen episodes experienced by 241 patients were included in the final analysis. Logistic regression analysis indicated that PD duration (OR 1.017; P 0.005), fibrinogen (OR 1.327; P 0.021), high-density lipoprotein (OR 0.443; P 0.032), fungal infection (OR 63.413; P &lt; 0.001), intestinal obstruction (OR 5.186, P 0.007), and diabetes mellitus (OR 2.451; P 0.018), hemodialysis history (OR 2.804, P 0.006) were independent predictors of treatment failure. The risk prediction score system showed a good calibration (P &gt; 0.05) and discrimination (AUROC 0.80, P &lt; 0.001).Conclusions: Fibrinogen, PD duration, fungal infection, hemodialysis history, concurrent intestinal obstruction, or diabetes mellitus were independent risk factors for a poor peritonitis outcome, while the high-density lipoprotein was a protective factor. This novel risk prediction score system may be used to predict a high risk of treatment failure effectively.
The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency
Authors: Chen Xiaoyan , Wang Rong , Huang Xusheng , Yang Fei , Yu Shengyuan 
Published: March 2021

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio &lt;3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P &lt; 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P &lt; 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.
Distance Neurological Supervision Using Telestroke Does Not Increase Door-to-Needle Time in Acute Ischemic Stroke Management: The Experience of Two Regional Stroke Units
Authors: Sood Radhika , Annoni Jean-Marie , Humm Andrea M. , Accolla Ettore , Bill Olivier , Toledo Sotomayor Guillermo , Niederhauser Julien , Medlin Friedrich 
Published: March 2021

Background and Aims: Timely administration of recombinant tissue plasminogen activator (r-tPA) improves clinical outcomes in acute ischemic stroke patients. This study aims to explore the influence of the systematic presence on site of a neurologist compared with telestroke management on door-to-needle time in acute ischemic stroke outside of working hours (OWH).Methods: This retrospective cohort study included all r-tPA-treated patients in the emergency rooms of two Swiss stroke units, Nyon Hospital [Groupement Hospitalier de l'Ouest Lémanique (GHOL)] and Fribourg Hospital [Hôpital de Fribourg (HFR)], between February 2014 and September 2018. Door-to-needle time was analyzed for patients admitted during working hours (WH' weekdays 08:00–18:00) and OWH (weekdays 18:00–08:00, weekends, and public holidays). The latter was compared between centers; OWH, every patient was evaluated prior to thrombolysis by a neurologist on site in GHOL, while HFR adopted distance neurological supervision with teleradiology, performed by telephone evaluation of relevant clinical information with online real-time access to brain imaging.Results: Data were analyzed for 157 patients in HFR and 101 patients in GHOL. No statistically significant differences in baseline characteristics were found for the 258 r-tPA-treated acute ischemic stroke patients, in terms of age, gender, cardiovascular risk factors (hypertension, diabetes, and atrial fibrillation), and pre-Modified Rankin Scale (pre-mRs) between centers, with the exception of smoking and anticoagulation status. Patients in HFR presented with more severe strokes {median National Institutes of Health Stroke Scale (NIHSS) [6 (SD 6.88) (GHOL), 8 (SD 6.98) (HFR), p = 0.005]}. No significant differences in baseline characteristics were found as per admission time independently of the center. Door-to-needle time was significantly longer in the HFR cohort when compared with GHOL, irrespective of admission time. Both centers demonstrated significantly longer median door-to-needle time OWH. However, analysis of the door-to-needle time differences between WH and OWH showed no significant interaction using robust ANCOVA WRS2 analysis (p = 0.952) and a Bayesian model (BF01 = 3.97).Conclusions: On-site systematic evaluation by a neurologist did not appear to influence door-to-needle time OWH, suggesting distance supervision may be time-efficient in thrombolysis. This supports existing prospective studies in hyperacute telestroke management. The relevance lies in optimizing resource use considering the increasing demand for emergency neurological management.
Silencing of HuR Inhibits Osteosarcoma Cell Epithelial-Mesenchymal Transition via AGO2 in Association With Long Non-Coding RNA XIST
Authors: Liu Yongming , Zhang Yuan , Zhang Jinxue , Ma Jingchang , Xu Xuexue , Wang Yuling , Zhou Ziqing , Jiang Dongxu , Shen Shen , Ding Yong , Zhou Yong , Zhuang Ran 
Published: March 2021

BackgroundOsteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.MethodsHuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.ResultsKnockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.
Newborn Screening for Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase and Mitochondrial Trifunctional Protein Deficiencies Using Acylcarnitines Measurement in Dried Blood Spots—A Systematic Review of Test Accuracy
Authors: Stinton Chris , Fraser Hannah , Geppert Julia , Johnson Rebecca , Connock Martin , Johnson Samantha , Clarke Aileen , Taylor-Phillips Sian 
Published: March 2021

Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare autosomal recessive fatty acid β-oxidation disorders. Their clinical presentations are variable, and premature death is common. They are included in newborn blood spot screening programs in many countries around the world. The current process of screening, through the measurement of acylcarnitines (a metabolic by-product) in dried blood spots with tandem mass spectrometry, is subject to uncertainty regarding test accuracy.Methods: We conducted a systematic review of literature published up to 19th June 2018. We included studies that investigated newborn screening for LCHAD or MTP deficiencies by tandem mass spectrometry of acylcarnitines in dried blood spots. The reference standards were urine organic acids, blood acylcarnitine profiles, enzyme analysis in cultured fibroblasts or lymphocytes, mutation analysis, or at least 10-year follow-up. The outcomes of interest were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Assessment of titles, abstracts, and full-text papers and quality appraisal were carried out independently by two reviewers. One reviewer extracted study data. This was checked by a second reviewer.Results: Ten studies provided data on test accuracy. LCHAD or MTP deficiencies were identified in 23 babies. No cases of LCHAD/MTP deficiencies were identified in four studies. PPV ranged from 0% (zero true positives and 28 false positives from 276,565 babies screened) to 100% (13 true positives and zero false positives from 2,037,824 babies screened). Sensitivity, specificity, and NPV could not be calculated as there was no systematic follow-up of babies who screened negative.Conclusions: Test accuracy estimates of screening for LCHAD and MTP deficiencies with tandem mass spectrometry measurement of acylcarnitines in dried blood were variable in terms of PPVs. Screening methods (including markers and thresholds) varied between studies, and sensitivity, specificity, and NPVs are unknown.
Mental Health Among School-Going Adolescents in Greater London: A Cross-Sectional Study
Authors: Al-Zawaadi Asmaa , Hesso Iman , Kayyali Reem 
Published: March 2021

Objectives: Mental health problems are among the leading causes of health-related disability among children and adolescents worldwide. However, there is still a global challenge in terms of gathering consistent epidemiological information about the issue. The present study was designed to describe various mental health issues and factors associated with negative feelings among adolescents in Greater London.Methods: This is a cross sectional study, using a self-administered questionnaire (Cronbach's alpha = 0.742). A convenience sampling strategy was used to recruit participants who were school/college-attending adolescents, aged 11–19. A minimum sample size of 199 was required (95% confidence interval, 5% margin of error, and 15.3% population proportion). The study was conducted between February and April 2016 in Greater London. Descriptive statistics and inferential statistics including chi square, Spearman correlation, and binary logistic regression were used to identify the key findings. Data analysis was performed using SPSS v21.Results: A total of 526 out of 1,920 surveys were collected across 18 secondary schools and two colleges, giving a response rate of 27.4%. More than half of the adolescents reported to be either neutral (41.4%), sad (7.8%), or very sad (2.8%), whereas 48% reported to be either happy (35%) or very happy (13%). Difficulties in relationships and hectic schedules were among the most stressful situations affecting adolescents' mental health. Discrimination was identified as the main predicting factor with five-fold increase in odds of having negative mental health symptomatology. Other significant risk factors identified were age, gender, smoking, and health comorbidities.Conclusion: Discrimination was identified as the most predictive factor influencing negative symptomatology among the study cohort. The study had several limitations, most notably the use of a non-validated surrogate measure for mental health, in addition to the exclusion of adolescents aged 10–11 years, school/college dropouts and non-school-going adolescents. A similar study on a national scale is highly recommended to determine the real magnitude of the problem, which would be the starting point toward proper tackling of mental health issues and associated complexities among the adolescent population across England.
Mood Symptoms, Suicide, and Associated Factors Among Jimma Community. A Cross-Sectional Study
Authors: Tesfaye Yonas , Agenagnew Liyew , Anand Susan , Tucho Gudina Terefe , Birhanu Zewdie , Ahmed Gutema , Getnet Masrie , Yitbarek Kiddus 
Published: March 2021

Background: The global burden of mental health problems is high and is predicted to rise. At present, mood symptoms are the foremost common psychological problems worldwide, yet little is known regarding their magnitude and associated factors in developing countries. Therefore, this study aimed to assess the magnitude and associated factors of anxiety, depressive, manic symptoms, and suicidal behavior among the rural Jimma community, Ethiopia.Methods: A community-based quantitative cross-sectional survey was employed on 423 households selected through systematic random sampling. An adapted version of the Mini International Neuropsychiatric Interview tool was used for the structured face-to-face interview. The collected data were checked for completeness, coded, and inserted into Epi Data version 3.1 and exported to SPSS version 23 for analysis. Variables with P &lt; g0.05 and odds ratio (OR) [95% confidence interval (CI)] on multivariate logistic regression analysis were considered as factors associated with the outcome variable.Results: Overall, 185 (44.0%), 55 (13.1%), 44 (10.5%), and 23 (5.5%) of the respondents had anxiety, depressive, manic symptom, and suicide behavior, respectively. The odds of having anxiety symptoms were nearly 5 times higher among those who had perceived discrimination and racism experience compared to their counterpart [adjusted OR (AOR), 5.02; 95% CI, 1.90–13.26]. Likewise, recently bereaved participants had 4-fold higher odds of reporting depressive symptoms (AOR, 3.9; 95% CI, 1.4–10.4) than the non-bereaved ones. Furthermore, respondents who had depressive symptoms were almost four and a half times more likely to have manic symptoms compared to those who did not (AOR, 4.3; 95% CI, 1.71–11.02).Conclusion: Anxiety, depressive, manic symptoms, and suicidal behavior were prevalent in the community and positively associated with multiple psychosocial factors. Implementing accessible and affordable community-based mental health services is recommended to mitigate the problems.
Higher Temperatures, Higher Solar Radiation, and Less Humidity Is Associated With Poor Clinical and Laboratory Outcomes in COVID-19 Patients
Authors: Hachim Mahmood Yaseen , Hachim Ibrahim Y. , Naeem Kashif , Hannawi Haifa , Al Salmi Issa , Hannawi Suad 
Published: March 2021

Background: The COVID-19 pandemic varies between countries, with suggestions that weather might contribute to the transmission mode, disease presentation, severity, and clinical outcomes. Yet the exact link between climate and COVID-19 is still not well-explored.Objectives: This study aimed to evaluate the effect of hot geographical region weather [like United Arab Emirates (UAE)] on COVID-19 clinical profile and outcomes. Temperature, wind speed, cloud cover, precipitation, and other weather-related variables were studied concerning COVID-19 patients outcomes and laboratory results.Methodology: A total of 434 COVID-19 positive patients admitted between January and June 2020, were recruited from Al Kuwait Hospital, Dubai, UAE. Temperature, wind speed, cloud cover, and precipitation rate were retrieved from history+ for the day when COVID-19 patients presented to the hospital. These weather parameters were correlated with COVID-19 clinical and laboratory parameters.Results: Our results showed that patients needed admission in days with higher temperatures, higher solar radiation, and less humidity were associated with higher deaths. This association can be linked to the association of these weather parameters with age at diagnosis; higher C-reactive protein (CRP), neutrophil count, white cell count (WCC), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and lower lymphocyte count, estimated glomerular filtration rate (eGFR), hemoglobin (Hb), Na, and albumin, all of which are considered poor prognostic factors for COVID-19.Conclusion: Our study highlighted the importance of weather-related variables on the dynamics of mortality and clinical outcomes of COVID-19. The hot weather might makes some people, especially those with comorbidities or older ages, develop aggressive inflammation that ends up with complications and mortality.