bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes
Authors: de Sá Nathalia Beatriz Ramos , de Souza Nara Cristina Silva , Neira-Goulart Milena , Ribeiro-Alves Marcelo , Da Silva Tatiana Pereira , Pilotto Jose Henrique , Rolla Valeria Cavalcanti , Giacoia-Gripp Carmem B. W. , de Oliveira Pinto Luzia Maria , Scott-Algara Daniel , Morgado Mariza Gonçalves , Teixeira Sylvia Lopes Maia 
Published: September 2022

BackgroundTuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset.MethodsThe individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations.ResultsA higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed.ConclusionsOur results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.
Analysis of the diagnostic efficacy of the QuantiFERON-TB Gold In-Tube assay for preoperative differential diagnosis of spinal tuberculosis
Authors: Hu Xiaojiang , Zhang Hongqi , Li Yanbin , Zhang Guang , Tang Bo , Xu Dongcheng , Tang Mingxing , Guo Chaofeng , Liu Shaohua , Gao Qile 
Published: September 2022

BackgroundDifferential diagnosis of spinal tuberculosis is important for the clinical management of patients, especially in populations with spinal bone destruction. There are few effective tools for preoperative differential diagnosis in these populations. The QuantiFERON-TB Gold In-Tube (QFT-GIT) test has good sensitivity and specificity for the diagnosis of tuberculosis, but its efficacy in preoperative diagnosis of spinal tuberculosis has rarely been investigated.MethodA total of 123 consecutive patients with suspected spinal tuberculosis hospitalized from March 20, 2020, to April 10, 2022, were included, and the QFT-GIT test was performed on each patient. We retrospectively collected clinical data from these patients. A receiver operating characteristic (ROC) curve was plotted with the TB Ag-Nil values. The cutoff point was calculated from the ROC curve of 61 patients in the study cohort, and the diagnostic validity of the cutoff point was verified in a new cohort of 62 patients. The correlations between TB Ag-Nil values and other clinical characteristics of the patients were analyzed.ResultsOf the 123 patients included in the study, 51 had confirmed tuberculosis, and 72 had non-tuberculosis disease (AUC=0.866, 95% CI: 0.798-0.933, P&lt;0.0001). In patients with spinal tuberculosis, the QFT-GIT test sensitivity was 92.16% (95% CI: 80.25%-97.46%), and the specificity was 67.14% (95% CI: 54.77%-77.62%). The accuracy of diagnostic tests in the validation cohort increased from 77.42% to 80.65% when a new cutoff point was selected (1.58 IU/mL) from the ROC curve of the study cohort. The TB Ag-Nil values in tuberculosis patients were correlated with the duration of the patients’ disease (r=0.4148, P=0.0025).ConclusionThe QFT-GIT test is an important test for preoperative differential diagnosis of spinal tuberculosis with high sensitivity but low specificity. The diagnostic efficacy of the QFT-GIT test can be significantly improved via application of a new threshold (1.58 IU/mL), and the intensity of the QFT-GIT test findings in spinal tuberculosis may be related to the duration of a patient’s disease.
Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal–ileal bypass with sleeve gastrectomy
Authors: Wang Lun , Wang Zeyu , Yu Yang , Ren Zhaoheng , Jia Yongheng , Wang Jinfa , Li Shixing , Jiang Tao 
Published: September 2022

BackgroundSingle-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known.ObjectiveTo explore the effects of SADI-S on metabolites in the stool of rats with T2DM.MethodsTwenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry.ResultsAt 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups, among which 8 metabolites were detectable under both the positive ion model and negative ion model. Therefore, a total of 237 differential metabolites were identified in our study which were mainly involved in tryptophan metabolism; cysteine and methionine metabolism; phenylalanine metabolism; phenylalanine; tyrosine and tryptophan biosynthesis; arginine biosynthesis; alanine, aspartate and glutamate metabolism; Arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; alpha-Linolenic acid metabolism; Linoleic acid metabolism; riboflavin metabolism; nicotinate and nicotinamide metabolism; pyrimidine metabolism; porphyrin and chlorophyll metabolism.ConclusionSADI-S significantly improved the glucose metabolism in T2DM rats. In addition, SADI-S significantly changed the composition of metabolites in T2DM rats which were involved in tryptophan metabolism pathway, linoleic acid metabolism pathway and so on. This may be the mechanism by which SADI-S improved T2DM.
Evaluation of the bioluminescence activity, biokinetics, and the effects of binary mixtures of inducers on the Pm-lux recombinant strain
Authors: Kong In Chul , Lee Sohyeon , Ha Kyoochul , Ko Kyung-Seok 
Published: September 2022

The bioluminescence activity and biokinetics of a recombinant Pseudomonas putida mt-2 were investigated in the presence of various inducers: three chlorotoluenes (CTs) and two nitrotoluenes (NTs). The effects of binary mixtures (40 combinations) of eleven inducers on the bioluminescence activity were also studied. Different responses and toxicities were observed depending on the type of inducers and concentrations. The intensity of the bioluminescent response at 1 mM of individual inducers was in the following order: o-CT &gt; p-CT &gt; m-CT &gt; o-NT and p-NT. The biokinetics calculated based on the bioluminescence activity was in the range of 0.109–8.417 mM for the half-saturation constant (Ks) and 6.083–19.880 h−1 for the maximum SBR (µmax). In the case of binary mixtures, the observed bioluminescence was 4–810% (avg. 80.4%) of the expected bioluminescence intensity depending on the combinations (0.0001 &lt; p &lt; 0.5226). Among these binary mixture combinations, 27 out of 40 combinations indicated antagonistic effects (3–83% of expected activity; p &lt; 0.0391) under the exposure of inducer mixtures. Overall, this study demonstrated that the proper biomonitoring for specific chemicals could be established by considering the characteristics of mixture pollutants for their possible usages as a preliminary rapid and field analytical bio-tool.
Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study
Authors: Bruni Flavio , Charitos Panteleimon , Lampart Maurin , Moser Stephan , Siegemund Martin , Bingisser Roland , Osswald Stefan , Bassetti Stefano , Twerenbold Raphael , Trendelenburg Marten , Rentsch Katharina M. , Osthoff Michael 
Published: September 2022

BackgroundThromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection.MethodsIn a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1.Results153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group.ConclusionsOur data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., “over”-activation).
The non-linear relationship between triglyceride-glucose index and risk of chronic kidney disease in hypertensive patients with abnormal glucose metabolism: A cohort study
Authors: Zhu Qing , Chen Yuan , Cai Xintian , Cai Li , Hong Jing , Luo Qin , Ren Yingli , Guo Yanying , Li Nanfang 
Published: September 2022

BackgroundTriglyceride–glucose (TyG) index has been reported to be associated with cardiovascular disease (CVD). However, few studies have focused on TyG index and the risk of chronic kidney disease (CKD). Thus, this study aims to explore the relationship between TyG index and CKD.MethodsA total of 2,033 participants with hypertension between January 2012 and May 2019 were included in the longitudinal observational study. All patients are grouped according to the TyG index quartile. CKD was defined as estimated glomerular filtration rate (eGFR) &lt; 60 ml/min per 1.73 m2 and/or positive proteinuria. Multivariate Cox proportional hazards models were used to investigate the relationship between TyG index and CKD.ResultsDuring a median follow-up of 31 months, 302 participants developed CKD, with a mean age of 55.5 years and median TyG of 8.94. Compared with those in the lowest quartile of TyG index, participants in the highest quartile of TyG index exhibited 1.63-fold higher hazard ratio (95% CI: 1.14–2.33, P = 0.007) for presence of CKD. And restricted cubic spline analysis showed the relationship between TyG index and CKD is non-linear (P non-linearity = 0.021). The hazard ratio for CKD first fell and after rising until around 8.94 of TyG index and started to increase rapidly afterward (P for TyG &lt; 0.001).ConclusionHigher TyG index is associated with the increased risk for CKD. Early intervention of metabolic factors may prevent the occurrence of CKD, thereby reducing the incidence of CVD and premature death.
Identification of the molecular subgroups in Alzheimer's disease by transcriptomic data
Authors: Li He , Wei Meiqi , Ye Tianyuan , Liu Yiduan , Qi Dongmei , Cheng Xiaorui 
Published: September 2022

BackgroundAlzheimer's disease (AD) is a heterogeneous pathological disease with genetic background accompanied by aging. This inconsistency is present among molecular subtypes, which has led to diagnostic ambiguity and failure in drug development. We precisely distinguished patients of AD at the transcriptome level.MethodsWe collected 1,240 AD brain tissue samples collected from the GEO dataset. Consensus clustering was used to identify molecular subtypes, and the clinical characteristics were focused on. To reveal transcriptome differences among subgroups, we certificated specific upregulated genes and annotated the biological function. According to RANK METRIC SCORE in GSEA, TOP10 was defined as the hub gene. In addition, the systematic correlation between the hub gene and “A/T/N” was analyzed. Finally, we used external data sets to verify the diagnostic value of hub genes.ResultsWe identified three molecular subtypes of AD from 743 AD samples, among which subtypes I and III had high-risk factors, and subtype II had protective factors. All three subgroups had higher neuritis plaque density, and subgroups I and III had higher clinical dementia scores and neurofibrillary tangles than subgroup II. Our results confirmed a positive association between neurofibrillary tangles and dementia, but not neuritis plaques. Subgroup I genes clustered in viral infection, hypoxia injury, and angiogenesis. Subgroup II showed heterogeneity in synaptic pathology, and we found several essential beneficial synaptic proteins. Due to presenilin one amplification, Subgroup III was a risk subgroup suspected of familial AD, involving abnormal neurogenic signals, glial cell differentiation, and proliferation. Among the three subgroups, the highest combined diagnostic value of the hub genes were 0.95, 0.92, and 0.83, respectively, indicating that the hub genes had sound typing and diagnostic ability.ConclusionThe transcriptome classification of AD cases played out the pathological heterogeneity of different subgroups. It throws daylight on the personalized diagnosis and treatment of AD.
Vestibular disorders in patients after COVID-19 infection
Authors: Pazdro-Zastawny Katarzyna , Dorobisz Karolina , Misiak Paula , Kruk-Krzemień Anna , Zatoński Tomasz 
Published: September 2022

IntroductionThe COVID-19 clinical symptoms are primarily related to the respiratory system but may also be involved in many others, including the nervous system. Recently, vertigo or dizziness has been described as one of the clinical manifestations and possible complications of COVID-19.Materials and methodsThis clinical study was designed to describe the otorhinolaryngological evaluation and videonystagmographic (VNG) findings in patients with an antecedent of COVID-19 infection in the last 6 months. In this study, we sought to investigate the presence of persistent vestibular damage in healed COVID-19 patients and to determine the origin of vertigo by conducting a comprehensive vestibular examination. To evaluate the association precisely, an otoneurological assessement was conducted on all participants. The study group included 58 patients aged 23–75 years with vertigo, who were diagnosed with COVID-19 infection 6 months before the examination. Each participant was submitted to an evaluation consisting of anamnesis, otorhinolaryngological evaluation, and VNG.ResultsSpontaneous nystagmus with closed eyes was reported in 8 patients (13.8%). Positional nystagmus was observed in 15 patients (24.1%). Asymmetrical optokinetic nystagmus was observed in 18 patients (31%). A distorted record in the tracking pendulum test was present in 23 patients (39.7%). Square waves were observed in 34 COVID-19 patients (58.6%). Unilateral weakness (UW) was observed in 23 subjects (39.7%); among those with UW, 22 patients (95.7%) also demonstrated directional preponderance contralateral to the UW. Another 16 patients (27.6%) presented only directional advantage. The post-caloric recruitment was present in 38% patients.ConclusionPatients who had been diagnosed with COVID-19 seem to be more likely to suffer from vertigo/dizziness and to compensate more slowly. COVID-19 infection may cause inner ear damage and lead to vestibular dysfunction. The role of the central nervous system in the onset of equilibrium disorders should be considered. The presence of vertigo of central origin may indicate the neurotropic effect of SARS-CoV-2 following COVID-19. Imbalance may be the only symptom of COVID-19 and may also be a late complication of the disease due to post-infectious inflammation of the nervous tissue. Comprehensive studies are needed to investigate whether COVID-19 can cause long-term vestibular deficits.
Association between blood viscosity and early neurological deterioration in lacunar infarction
Authors: Lee Hyungwoo , Heo JoonNyung , Lee Il Hyung , Kim Young Dae , Nam Hyo Suk 
Published: September 2022

BackgroundUnderstanding the factors related to early neurologic deterioration (END) is crucial in the management of patients with lacunar infarction. Blood viscosity is a significant factor for microvascular perfusion. We investigated the association between blood viscosity and occurrence of END in lacunar infarction.MethodsWe included consecutive patients admitted for lacunar infarction within 72 h from symptoms onset. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score ≥2 within 24 h of admission. Viscosity was measured within 24 h of hospitalization with a scanning capillary tube viscometer. Viscosity measured at a shear rate of 300 s−1 was defined as systolic blood viscosity (SBV), whereas that measured at a shear rate of 5 s−1 as diastolic blood viscosity (DBV).ResultsOf the 178 patients included (median age, 65.5; interquartile range [IQR], 56.0, 76.0], END occurred in 33 (18.5%). DBV was significantly higher in patients with END than those without END (13.3 mPa·s [IQR 11.8, 16.0] vs. 12.3 mPa·s [IQR11.0, 13.5]; P = 0.023). In the multivariate analysis, DBV was independently associated with the occurrence of END (odds ratio 1.17; 95% confidence interval 1.01–1.36; P = 0.043). Subgroup analysis showed no heterogeneity in the effect of viscosity on the occurrence of END.ConclusionsBlood viscosity at a low shear rate (DBV) was associated with the occurrence of END in patients with lacunar infarction. Blood rheology may be important in pathophysiology of END in patients with lacunar infarction.
Felbamate for pediatric epilepsy—should we keep on using it as the last resort?
Authors: Rabinowicz Shira , Schreiber Tal , Heimer Gali , Bar-Yosef Omer , Nissenkorn Andreea , E Zohar-Dayan , Arkush Leo , Hamed Nasrin , Ben-Zeev Bruria , Tzadok Michal 
Published: September 2022

IntroductionConcerns regarding felbamate adverse effects restrict its widespread use in children with drug-resistant epilepsy. We aimed to examine the efficacy and safety of felbamate in those children and identify the ones who may benefit most from its use.MethodsWe retrospectively reviewed the medical files of all patients who were treated with felbamate in a tertiary pediatric epilepsy clinic between 2009–2021. Drug efficacy was determined at the first 3 months of treatment and thereafter. Therapeutic response and adverse reactions were monitored throughout the course of treatment.ResultsOur study included 75 children (age 8.9 ± 3.7 years), of whom 53 were treated with felbamate for seizures, 16 for electrical status epilepticus during sleep and 6 for both. The median follow-up time was 16 months (range 1–129 months). The most common cause for epilepsy was genetic (29%). The median number of previous anti-seizure medications was six [4–8]. A therapeutic response ≥50% was documented in 37 (51%) patients, and a complete response in 9 (12%). Nineteen patients (25%) sustained adverse reactions, including three cases of elevated liver enzymes and one case of neutropenia with normal bone marrow aspiration. In all cases, treatment could be continued. All children with intractable epilepsy following herpes encephalitis showed a response to felbamate.ConclusionFelbamate is an efficacious and safe anti-seizure medication in the pediatric population.
Risk factors for postoperative pulmonary complications in elderly patients receiving elective colorectal surgery: A retrospective study
Authors: Dai Yuanqiang , Sun Guolin , Hu Hongli , Wang Chun , Wang Hengyue , Zha Yanping , Sheng Ying , Hou Jiong , Bian Jinjun , Bo Lulong 
Published: September 2022

Study objectivePostoperative pulmonary complications (PPCs) are common and associated with adverse outcomes impairing long-term survival and quality of recovery. This single-centered retrospective study aimed to examine factors associated with PPCs in patients receiving elective colorectal surgery aged ≥60 years.MethodsBetween January 2019 and December 2019, 638 patients at the Shanghai Changhai Hospital who had received elective surgery for colorectal cancer were enrolled in this study. Patients were divided into the PPC group (n=38) and non-PPC group (n=600). Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), red blood cell distribution width (RDW), and systemic inflammatory index (SII) were selected and caculated to indicate preoperative and postoperative inflammatory status. Receiver operating characteristic curve and bivariate correlation analyses were performed to evaluate the identified risk factors.Main resultsThe overall incidence of PPCs was approximately 5.96%. Multivariate regression analysis identified age (OR = 1.094, 95%CI 1.038–1.153, P = 0.001), preoperative RDW (OR = 1.159, 95%CI 1.025–1.309, P = 0.018), and preoperative SII (OR = 1.001, 95%CI 1.000–1.003, P = 0.035) as independent risk factors for PPCs. The cut-off values of age, preoperative RDW, and preoperative SII for predicting PPCs were 69.5 (sensitivity 0.658, specificity 0.653), 13.2 (sensitivity 0.789, specificity 0.552) and 556.1 (sensitivity 0.579, specificity 0.672), respectively.ConclusionsAge, preoperative RDW, and preoperative SII were identified as independent risk factors for PPC occurrence in elderly patients receiving elective colorectal surgery. Further studies are warranted to evaluate whether normalization of preoperative RDW and SII, as modifiable risk factors, are associated with improved surgical outcomes.