Category: Nevin Manimala

Comput Biol Med. 2021 Apr 30;134:104452. doi: 10.1016/j.compbiomed.2021.104452. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear.

METHOD: A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT.

RESULTS: We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT’s treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway.

CONCLUSIONS: LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

PMID:33984751 | DOI:10.1016/j.compbiomed.2021.104452

Clin Neurol Neurosurg. 2021 Apr 27;206:106669. doi: 10.1016/j.clineuro.2021.106669. Online ahead of print.

ABSTRACT

BACKGROUND: Standardized uptake values (SUVs) are important indexes for evaluating the accuracy of disease diagnoses achieved via fluoro-18 deoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). The purpose of this study is to describe normal cerebral FDG uptake in the pediatric population and compare SUVmax/mean results for brain images obtained from PET/CT and PET/MRI in neurologically healthy pediatric examinees.

METHODS: This study included 20 patients who were < 18 years of age and were without intracranial malignancy and/or brain disorders. Patients underwent either PET/CT imaging (n = 10) or PET/MRI imaging (n = 10) after 70-80 min of F-18 FDG injection. The SUVmax and SUVmean for various brain regions were calculated and compared between sides and imaging modalities using with appropriate statistical tests.

RESULTS: The median SUVmax/SUVmean values of the right-sided frontal, parietal, temporal, and occipital lobes were 8.63/ 6.18, 8.85 / 6.97, 6.88 / 4.99, and 11.06 / 7.02 in PET/CT, respectively, and 11.45 / 8.59, 10.16 / 8.47, 8.82 / 6.6, and 11.71 / 8.25 in PET/MRI, respectively. The median SUVmax/SUVmean values of the left-sided frontal, parietal, temporal, and occipital lobes were 9.05 / 6.86, 8.03 / 6.62, 6.49 / 4.77, and 10.6 / 7.73 in PET/CT, respectively, and 10.7 / 8.16, 11.06 / 7.88, 8.13 / 6.09, and 10.96 / 9.22 in PET/MRI, respectively.

CONCLUSIONS: These results showed that there was no statistically significant difference in SUVs values between the two brain imaging modalities except from SUVmax value of left-sided parietal lobe and no asymmetric radiopharmaceutical uptake between the left and right brain regions or cerebellums in each modality, suggested that in brain imaging, PET/MRI can be used reliably instead of PET/CT.

PMID:33984753 | DOI:10.1016/j.clineuro.2021.106669

Vet Microbiol. 2021 May 4;258:109100. doi: 10.1016/j.vetmic.2021.109100. Online ahead of print.

ABSTRACT

The purpose of this experimental study was to evaluate the efficacy of a new trivalent vaccine containing porcine circovirus types 2a/b (PCV2a/b) and Mycoplasma hyopneumoniae. Pigs were administered the vaccine intramuscularly as either at 3 and 24 days of age with 1.0 mL or at 21 days of age with 2.0 mL according to the manufacturer’s recommendations. The pigs were challenged at 42 days of age with either PCV2d (intranasal route) or M. hyopneumoniae (intratracheal route), or both. No statistical differences were observed between the one-dose and two-dose experiments based on clinical (growth performance), immunological (protective immunity), microbiological (viremia and laryngeal swab), and pathological (pulmonary and lymphoid lesion) outcomes. Pigs in vaccinated/challenged and unvaccinated/unchallenged groups showed significant difference in growth performance compared to pigs in the unvaccinated/challenged group in both dosage experiments. Vaccinated pigs elicited a significant amount of protective immunity for PCV2d-specific neutralizing antibodies and interferon-γ secreting cells (IFN-γ-SC) as well as M. hyopneumoniae-specific IFN-γ-SC significantly post-challenge compared to unvaccinated/challenged pigs. Vaccination and challenge reduced the viral load amount of PCV2d in the blood and reduced the M. hyopneumoniae load in laryngeal swab, while simultaneously reducing both pulmonary and lymphoid lesion severity when compared to unvaccinated/challenged pigs. Trivalent vaccination provided good protection against a single PCV2d challenge, single M. hyopneumoniae challenge, and a PCV2d/M. hyopneumoniae dual challenge.

PMID:33984792 | DOI:10.1016/j.vetmic.2021.109100

Neural Netw. 2021 Apr 30;142:57-72. doi: 10.1016/j.neunet.2021.04.036. Online ahead of print.

ABSTRACT

Even when neural networks are widely used in a large number of applications, they are still considered as black boxes and present some difficulties for dimensioning or evaluating their prediction error. This has led to an increasing interest in the overlapping area between neural networks and more traditional statistical methods, which can help overcome those problems. In this article, a mathematical framework relating neural networks and polynomial regression is explored by building an explicit expression for the coefficients of a polynomial regression from the weights of a given neural network, using a Taylor expansion approach. This is achieved for single hidden layer neural networks in regression problems. The validity of the proposed method depends on different factors like the distribution of the synaptic potentials or the chosen activation function. The performance of this method is empirically tested via simulation of synthetic data generated from polynomials to train neural networks with different structures and hyperparameters, showing that almost identical predictions can be obtained when certain conditions are met. Lastly, when learning from polynomial generated data, the proposed method produces polynomials that approximate correctly the data locally.

PMID:33984736 | DOI:10.1016/j.neunet.2021.04.036

J Stroke Cerebrovasc Dis. 2021 May 10;30(7):105844. doi: 10.1016/j.jstrokecerebrovasdis.2021.105844. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to analyse the relationship between specific inflammatory biomarkers’ levels and the temporal pattern of cerebral venous thrombosis (CVT) symptoms.

MATERIALS AND METHODS: We performed a retrospective study of adult CVT patients admitted between Jan 01 2006 and Dec 31 2019. We excluded patients with infection at admission, autoimmune, inflammatory or haematological disorders. We evaluated serum inflammatory biomarkers at admission: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), absolute neutrophil count, absolute lymphocyte count, platelet count, monocyte count, neutrophile-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), bilirubin and monocyte-to-HDL ratio (M-HDLR). These were evaluated according to the time from symptom onset (acute, subacute or chronic).

RESULTS: We included 78 patients with CVT (mean age 41 ± 13 years). Neutrophil count (p = 0.017), monocyte (p = 0.024), CRP (p = 0.004), NLR (p<0.001) and LMR (p = 0.004) showed significant variation with CVT duration. Acute onset CVT exhibited higher absolute neutrophil count and NLR but lower LMR. The subacute group had higher monocyte values, and the chronic phase patients displayed higher LMR, but lower CRP. ESR, PLR and M-HDLR showed a tendency to decrease in the chronic phase. We did not observe any statistical difference between the duration of symptoms and levels of bilirubin.

CONCLUSIONS: CVT patients present a differential inflammatory pattern along the time course of the disease: higher NLR and lower LMR in acute phase, and higher LMR and lower CRP level during the chronic phase. These differences may help to ascertain the onset of poorly defined symptoms and provide input regarding anticoagulation management.

PMID:33984744 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105844

Int Immunopharmacol. 2021 May 10;96:107742. doi: 10.1016/j.intimp.2021.107742. Online ahead of print.

ABSTRACT

BACKGROUND: CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy has shown promising clinical outcomes in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) patients. However, some patients did not respond to this therapy or relapsed after remission. Regulatory T cells (Tregs) have shown great importance in promoting tumor escape, but little is known about their role in R/R B-ALL patients with CAR-T therapy. Our previous study has proved that higher Tregs before infusion was an independent high-risk factor for relapse-free survival (RFS). To further clarify the relationship between Tregs and the efficacy of CAR-T therapy, the present study tested the levels of CD4⁺CD25⁺CD127^low Tregs in peripheral blood (PB) of R/R B-ALL patients at different stages of CD19 CAR-T therapy, and evaluate their impact on the efficacy and prognosis of CAR-T therapy.

METHODS: From November 2015 to May 2019, 47 R/R B-ALL patients successfully received CD19 CAR-T therapy at our institution and followed up for at least 1 month. Among them, one patient did not tested for Tregs, so 46 patients enrolled in this study. We collected clinical information of them and dynamically detected the frequency of CD4⁺CD25⁺CD127^low Tregs within CD4 + T cells at different time points (before infusion and at 1 week after infusion) by flow cytometry, and validated the relationship of circulating Tregs with clinical efficacy, OS, and recurrence of CAR-T therapy.

RESULTS: Circulating Tregs of R/R B-ALL patients in pre-infusion group (median 6.67%) and in 1 week after infusion group (median 6.80%) were all higher than that of the healthy control group (median 5.04%), with statistical significance (P < 0.05). The frequencies of Tregs in not remission (NR) group at baseline (pre-infusion) and at 1 week after infusion were all significantly higher than those in remission group. With cut-off values of 11.54% (before infusion) and 13.56% (1 week after infusion), the specificity for Tregs were 94.6% and 100% , respectively. In remission group, 11 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving remission by Sino 19 cell therapy. No significant differences of Tregs expression were found between transplantation and non-transplantation groups. Time-dependent Cox model showed that transplantation group had lower risk of relapse and death when compared with non-transplantation group (HR = 0.664 for RFS and HR = 0.364 for OS), however, no statistical significances were found (P = 0.403 and 0.106, respectively). Higher Tregs before infusion and at 1 week after infusion were significant associated with shorter RFS and OS by Kaplan-Meier analysis. Multivariate analysis showed that higher Tregs at 1 week after infusion was the independently factor for poor RFS (P = 0.032) and shorter OS (P = 0.025) in R/R B-ALL patients with CD19 CAR-T therapy. Besides, Tregs levels before and at 1 week after infusion were negatively correlated with the persistence time of Sino 19 cell.

CONCLUSION: Higher circulating Tregs, especially 1 week after CD19 CAR-T cell infusion, was a poor predict indicator for CD19 CAR-T therapy in R/R B-ALL patients.

PMID:33984717 | DOI:10.1016/j.intimp.2021.107742

Int Immunopharmacol. 2021 Apr 30;96:107743. doi: 10.1016/j.intimp.2021.107743. Online ahead of print.

ABSTRACT

OBJECTIVE: Ozone therapy has tremendous therapeutic potential owing to its antiviral, anti-inflammatory and antioxidant properties, and potential to improve oxygenation. A pilot clinical trial was conducted to evaluate the safety and efficacy ofintravenous ozonised saline treatment in patients with moderate COVID-19 pneumonia.

PATIENTS AND METHODS: 10 patients were administered 200 ml freshly prepared ozonised saline intravenously over 1 h once a day for 8 days along with standard medical treatment. Clinical symptoms were monitored everyday and laboratory biomarkers, radiological findings at 1,3,6,10 days. Telephonic follow up was done for all after discharge till Day 14. 7 out of 10 patients required oxygen supplementation at recruitment.

RESULTS: There was severe adverse event recorded in the study group.All patients improved from moderate to mild category in average 8 days and were discharged in average 9.7 days. None deteriorated to severe stage. All clinical symptoms resolved within 6 days and oxygen supplementation requirement reduced to none within 4.1 days. There wasstatistically significant reduction inCRP (p = 0.003), D-Dimer (p = 0.049), IL6 (p = 0.002)and statistically significant improvement (p = 0.001) in SpO2/FiO2 ratio. Change in LDH was borderline statistically not significant (p = 0.058).All patients showed significant resolution of bilateral interstitial infiltrates at the end of 10 days.

CONCLUSION: Resolved clinical symptoms, improved oxygenation, clearance of infiltrates on Chest X-ray and improvement in biomarkers in a short period with non-progression of the disease showed that IV ozonised saline therapy was safe and effective to prevent disease progression in COVID-19, making it an effective novel therapeutic tool.

PMID:33984718 | DOI:10.1016/j.intimp.2021.107743

J Surg Res. 2021 Apr 30;266:62-68. doi: 10.1016/j.jss.2021.04.024. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether any specific acute care surgery patient populations are associated with a higher incidence of COVID-19 infection.

BACKGROUND: Acute care providers may be exposed to an increased risk of contracting the COVID-19 infection since many patients present to the emergency department without complete screening measures. However, it is not known which patients present with the highest incidence.

METHODS: All acute care surgery (ACS) patients who presented to our level I trauma center between March 19, 2020, and September 20, 2020 and were tested for COVID-19 were included in the study. The patients were divided into two cohorts: COVID positive (+) and COVID negative (-). Patient demographics, type of consultation (emergency general surgery consults [EGS], interpersonal violence trauma consults [IPV], and non-interpersonal violence trauma consults [NIPV]), clinical data and outcomes were analyzed. Univariate and multivariate analyses were used to compare differences between the groups.

RESULTS: In total, 2177 patients met inclusion criteria. Of these, 116 were COVID+ (5.3%) and 2061 were COVID- (94.7%). COVID+ patients were more frequently Latinos (64.7% versus 61.7%, P = 0.043) and African Americans (18.1% versus 11.2%, P < 0.001) and less frequently Caucasian (6.0% versus 14.1%, P < 0.001). Asian/Filipino/Pacific Islander (7.8% versus 7.2%, P = 0.059) and Native American/Other/Unknown (3.4% versus 5.8%, P = 0.078) groups showed no statistical difference in COVID incidence. Mortality, hospital and ICU lengths of stay were similar between the groups and across patient populations stratified by the type of consultation. Logistic regression demonstrated higher odds of COVID+ infection amongst IPV patients (OR 2.33, 95% CI 1.62-7.56, P < 0.001) compared to other ACS consultation types.

CONCLUSION: Our findings demonstrate that victims of interpersonal violence were more likely positive for COVID-19, while in hospital outcomes were similar between COVID-19 positive and negative patients.

LEVEL OF EVIDENCE: Level III, Prognostic and Epidemiological.

PMID:33984732 | DOI:10.1016/j.jss.2021.04.024

ESMO Open. 2021 May 10;6(3):100151. doi: 10.1016/j.esmoop.2021.100151. Online ahead of print.

ABSTRACT

BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm.

PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status.

RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS.

CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.

PMID:33984674 | DOI:10.1016/j.esmoop.2021.100151

Sci Total Environ. 2021 May 6;786:147534. doi: 10.1016/j.scitotenv.2021.147534. Online ahead of print.

ABSTRACT

The presence of SARS-CoV-2 in wastewater pose the question of whether this new pandemic virus could be released into watercourses and potentially continue to finally reach coastal waters. In this study, we employed two bivalve molluscan species from the genus Ruditapes as sentinel organisms to investigate the presence of SARS-CoV-2 signals in the marine coastal environment. Estuarine sediments from the natural clam banks were also analyzed. Viral RNA was detected by RT-qPCR, targeting IP4, E and N1 genomic regions. Positive samples were also subjected to a PMAxx-triton viability RT-qPCR assay in order to discriminate between intact and altered capsids, obtaining indirect information about the viability of the virus. SARS-CoV-2 RNA traces were detected in 9/12 clam samples by RT-qPCR, from which 4 were positive for two different target regions. Viral quantification ranged from <LoQ to 4.48 Log genomic copies/g of digestive tissue. Regarding the sediment samples, 3/12 were positive by RT-qPCR, but only IP4 region was successfully amplificated. Quantification values for sediment samples ranged from <LoQ to 3.60 Log genomic copies/g of sediment. RNA signals disappeared in the PMAxx-triton viability RT-qPCR assay, indicating non-infectious potential. In addition, the recently discovered human-specific gut associated bacteriophage crAssphage was also quantified as a biomarker for the presence of human-derived wastewater contamination on the study area. CrAssphage was detected in 100% of both types of samples with quantification values ranging from <LoQ to 5.94 Log gc/g digestive tissue and from <LoQ to 4.71 Log gc/g sediment. Statistical analysis also showed that quantification levels for the crAssphage in clams are significantly higher than in sediments. These findings represent the first detection of SARS-CoV-2 RNA in the marine environment, demonstrating that it can reach these habitats and make contact with the marine life.

PMID:33984699 | DOI:10.1016/j.scitotenv.2021.147534