Nevin Manimala

J Ginseng Res. 2023 Mar;47(2):246-254. doi: 10.1016/j.jgr.2022.08.003. Epub 2022 Aug 26.

ABSTRACT

BACKGROUND: Here, we aimed to assess the inhibitory effect of a new compound from Panax ginseng on the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs).

METHODS: A new compound, ginsenglactone A (1), was isolated from ginseng roots, together with seven known compounds (2–8). Spectroscopic data were used to elucidate the chemical structure of 1. The tubular structure formation in HUVECs was assessed by Mayer’s hematoxylin staining. The migration of A2780 cells was evaluated using the scratch wound healing assay.

RESULTS: HUVECs treated with 1 had the statistically significant decrease in tubular structure formation compared to the HUVECs treated with compounds 2–8. This effect was enhanced by co-treatment with inhibitors for phosphatidylinositol 3-kinase (PI3K) (LY294002) and extracellular signal-regulated kinase (ERK) (U0126). Treatment with 1 decreased the expression of phosphorylation of ERK, PI3K, vascular endothelial growth factor receptor2 (VEGFR2), Akt, and mammalian target of rapamycin (mTOR). In addition, the ability of A2780 cells to cover the scratched area were also decreased. This effect was enhanced by co-treatment with U0126. Lastly, treatment with 1 decreased the phosphorylation of ERK, matrix metalloproteinase-9 (MMP-9), and MMP-2.

CONCLUSION: These results suggest that ginsenglactone A is a potential inhibitor of HUVEC tubular structure formation and A2780 cellular migration, which may be helpful for understanding its anticancer mechanism.

PMID:36926606 | PMC:PMC10014176 | DOI:10.1016/j.jgr.2022.08.003

JAMIA Open. 2023 Mar 14;6(1):ooad016. doi: 10.1093/jamiaopen/ooad016. eCollection 2023 Apr.

ABSTRACT

OBJECTIVES: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

MATERIALS AND METHODS: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

RESULTS: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

DISCUSSION: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

CONCLUSION: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.

PMID:36926600 | PMC:PMC10013630 | DOI:10.1093/jamiaopen/ooad016

Curr Res Neurobiol. 2023 Mar 1;4:100080. doi: 10.1016/j.crneur.2023.100080. eCollection 2023.

ABSTRACT

Statistical learning (SL) is an innate mechanism by which the brain automatically encodes the n-th order transition probability (TP) of a sequence and grasps the uncertainty of the TP distribution. Through SL, the brain predicts a subsequent event (e _n+1 ) based on the preceding events (e _n ) that have a length of “n”. It is now known that uncertainty modulates prediction in top-down processing by the human predictive brain. However, the manner in which the human brain modulates the order of SL strategies based on the degree of uncertainty remains an open question. The present study examined how uncertainty modulates the neural effects of SL and whether differences in uncertainty alter the order of SL strategies. It used auditory sequences in which the uncertainty of sequential information is manipulated based on the conditional entropy. Three sequences with different TP ratios of 90:10, 80:20, and 67:33 were prepared as low-, intermediate, and high-uncertainty sequences, respectively (conditional entropy: 0.47, 0.72, and 0.92 bit, respectively). Neural responses were recorded when the participants listened to the three sequences. The results showed that stimuli with lower TPs elicited a stronger neural response than those with higher TPs, as demonstrated by a number of previous studies. Furthermore, we found that participants adopted higher-order SL strategies in the high uncertainty sequence. These results may indicate that the human brain has an ability to flexibly alter the order based on the uncertainty. This uncertainty may be an important factor that determines the order of SL strategies. Particularly, considering that a higher-order SL strategy mathematically allows the reduction of uncertainty in information, we assumed that the brain may take higher-order SL strategies when encountering high uncertain information in order to reduce the uncertainty. The present study may shed new light on understanding individual differences in SL performance across different uncertain situations.

PMID:36926596 | PMC:PMC10011828 | DOI:10.1016/j.crneur.2023.100080

Front Netw Physiol. 2023 Feb 6;3:1125023. doi: 10.3389/fnetp.2023.1125023. eCollection 2023.

ABSTRACT

The approach introduced by Network Physiology intends to find and quantify connectedness between close- and far related aspects of a person’s Physiome. In this study I applied a Network-inspired analysis to a set of measurement data that had been assembled to detect prospective orthostatic intolerant subjects among people who were destined to go into Space for a two weeks mission. The advantage of this approach being that it is essentially model-free: no complex physiological model is required to interpret the data. This type of analysis is essentially applicable to many datasets where individuals must be found that “stand out from the crowd”. The dataset consists of physiological variables measured in 22 participants (4f/18 m; 12 prospective astronauts/cosmonauts, 10 healthy controls), in supine, + 30° and + 70° upright tilted positions. Steady state values of finger blood pressure and derived thereof: mean arterial pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance; middle cerebral artery blood flow velocity and end-tidal pCO2 in tilted position were (%)-normalized for each participant to the supine position. This yielded averaged responses for each variable, with statistical spread. All variables i.e., the “average person’s response” and a set of %-values defining each participant are presented as radar plots to make each ensemble transparent. Multivariate analysis for all values resulted in obvious dependencies and some unexpected ones. Most interesting is how individual participants maintained their blood pressure and brain blood flow. In fact, 13/22 participants had all normalized Δ-values (i.e., the deviation from the group average, normalized for the standard deviation), both for +30° and +70°, within the 95% range. The remaining group demonstrated miscellaneous response patterns, with one or more larger Δ-values, however of no consequence for orthostasis. The values from one prospective cosmonaut stood out as suspect. However, early morning standing blood pressure within 12 h after return to Earth (without volume repletion) demonstrated no syncope. This study demonstrates an integrative way to model-free assess a large dataset, applying multivariate analysis and common sense derived from textbook physiology.

PMID:36926547 | PMC:PMC10012999 | DOI:10.3389/fnetp.2023.1125023

N Am Spine Soc J. 2023 Jan 29;14:100201. doi: 10.1016/j.xnsj.2023.100201. eCollection 2023 Jun.

ABSTRACT

BACKGROUND: Strong innervation of the vertebral endplates by the basivertebral nerve makes it an ideal target for ablation in the treatment of vertebrogenic low back pain with Modic changes. This data represents the clinical outcomes for 16 consecutively treated patients in a community practice setting.

METHODS: Basivertebral nerve ablations were performed on 16 consecutive patients by a single surgeon (WS) utilizing the INTRACEPT® device (Relievant Medsystems, Inc.). Evaluations were performed at baseline, 1 month, 3 months, and 6 months. The Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and SF-36 were recorded in Medrio electronic data capture software. All patients (n = 16) completed the baseline, 1 month, 3 months, and 6 months follow-up.

RESULTS: The ODI, VAS, and SF-36 Pain Component Summary showed statistically significant improvements above minimal clinically important differences at 1 month, 3 months, and 6 months (all p values <0.05). Change in ODI pain impact declined 13.1 points [95% CI: 0.01,27.2] at one month from baseline, 16.5 points [95% CI: 2.5,30.6] at three months from baseline, and 21.1 points [95% CI: 7.0,35.2] six-months from baseline. SF-36 Mental Component Summary also showed some improvements, but with significance only at 3 months (p = 0.0091).

CONCLUSIONS: Basivertebral nerve ablation appears to be a durable, minimally invasive treatment for the relief of chronic low back pain that can be successfully implemented in a community practice setting. To our knowledge, this is the first independently funded US study on basivertebral nerve ablation.

PMID:36926532 | PMC:PMC10011817 | DOI:10.1016/j.xnsj.2023.100201

Front Immunol. 2023 Feb 28;13:1110992. doi: 10.3389/fimmu.2022.1110992. eCollection 2022.

ABSTRACT

BACKGROUND: WBP216 is a novel human immunoglobulin G1 (IgG1) monoclonal antibody for interleukin (IL)-6. We aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single ascending dose (SAD) of WBP216 in patients with rheumatoid arthritis (RA).

METHODS: In this double-blind, placebo-controlled, SAD, phase Ia study, patients with RA were randomized in a 3:1 (Group A1, 10 mg) and 6:2 (Group A2, 30 mg; Group A3, 75 mg; Group A4, 150 mg; Group A5, 300 mg) ratios to receive either ascending doses of WBP216 or placebo subcutaneously. The primary endpoint was the incidence of adverse events (AEs), while the secondary endpoints were characterization of PK, PD, and immunogenicity of WBP216 and the exploratory endpoints included improvements in RA clinical metrics. All statistical analyses were performed using SAS^® version 9.2.

RESULTS: A total of 41 subjects (34 females and 7 males) were enrolled in the study. WBP216 was well tolerated in all doses (10-300 mg). Most treatment-emergent AEs (TEAEs; 97.6%) were of grade 1 severity and resolved without any treatment. No subjects experienced TEAEs leading to withdrawal or death during the study. An increase in serum concentration and total IL-6 from baseline was observed, while a substantial decrease in high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) was observed in all the WBP216 groups. Anti-drug antibodies were detected in only one subject after dosing, indicating an acceptable immunogenicity profile. Limited ACR20 and ACR50 response was observed in the WBP216 groups and no response in the placebo group.

CONCLUSION: WBP216 demonstrated a good safety profile and evidence of potential efficacy in the treatment of patients with RA.

CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20170306.

PMID:36926529 | PMC:PMC10011485 | DOI:10.3389/fimmu.2022.1110992

ACS Pharmacol Transl Sci. 2023 Feb 24;6(3):399-409. doi: 10.1021/acsptsci.2c00212. eCollection 2023 Mar 10.

ABSTRACT

Breast cancer is one of the major causes of death in women worldwide. It is a diverse illness with substantial intersubject heterogeneity, even among individuals with the same type of tumor, and customized therapy has become increasingly important in this sector. Because of the clinical and physical variability of different kinds of breast cancers, multiple staging and classification systems have been developed. As a result, these tumors exhibit a wide range of gene expression and prognostic indicators. To date, no comprehensive investigation of model training procedures on information from numerous cell line screenings has been conducted together with radiation data. We used human breast cancer cell lines and drug sensitivity information from Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases to scan for potential drugs using cell line data. The results are further validated through three machine learning approaches: Elastic Net, LASSO, and Ridge. Next, we selected top-ranked biomarkers based on their role in breast cancer and tested them further for their resistance to radiation using the data from the Cleveland database. We have identified six drugs named Palbociclib, Panobinostat, PD-0325901, PLX4720, Selumetinib, and Tanespimycin that significantly perform on breast cancer cell lines. Also, five biomarkers named TNFSF15, DCAF6, KDM6A, PHETA2, and IFNGR1 are sensitive to all six shortlisted drugs and show sensitivity to the radiations. The proposed biomarkers and drug sensitivity analysis are helpful in translational cancer studies and provide valuable insights for clinical trial design.

PMID:36926455 | PMC:PMC10012252 | DOI:10.1021/acsptsci.2c00212

Virus Evol. 2023 Mar 7;9(1):vead007. doi: 10.1093/ve/vead007. eCollection 2023.

ABSTRACT

Transmission trees can be established through detailed contact histories, statistical or phylogenetic inference, or a combination of methods. Each approach has its limitations, and the extent to which they succeed in revealing a ‘true’ transmission history remains unclear. In this study, we compared the transmission trees obtained through contact tracing investigations and various inference methods to identify the contribution and value of each approach. We studied eighty-six sequenced cases reported in Guinea between March and November 2015. Contact tracing investigations classified these cases into eight independent transmission chains. We inferred the transmission history from the genetic sequences of the cases (phylogenetic approach), their onset date (epidemiological approach), and a combination of both (combined approach). The inferred transmission trees were then compared to those from the contact tracing investigations. Inference methods using individual data sources (i.e. the phylogenetic analysis and the epidemiological approach) were insufficiently informative to accurately reconstruct the transmission trees and the direction of transmission. The combined approach was able to identify a reduced pool of infectors for each case and highlight likely connections among chains classified as independent by the contact tracing investigations. Overall, the transmissions identified by the contact tracing investigations agreed with the evolutionary history of the viral genomes, even though some cases appeared to be misclassified. Therefore, collecting genetic sequences during outbreak is key to supplement the information contained in contact tracing investigations. Although none of the methods we used could identify one unique infector per case, the combined approach highlighted the added value of mixing epidemiological and genetic information to reconstruct who infected whom.

PMID:36926449 | PMC:PMC10013732 | DOI:10.1093/ve/vead007

Adv Biomed Res. 2023 Jan 27;12:8. doi: 10.4103/abr.abr_353_21. eCollection 2023.

ABSTRACT

BACKGROUND: This study investigated the feasibility of channelized hoteling observer (CHO) model in computed tomography (CT) protocol optimization regarding the image quality and patient exposure. While the utility of using model observers such as to optimize the clinical protocol is evident, the pitfalls associated with the use of this method in practice require investigation.

MATERIALS AND METHODS: This study was performed using variable tube current and adaptive statistical iterative reconstruction (ASIR) level (ASIR 10% to ASIR 100%). Various criteria including noise, high-contrast spatial resolution, CHOs model were used to compare image quality at different captured levels. For the implementation of CHO, we first tuned the model in a restricted dataset and then it to the evaluation of a large dataset of images obtained with different reconstruction ASIR and filtered back projection (FBP) levels.

RESULTS: The results were promising in terms of CHO use for the stated purposes. Comparisons of the noise of reconstructed images with 30% ASIR and higher levels of noise in rebuilding images using the FBP approach showed a significant difference (P < 0.05). The spatial resolution obtained using various ASIR levels and tube currents were 0.8 pairs of lines per millimeter, which did not differ significantly from the FBP method (P > 0.05).

CONCLUSIONS: Based on the results, using 80% ASIR can reduce the radiation dose on lungs, abdomen, and pelvis CT scans while maintaining image quality. Furthermore using ASIR 60% only for the reconstruction of lungs, abdomen, and pelvis images at standard radiation dose leads to optimal image quality.

PMID:36926443 | PMC:PMC10012030 | DOI:10.4103/abr.abr_353_21

Adv Biomed Res. 2023 Jan 27;12:12. doi: 10.4103/abr.abr_295_21. eCollection 2023.

ABSTRACT

BACKGROUND: Despite recognizing the traditional coronary artery disease (CAD) risk factors, some secondary factors, such as opioid substance abuse, have to be considered. We aimed to assess the relationship between opioid consumption and emergency percutaneous coronary intervention (PCI) revascularization results, according to Thrombolysis in Myocardial Infarction (TIMI) flow and in-hospital survival outcomes in ST-elevation myocardial infarction (STEMI) patients.

MATERIALS AND METHODS: This case-control study was conducted on 186 patients (93 patients in each group) with acute STEMI, who were referred to Chamran Heart Center, Isfahan, Iran. Opioid addiction was diagnosed by patients’ records and confirmed by conducting an interview based on the Diagnostic and Statistical Manual of Mental Disorders, 4^th Edition (DSM-IV) criteria. Patients in both groups were evaluated and compared for angioplasty results based on the TIMI flow grade and in-hospital cardiovascular events and complications.

RESULTS: Ninety-one patients (97.84%) of each group were male, and opioid-addicted patients were younger than the non-opioid users (52.95 9.91 vs. 57.90 12.17, P = 0.003). Among the CAD risk factors, prevalence of dyslipidemia was significantly higher in non-opioid users, whereas cigarette smoking was higher in opioid-addicted patients (P < 0.050). There was no significant difference between the two groups regarding pre- and post-procedural myocardial infarction complications as well as mortality rate (P > 0.050). Also, there were no significant differences between the opioid and non-opioid users regarding TIMI flow grading, and successful PCI rate based on achieving TIMI III was 60.21% versus 59.1% in opiate-dependent and non-opioid users, respectively (P = 0.621).

CONCLUSION: Opioid addiction has no effects on post-PCI angiographic results and in-hospital survival outcomes in STEMI patients which undergoing emergency PCI.

PMID:36926439 | PMC:PMC10012017 | DOI:10.4103/abr.abr_295_21