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Nevin Manimala Statistics

An exploration of the relationship between wastewater viral signals and COVID-19 hospitalizations in Ottawa, Canada

Infect Dis Model. 2023 Sep;8(3):617-631. doi: 10.1016/j.idm.2023.05.011. Epub 2023 Jun 7.

ABSTRACT

Monitoring of viral signal in wastewater is considered a useful tool for monitoring the burden of COVID-19, especially during times of limited availability in testing. Studies have shown that COVID-19 hospitalizations are highly correlated with wastewater viral signals and the increases in wastewater viral signals can provide an early warning for increasing hospital admissions. The association is likely nonlinear and time-varying. This project employs a distributed lag nonlinear model (DLNM) (Gasparrini et al., 2010) to study the nonlinear exposure-response delayed association of the COVID-19 hospitalizations and SARS-CoV-2 wastewater viral signals using relevant data from Ottawa, Canada. We consider up to a 15-day time lag from the average of SARS-CoV N1 and N2 gene concentrations to COVID-19 hospitalizations. The expected reduction in hospitalization is adjusted for vaccination efforts. A correlation analysis of the data verifies that COVID-19 hospitalizations are highly correlated with wastewater viral signals with a time-varying relationship. Our DLNM based analysis yields a reasonable estimate of COVID-19 hospitalizations and enhances our understanding of the association of COVID-19 hospitalizations with wastewater viral signals.

PMID:37342365 | PMC:PMC10245285 | DOI:10.1016/j.idm.2023.05.011

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Nevin Manimala Statistics

Association between radiomics features of DCE-MRI and CD8+ and CD4+ TILs in advanced gastric cancer

Pathol Oncol Res. 2023 Jun 5;29:1611001. doi: 10.3389/pore.2023.1611001. eCollection 2023.

ABSTRACT

Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer. Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density. Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630-0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = -0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = -0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856). Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.

PMID:37342362 | PMC:PMC10277864 | DOI:10.3389/pore.2023.1611001

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Nevin Manimala Statistics

Cytokine-induced killer cell treatment is superior to chemotherapy alone in esophageal cancer

Pathol Oncol Res. 2023 Jun 5;29:1610710. doi: 10.3389/pore.2023.1610710. eCollection 2023.

ABSTRACT

Background: The therapeutic efficacy of cytokine-induced killer (CIK) cells versus dendritic cells (DC) co-cultured with CIK cells (DC-CIK) in treating esophageal cancer (EC) remains unclear due to the absence of a direct comparison of these two regimens. This study evaluated the comparative efficacy and safety of CIK cells versus DC-CIK using network meta-analysis in treating EC. Material and methods: We identified eligible studies from previous meta-analyses, then conducted an updated search to retrieve additional trials between February 2020 and July 2021. The primary outcomes included overall survival (OS), objective response rate (ORR), and disease control rate (DCR), and the secondary outcomes included quality of life improved rate (QLIR) and adverse events (AEs). A network meta-analysis of 12 studies was conducted using ADDIS software. Results: Twelve studies were identified, including six comparing CIK or DC-CIK plus chemotherapy (CT) with CT alone. Immunotherapy plus CT significantly improved overall survival (OS) (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.23-13.69), objective response rate (ORR) (OR 2.72, 95% CI 1.79-4.11), disease control rate (DCR) (OR 3.45, 95% CI 2.32-5.14), and quality of life improvement rate (QLIR) (OR 3.54, 95% CI 2.31-5.41). DC-CIK+CT decreased the risk of leukopenia compared with CT alone. However, no statistical difference was detected between CIK-CT and DC-CIK+CT. Conclusion: Based on the available evidence, we concluded that CIK cell treatment is superior to CT alone, but CIK-CT and DC-CIK+CT may be comparable in treating EC. However, comparing CIK-CT and DC-CIK+CT is only based on indirect evidence, so it is undoubtedly necessary to conduct studies to compare CIK-CT with DC-CIK+CT in EC patients directly.

PMID:37342361 | PMC:PMC10277884 | DOI:10.3389/pore.2023.1610710

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Nevin Manimala Statistics

Physiologic effects of surgical masking in children versus adults

PeerJ. 2023 Jun 16;11:e15474. doi: 10.7717/peerj.15474. eCollection 2023.

ABSTRACT

BACKGROUND: Surgical masks remain a focal part of the CDC guidelines to decrease COVID-19 transmission. Evidence refuting significant effects of masking on ventilation is mostly limited to small studies, with a paucity of studies on children, and none comparing children to adults.

METHODS: A total of 119 subjects were enrolled (71 adults, 49 children) in a prospective interventional study with each subject serving as their own mask-free control. End tidal CO2 (ETCO2), inspired CO2 (ICO2), and respiratory rate were measured by nasal cannula attached to an anesthesia machine D-fend module. Pulse oximetry and heart rate were also followed. After the mask-free period, an ASTM Level 3 disposable surgical mask was donned and 15 min of mask-worn data were collected.

RESULTS: A steady state was confirmed for ETCO2 and ICO2 over the masked period, and mean ICO2 levels rose significantly (p < 0.001) after masking in all age groups. The increase in ICO2 for the 2- to 7-year-old group of 4.11 mmHg (3.23-4.99), was significantly higher (p < 0.001) than the final ΔICO2 levels for both the 7- to 14-year-old group, 2.45 mmHg (1.79-3.12), and adults, 1.47 mmHg (1.18-1.76). For the pediatric group there was a negative, significant correlation between age and ΔICO2, r = -0.49, p < 0.001. Masking resulted in a statistically significant (p < 0.01) rise in ETCO2 levels of 1.30 mmHg in adults and 1.36 mmHg in children. The final respective ETCO2 levels, 34.35 (33.55-35.15) and 35.07 (34.13-36.01), remained within normal limits. Pulse oximetry, heart rate, and respiratory rate were not significantly affected.

DISCUSSION: The physiology of mechanical dead space is discussed, including the inverse relationship of subject age vs ICO2. The methodology and results are compared to previously published studies which detracted from the physiologic safety of surgical masking.

CONCLUSIONS: The wearing of a surgical mask results in a statistically significant rise in ICO2 and a smaller rise in ETCO2. Because ETCO2 and other variables remain well within normal limits, these changes are clinically insignificant.

PMID:37342359 | PMC:PMC10278594 | DOI:10.7717/peerj.15474

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Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer

Front Aging Neurosci. 2023 Jun 5;15:1123089. doi: 10.3389/fnagi.2023.1123089. eCollection 2023.

ABSTRACT

PURPOSE: To compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients.

METHODS: From June to December 2022, 104 elderly patients (aged 65-80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100β protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively.

RESULTS: At 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p < 0.05). Between group R and group D, there were no statistically significant changes (p > 0.05) in the levels of TNF-α and S-100β protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group’s concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p < 0.05). At all three time points-following induction (T2), 30 min into the operation (T3), and at the conclusion of the surgery (T4)-the heart rate and blood pressure in group R were greater than those in groups D and C. Statistics showed that the differences were significant (p < 0.05). The incidence of intraoperative hypotension was highest in group D and lowest in group R (p < 0.05). The dose of propofol and remifentanil, group C > group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p < 0.05). The VAS scores between the three groups at 72 h (T6) and 7 days (T7) were not statistically significant (p > 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p < 0.05).

CONCLUSION: Remimazolam is similarly beneficial as dexmedetomidine in lowering the incidence of early POCD in aged patients after radical gastric cancer resection, probably due to reduced inflammatory response.

PMID:37342357 | PMC:PMC10277633 | DOI:10.3389/fnagi.2023.1123089

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Nevin Manimala Statistics

Pregnancy-associated systemic gene expression compared to a pre-pregnancy baseline, among healthy women with term pregnancies

Front Immunol. 2023 Jun 5;14:1161084. doi: 10.3389/fimmu.2023.1161084. eCollection 2023.

ABSTRACT

BACKGROUND: Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies.

METHODS: Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline.

RESULTS: Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes.

CONCLUSION: Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a “normal” reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal.

PMID:37342349 | PMC:PMC10277629 | DOI:10.3389/fimmu.2023.1161084

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Analyzing the effect of the COVID-19 vaccine on Parkinson’s disease symptoms

Front Immunol. 2023 Jun 5;14:1158364. doi: 10.3389/fimmu.2023.1158364. eCollection 2023.

ABSTRACT

BACKGROUND: Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases. PD has recently received more attention by researchers in the midst of the COVID-19 pandemic.

OBJECTIVE: Yet to be researched is the effect of the COVID-19 vaccines on PD patients. Several PD patients are still hesitant to the vaccine due to this unaddressed fear. The purpose of this study is to address this gap.

METHODS: Surveys were administered to PD patients 50 years and older at UF Fixel Institute who received at least one dose of the COVID-19 vaccine. Survey questions included patients’ severity of PD symptoms before and after the vaccine and extent of worsening PD symptoms post-vaccination. After three weeks of collecting responses, the data was analyzed.

RESULTS: 34 respondents were eligible for data consideration because they fell within the age range being studied. A total of 14 respondents out of 34 (41%, p=0. 0001) reported that their PD symptoms worsened after the COVID-19 vaccine to some extent.

CONCLUSION: There was strong evidence of worsening of PD symptoms post COVID-19 vaccination, however it was mostly mild and limited to a couple of days. The worsening had statistically significant moderate positive correlation with vaccine hesitancy and post-vaccine general side effects. A possible causative mechanism of PD symptom worsening using existing scientific knowledge would be stress and anxiety associated with vaccine hesitancy and the extent of post-vaccine general side effects (fever, chills, pain), likely via simulating a mild systemic infection/inflammation the latter already established causes of PD symptom worsening.

PMID:37342344 | PMC:PMC10278957 | DOI:10.3389/fimmu.2023.1158364

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Immunohistochemical scoring of LAG-3 in conjunction with CD8 in the tumor microenvironment predicts response to immunotherapy in hepatocellular carcinoma

Front Immunol. 2023 Jun 5;14:1150985. doi: 10.3389/fimmu.2023.1150985. eCollection 2023.

ABSTRACT

INTRODUCTION: Immune checkpoint blockade (ICB) is a systemic therapeutic option for advanced hepatocellular carcinoma (HCC). However, low patient response rates necessitate the development of robust predictive biomarkers that identify individuals who will benefit from ICB. A 4-gene inflammatory signature, comprising CD8, PD-L1, LAG-3, and STAT1, was recently shown to be associated with a better overall response to ICB in various cancer types. Here, we examined whether tissue protein expression of CD8, PD-L1, LAG-3, and STAT1 predicts response to ICB in HCC.

METHODS: HCC samples from 191 Asian patients, comprising resection specimens from 124 patients (ICB-naïve) and pre-treatment specimens from 67 advanced HCC patients treated with ICB (ICB-treated), were analyzed for CD8, PD-L1, LAG-3, and STAT1 tissue expression using multiplex immunohistochemistry followed by statistical and survival analyses.

RESULTS: Immunohistochemical and survival analyses of ICB-naïve samples showed that high LAG-3 expression was associated with shorter median progression-free survival (mPFS) and overall survival (mOS). Analysis of ICB-treated samples revealed that high proportions of LAG-3+ and LAG-3+CD8+ cells pre-treatment were most closely associated with longer mPFS and mOS. Using a log-likelihood model, adding the total LAG-3+ cell proportion to the total CD8+ cell proportion significantly increased the predictive values for mPFS and mOS, compared with the total CD8+ cell proportion alone. Moreover, levels of CD8 and STAT1, but not PD-L1, were significantly correlated with better responses to ICB. After analyzing viral-related and non-viral HCC samples separately, only the LAG3+CD8+ cell proportion was significantly associated with responses to ICB regardless of viral status.

CONCLUSION: Immunohistochemical scoring of pre-treatment levels of LAG-3 and CD8 in the tumor microenvironment may help predict ICB benefits in HCC patients. Furthermore, immunohistochemistry-based techniques offer the advantage of being readily translatable in the clinical setting.

PMID:37342338 | PMC:PMC10277502 | DOI:10.3389/fimmu.2023.1150985

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How the Rise of Problematic Pornography Consumption and the COVID-19 Pandemic Has Led to a Decrease in Physical Sexual Interactions and Relationships and an Increase in Addictive Behaviors and Cluster B Personality Traits: A Meta-Analysis

Cureus. 2023 Jun 16;15(6):e40539. doi: 10.7759/cureus.40539. eCollection 2023 Jun.

ABSTRACT

On January 13, 2018, an alert was sent to Hawaii’s people that a missile was heading toward them. People were in a state of alarm for 30 minutes before the government sent out a false alarm statement. Fifteen minutes after the message that told the people of Hawaii that they were not in danger went out, Pornhub’s views spiked by 48%. On March 11, 2020, coronavirus disease 2019 (COVID-19) was designated a pandemic. By March 25, 2020, Pornhub’s views had spiked to over 24%. We took the research available on problematic pornography consumption, also referred to as internet sex addiction, pornography addiction, and cybersex addiction, and compared that to the rise of pornography use since the year 2000 and how the COVID-19 pandemic impacted pornography use and the effects it had on sexual and social relations. We also wanted to see if there is any association between pornography consumption and other addictive disorders and cluster B personality traits. There is currently no Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis for pornography addiction. We want to see if the data we gather can aid in identifying whether problematic pornography use has a place alongside other addictive disorders in the DSM-5. We hypothesize that inappropriate pornography consumption has increased since 2000, only to increase further during the pandemic. The null hypothesis, Ho, states there has been no change in the consumption of pornography since the 2000s. The alternative theory, Ha, says that the proportion of people who use pornography has increased over the past 23 years. As for other addictive disorders and cluster B personality traits, we hypothesize the research will show that greater than 50% of people exhibiting problematic pornography consumption will also have an additional addictive disorder and a cluster B personality trait. Our results support our hypothesis that during the COVID-19 pandemic, pornography consumption increased beyond the baseline. The results did not support our prediction of a significant association between other addictive disorders and cluster B personality traits with pornography consumption.

PMID:37342297 | PMC:PMC10277752 | DOI:10.7759/cureus.40539

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Echocardiographic assessment of right ventricular blood flow and tricuspid annular plane systolic excursion in apparently healthy domestic short-haired cats

Vet Res Forum. 2023;14(5):275-279. doi: 10.30466/vrf.2022.548794.3387. Epub 2023 May 15.

ABSTRACT

Right ventricular parameters change in many cardiovascular diseases; so, the presence of normal right ventricular parameters is necessary to diagnose these diseases. Ten clinically healthy adult domestic short-haired cats including six males and four females in the range of 2.70 to 4.80 kg were studied using echocardiography without sedation. The speed and pressure of blood flow through the tricuspid and pulmonary valves, speed of the movement of tricuspid valve and tricuspid annular plane systolic excursion (TAPSE) were recorded using conventional pulsed-wave (PW) Doppler, tissue Doppler imaging (TDI) and M-mode, respectively. No significant statistical differences were observed between the measured values and sex, heart rate and body weight. A positive correlation was observed between the maximum velocity of the right ventricular outflow tract and heart rate and also between TAPSE slope and body weight. With determining the normal values of PW-TDI of the right ventricle in apparently healthy domestic short-haired cats, it is expected that with providing normal reference values, the diagnosis of heart diseases especially asymptomatic heart disease be achieved as soon as possible to provide the best appropriate therapeutic management and monitoring decision about them.

PMID:37342286 | PMC:PMC10278901 | DOI:10.30466/vrf.2022.548794.3387