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Association Between HSPA5 Promoter Polymorphisms and a Reduced Risk of Normal Tension Glaucoma

Ophthalmic Res. 2022 Apr 4. doi: 10.1159/000524173. Online ahead of print.

ABSTRACT

INTRODUCTION: In Normal Tension Glaucoma (NTG), factors other than elevated Intraocular Pressure (IOP) are likely to play a role in the pathogenesis of optic neuropathy. The potential similarities between Alzheimer’s disease and NTG in cellular apoptosis leading to neuro-degeneration have been shown in recent studies. HSPA5 (Heat Shock Protein family A member 5) promoter polymorphisms have been reported to be associated with a risk of Alzheimer’s Disease (AD). The purpose of our study was to investigate the role of HSPA5 promoter polymorphisms in NTG patients.

METHODS: A total of 222 patients with NTG, along with 236 normal controls were enrolled in this study. Genomic DNA was amplified through a Polymerase Chain Reaction (PCR) and identified for the polymorphic HSPA5 (-415 and -370) by Xmn1 and BstY1 restriction digestion, respectively. PCR fragments with potential polymorphic HSPA5 (-180) were subjected to sequence-analyses by a Hex-labeled primer. Genotypes for both the NTG patients and control groups were compared for statistically significant differences.

RESULTS: Polymorphisms (-415) G/A and (-180) del/G were completely linked in our population. The genotype and allele frequency distribution at the -415 G/A and -180 del/G sites showed a significant difference between the NTG cases and controls. The genotype frequency of HSPA5 (-415) AA / (-180) GG and the allele frequency of HSPA5 (-415) A / (-180) G were significantly lower (p=0.04 and p= 0.01, respectively) in the NTG patients when compared with those in the control group. There was no significant difference in genotype or allele frequency distribution of the HSPA5 (-370) C/T between the NTG and control groups. There was a reduced risk of NTG associated with the carriers for the HSPA5 (-415) A / (-180 ) G allele compared with that in the control population (p=0.01).

CONCLUSION: HSPA5 (-415) A and (-180) G allele polymorphisms may be protective factors in the development of NTG.

PMID:35378534 | DOI:10.1159/000524173

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Comparison of 68Ga-DOTATOC and 18F-FDG Thoracic Lymph Node and Pulmonary Lesion Uptake Using PET/CT in Postprimary Tuberculosis

Am J Trop Med Hyg. 2022 Apr 4:tpmd210416. doi: 10.4269/ajtmh.21-0416. Online ahead of print.

ABSTRACT

Tuberculosis (TB) remains one of the world’s leading infectious cause of morbidity and mortality. Positron emission tomography (PET) associated with computed tomography (CT) allows a structural and metabolic evaluation of TB lesions, being an excellent noninvasive alternative for understanding its pathogenesis. DOTATOC labeled with gallium-68 (68Ga-DOTATOC) can bind to somatostatin receptors present in activated macrophages and lymphocytes, cells with a fundamental role in TB pathogenesis. We describe 68Ga-DOTATOC uptake distribution and patterns in thoracic lymph nodes (LN) and pulmonary lesions (PL) in immunocompetent patients with active postprimary TB, analyze the relative LN/PL uptake, and compare this two tracer’s uptake. High uptake of both radiotracers in PL and LN was demonstrated, with higher LN/PL ratio on 68Ga-DOTATOC (P < 0.05). Considering that LN in immunocompetent patients are poorly studied, 68Ga-DOTATOC can contribute to the understanding of the complex immunopathogenesis of TB.

PMID:35378506 | DOI:10.4269/ajtmh.21-0416

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Mechanical Thrombectomy for Mild Acute Ischemic Stroke with Large-Vessel Occlusion: A Systematic Review and Meta-Analysis

Cerebrovasc Dis. 2022 Apr 4:1-8. doi: 10.1159/000523838. Online ahead of print.

ABSTRACT

BACKGROUND: The functional prognosis of mechanical thrombectomy (MT) for mild acute ischemic stroke (AIS) with large-vessel occlusion (LVO) is controversial. To explore a more precise estimation, a meta-analysis was conducted.

METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Collaboration Database until October 2021. The pooled analysis, subgroup analysis, sensitivity analysis, and publication bias examination were all conducted. The meta-analysis was performed by using Stata 12.0.

RESULTS: Eleven studies were included with a total of 1,929 subjects, including 794 patients receiving MT and 1,135 patients receiving medical management. The pooled analysis showed that MT might be not associated with functional prognosis among mild AIS with LVO (excellent functional prognosis: risk ratio (RR) = 1.07, 95% confidence interval (CI) = 0.94-1.21, p = 0.294; favorable functional prognosis: RR = 1.01, 95% CI = 0.96-1.06, p = 0.823). The statistical stability and reliability were demonstrated by the sensitivity analysis and publication bias outcomes.

CONCLUSION: Our meta-analysis suggests that MT may be not associated with functional prognosis of mild AIS with LVO.

PMID:35378529 | DOI:10.1159/000523838

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TinyLev acoustically levitated water: Direct observation of collective, inter-droplet effects through morphological and thermal analysis of multiple droplets

J Colloid Interface Sci. 2022 Mar 28;619:84-95. doi: 10.1016/j.jcis.2022.03.082. Online ahead of print.

ABSTRACT

HYPOTHESIS: Understanding the crystallization of atmospheric water can require levitation techniques to avoid the influence of container walls. Recently, an acoustic levitation device called the TinyLev was designed, which can levitate multiple droplets at room temperature. Proximal crystallization may affect droplet phase change and morphological characteristics.

METHODOLOGY: In this study, acoustically levitated pure water droplets were frozen individually and in pairs or triplets using a TinyLev device. Nucleation, bulk crystal growth, and melting were observed using digital and infrared cameras concurrently.

FINDINGS: Initially, the acoustic field forced the droplets into an oblate spheroid shape, though the counteracting force of the cooling stream caused them to circularize. Droplet geometry was thus the net result of streaming forces and surface tension at the acoustic boundary layer/air-liquid interface. Nucleation was determined to be neither homogeneous nor heterogeneous but secondary, and thus dependent on the cooling rate and not on the degree of supercooling. It was likely initiated by aerosolized ice particles from the air or from droplets that had already nucleated and broken up. The latter secondary ice production process resulted in multi-drop systems with statistically identical nucleation times. Notably, this meant that the presence of interfacial rupture at an adjacent droplet could influence the crystallization behaviour of another. After the formation of an initial ice shell around the individual droplets, dendritic protrusions grew from the droplet surface, likely seeded by the same ice particles that caused nucleation, but at a quasi-liquid layer. When freezing was complete, it was determined that the frozen core had undergone a volumetric expansion of 30.75%, compared to 9% for pure, sessile water expansion. This significantly greater expansion may have resulted from entrained air bubbles at the inner solid-liquid interface and oscillations at the moving phase boundary caused by changes in local acoustic forces. Soon after melting began, acoustic streaming, the buoyancy of the remaining ice, and convective currents caused by both an inner thermal gradient and thermocapillary effects along the air-liquid interface, all contributed to the droplet spinning about the horizontal axis.

PMID:35378478 | DOI:10.1016/j.jcis.2022.03.082

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Palbociclib and letrozole in hormone-receptor positive advanced breast cancer: Predictive response and prognostic factors

Curr Probl Cancer. 2022 Mar 28;46(3):100859. doi: 10.1016/j.currproblcancer.2022.100859. Online ahead of print.

ABSTRACT

CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.

PMID:35378469 | DOI:10.1016/j.currproblcancer.2022.100859

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Epidemiology of paratuberculosis in sheep and goats in southern Spain

Prev Vet Med. 2022 Apr 1;202:105637. doi: 10.1016/j.prevetmed.2022.105637. Online ahead of print.

ABSTRACT

Paratuberculosis is a worldwide, chronic infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminant species. This disease has a significant economic impact on small ruminant production due to the costs of implementing control measures and production losses. A cross-sectional study was carried out to determine the seroprevalence, spatial distribution and risk factors associated with MAP exposure in sheep and goats in Andalusia (southern Spain). Serum samples from 4134 small ruminants (2266 sheep and 1868 goats) in 153 flocks were tested by an in-house ELISA for antibodies against MAP using paratuberculosis protoplasmic antigen 3 (PPA3) as coating antigen. Antibodies against MAP were detected in 8.1% (183/2266; 95% CI: 7.0-9.2%) of sheep and 20.0% (374/1868; 95% CI: 18.2-21.8%) of goats. The true individual seroprevalence was 8.4% (95% CI: 6.9-10.1%) in sheep and 25.2% (95% CI: 22.7-27.8%) in goats. Seropositivity was detected in 66.3% (55/83; 95% CI: 56.1-76.4%) of sheep herds and 90.0% (63/70; 95% CI: 83.0-97.0%) of goat herds. Spatial analysis identified three statistically significant clusters (p < 0.05) associated with areas with higher seroprevalence of MAP. The main risk factors potentially associated with MAP exposure were: species (goat) and absence of perimeter livestock fencing. The results of this study show that MAP is widespread in small ruminant populations in southern Spain and suggest that goats may play a more important role than sheep in the transmission and maintenance of MAP. Because of animal health concerns and the economic consequences of paratuberculosis, appropriate surveillance and control programs are required to reduce the risk of MAP infections in small ruminant flocks in this country.

PMID:35378433 | DOI:10.1016/j.prevetmed.2022.105637

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COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients

Comput Biol Med. 2022 Mar 29;145:105467. doi: 10.1016/j.compbiomed.2022.105467. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients.

METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported.

RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance.

CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

PMID:35378436 | DOI:10.1016/j.compbiomed.2022.105467

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Seasonal changes of heavy metals and health risk assessment based on Monte Carlo simulation in alternate water sources of the Xinbian River in Suzhou City, Huaibei Plain, China

Ecotoxicol Environ Saf. 2022 Apr 1;236:113445. doi: 10.1016/j.ecoenv.2022.113445. Online ahead of print.

ABSTRACT

The urban alternate water source (AWS) is of great significance to the sustainable development of the city, the pollution degree, and source of heavy metals (HMs) in AWS, and whether it will adversely affect human health has received widespread attention. In this study, the urban AWS of Xinbian River in Suzhou City, Huaibei Plain, China, was used as the research object to study the seasonal changes of HMs (As, Cr, Cu, Cd, Pb, and Zn), quantitative identification of pollution sources, and human health risks (HHR). Research results show that the contents of those HMs, except As, are less than the drinking standards limit set by the World Health Organization (WHO), and the contents of As, Cr, and Zn are the largest in summer. The multivariate statistical analysis combined with positive matrix factorization (PMF) model analysis revealed that industrial sources accounted for 44.83%, and agricultural sources accounted for 55.17%. HHR assessment based on Monte Carlo simulation shows that the noncarcinogenic risks of adults and children are in the acceptable range (hazardous ingestion (HI) < 1), and the probability of carcinogenic risk values of children and adults are 95.03% and 38.96%, respectively, which are exceed the acceptable range (1 × 10-4) recommended by the United States Environment Protection Agency (USEPA). Approximately 30.75% of the carcinogenic risk value of agricultural source HMs to children exceeds the acceptable range (1 × 10-4). The above research results indicate that the effect of agricultural non-point source pollution on AWS should be prevented.

PMID:35378402 | DOI:10.1016/j.ecoenv.2022.113445

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Positive psychology mediates the relationship between symptom frequency and quality of life among colorectal cancer survivors during acute cancer survivorship

Eur J Oncol Nurs. 2022 Mar 28;58:102136. doi: 10.1016/j.ejon.2022.102136. Online ahead of print.

ABSTRACT

PURPOSE: Colorectal cancer (CRC) survivors are living longer; therefore, factors that improve outcomes, like symptom management and quality of life (QoL), have increasingly become important. This study examined CRC survivors’ symptom(s) characteristics, positive psychology (benefit finding and post-traumatic growth), and QoL, and determined whether positive psychology mediates symptom(s) and QoL relationship during acute cancer survivorship.

METHODS: A cross-sectional study of 117 CRC survivors was conducted at a National Cancer Institute-Designated Cancer Center. Data were collected by demographic questionnaire, Therapy-Related Symptom Checklist, QoL Inventory, and positive psychology assessed by Carver Benefit-Finding Scale and Post-Traumatic Growth Inventory. Descriptive statistics, between-group differences, multiple linear regression, and mediation analyses were performed.

RESULTS: Top common symptoms were peripheral neuropathy, fatigue/feeling sluggish, skin changes, sleep disturbances, and weakness. Psychological distress symptoms were reported in 38.46% of CRC survivors, and moderate-to-high positive psychology (3.21 ± 1.09) and QoL (5.15 ±0 .52) levels were reported during acute cancer survivorship. Significant (p < 0.05) relationships were observed between QoL and (a) number of symptoms, (b) psychological distress symptoms, (c) benefit finding, (d) post-traumatic growth, and (e) positive psychology. Positive psychology partially mediated the relationship between symptom frequency and QoL (p < 0.05).

CONCLUSION: Our study’s findings suggest that CRC survivors positively cope with their cancer and treatment, and positive psychology partially mediates the relationship between symptoms frequency (almost daily and daily vs. random) and QoL across acute cancer survivorship. Identifying how CRC survivors adjust to their cancer may help healthcare teams provide tailored self-management skills to promote QoL and reduce symptom burden throughout cancer survivorship.

PMID:35378393 | DOI:10.1016/j.ejon.2022.102136

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The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study

Placenta. 2022 Mar 26;122:1-8. doi: 10.1016/j.placenta.2022.03.124. Online ahead of print.

ABSTRACT

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women.

METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value.

RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w.

DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.

PMID:35378370 | DOI:10.1016/j.placenta.2022.03.124