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Nevin Manimala Statistics

The clinical value of kinesin superfamily protein 2A in hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2021 Mar 10;45(4):101527. doi: 10.1016/j.clinre.2020.08.005. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the clinical value of kinesin superfamily protein 2A (KIF2A) in hepatocellular carcinoma (HCC) patients.

METHODS: This study retrospectively analyzed 196 HCC patients who underwent hepatic resection, and their preoperative clinical characteristics were collected from the medical records. Immunohistochemical (IHC) assay was performed to detect KIF2A expression, subsequently KIF2A expression was evaluated by a semi-quantitative IHC score (according to IHC staining density and intensity of positively stained cells) and then graded as KIF2A/KIF2A+/KIF2A++/KIF2A+++ for analysis. Overall survival (OS) was calculated from the date of resection to the date of death.

RESULTS: Compared to adjacent tissue, both KIF2A IHC score and grade were higher in tumor tissue (Both P < 0.001). Tumor KIF2A expression was positively correlated with performance status score (P = 0.001), multifocal tumor nodule (P = 0.018), largest tumor size (P = 0.015) and Barcelona clinic liver cancer stage (P < 0.001). Regarding live function indexes, tumor KIF2A expression was positively associated with aspartate aminotransferase (P = 0.006). As to tumor markers, tumor KIF2A expression showed a trend to be positively correlated with alpha fetoprotein (P = 0.060) and carbohydrate antigen 199 (P = 0.053), but no statistical significance. Kaplan-Meier curve showed that tumor higher KIF2A expression was associated with worse OS (P < 0.001), which was further validated by multivariate Cox’s regression analysis as higher an independent factor predicting shorter OS (P = 0.001).

CONCLUSION: KIF2A is upregulated in tumor tissue than adjacent tissue, importantly, tumor KIF2A is associated with worse liver function, raised tumor stage and poor OS in HCC patients.

PMID:33713978 | DOI:10.1016/j.clinre.2020.08.005

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The longitudinal changes of anxiety and depression, their related risk factors and prognostic value in colorectal cancer survivors: a 36-month follow-up study

Clin Res Hepatol Gastroenterol. 2021 Mar 10;45(4):101511. doi: 10.1016/j.clinre.2020.07.016. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was to investigate the longitudinal change of post-operative anxiety and depression, their related risk factors and prognostic value in colorectal cancer (CRC) patients after resection.

METHODS: Totally, 302 CRC patients who underwent resection were consecutively recruited. Their anxiety and depression were assessed by hospital anxiety and depression scale (HADS) at Month 0 (M0) and then every 3 months till Month 36 (M36).

RESULTS: Within 36-month follow-up period, HADS-A score (from 8.3 ± 3.3 at M0 to 8.8 ± 3.4 at M36, P = 0.179) exhibited an upward trend with time but without statistical significance; while anxiety rate (from 46.4% at M0 to 52.6% at M36, P = 0.019) was increased steadily with time longitudinally. Meanwhile, both HADS-D score (from 7.4±3.0 at M0 to 9.2±3.5 at M36, P < 0.001) and depression rate (from 33.8% at M0 to 57.9% at M36, P < 0.001) were elevated greatly with time longitudinally. Furthermore, multivariate logistic regression revealed that female and tumor size (≥5 cm) were common independent risk factors for baseline/1-year/2-year/3-year anxiety (all P < 0.05); meanwhile, female, marry status (single/divorced/widowed vs. married) and advanced TNM stage were common independent risk factors for baseline/1-year/2-year/3-year depression (all P < 0.05). As for new-onset anxiety and depression, no independent factor associated with new-onset anxiety was observed; meanwhile, female and TNM stage were independent risk factors for new-onset depression (both P < 0.05). Additionally, baseline/1-year anxiety and baseline/1-year/2-year/3-year depression were associated with lower accumulating OS (all P < 0.05).

CONCLUSION: Post-operative anxiety and depression are highly prevalent and continuously progress, which also correlate with worse survival prognosis in CRC patients.

PMID:33713979 | DOI:10.1016/j.clinre.2020.07.016

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Impact of anastomotic leakage on postoperative survival of patients with colorectal cancer: A meta-analysis using propensity score matching studies

Surg Oncol. 2021 Mar 6;37:101538. doi: 10.1016/j.suronc.2021.101538. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the influence of anastomotic leakage (AL) on postoperative survival in patients with colorectal cancer (CRC).

BACKGROUND: Although several studies have compared the postoperative survival of patients with CRC with and without AL, the background characteristics of the two groups were not aligned in most studies.

METHODS: We performed a comprehensive electronic search of the literature up to March 2020 to identify propensity score matching (PSM) studies that compared postoperative survival between CRC patients with and without AL. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I (Akiyoshi et al., 2011) [2] statistics.

RESULTS: Four PSM studies involving a total of 1676 patients with CRC undergoing surgery were included in this meta-analysis. Among 234 patients who had AL, 163 (69.7%) survived at 5 years after surgery, whereas among 1422 patients who did not have AL, 1156 (81.3%) survived at 5 years after surgery. Background characteristics of the two groups were adjusted with PSM in all 4 studies. The result of the meta-analysis revealed a significant difference between the two groups (RR, 1.63; 95% CI, 1.09-2.45; P = 0.02; I2 = 66%) in 5-year overall survival (OS).

CONCLUSIONS: The results of this meta-analysis demonstrate a significantly decreased 5-year OS in patients with CRC who had AL compared with patients with CRC who did not have AL.

PMID:33713973 | DOI:10.1016/j.suronc.2021.101538

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Easing COVID-19 lockdown measures while protecting the older restricts the deaths to the level of the full lockdown

Sci Rep. 2021 Mar 12;11(1):5839. doi: 10.1038/s41598-021-82932-8.

ABSTRACT

Guided by a rigorous mathematical result, we have earlier introduced a numerical algorithm, which using as input the cumulative number of deaths caused by COVID-19, can estimate the effect of easing of the lockdown conditions. Applying this algorithm to data from Greece, we extend it to the case of two subpopulations, namely, those consisting of individuals below and above 40 years of age. After supplementing the Greek data for deaths with the data for the number of individuals reported to be infected by SARS-CoV-2, we estimated the effect on deaths and infections in the case that the easing of the lockdown measures is different for these two subpopulations. We found that if the lockdown measures are partially eased only for the young subpopulation, then the effect on deaths and infections is small. However, if the easing is substantial for the older population, this effect may be catastrophic.

PMID:33712637 | DOI:10.1038/s41598-021-82932-8

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Role of vitamin D serum levels in prevention of primary and recurrent melanoma

Sci Rep. 2021 Mar 12;11(1):5815. doi: 10.1038/s41598-021-85294-3.

ABSTRACT

Patients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p < 0.0001). No correlation between VDSL and both Breslow’s depth and Clark’s level was discovered, but the VDSL comparison between thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p < 0007). Nevertheless, no connection was found between VDSL and both ulceration and positive sentinel nodes (p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.

PMID:33712642 | DOI:10.1038/s41598-021-85294-3

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CT assessment of the increased density of cerebral vessels in plateau region

Sci Rep. 2021 Mar 12;11(1):5851. doi: 10.1038/s41598-021-85448-3.

ABSTRACT

In this study, the relationship between the brain parenchymal density, the cerebral vessel density, the mean corpuscular hemoglobin (MCH) content, the mean corpuscular hemoglobin concentration (MCHC), and the morbidity associated with lacunar infarction of residents living in either the plains or the plateau regions were analyzed and compared for their potential clinical implications. Clinical data from the brain CT scans of individuals living in either the plain or plateau regions (129 each) were collected. Specifically, the CT values for basal ganglia, the middle cerebral artery, and the superior sagittal sinus, along with the number of patients with lacunar infarction, were collected. In addition, the MCH and MCHC values were measured in blood samples collected within 48 h following the CT scans. For statistical analysis, an independent sample t-test, Pearson’s correlation test (permutation test), and Chi-squared test were employed. The inhabitants of the plateau had a significantly higher CT value of basal ganglia, the middle cerebral artery, and superior sagittal sinus and also higher levels of MCH and MCHC in the blood (ps < 0.001) than the inhabitants of the plains region. Further, there was a significant positive correlation between the three aforementioned CT values and the MCH and MCHC findings. However, no significant differences were found in the morbidity of lacunar infarction between these two regions (p > 0.05). The inhabitants in the plateau have a significantly higher brain parenchymal density, higher CT value for cerebral vessels density, and higher blood MCH and MCHC levels in comparison with individuals occupying the plains. Concurrently, the parenchymal density and the CT values are shown to be positively correlated with the MCH and MCHC content in the blood.

PMID:33712677 | DOI:10.1038/s41598-021-85448-3

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Nevin Manimala Statistics

A deep learning method for HLA imputation and trans-ethnic MHC fine-mapping of type 1 diabetes

Nat Commun. 2021 Mar 12;12(1):1639. doi: 10.1038/s41467-021-21975-x.

ABSTRACT

Conventional human leukocyte antigen (HLA) imputation methods drop their performance for infrequent alleles, which is one of the factors that reduce the reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping due to inter-ethnic heterogeneity in allele frequency spectra. We develop DEEP*HLA, a deep learning method for imputing HLA genotypes. Through validation using the Japanese and European HLA reference panels (n = 1,118 and 5,122), DEEP*HLA achieves the highest accuracies with significant superiority for low-frequency and rare alleles. DEEP*HLA is less dependent on distance-dependent linkage disequilibrium decay of the target alleles and might capture the complicated region-wide information. We apply DEEP*HLA to type 1 diabetes GWAS data from BioBank Japan (n = 62,387) and UK Biobank (n = 354,459), and successfully disentangle independently associated class I and II HLA variants with shared risk among diverse populations (the top signal at amino acid position 71 of HLA-DRβ1; P = 7.5 × 10-120). Our study illustrates the value of deep learning in genotype imputation and trans-ethnic MHC fine-mapping.

PMID:33712626 | DOI:10.1038/s41467-021-21975-x

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Exoskeletal-assisted walking may improve seated balance in persons with chronic spinal cord injury: a pilot study

Spinal Cord Ser Cases. 2021 Mar 12;7(1):20. doi: 10.1038/s41394-021-00384-8.

ABSTRACT

STUDY DESIGN: Pre-post intervention.

OBJECTIVE: To explore the potential effect of exoskeletal-assisted walking (EAW) on seated balance for persons with chronic motor complete spinal cord injury (SCI).

SETTING: A SCI research center.

METHODS: Eight participants who were over 18 years of age with chronic SCI and used a wheelchair for mobility were enrolled. Seven able-bodied participants were used for normal seated balance comparative values. Participants with chronic SCI received supervised EAW training using a powered exoskeleton (ReWalkTM) for a median 30 sessions (range from 7 to 90 sessions). Before and after EAW training, seated balance testing outcomes were collected using computerized dynamic posturography, providing measurements of endpoint excursion (EPE), maximal excursion (MXE), and directional control (DCL). Modified functional reach test (MFRT) and the sub-scales of physical functioning and role limitations due to physical health from the Short Form (36) Health Survey (SF-36) were used to identify changes in functional activities.

RESULTS: After EAW training, seated balance significantly improved in total-direction EPE and MXE (P < 0.01 and P < 0.017 respectively). The results of MFRT and sub-scales of physical functioning and role limitations due to physical health improved after EAW training but were not statistically significant.

CONCLUSIONS: EAW training may have the potential to improve seated balance for persons with chronic motor complete SCI. Due to the limitations of the study, such as small sample size and lack of a control group, further studies are needed to clarify the effect of improving seated balance through EAW training.

PMID:33712561 | DOI:10.1038/s41394-021-00384-8

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Integrated cross-study datasets of genetic dependencies in cancer

Nat Commun. 2021 Mar 12;12(1):1661. doi: 10.1038/s41467-021-21898-7.

ABSTRACT

CRISPR-Cas9 viability screens are increasingly performed at a genome-wide scale across large panels of cell lines to identify new therapeutic targets for precision cancer therapy. Integrating the datasets resulting from these studies is necessary to adequately represent the heterogeneity of human cancers and to assemble a comprehensive map of cancer genetic vulnerabilities. Here, we integrated the two largest public independent CRISPR-Cas9 screens performed to date (at the Broad and Sanger institutes) by assessing, comparing, and selecting methods for correcting biases due to heterogeneous single-guide RNA efficiency, gene-independent responses to CRISPR-Cas9 targeting originated from copy number alterations, and experimental batch effects. Our integrated datasets recapitulate findings from the individual datasets, provide greater statistical power to cancer- and subtype-specific analyses, unveil additional biomarkers of gene dependency, and improve the detection of common essential genes. We provide the largest integrated resources of CRISPR-Cas9 screens to date and the basis for harmonizing existing and future functional genetics datasets.

PMID:33712601 | DOI:10.1038/s41467-021-21898-7

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Effects of implementing Pressure Ulcer Prevention Practice Guidelines (PUPPG) in the prevention of pressure ulcers among hospitalised elderly patients: a systematic review protocol

BMJ Open. 2021 Mar 12;11(3):e043042. doi: 10.1136/bmjopen-2020-043042.

ABSTRACT

INTRODUCTION: Pressure ulcers are serious and potentially life-threatening problems across all age groups and across all medical specialties and care settings. The hospitalised elderly population is the most common group to develop pressure ulcers. This study aims to systematically review studies implementing pressure ulcer prevention strategies recommended in the Pressure Ulcer Prevention Practice Guidelines for the prevention of pressure ulcers among hospitalised elderly patients globally.

METHODS AND ANALYSIS: A systematic review of all studies that have assessed the use of pressure ulcer prevention strategies in hospital settings among hospitalised elderly patients shall be conducted. A comprehensive search of all published articles in Medline Ovid, Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, Cochrane library, Scopus and Web of Science will be done using terms such as pressure ulcers, prevention strategies, elderly patients and hospital. Studies will be screened for eligibility through title, abstract and full text by two independent reviewers. Study quality and risk of bias will be assessed using the Joanna Briggs Institute for Meta-Analysis of Statistics Assessment and Review Instrument. If sufficient data are available, a meta-analysis will be conducted to synthesise the effect size reported as OR with 95% CIs using both fixed and random effect models. I2 statistics and visual inspection of the forest plots will be used to assess heterogeneity and identify the potential sources of heterogeneity. Publication bias will be assessed by visual inspections of funnel plots and Egger’s test.

ETHICS AND DISSEMINATION: No formal ethical approval or consent is required as no primary data will be collected. We aim to publish the research findings in a peer-reviewed scientific journal to promote knowledge transfer, as well as in conferences, seminars, congresses or symposia in a traditional manner.

PROSPERO REGISTRATION NUMBER: CRD42019129088.

PMID:33712523 | DOI:10.1136/bmjopen-2020-043042