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Nevin Manimala Statistics

Discovery of Cancer-Specific and Independent Prognostic Gene Subsets of the Slit-Robo Family Using TCGA-PANCAN Datasets

OMICS. 2021 Nov 10. doi: 10.1089/omi.2021.0097. Online ahead of print.

ABSTRACT

The Slit-Robo family of axon guidance molecules works in concert, playing important roles in organ development and cancer. Expressions of individual Slit-Robo genes have been used in calculating univariable hazard ratios (HRuni) for predicting cancer prognosis in the literature. However, Slit-Robo members do not act independently; hence, hazard ratios from multivariable Cox regression (HRmulti) on the whole gene set can further lead to identification of cancer-specific, novel, and independent prognostic gene pairs or modules. Herein, we obtained mRNA expressions of the Slit-Robo family consisting of four Robos (ROBO1/2/3/4) and three Slits (SLIT1/2/3), along with four types of survival outcome across cancers found in the Cancer Genome Atlas (TCGA). We used cluster heat maps to visualize closely associated pairs/modules of prognostic genes across 33 different cancers. We found a smaller number of significant genes in HRmulti than in HRuni, suggesting that the former analysis was less redundant. High ROBO4 expression emerged as relatively protective within the family, in both types of HR analyses. Multivariable Cox regression, on the other hand, revealed significantly more HR signatures containing Slit-Robo pairs acting in opposing directions than those containing Slit-Slit or Robo-Robo pairs for disease-specific survival. Furthermore, we discovered, through the online app SmulTCan’s lasso regression, Slit-Robo gene subsets that significantly differentiated between high- versus low-risk prognosis patient groups, particularly for renal cancers and low-grade glioma. The statistical pipeline reported herein can help test independent and significant pairs/modules within a codependent gene family for cancer prognostication, and thus should also prove useful in personalized/precision medicine research.

PMID:34757814 | DOI:10.1089/omi.2021.0097

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COVID-19 Case Surge and Telemedicine Utilization in a Tertiary Hospital in Korea

Telemed J E Health. 2021 Nov 9. doi: 10.1089/tmj.2021.0157. Online ahead of print.

ABSTRACT

Background: Faced with the coronavirus disease 2019 (COVID-19) pandemic, Korea has allowed telemedicine use for a limited time. This study examined whether the surge in COVID-19 cases led to increased telemedicine use and the associated factors. Methods: Data from the electronic medical records of 929,753 outpatient episodes between March 4 and September 4, 2020, in a tertiary hospital in Korea were used. A comparison group was chosen by matching, adjusting for age and sex because only a small portion (1.0%) of the sample used telemedicine. The final sample comprised 57,972 episodes. Multivariable logistic regression analyses were performed to examine the association of independent variables with the dichotomous dependent variable (i.e., telemedicine visit/in-person visit). Results: The surge in confirmed COVID-19 cases led to significantly increased telemedicine use (101-300 new cases odds ratio [OR]: 3.00; 301-500 new cases OR: 5.82; and ≥501 new cases OR: 42.18; all p < 0.0001). Telemedicine use was also statistically associated with sex (female patients OR: 2.08), age ˃19 years, distance from the hospital (Incheon, Gyeonggi, region, OR: 1.30; and other regions, OR: 4.33), and the number of days from diagnosis (3-6 months OR: 1.21; 6-12 months OR: 1.56; 12-36 months OR: 1.98; and ≥36 months OR: 2.49). Medical Aid patients (OR: 0.83) were less likely to use telemedicine than those with National Health Insurance. Conclusions: Telemedicine can be effective in delivering health services during an outbreak. Policymakers and health care organizations are encouraged to use the results of this study to tailor telemedicine to meet the needs of patients.

PMID:34757827 | DOI:10.1089/tmj.2021.0157

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Competing risks analysis of Merkel cell carcinoma with concurrent chronic lymphocytic leukemia and non-Hodgkin lymphoma

Dermatol Online J. 2021 Aug 15;27(8). doi: 10.5070/D327854684.

ABSTRACT

BACKGROUND: Although hematogenous malignancy is a risk factor for poorer prognosis in Merkel cell carcinoma (MCC), current guidelines make no specific recommendations for surveillance.

OBJECTIVE: We aim to characterize MCC-specific mortality compared to other causes of death for patients with hematologic malignancy in MCC, which will guide workup and surveillance strategies.

METHODS: The Surveillance, Epidemiology, and End Results-18 registry was queried for MCC patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL).

RESULTS: Of 8519 patients with MCC, 146 (1.7%) had CLL and 234 (2.8%) had NHL. Chronic lymphocytic leukemia patients had 5-year cumulative incidence of MCC-specific mortality of 38.4% versus 28.4% in patients without CLL/NHL. For both cohorts, oncologic risk was highest within the first three years of diagnosis with competing risks favored thereafter. On competing risk regression, a history of CLL trended toward statistical significance with poorer MCC-specific mortality (subdistribution hazard ratio: 1.33, 95% CI: 0.963-1.834, P=0.084), while NHL was not prognostic.

CONCLUSIONS: Merkel cell carcinoma patients with CLL may benefit from more aggressive initial management. Surveillance for similar length in CLL patients with MCC may be appropriate; this co-morbidity did not affect the timeframe by which the risk of competing causes of death exceeded oncologic risks.

PMID:34755954 | DOI:10.5070/D327854684

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Prevalence of radix entomolaris in India and its comparison with rest of world- a systemic review and meta analysis

Minerva Dent Oral Sci. 2021 Nov 10. doi: 10.23736/S2724-6329.21.04561-7. Online ahead of print.

ABSTRACT

INTRODUCTION: A successful endodontic treatment can be achieved by proper cleaning, shaping and disinfection and obturation of the root canal system. Mandibular molars requiring endodontic therapy have several variations. A mandibular molar usually has two roots but occasionally, it might have additional roots also. The purpose of this article is to determine the regional predilection of Radix Entomolaris in permanent mandibular first molar in India and its comparison to rest of world.

EVIDENCE ACQUISITION: A search was undertaken to identify published research articles related to radix entomolaris in mandibular first molars. Sixty four research articles were analyzed.

EVIDENCE SYNTHESIS: Articles were assessed in relation to demographic location of radix entomolaris. Also the type of study and the analytic tool employed for its assessment was evaluated. Results were tabulated and statistically analyzed. Statistical test revealed a significant variation between the India and rest of world.

CONCLUSIONS: This research reported that regional predilection of radix entomolaris in mandibular first molar varies significantly. In India the highest incidence of radix entomolaris was observed in north India with 24%, whereas in world China reported the highest prevalence of 32% and the minimum was observed in Africa at 0%. India relied on conventional radiography for its diagnosis whereas rest of the world primarily utilized in vitro studies and advanced radiography for its diagnosis.

PMID:34755993 | DOI:10.23736/S2724-6329.21.04561-7

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Data on multiple regression analysis between boron, nickel, arsenic, antimony, and biological substrates in horses: The role of hematological biomarkers

J Biochem Mol Toxicol. 2021 Nov 10:e22955. doi: 10.1002/jbt.22955. Online ahead of print.

ABSTRACT

The objective of this study was to evaluate the biomarkers of exposure to boron, nickel, arsenic, and antimony in an industrial region, evaluating the bioaccumulation in biological substrates and the correlation with biomarkers such as hematological parameters. Through indication of the accumulation of some minerals in the horse’s biological substrates reflects environmental pollution. Moreover, an additional aim of the study was to show whether these contaminants have an influence on the hematological parameters in horses. Blood, serum, mane, and tail samples from 20 horses from an industrial area were analyzed to determine boron (B), nickel (Ni), arsenic (As), antimony (Sb) concentration. Hematological parameters (red blood cell [RBC], white blood cells [WBC], hemoglobin [Hb], hematocrit [Hct], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelet [PLT]) as a biomarker of blood in relation to the bioaccumulation of these elements were analyzed also. Descriptive statistical analysis was performed and single regression analysis (Pearson) and multiple regression analysis (p < 0.05) between blood factors, As, B, Ni, and Sb concentrations, and for each mineral in different substrate, respectively. Results showed a significant correlation between tail and mane concentrations with serum and blood for boron concentration (r = -1 p < 0.05). No significant correlation between sample (feed, hay, mane, tail, and water) concentrations and As, Ni, and Sb were found. A significantly negative correlation with blood parameters (r = -1 p < 0.05) was observed in Boron concentration for mane and tail. This suggests that the mane and tail may be a potential means to investigate suspected exposure to excessive levels of trace minerals.

PMID:34755932 | DOI:10.1002/jbt.22955

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The Human Disease Ontology 2022 update

Nucleic Acids Res. 2021 Nov 10:gkab1063. doi: 10.1093/nar/gkab1063. Online ahead of print.

ABSTRACT

The Human Disease Ontology (DO) (www.disease-ontology.org) database, has significantly expanded the disease content and enhanced our userbase and website since the DO’s 2018 Nucleic Acids Research DATABASE issue paper. Conservatively, based on available resource statistics, terms from the DO have been annotated to over 1.5 million biomedical data elements and citations, a 10× increase in the past 5 years. The DO, funded as a NHGRI Genomic Resource, plays a key role in disease knowledge organization, representation, and standardization, serving as a reference framework for multiscale biomedical data integration and analysis across thousands of clinical, biomedical and computational research projects and genomic resources around the world. This update reports on the addition of 1,793 new disease terms, a 14% increase of textual definitions and the integration of 22 137 new SubClassOf axioms defining disease to disease connections representing the DO’s complex disease classification. The DO’s updated website provides multifaceted etiology searching, enhanced documentation and educational resources.

PMID:34755882 | DOI:10.1093/nar/gkab1063

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Oral and parenteral anti-neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta-analysis

Neurogastroenterol Motil. 2021 Nov 10:e14289. doi: 10.1111/nmo.14289. Online ahead of print.

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS.

METHODS: We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes.

KEY RESULTS: We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics.

CONCLUSIONS AND INFERENCES: Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline’s efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.

PMID:34755926 | DOI:10.1111/nmo.14289

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Epidemiology of paracoccidioidomycosis in Venezuela: a retrospective study from 1954 to 2019

Mem Inst Oswaldo Cruz. 2021 Nov 8;116:e210203. doi: 10.1590/0074-02760210203. eCollection 2021.

ABSTRACT

BACKGROUND: Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Etiological agents are Paracoccidioides species that diverge phylogenetically throughout South America.

OBJECTIVES: This study aimed to document the epidemiology of PCM in Venezuela.

METHODS: We have performed a retrospective cross-sectional descriptive study in 31,081 clinical records of patients from two reference centres during 65 years (1954-2019).

FINDINGS: PCM diagnosis was confirmed in 745 patients. Chronic PCM was the most prevalent form (90.06% cases); 80.67% were male and the most affected age range was 41-60. Farming and construction were the most prevalent occupation and Miranda State had a higher prevalence. Lung and skin were the most affected organs, followed by oral manifestations. Direct examination, culture and serology showed a high sensibility, and no statistical difference was observed among the diagnostic tools. Out of 17 Paracoccidioides isolates genotyped from Venezuela, one was typed as Paracoccidioides americana and 16 as Paracoccidioides venezuelensis.

MAIN CONCLUSIONS: Clinical manifestations observed, information about the epidemiology and molecular profile is essential not only for diagnosis but also for understanding therapeutic responses to mycotic drugs and prognosis. Therefore, it is necessary to sequence all positive isolated strains in order to confirm the dominance of P. venezuelensis in Venezuela.

PMID:34755819 | DOI:10.1590/0074-02760210203

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Influence of testing environment on static fatigue behavior of a glass and a polycrystalline ceramic

Braz Dent J. 2021 May-Jun;32(3):56-64. doi: 10.1590/0103-6440202103961.

ABSTRACT

It aims on evaluate the effect of the test environment on static fatigue behavior of lithium disilicate-based (LD), and yttrium oxide-stabilized zirconia (YSZ) ceramics. Specimens of LD (IPS e.max CAD, Ivoclar Vivadent) and YSZ (IPS e.max ZirCAD MO, 3 mol% Y2O3, Ivoclar Vivadent) were randomly allocated into three groups: tested in air, inert (paraffin oil, Sigma Aldrich) or distilled water. The static fatigue test (n=15) was performed using a piston-on-three ball assembly, adapted from ISO 6872, as follows: starting load 100 N for LD and 300 N for YSZ; loading application time set to 1 hour for each loading step; step size of 50 N for LD and 100 N for YSZ, applied successively until fracture. Data from static fatigue strength (MPa) and time to fracture (hours) were recorded. Fractographic analysis was executed. Survival analysis corroborates absence of influence of environment on static fatigue outcomes (fatigue strength, time to fracture and survival rates) for YSZ. For LD, specimens tested in air presented statistically superior survival rate and static fatigue strength (p= 0.025). In regards of time to fracture, LD tested in air were superior than when tested in distilled water (p=0.019) or inert (p=0.017) environments. No statistical differences for Weibull modulus were observed. Failures started on the tensile stress surface. Thus, the test environment did not affect slow crack growth (SCG) mechanisms during static fatigue test of YSZ ceramics, but it plays a significant role for the static fatigue behavior of lithium disilicate-based glass ceramics, indicating a high susceptibility to SCG.

PMID:34755790 | DOI:10.1590/0103-6440202103961

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Coadministration of ibuprofen/caffeine on bleaching-induced tooth sensitivity: A randomized clinical trial

Braz Dent J. 2021 May-Jun;32(3):105-115. doi: 10.1590/0103-6440202104138.

ABSTRACT

This clinical trial evaluated the effect of the coadministration of ibuprofen/caffeine on bleaching-induced tooth sensitivity (TS). A triple-blind, parallel-design, randomized clinical trial was conducted on 84 patients who received ibuprofen/caffeine or placebo capsules. The drugs were administered for 48 hours, starting 1 hour before the in-office bleaching. Two bleaching sessions were performed with 35% hydrogen peroxide gel with 1-week interval. TS was recorded up to 48 hours after dental bleaching with a 0-10 visual analogic scale (VAS) and a 5-point numeric rating scale (NRS). The color was evaluated with VITA Classical and VITA Bleachedguide scales (ΔSGU) and VITA Easyshade spectrophotometer (ΔE*ab and ΔE00). The absolute risk of TS in both groups was evaluated using Fischer’s exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney test and a two-way repeated measures ANOVA, respectively. The color alteration between the groups was compared with the Student’s t test. The significance level was 5%. There was no statistically significant difference between the groups for the absolute risk of TS (p = 1.00) or for the intensity of TS (p > 0.05). A bleaching of approximately 7 shade guide units was observed on the Vita Classical and Vita Bleachedguide scales, with no statistical difference between the groups. It was concluded that coadministration of ibuprofen and caffeine did not reduce the absolute risk or intensity of TS and did not interfere with the efficacy of dental bleaching.

PMID:34755785 | DOI:10.1590/0103-6440202104138