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Nevin Manimala Statistics

Insight into the structural requirement of aryl sulphonamide based gelatinases (MMP-2 and MMP-9) inhibitors – Part I: 2D-QSAR, 3D-QSAR topomer CoMFA and Naïve Bayes studies – First report of 3D-QSAR Topomer CoMFA analysis for MMP-9 inhibitors and jointly inhibitors of gelatinases together

SAR QSAR Environ Res. 2021 Aug;32(8):655-687. doi: 10.1080/1062936X.2021.1955414.

ABSTRACT

Gelatinases [gelatinase A – matrix metalloproteinase-2 (MMP-2), gelatinase B – matrix metalloproteinase-9 (MMP-9)] play key roles in many disease conditions including cancer. Despite some research work on gelatinases inhibitors both jointly and individually had been reported, challenges still exist in achieving potency as well as selectivity. Here in part I of a series of work, we have reported the structural requirement of some arylsulfonamides. In particular, regression-based 2D-QSARs, topomer CoMFA (comparative molecular field analysis) and Bayesian classification models were constructed to refine structural features for attaining better gelatinase inhibitory activity. The 2D-QSAR models exhibited good statistical significance. The descriptors nsssN, SHBint6, SHBint7, PubchemFP629 were directly correlated with the MMP-2 binding affinities whereas nsssN, SHBint10 and AATS2i were directly proportional to MMP-9 binding affinities. The topomer CoMFA results indicated that the steric and electrostatic fields play key roles in gelatinase inhibition. The established Naïve Bayes prediction models were evaluated by fivefold cross validation and an external test set. Furthermore, important molecular descriptors related to MMP-2 and MMP-9 binding affinities and some active/inactive fragments were identified. Thus, these observations may be helpful for further work of aryl sulphonamide based gelatinase inhibitors in future.

PMID:34355614 | DOI:10.1080/1062936X.2021.1955414

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Nevin Manimala Statistics

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica

Hemoglobin. 2021 Aug 6:1-8. doi: 10.1080/03630269.2021.1954943. Online ahead of print.

ABSTRACT

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers’ behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

PMID:34355623 | DOI:10.1080/03630269.2021.1954943

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Nevin Manimala Statistics

Evaluation of Auto-Planning for Left-Side Breast Cancer After Breast-Conserving Surgery Based on Geometrical Relationship

Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211033050. doi: 10.1177/15330338211033050.

ABSTRACT

PURPOSE: This study aimed to evaluate (1) the performance of the Auto-Planning module embedded in the Pinnacle treatment planning system (TPS) with 30 left-side breast cancer plans and (2) the dose-distance correlations between dose-based patients and overlap volume histogram-based (OVH) patients.

METHOD: A total of 30 patients with left-side breast cancer after breast-conserving surgery were enrolled in this study. The clinical manual-planning (MP) and the Auto-Planning (AP) plans were generated by Monaco and by the Auto-Planning module in Pinnacle respectively. The geometric information between organ at risk (OAR) and planning target volume (PTV) of each patient was described by the OVH. The AP and MP plans were ranked to compare with the geometry-based patients from OVH. The Pearson product-moment correlation coefficient (R) was used to describe the correlations between dose-based patients (APs and MPs) and geometry-based patients (OVH). Dosimetric differences between MP and AP plans were evaluated with statistical analysis.

RESULT: The correlation coefficient (mean R = 0.71) indicated that the AP plans have a high correlation with geometry-based patients from OVH, whereas the correlation coefficient (mean R = 0.48) shows a weak correlation between MP plans and geometry-based patients. The dosimetric comparison revealed a statistically significant improvement in the ipsilateral lung V5Gy and V10Gy, and in the heart V5Gy of AP plans compared to MP plans, while statistical reduction was seen in PTV V107% for MP plans compared to AP plans.

CONCLUSION: The overall results of AP plans were superior to MP plans. The dose distribution in AP plans was more consistent with the distance-dose relationship described by OVH. After eliminating the interference of human factors, the AP was able to provide more stable and objective plans for radiotherapy patients.

PMID:34355592 | DOI:10.1177/15330338211033050

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Nevin Manimala Statistics

Anti-gravity treadmill rehabilitation improves gait and muscle atrophy in patients with surgically treated ankle and tibial plateau fractures after one year: A randomised clinical trial

Clin Rehabil. 2021 Aug 6:2692155211037148. doi: 10.1177/02692155211037148. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the one-year postoperative outcomes of anti-gravity treadmill rehabilitation with those of standard rehabilitation in patients with ankle or tibial plateau fractures.

DESIGN: An open-label prospective randomised study.

SETTING: Three trauma centres.

SUBJECTS: Patients were randomised into the intervention (anti-gravity treadmill) or control (standard protocol) rehabilitation group.

MAIN MEASURES: The primary endpoint was changes in the Foot and Ankle Outcome Score for ankle fractures and Knee Injury and Osteoarthritis Outcome Score for tibial plateau fractures from baseline to 12 months after operation. Secondary endpoints were the subscores of these scores, muscle atrophy (leg circumference at 20 cm above and 10 cm below the knee joint) and the Dynamic Gait Index.

RESULTS: Initially, 73 patients (37 vs 36) underwent randomisation. After 12 months, 29 patients in the intervention group and 24 patients in the control group could be analysed. No significant difference was noted in the Foot and Ankle Outcome Score (80.8 ± 18.4 and 78.4 ± 21.1) and Knee Injury and Osteoarthritis Outcome Score (84.8 ± 15.2 and 81.7 ± 17.0). The change in the Dynamic Gait Index from 12 weeks to 12 months differed significantly between the groups (P = 0.04). Patients with tibial plateau fractures had a 3 cm wider thigh circumference in the intervention group than those in the control group (95% confidence interval: -0.2 to 6.3 cm, P = 0.08).

CONCLUSION: One year after surgery, patients who had undergone anti-gravity treadmill rehabilitation showed better gait than patients in the control group, and those with tibial plateau fractures had less muscle atrophy.

PMID:34355605 | DOI:10.1177/02692155211037148

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Nevin Manimala Statistics

Comparing Healthcare Utilization and Diagnoses in Immigrant Versus Nonimmigrant Youth

Hisp Health Care Int. 2021 Aug 6:15404153211036985. doi: 10.1177/15404153211036985. Online ahead of print.

ABSTRACT

INTRODUCTION: To inform efforts to provide healthcare to uninsurable, immigrant youth, we describe The Access Partnership (TAP) hospital-based charity care program and compare healthcare utilization and diagnoses among TAP and Medicaid patients.

METHODS: We use propensity scores to match each TAP patient to three Medicaid patients receiving care at a pediatric clinic from October 2010 to June 2015 on demographic characteristics. We use descriptive statistics to compare healthcare visits and diagnoses.

RESULTS: TAP (n = 78) and Medicaid patients (n = 234) had similar healthcare utilization, though Medicaid patients had more outpatient visits (10.8 vs. 7.7, p = .002), and TAP patients were more likely to have ever received subspecialty care (38.5% vs. 22.2%, p = .005). Diagnoses were similar between groups, with some exceptions: TAP patients more likely to present with genital and reproductive disease (33.3% vs. 19.7%, p = .013); Medicaid patients more likely to present with endocrine, metabolic, and nutritional disease (52.1% vs. 28.2%, p < .001), psychiatric, behavioral disease, and substance abuse (41.0, 26.9%, p = .026).

CONCLUSIONS: TAP patients had similar healthcare utilization and diagnoses to matched sample of Medicaid patients. Findings indicate policy proposals that extend public health insurance to all children would likely benefit immigrant children and not incur higher costs than those of low-income U.S. citizen children.

PMID:34355584 | DOI:10.1177/15404153211036985

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Nevin Manimala Statistics

A web-based survey of contact lens-related adverse events among the Japanese female population

Sci Rep. 2021 Aug 5;11(1):15939. doi: 10.1038/s41598-021-95318-7.

ABSTRACT

To assess the safety of cosmetic contact lenses and to identify other factors of contact lens (CL)-related complications for Japanese females. A web-based, cross-sectional, observational survey of complications related to CL use was performed. The frequencies of complications were compared between transparent and cosmetic CLs. Besides lens pigmentation, age, replacement schedule, total experience, daily wear time, location of purchase, stacking of CLs, CL exchange with friends, compliance to hygiene procedure, replacement of CLs at intervals longer than recommended, and CL wear overnight were considered as risk factors. Logistic regression analyses were performed to calculate the odds ratios. A total of 3803 Japanese females were analyzed. The frequency of adverse events was 33.4% (95%CI 31.3-35.4%) and 35.7% (95%CI 33.5-38.0%) for transparent and cosmetic CLs, respectively. In a multivariate model, statistically significant factors associated with complications included the following: quarterly schedule lenses, replacement at intervals longer than recommended, compliance to hygiene procedure, overnight wearing, purchase at physical shops and on the internet, and longer daily wearing time. Most of the risk-increasing behaviors are preventable. The role of public health ophthalmology is to increase awareness and to improve CL use behaviors.

PMID:34354150 | DOI:10.1038/s41598-021-95318-7

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Nevin Manimala Statistics

Automated tumor proportion score analysis for PD-L1 (22C3) expression in lung squamous cell carcinoma

Sci Rep. 2021 Aug 5;11(1):15907. doi: 10.1038/s41598-021-95372-1.

ABSTRACT

Programmed cell death ligend-1 (PD-L1) expression by immunohistochemistry (IHC) assays is a predictive marker of anti-PD-1/PD-L1 therapy response. With the popularity of anti-PD-1/PD-L1 inhibitor drugs, quantitative assessment of PD-L1 expression becomes a new labor for pathologists. Manually counting the PD-L1 positive stained tumor cells is an obviously subjective and time-consuming process. In this paper, we developed a new computer aided Automated Tumor Proportion Scoring System (ATPSS) to determine the comparability of image analysis with pathologist scores. A three-stage process was performed using both image processing and deep learning techniques to mimic the actual diagnostic flow of the pathologists. We conducted a multi-reader multi-case study to evaluate the agreement between pathologists and ATPSS. Fifty-one surgically resected lung squamous cell carcinoma were prepared and stained using the Dako PD-L1 (22C3) assay, and six pathologists with different experience levels were involved in this study. The TPS predicted by the proposed model had high and statistically significant correlation with sub-specialty pathologists’ scores with Mean Absolute Error (MAE) of 8.65 (95% confidence interval (CI): 6.42-10.90) and Pearson Correlation Coefficient (PCC) of 0.9436 ([Formula: see text]), and the performance on PD-L1 positive cases achieved by our method surpassed that of non-subspecialty and trainee pathologists. Those experimental results indicate that the proposed automated system can be a powerful tool to improve the PD-L1 TPS assessment of pathologists.

PMID:34354151 | DOI:10.1038/s41598-021-95372-1

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Nevin Manimala Statistics

“Guilt by association” is not competitive with genetic association for identifying autism risk genes

Sci Rep. 2021 Aug 5;11(1):15950. doi: 10.1038/s41598-021-95321-y.

ABSTRACT

Discovering genes involved in complex human genetic disorders is a major challenge. Many have suggested that machine learning (ML) algorithms using gene networks can be used to supplement traditional genetic association-based approaches to predict or prioritize disease genes. However, questions have been raised about the utility of ML methods for this type of task due to biases within the data, and poor real-world performance. Using autism spectrum disorder (ASD) as a test case, we sought to investigate the question: can machine learning aid in the discovery of disease genes? We collected 13 published ASD gene prioritization studies and evaluated their performance using known and novel high-confidence ASD genes. We also investigated their biases towards generic gene annotations, like number of association publications. We found that ML methods which do not incorporate genetics information have limited utility for prioritization of ASD risk genes. These studies perform at a comparable level to generic measures of likelihood for the involvement of genes in any condition, and do not out-perform genetic association studies. Future efforts to discover disease genes should be focused on developing and validating statistical models for genetic association, specifically for association between rare variants and disease, rather than developing complex machine learning methods using complex heterogeneous biological data with unknown reliability.

PMID:34354131 | DOI:10.1038/s41598-021-95321-y

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Nevin Manimala Statistics

Bacterial profile, antimicrobial susceptibility patterns, and associated factors among bloodstream infection suspected patients attending Arba Minch General Hospital, Ethiopia

Sci Rep. 2021 Aug 5;11(1):15882. doi: 10.1038/s41598-021-95314-x.

ABSTRACT

Bacterial bloodstream infections are of great concern globally. Of late, the emergence of drug resistant bacteria worsen the related morbidity and mortality. This study was aimed to determine the bacterial profile, antimicrobial susceptibility patterns, and associated factors among the blood stream infection (BSI) suspected patients attending the Arba Minch General Hospital (AMGH), southern Ethiopia, from 01 June through 31st August, 2020. A cross-sectional study was conducted among 225 BSI suspected patients. Systematic random sampling method was used to select patients. Blood culture was done to isolate bacterial pathogens. Antimicrobial susceptibility test was performed by employing the Kirby-Bauer disc diffusion method. Descriptive statistics and multivariable logistic regression analysis were done by Statistical Package for Social Service (SPSS) version 22. The rate of prevalence of bacteriologically confirmed cases was 22/225 (9.8%). Majority of BSI were caused by Gram-positive cocci, 13/22 (59.1%), particularly the isolates of S. aureus, 7/22 (31.8%) followed by Enterococci species, 4/22 (18.2%) and coagulase-negative Staphylococci (CoNS), 2/22 (9.1%). Among the Gram-negative bacteria 9/22 (41.1%), Klebsiella species 4/22 (18.2%) was the prominent one followed by Escherichia coli 2/22 (9.1%), Pseudomonas aeruginosa 2/22 (9.1%), and Enterobacter species 1/22 (4.5%). All the isolates of Gram-negative bacteria were susceptible to meropenem whereas 69.2% of the isolates of Gram-positive counterparts were susceptible to erythromycin. Slightly above two third (68.2%) of the total isolates were multidrug resistant. Insertion of a peripheral intravenous line was significantly associated with BSI [p = 0.03; Adjusted Odds Ratio = 4.82; (Confidence Interval: 1.08-21.46)]. Overall results revealed that eventhough the prevalence of BSI in Arba Minch is comparatively lower (9.8%), multidrug resistance is alarmingly on the rise, which is to be addressed through effective surveillance and control strategies.

PMID:34354138 | DOI:10.1038/s41598-021-95314-x

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Nevin Manimala Statistics

Prevalence and genetic characteristics of Blastocystis hominis and Cystoisospora belli in HIV/AIDS patients in Guangxi Zhuang Autonomous Region, China

Sci Rep. 2021 Aug 5;11(1):15904. doi: 10.1038/s41598-021-94962-3.

ABSTRACT

Blastocystis hominis and Cystoisospora belli are considered to be common opportunistic intestinal protozoa in HIV/AIDS patients. In order to investigate the prevalence and genetic characteristics of B. hominis and C. belli in HIV/AIDS patients, a total of 285 faecal samples were individually collected from HIV/AIDS patients in Guangxi, China. B. hominis and C. belli were investigated by amplifying the barcode region of the SSU rRNA gene and the internal transcribed spacer 1 (ITS-1) region of the rRNA gene, respectively. Chi-square test or Fisher’s exact test were conducted to assess the risk factors related to B. hominis and C. belli infection. The prevalence of B. hominis and C. belli was 6.0% (17/285) and 1.1% (3/285) respectively. Four genotypes of B. hominis were detected, with ST3 (n = 8) and ST1 (n = 6) being predominant, followed by ST6 (n = 2) and ST7 (n = 1). Females had a statistically higher prevalence of B. hominis (11.6%) than males (4.2%). The statistical analysis also showed that the prevalence of B. hominis was significantly associated with age group and educational level. Our study provides convincing evidence for the genetic diversity of B. hominis, which indicates its potential zoonotic transmission and is the first report on the molecular characteristics of C. belli in HIV/AIDS patients in China.

PMID:34354101 | DOI:10.1038/s41598-021-94962-3