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Nevin Manimala Statistics

An SVM approach towards breast cancer classification from H&E-stained histopathology images based on integrated features

Med Biol Eng Comput. 2021 Jul 24. doi: 10.1007/s11517-021-02403-0. Online ahead of print.

ABSTRACT

Breast cancer is one among the most frequent reasons of women’s death worldwide. Nowadays, healthcare informatics is mainly focussing on the classification of breast cancer images, due to the lethal nature of this cancer. There are chances of inter- and intra-observer variability that may lead to misdiagnosis in the detection of cancer. This study proposed an automatic breast cancer classification system that uses support vector machine (SVM) classifier based on integrated features (texture, geometrical, and color). The University of California Santa Barbara (UCSB) dataset and BreakHis dataset, which are available in public domain, were used. A classification comparison module which involves SVM, k-nearest neighbor (k-NN), random forest (RF), and artificial neural network (ANN) was also proposed to determine the classifier that best suits for the application of breast cancer detection from histopathology images. The performance of these classifiers was analyzed against metrics like accuracy, specificity, sensitivity, balanced accuracy, and F-score. Results showed that among the classifiers, the SVM classifier performed better with a test accuracy of approximately 90% on both the datasets. Additionally, the significance of the proposed integrated SVM model was statistically analyzed against other classifier models.

PMID:34302269 | DOI:10.1007/s11517-021-02403-0

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Delay differential equations based models in NONMEM

J Pharmacokinet Pharmacodyn. 2021 Jul 23. doi: 10.1007/s10928-021-09770-z. Online ahead of print.

ABSTRACT

Delay differential equations (DDEs) are commonly used in pharmacometric models to describe delays present in pharmacokinetic and pharmacodynamic data analysis. Several DDE solvers have been implemented in NONMEM 7.5 for the first time. Two of them are based on algorithms already applied elsewhere, while others are extensions of existing ordinary differential equations (ODEs) solvers. The purpose of this tutorial is to introduce basic concepts underlying DDE based models and to show how they can be developed using NONMEM. The examples include previously published DDE models such as logistic growth, tumor growth inhibition, indirect response with precursor pool, rheumatoid arthritis, and erythropoiesis-stimulating agents. We evaluated the accuracy of NONMEM DDE solvers, their ability to handle stiff problems, and their performance in parameter estimation using both first-order conditional estimation (FOCE) and the expectation-maximization (EM) method. NONMEM control streams and excerpts from datasets are provided for all discussed examples. All DDE solvers provide accurate and precise solutions with the number of significant digits controlled by the error tolerance parameters. For estimation of population parameters, the EM method is more stable than FOCE regardless of the DDE solver.

PMID:34302262 | DOI:10.1007/s10928-021-09770-z

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Fetal MRI mediastinal shift angle and respiratory and cardiovascular pharmacological support in newborns with congenital diaphragmatic hernia

Eur J Pediatr. 2021 Jul 23. doi: 10.1007/s00431-021-04207-8. Online ahead of print.

ABSTRACT

In newborns with congenital diaphragmatic hernia (CDH), the mediastinal shift caused by the herniated organs negatively affects lung development. Assessment of the fetal magnetic resonance imaging (MRI) mediastinal shift angle (MSA) was shown to have an inverse correlation with the total fetal lung volume (TFLV), being associated with neonatal survival. However, a possible association with postnatal morbidity has never been investigated. We hypothesize that the degree of the mediastinal shift could be associated with higher respiratory and cardiocirculatory impairment, requiring intensive treatments and extended hospitalization in survivors. We retrospectively consider a cohort of isolated, left-sided CDH, for whom we calculated the MSA and the observed/expected (O/E) TFLV at fetal MRI. We performed a data collection regarding inotropic or vasoactive support, treatment with pulmonary vasodilators, mechanical ventilation, and length of stay. General linear models were performed. The MSA and O/E TFLV were inversely correlated (Pearson’s coefficient – 0.65, p < 0.001), and deceased patients showed higher MSA values then survivors (p = 0.011). Among survivors, an increase in MSA was associated with longer pharmacological treatments (dobutamine: p = 0.016; dopamine: p = 0.049; hydrocortisone: p = 0.003; nitric oxide: p = 0.002; sildenafil: p = 0.039; milrinone: p = 0.039; oxygen: p = 0.066), and mechanical ventilation (p = 0.005), with an increasing trend in the length of hospitalization (p = 0.089).Conclusion: The MSA indirectly reflects lung hypoplasia and is associated with a higher neonatal intensity of cares. However, further studies are needed to consolidate the results.Trial registration: The study is an exploratory post hoc analysis of the registered NeoAPACHE protocol at ClinicalTrials.gov with the identifier NCT04396028. What is Known: • In congenital diaphragmatic hernia, the lung size, liver position, and defect side are the most common prenatal prognostic parameters used in clinical practice for morbidity and mortality prediction. • Lung hypoplasia, strictly associated with lung size, is estimated by observed/expected lung to head ratio and observed/expected total fetal lung volume with prenatal ultrasound and fetal magnetic resonance imaging, respectively. What is New: • A new, faster, more straightforward, and less operator-dependent tool to assess CDH severity could be the mediastinal shift angle calculation with fetal magnetic resonance imaging. • Postnatal clinical severity, considered as a postnatal cardiovascular and respiratory impairment that indirectly reflects lung hypoplasia, is associated with an increased mediastinal shift angle calculation.

PMID:34302257 | DOI:10.1007/s00431-021-04207-8

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Prognostic Factors for Survival in Transverse Colon Cancers

J Gastrointest Cancer. 2021 Jul 24. doi: 10.1007/s12029-021-00675-1. Online ahead of print.

ABSTRACT

BACKGROUND: Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure.

PATIENTS AND METHODS: We evaluated local and locally advanced TCC patients between 2007 and 2020 years for demographics data, symptoms, treatment status, and histopathological and molecular features.

RESULTS: Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5 months. Median disease-free survival (DFS) was 5.19 months, and median OS was 88.3 months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42-10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location.

CONCLUSION: TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.

PMID:34302255 | DOI:10.1007/s12029-021-00675-1

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Corticosteroid monotherapy for the management of Takayasu arteritis-a systematic review and meta-analysis

Rheumatol Int. 2021 Jul 23. doi: 10.1007/s00296-021-04958-5. Online ahead of print.

ABSTRACT

We evaluated clinical response, normalization of inflammatory markers, angiographic stabilization (primary outcomes), relapses and adverse events (secondary outcomes) in Takayasu arteritis (TAK) patients following corticosteroid monotherapy. MEDLINE, EMBASE, Web of Science, Scopus, Pubmed Central, Cochrane library, clinical trial databases and major international Rheumatology conferences were searched for studies reporting outcomes in TAK following corticosteroid monotherapy (without language/date restrictions). Risk ratios were calculated for controlled studies. Proportions were pooled for uncontrolled studies. Heterogeneity was assessed using I2 statistic. Quality assessment of individual studies utilized the Newcastle-Ottawa scale. GRADE methodology ascertained certainty of individual outcomes across studies. Twenty-eight observational studies (1098 TAK) were identified. Twenty-three uncontrolled studies (580 TAK) were synthesized in meta-analysis. Clinical response was observed in 60% (95% CI 45-74%, 19 studies), normalization of inflammatory markers in 84% (95% CI 54-100%, 4 studies) and angiographic stabilization in 28% (95% CI 6-57%, 4 studies). Relapses occurred in 66% (95% CI 18-99%, 4 studies). Adverse events were reported in 51% (95% CI 2-99%, 4 studies). All pooled estimates had considerable heterogeneity, unexplained by subgroup analyses (time period, geographic location or number of patients). Two studies reported lesser restenosis following vascular surgery and fewer relapses when corticosteroids were combined with immunosuppressants compared with corticosteroid monotherapy. All outcomes had very low certainty. While corticosteroid monotherapy induces clinical response in most TAK patients, angiographic stabilization is observed in fewer than one-third. Most patients relapse following corticosteroid withdrawal. Preliminary evidence supports up-front addition of immunosuppressants to retard angiographic progression and reduce relapses (PROSPERO identifier CRD42021242910).

PMID:34302232 | DOI:10.1007/s00296-021-04958-5

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Intra-operative monitoring as an adjuvant to standard vagus nerve stimulation implantation

Childs Nerv Syst. 2021 Jul 23. doi: 10.1007/s00381-021-05295-5. Online ahead of print.

ABSTRACT

PURPOSE: The treatment of refractory epilepsy by vagus nerve stimulation (VNS) is a well-established therapy. Complications following VNS insertion may be procedure-related or stimulation-related. Herein, we describe our technique of intra-operative neuro-monitoring (IONM) in an attempt to diminish these adverse events.

METHODS: This retrospective study describes 66 consecutive patients between the ages of 3 and 12 years who had undergone primary VNS implantation. The study population consisted of two cohorts, one in which the VNS device was implanted according to the standard described technique and a second group in which IONM was used as an adjuvant during the VNS device placement. Prior to VNS insertion, a Pediatric Voice Handicap Index (PVHI) was performed to assess voice-related quality of life, and this was repeated at 3 months following VNS insertion.

RESULTS: Sixty-six patients underwent the VNS implantation. Forty-three patients had a “standard” VNS insertion technique performed, whereas 23 had IONM performed during the VNS implantation. There were significant changes in the PVHI scores across both cohorts at 3-month follow-up. There were no statistically significant differences in PVHI scores between the monitored group and non-monitored group at 3-month follow up.

CONCLUSIONS: IONM can be used during VNS insertions to ensure correct placement of the leads on CNX. IONM may minimise vocal cord stimulation by placing the lead coils on the area of nerve eliciting the least amount of vocal cord EMG response. IONM however does not appear to improve voice outcomes at early follow up.

PMID:34302220 | DOI:10.1007/s00381-021-05295-5

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Effortful Control Moderates the Relation Between Negative Emotionality and Child Anxiety and Depressive Symptom Severity in Children with Anxiety Disorders

Child Psychiatry Hum Dev. 2021 Jul 24. doi: 10.1007/s10578-021-01218-2. Online ahead of print.

ABSTRACT

The present study investigated the interactive effect of reactive (negative emotionality) and regulatory (effortful control) aspects of temperament in the prediction of child anxiety and depressive symptoms. Clinically anxious children and their mothers completed a battery of questionnaires that included self- and mother-ratings of child effortful control, negative emotionality, anxiety, and depressive symptoms. Multiple regression analyses were conducted to examine the moderating effect of effortful control on the relation between negative emotionality and child anxiety and depressive symptom severity. The interaction between negative emotionality and effortful control was statistically significant and simple slopes revealed that as effortful control increased, the relationship between negative emotionality and anxiety and depressive symptoms weakened. Among anxious children high in negative emotionality, greater effortful control was related to less severe anxiety and depressive symptoms. Future work should evaluate whether targeting effortful control leads to reductions in internalizing symptoms among clinically anxious youth.

PMID:34302209 | DOI:10.1007/s10578-021-01218-2

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Prevalence of Strongyloides stercoralis in the immunocompetent and immunocompromised individuals in Iran: a systematic review and meta-analysis

Trans R Soc Trop Med Hyg. 2021 Jul 23:trab104. doi: 10.1093/trstmh/trab104. Online ahead of print.

ABSTRACT

Strongyloidiasis is a neglected tropical disease mostly distributed in tropical and subtropical regions. The current study evaluated the prevalence of Strongyloides stercoralis in immunocompetent and immunodeficient patients in Iran. The available online literature published from June 1994 to October 2020 was obtained from multiple English databases (PubMed, Science Direct, Scopus, Web of Science and Google Scholar) and four Persian databases (Magiran, Iran Medex, Iran Doc and SID). All statistical analyses were performed using R software (version 3.6) meta-package and p-values <0.05 were considered significant. From 1051 articles, 74 studies (248 656 individuals) met the inclusion criteria. The pooled prevalence of S. stercoralis was 2% (95% confidence interval [CI] 1 to 3) and 4% (95% CI 1 to 8) in immunocompetent and immunodeficient patients, respectively. In immunodeficient cases, the pooled prevalence of studies utilizing serology, culture and microscopic methods was 10% (95% CI 2 to 23), 1% (95% CI 0 to 6) and 1% (95% CI 0 to 1), respectively. In immunocompetent cases, the pooled prevalence of studies utilizing microscopic, culture and molecular methods was 2% (95% CI 1 to 3), 2% (95% CI 1 to 4) and 2% (95% CI 0 to 6), respectively. We propose an appropriate screening and control program along with comprehensive research regarding the frequency of strongyloidiasis in the country.

PMID:34302179 | DOI:10.1093/trstmh/trab104

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General- and Oral-Health-Related Predisposing Factors for Interrupting Military Service in the Finnish Defence Forces

Mil Med. 2021 Jul 24:usab311. doi: 10.1093/milmed/usab311. Online ahead of print.

ABSTRACT

INTRODUCTION: Finland’s security policy relies heavily on its own independent national defense, which is based on conscription. In 2011, 26,492 conscripts started their military service in Finland. Of these, 1,706 interrupted their military service and 191 changed to civilian service. Conscripts who interrupt their service seem to have an increased tendency to smoking, alcohol consumption, and taking snuff, which previous studies suggest to have strong associations with the need for restorative dental treatment and with lower socioeconomic status. The aim of this study was to compare the general and oral health habits between Finnish conscripts who interrupt their service and those who completed their military service and to find out what general- and oral-health-related factors could be used in predicting interruption of service.

METHODS: The study population consisted of 13,819 conscripts taking an oral examination during the service. Of these, 8,449 answered a computer-based anamnestic questionnaire and 264 interrupted their service.Predisposing factors on the anamnestic questionnaire for interrupting military service were evaluated by using a binary logistic regression model. The statistically significant factors were selected to form a sum variable which finally consisted of seven predisposing questions. Odds ratio (OR) values and 95% confidence intervals were calculated for each question and for the sum variable. Predictive accuracy was assessed by area under the receiver-operating curve.

RESULTS: The most obvious predisposing factor among those who interrupted their service compared to the reference group was lack of weekly physical exercise (OR = 5.80). The risk for interruption of military service was 68.6 times higher in cases where a subject exhibited six predisposing factors out of seven compared to those who had none.

CONCLUSION: As a conclusion, a set of statistically chosen anamnestic questions could help identify conscripts who have an increased risk of interruption of military service in addition to a risk of dental problems.

PMID:34302171 | DOI:10.1093/milmed/usab311

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The effects of chromium supplementation on blood pressure: a systematic review and meta-analysis of randomized clinical trials

Eur J Clin Nutr. 2021 Jul 23. doi: 10.1038/s41430-021-00973-8. Online ahead of print.

ABSTRACT

Results of studies on the effect of chromium supplementation on blood pressure (BP) are contradictory. The purpose of the current study was to carry out a meta-analysis on the effects of chromium supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). We conducted a systematic literature search of PubMed, SCOPUS, Cochrane Library, Web of Science, and Embase databases from inception up to July 2020 for randomized controlled trials (RCTs) that evaluate the impacts of chromium on SBP and DBP. A random-effects model was used to compute weighted mean differences (WMDs) with 95% confidence intervals (CIs). Heterogeneity was determined by I2 statistics and the Cochrane Q test. Sensitivity analysis was performed by eliminating each study one by one and recalculating the pooled effect. Ten studies comprising a total of 624 subjects were included in our meta-analysis. Chromium supplementation did not significantly change SBP (WMD: -0.642: 95% CI: (-2.15, 1.30) mmHg; p = 0.312; I2 = 12.7%) and DBP (WMD: -0.10; 95% CI: (-1.39, 1.18) mmHg; p = 0.070; I2 = 37.6%). Subgroup analysis based on dose and duration of chromium supplementation also did not significantly change the mean of SBP and DBP. The present meta-analysis of RCTs did not show the beneficial effects of chromium supplementation on BP in adults.

PMID:34302131 | DOI:10.1038/s41430-021-00973-8