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Nevin Manimala Statistics

Persistent homology analysis distinguishes pathological bone microstructure in non-linear microscopy images

Sci Rep. 2023 Feb 13;13(1):2522. doi: 10.1038/s41598-023-28985-3.

ABSTRACT

We present a topological method for the detection and quantification of bone microstructure from non-linear microscopy images. Specifically, we analyse second harmonic generation (SHG) and two photon excited autofluorescence (TPaF) images of bone tissue which capture the distribution of matrix (fibrillar collagen) structure and autofluorescent molecules, respectively. Using persistent homology statistics with a signed Euclidean distance transform filtration on binary patches of images, we are able to quantify the number, size, distribution, and crowding of holes within and across samples imaged at the microscale. We apply our methodology to a previously characterized murine model of skeletal pathology whereby vascular endothelial growth factor expression was deleted in osteocalcin-expressing cells (OcnVEGFKO) presenting increased cortical porosity, compared to wild type (WT) littermate controls. We show significant differences in topological statistics between the OcnVEGFKO and WT groups and, when classifying the males, or females respectively, into OcnVEGFKO or WT groups, we obtain high prediction accuracies of 98.7% (74.2%) and 77.8% (65.8%) respectively for SHG (TPaF) images. The persistence statistics that we use are fully interpretable, can highlight regions of abnormality within an image and identify features at different spatial scales.

PMID:36781895 | DOI:10.1038/s41598-023-28985-3

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Nevin Manimala Statistics

Incidence and risk factors of opportunistic infections after autologous stem cell transplantation: a nationwide, population-based cohort study in Korea

Sci Rep. 2023 Feb 13;13(1):2551. doi: 10.1038/s41598-023-27465-y.

ABSTRACT

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection.

PMID:36781859 | DOI:10.1038/s41598-023-27465-y

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Nevin Manimala Statistics

Impact of opioids on treatment response among idiopathic esophagogastric junction outflow obstruction patients: A retrospective cohort study

Indian J Gastroenterol. 2023 Feb 13. doi: 10.1007/s12664-022-01311-x. Online ahead of print.

ABSTRACT

BACKGROUND: Esophageal dysmotility has been attributed to opioid use. The goal was to assess the differences in pre- and post-treatment timed-barium esophagram (TBE) barium heights at 1 and 5 minutes and symptomatic response to treatment in esophagogastric junction outflow obstruction (EGJOO) patients according to opioid use status.

METHODS: We performed a retrospective cohort study. Consecutive patients with EGJOO were eligible for inclusion. Data were collected on demographics, pre and post-treatment 1 and 5 minutes TBE barium heights and symptom outcomes. Groups were compared according to opioid use.

RESULTS: Thirty-one EGJOO patients met the inclusion criteria. All patients were treated with pneumatic dilation. Of the 31 patients, 11 (35%) had opioid exposure and 20 (65%) did not. The median follow-up post-treatment was two months (range 1-47 months). There was no statistically significant difference in post-treatment outcomes for opioid exposed vs. unexposed groups. The median per cent decrease in the TBE barium height at 1 minute was 100% for the opioid exposed vs. 71% for the unexposed group (p = 0.92). The median per cent decrease in the TBE barium height at 5 minutes was zero % for the opioid exposed and unexposed groups (p = 0.67). The incidence of symptomatic improvement was 82% (9/11) for the opioid exposed group vs 95% (19/20) for the unexposed group (p = 0.28).

CONCLUSIONS: Patients with EGJOO seem to respond to treatment similarly regardless of being on opioids.

PMID:36781814 | DOI:10.1007/s12664-022-01311-x

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Nevin Manimala Statistics

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence

J Urban Health. 2023 Feb 13. doi: 10.1007/s11524-023-00718-x. Online ahead of print.

ABSTRACT

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

PMID:36781812 | DOI:10.1007/s11524-023-00718-x

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Nevin Manimala Statistics

Profiling Serum Intact N-Glycopeptides Using Data-Independent Acquisition Mass Spectrometry

Methods Mol Biol. 2023;2628:365-391. doi: 10.1007/978-1-0716-2978-9_24.

ABSTRACT

Large-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data-independent acquisition (DIA) mass spectrometry is an emerging technology with deep proteome coverage as well as accurate quantitative capability for large-scale proteomics studies and has also been applied to the field of glycoproteomics. In this protocol, we describe how to analyze data from a DIA experiment for profiling serum intact N-glycopeptides. We present a comprehensive data analysis workflow using GproDIA, including glycopeptide spectral library building, chromatographic feature extraction from the DIA data, and feature scoring with appropriate statistical control of error rates. We anticipate that this method could provide a powerful tool to explore the serum glycoproteome.

PMID:36781798 | DOI:10.1007/978-1-0716-2978-9_24

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Nevin Manimala Statistics

Early Cancer Biomarker Discovery Using DIA-MS Proteomic Analysis of EVs from Peripheral Blood

Methods Mol Biol. 2023;2628:127-152. doi: 10.1007/978-1-0716-2978-9_9.

ABSTRACT

One of the cornerstones of effective cancer treatment is early diagnosis. In this context, the identification of proteins that can serve as cancer biomarkers in bodily fluids (“liquid biopsies”) has gained attention over the last decade. Plasma and serum fractions of blood are the most commonly investigated sources of potential cancer liquid biopsy biomarkers. However, the high complexity and dynamic range typical of these fluids hinders the sensitivity of protein detection by the most commonly used mass spectrometry technology (data-dependent acquisition mass spectrometry (DDA-MS)). Recently, data-independent acquisition mass spectrometry (DIA-MS) techniques have overcome the limitations of DDA-MS, increasing sensitivity and proteome coverage. In addition to DIA-MS, isolating extracellular vesicles (EVs) can help to increase the depth of serum/plasma proteome coverage by improving the identification of low-abundance proteins which are a potential treasure trove of diagnostic molecules. EVs, the nano-sized membrane-enclosed vesicles present in most bodily fluids, contain proteins which may serve as potential biomarkers for various cancers. Here, we describe a detailed protocol that combines DIA-MS and EV methodologies for discovering and validating early cancer biomarkers using blood serum. The pipeline includes size exclusion chromatography methods to isolate serum-derived extracellular vesicles and subsequent EV sample preparation for liquid chromatography and mass spectrometry analysis. Procedures for spectral library generation by DDA-MS incorporate methods for off-line peptide separation by microflow HPLC with automated fraction concatenation. Analysis of the samples by DIA-MS includes recommended protocols for data processing and statistical methods. This pipeline will provide a guide to discovering and validating EV-associated proteins that can serve as sensitive and specific biomarkers for early cancer detection and other diseases.

PMID:36781783 | DOI:10.1007/978-1-0716-2978-9_9

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Nevin Manimala Statistics

EndoTrainer: a novel hybrid training platform for endoscopic surgery

Int J Comput Assist Radiol Surg. 2023 Feb 13. doi: 10.1007/s11548-023-02837-x. Online ahead of print.

ABSTRACT

PURPOSE: Endoscopy implies high demanding procedures, and their practice requires structured formation curricula supported by adequate training platforms. Physical platforms are the most standardised solution for surgical training, but over the last few years, virtual platforms have been progressively introduced. This research work presents a new hybrid, physic-virtual, endoscopic training platform that exploits the benefits of the two kind of platforms combining realistic tools and phantoms together with the capacity of measuring all relevant parameters along the execution of the exercises and of providing an objective assessment performance.

METHODS: The developed platform, EndoTrainer, has been designed to train and assess surgical skills in hysteroscopy and cystoscopy following a structured curricula. The initial development and validation is focused on hysteroscopic exercises proposed in the Gynaecological Endoscopic Surgical Education and Assessment (GESEA) Certification Programme from The Academy and European Society for Gynaecological Endoscopy (ESGE) and analyses the obtained results of an extensive study with 80 gynaecologists executing 30 trials of the standard 30 degree endoscope navigation exercise.

RESULTS: The experiments demonstrate the benefits of the presented hybrid platform. Multi-variable statistical analysis points out that all subjects have obtained statistically significant improvement in all relevant parameters: shorter and safer trajectories, improved 30-degree endoscope navigation, accurate positioning over the targets and reduction of the execution time.

CONCLUSION: This paper presents a new hybrid approach for training, and evaluating whether it provides an objectivable improvement of camera navigation endoscopic basic skills. The obtained results demonstrate the initial hypothesis: all subjects have improved their camera handling and navigation skills.

PMID:36781742 | DOI:10.1007/s11548-023-02837-x

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Nevin Manimala Statistics

RNA Modification Detection Using Nanopore Direct RNA Sequencing and nanoDoc2

Methods Mol Biol. 2023;2632:299-319. doi: 10.1007/978-1-0716-2996-3_21.

ABSTRACT

RNA modifications regulate multiple aspects of cellular function including RNA splicing, translation, export, decay, stability, and phase separation. One of the comprehensive ways to detect such modifications is by the recent advancement of direct RNA sequencing from Oxford Nanopore Technologies (ONT). However, this method obtains a large amount of data with high complexity in the form of raw current signal that poses a new informatics challenge to accurately detect those modifications. Here, we provide nanoDoc2, a software to detect multiple types of RNA modification from nanopore direct RNA sequencing data. The nanoDoc2 includes a novel signal segmentation algorithm based on the trace value-a base probability feature that is added by the Guppy basecalling program from ONT during processing of the raw signal. The core of nanoDoc2 includes a machine learning algorithm in which a 6-mer segmented raw current signal is analyzed by deep one-class classification using a WaveNet-based neural network. As an output, an RNA modification is detected by a statistical score in each candidate position. Herein, we describe the detailed instructions on how to use nanoDoc2 for signal segmentation, train/test the neural network, and finally predict RNA modifications present in nanopore direct RNA sequencing data.

PMID:36781737 | DOI:10.1007/978-1-0716-2996-3_21

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Nevin Manimala Statistics

Effects of trastuzumab and trastuzumab emtansine on corrected QT interval and left ventricular ejection fraction in patients with metastatic (HER2+) breast cancer

Egypt Heart J. 2023 Feb 13;75(1):11. doi: 10.1186/s43044-023-00331-y.

ABSTRACT

BACKGROUND: Trastuzumab and trastuzumab emtansine are specific antibody and antibody-drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment.

RESULTS: A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment.

CONCLUSION: Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.

PMID:36781707 | DOI:10.1186/s43044-023-00331-y

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Nevin Manimala Statistics

Predictors of Knowledge, Attitude, and Practice (KAP) Towards Family Planning (FP) Among Pregnant Women in Fiji

Matern Child Health J. 2023 Feb 13. doi: 10.1007/s10995-023-03618-3. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to determine the predictors of Knowledge, Attitude and Practice (KAP) towards Family Planning (FP) among pregnant Fijian women.

METHODS: A cross-sectional study was conducted over two months in 2019 with adult pregnant women attending the Antenatal Clinic (ANC) at Ba Mission Hospital (BMH), Fiji. Data was collected using a self-administrated questionnaire. Statistical analysis included correlation tests and regression analysis in determining predictors of KAP.

RESULTS: 240 pregnant women participated in this study with a mean age of 26.02 (± SD = 4.13). The results showed a moderate level of knowledge (mean 14.95, SD ± 3.15), positive attitude (mean 20.56, SD ± 5.68), and good practice (mean 4.97, SD ± 1.73). Linear regression identified that women with more than seven children had a knowledge score of 3.65, lower than null parity (t value = -2.577, p = 0.011). Women aged 20 to 24 had a 6.47 lower attitude score than women aged 18 to 19 (t value = -2.142, p = 0.033). Women in defacto relationships had a 2.12 lower attitude score compared to the married category (t value = -2.128, p = 0.034). Fijian women of Indian descent had a 1.98 lower attitude score than the I Taukei women (t value = -2.639, p = 0.009). Women aged 30-34 had 2.41 lower practice scores than those aged 18-19 (t value = -2.462, p = 0.015).

CONCLUSION: This study found a medium knowledge of FP among pregnant women. These findings support a recommendation for further research to implement effective strategies.

PMID:36781695 | DOI:10.1007/s10995-023-03618-3