Category: Nevin Manimala

Phys Biol. 2023 Apr 19. doi: 10.1088/1478-3975/acce8d. Online ahead of print.

ABSTRACT

This paper concerns the identification of gene co-expression modules in transcriptomics data, i.e., collections of genes which are highly co-expressed and potentially linked to a biological mechanism. WGCNA (Weighted Gene Co-expression Network Analysis) is a widely used method for module detection based on the computation of eigengenes, the weights of the first principal component for the module gene expression matrix. This eigengene has been used as a centroid in a $k$-means algorithm to improve module memberships. In this paper, we present four new module representatives: the eigengene subspace, flag mean, flag median and module expression vector. The eigengene subspace, flag mean and flag median are subspace module representatives which capture more variance of the gene expression within a module. The module expression vector is a weighted centroid of the module which leverages the structure of the module gene co-expression network. We use these module representatives in LBG (Linde-Buzo-Gray) clustering algorithms to refine WGCNA module membership. We evaluate these methodologies on two transcriptomics data sets. We find that most of our module refinement techniques improve upon the WGCNA modules by two statistics: 1) module classification between phenotype and 2) module biological significance according to Gene Ontology (GO) terms.

PMID:37075776 | DOI:10.1088/1478-3975/acce8d

Chin Med J (Engl). 2023 Apr 19. doi: 10.1097/CM9.0000000000002600. Online ahead of print.

ABSTRACT

BACKGROUND: There is limited data to comprehensively evaluate the epidemiological characteristics of multiple myeloma (MM) in China; therefore, this study determined the characteristics of the disease burden of MM at national and provincial levels in China.

METHODS: The burden of MM, including incidence, mortality, prevalence, and disability-adjusted life years (DALYs), with a 95% uncertainty interval (UI), was determined in China following the general analytical strategy used in the Global Burden of Disease, Injuries, and Risk Factors Study 2019. The trends in the burden of MM from 1990 to 2019 were also evaluated.

RESULTS: There were an estimated 347.45 thousand DALYs with an age-standardized DALY rate of 17.05 (95% UI, 12.31-20.77) per 100,000 in 2019. The estimated number of incident case and deaths of MM were 18,793 and 13,421, with age-standardized incidence and mortality rates of 0.93 (95% UI, 0.67-1.15) and 0.67 (95% UI, 0.50-0.82) per 100,000, respectively. The age-specific DALY rates per 100,000 increased to more than 10.00 in the 40 to 44 years age group reaching a peak (93.82) in the 70 to 74 years age group. Males had a higher burden than females, with approximately 1.5 to 2.0-fold sex difference in age-specific DALY rates in all age groups. From 1990 to 2019, the DALYs of MM increased 134%, from 148,479 in 1990 to 347,453 in 2019.

CONCLUSION: The burden of MM has doubled over the last three decades, which highlights the need to establish effective disease prevention and control strategies at both the national and provincial levels.

PMID:37075767 | DOI:10.1097/CM9.0000000000002600

Chin Med J (Engl). 2023 Apr 19. doi: 10.1097/CM9.0000000000002655. Online ahead of print.

ABSTRACT

BACKGROUND: Three-dimensional shear wave elastography ((3D-SWE) is a promising method in distinguishing benign and malignant thyroid nodules recently. By combining with conventional method, it may further improve the diagnostic value. The study aimed to assess the diagnostic value of American College of Radiology (ACR) thyroid imaging reporting and data system (TI-RADS) combined with 3D-SWE in ACR TI-RADS 4 and 5 thyroid nodules.

METHODS: All nodules were examined by conventional ultrasonography, ACR TI-RADS classification, and 3D-SWE examination. Conventional ultrasonography was used to observe the location, size, shape, margin, echogenicity, taller-than-wide sign, microcalcification, and blood flow of thyroid nodules, and then ACR TI-RADS classification was performed. The Young’s modulus values (3D-C-Emax, 3D-C-Emean, and elastography standard deviation [3D-C-Esd]) were measured on the reconstructed coronal plane images. According to the receiver operating characteristic (ROC) curve, the best diagnostic efficiency among 3D-C-Emax, 3D-C-Emean, and 3D-C-Esd was selected and the cut-off threshold was calculated. According to the surgical pathology, they were divided into benign group and malignant group. And appropriate statistical methods such as t-test and Mann-Whitney U test were used to compare the difference between the two groups. On this basis, 3D-SWE combined with conventional ACR TI-RADS was reclassified as combined ACR TI-RADS to determine benign or malignant thyroid nodules.

RESULTS: Of the 112 thyroid nodules, 62 were malignant and 50 were benign. The optimal cut-off value of three-dimensional maximum Young’s modulus in coronal plane (3D-C-Emax) was 51.5 kPa and the area under the curve (AUC) was 0.798. The AUC, sensitivity, specificity, and accuracy of conventional ACR TI-RADS were 0.828, 83.9%, 66.0%, and 75.9%, respectively. The AUC, sensitivity, specificity, and accuracy of combined ACR TI-RADS were 0.845, 90.3%, 66.0%, and 79.5%, respectively. The difference between the two AUC values was statistically significant.

CONCLUSIONS: Combined ACR TI-RADS has higher diagnostic efficiency than conventional ACR TI-RADS. The sensitivity and accuracy of combined ACR TI-RADS showed significant improvements. It can be used as an effective method in the diagnosis of thyroid nodules.

PMID:37075764 | DOI:10.1097/CM9.0000000000002655

ESC Heart Fail. 2023 Apr 19. doi: 10.1002/ehf2.14376. Online ahead of print.

ABSTRACT

AIMS: Left ventricular assist devices (LVADs) support the hearts of patients with advanced heart failure. Following LVAD implantation, patients face a complex regimen of self-care behaviours including self-care maintenance, self-care monitoring and self-care management. However, during the COVID-19 pandemic, symptoms of anxiety and depression may have interfered with their self-care. Currently, little is known on how specific self-care behaviours of LVAD-implanted patients changed during the COVID-19 pandemic. We aim to describe the changes in self-care behaviours among patients with an implanted LVAD in Israel during the COVID-19 pandemic and explore the factors related to self-care behaviour change.

METHODS: A prospective observational cross-sectional study design. A convenience sample of 27 Israeli LVAD-implanted patients (mean age 62.4 ± 9, 86% male, 78.6% living with a partner) completed the LVAD Self-Care Behaviour Scale (1 = never to 5 = always) and Hospital Anxiety and Depression Scale (0 = not at all to 3 = most of the time). Data were collected before and after the onset of the COVID-19 pandemic in Israel. Statistical analyses included paired t-tests, Pearson’s correlations, and one-way repeated measures ANOVAs.

RESULTS: During the COVID-19 pandemic, a significant decrease was found in patients’ adherence to checking and recording their LVAD speed, flow, power and PI (Pulsatility Index) (P = 0.05), checking their INR (P = 0.01), and daily weighing (P < 0.01). The prevalence of some behaviours (e.g. regularly exercising) increased in some patients and decreased in others. Patients living without a partner worsened their adherence to some of the self-care behaviours (e.g. taking medicines as prescribed), compared with those living with a partner (M_b = 5.0 ± 0 and M_d = 5.0 ± 0, delta = 0 vs. M_b = 5.0 ± 0 and M_d = 4.6 ± 0.9, delta = -0.4, respectively; F = 4.9, P = 0.04). Women, and not men, tended to improve their adherence to the self-care behaviour such as avoiding kinking, pulling, or moving the LVAD driveline at the exit site (M_b = 4.0 ± 1.0 and M_d = 5.0 ± 0, delta = 1.0 vs. M_b = 4.5 ± 0.9 and M_d = 4.4 ± 1.2, delta = -0.1, F = 4.7, P = 0.04, respectively). In total, 41% (11) patients reported neither anxiety nor depression, 11% (3) reported anxiety, 15% (4) reported depression, and 44% (12) reported both anxiety and depression. No associations between anxiety and/or depression and self-care behaviours were found.

CONCLUSIONS: Priorities in self-care behaviours among patients with implanted LVAD changed after the onset of the COVID-19 pandemic. Factors that assisted with adherence to self-care behaviours included living with a partner and being female. The current results may guide further research on identifying behaviours that are at risk of not being maintained during a time of emergency.

PMID:37075748 | DOI:10.1002/ehf2.14376

Ann Clin Psychiatry. 2023 May;35(2):110-117. doi: 10.12788/acp.0110.

ABSTRACT

BACKGROUND: Transcranial magnetic stimulation (TMS) is a neuro-modulation technique for treatment-resistant major depressive disorder (MDD). Standard TMS protocols for MDD involve once-daily treatment for 6 to 9 weeks. We report a case series of an accelerated TMS protocol for outpatient MDD treatment.

METHODS: From July 2020 through January 2021, patients deemed appropriate candidates for TMS treatment were offered an accelerated TMS protocol consisting of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex, localized by the Beam F3 method, and consisting of 5 treatments daily for 5 days. Assessment scales were obtained as part of standard clinical care.

RESULTS: A total of 19 veterans received the accelerated protocol and 17 completed treatment. Statistically significant mean reductions from baseline to end of treatment were observed across all assessment scales. Remission and response rates, as defined by changes in Montgomery-Åsberg Depression Rating Scale scores, were 47.1% and 64.7%, respectively. Treatments were well tolerated without unexpected or serious adverse events.

CONCLUSIONS: This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days. Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.

PMID:37074971 | DOI:10.12788/acp.0110

Ann Clin Psychiatry. 2023 May;35(2):103-108. doi: 10.12788/acp.0107.

ABSTRACT

BACKGROUND: Although major depressive disorder (MDD) and bipolar depression can present with similar symptoms, biological differences exist. One difference is the possible variance in adverse effects associated with treatment. This study examined the association of cognitive impairment and delirium in patients treated with electroconvulsive therapy (ECT) plus lithium for MDD or bipolar depression.

METHODS: The Nationwide Inpatient Sample included 210 adults receiving ECT plus lithium. Descriptive statistics and a Chi-square test were used to evaluate the differences between mild cognitive impairment and drug-induced delirium for those with MDD or bipolar depression. We calculated the odds ratio (OR) for drug-induced delirium in inpatients with MDD (compared to inpatients with bipolar depression) using a binomial logistic regression model.

RESULTS: Mild cognitive impairment was observed in 9.1% of patients with MDD (n = 110), compared to 0 in bipolar depression (n = 100) (P = .002). Drug-induced delirium was more prevalent in MDD (OR 1.19; 95% CI, 1.11 to 1.30).

CONCLUSIONS: ECT plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to MDD. This study may also support biological differences between the 2 types of depression.

PMID:37074968 | DOI:10.12788/acp.0107

Plast Reconstr Surg. 2023 Apr 20. doi: 10.1097/PRS.0000000000010567. Online ahead of print.

ABSTRACT

INTRODUCTION: The traditional design for truncal perforator flaps are ipsilateral without midline decussation. The presumed rational is to minimize the risk of distal flap necrosis. In this paper we present our experience and results contralateral truncal perforator flaps designed and raised crossing the midline.

METHODS: This retrospective analysis included 43 patients (25 men and 18 women) who underwent reconstructive surgery from 1984 to 2021 using a contralateral flap design crossing the midline in the anterior trunk and upper back. Considerations included: pathology, location, as well as the dimensions of the defect and flap. An arithmetic and weighted mean with their 95% CI was estimated to compare ipsilateral and contralateral techniques.

RESULTS: Contralateral flaps utilized included the internal mammary perforator flap (n=28) superficial superior epigastric artery (n=8), superior epigastric perforator (n=2), and the 2 nd or 9 th dorsal intercostal artery perforator flaps (n=5). All of these flaps excluding the superficial superior epigastric artery demonstrated length and coverage surface averages that were significantly greater than those traditional ipsilateral flaps. However, with the contralateral superficial superior epigastric artery, both measures were statistically similar to those traditional ipsilateral flaps.

CONCLUSIONS: The anatomic variation design suggests that trunk midline is not a barrier and that perforator flaps in these two regions may be raised on different longitudinal axes without compromising vitality.

PMID:37075277 | DOI:10.1097/PRS.0000000000010567

Inflamm Bowel Dis. 2023 Apr 19:izad059. doi: 10.1093/ibd/izad059. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy-onset inflammatory bowel disease (PO-IBD) may pose a clinical challenge. We investigated the clinical course of PO-IBD, including time to diagnosis, medical treatment, and the impact on birth outcomes.

METHODS: All pregnancies in women with IBD at a tertiary IBD center in Denmark were identified from 2008 to 2021. Maternal and offspring outcome data, retrieved from medical records of women with new onset IBD during pregnancy, were compared with the outcomes of women with IBD diagnosed prior to pregnancy (controls). Outcomes included subtype of IBD, disease location, medical treatment, birth weight, intrauterine growth retardation (IUGR), gestational age at birth, caesarean section, stillbirth, congenital malformations, and time elapsed from onset of symptoms to diagnosis.

RESULTS: In total, 378 women contributed with 583 pregnancies. Pregnancy-onset IBD affected 34 (9.0%) women. Ulcerative colitis (UC; n = 32) was more prevalent than Chron’s disease (CD; n = 2). Birth outcomes in pregnancies affected by PO-IBD were comparable to that of the 549 controls. Women with PO-IBD received more corticosteroids and biologics following their diagnosis than did the controls (5 [14.7%] vs 2 [2.9%]; P = .07; and 14 [41.2%] vs 9 [13.2%]; P = .003, respectively). Concerning time to IBD diagnosis, there was no statistically significant difference between the 2 groups (PO-IBD, 2.5 months, interquartile range [2-6] vs controls 2 months [1-4.5]; P = .27).

CONCLUSION: Although we observed a trend towards a diagnostic delay, PO-IBD was not associated with a significantly increased time to diagnosis. Birth outcomes in women with PO-IBD were comparable to those diagnosed with IBD prior to pregnancy.

PMID:37075485 | DOI:10.1093/ibd/izad059

Inflamm Bowel Dis. 2023 Apr 19:izad063. doi: 10.1093/ibd/izad063. Online ahead of print.

ABSTRACT

BACKGROUND: Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy.

METHODS: A total of 994 sequential 1-mm digital microscopic images (virtual biopsies) from consecutive colectomies from patients with clinically severe UC were scored by 2 pathologists. Agreement statistics for Geboes subscores and Nancy (NHI) and Robarts Histological Indices (RHI) between random samples from 1 to 10 biopsies and a reference mean score across a 2-cm region of mucosa were calculated using bootstrapping with 2500 iterations.

RESULTS: The agreement statistics improved across all indices as the biopsy density increased, with the largest proportional gains occurring with addition of the second and third biopsies. One biopsy achieved moderate to good agreement with 95% confidence for NHI and RHI corresponding to scale-specific errors of 0.40 (0.25-0.66) and 3.02 (2.08-5.36), respectively; and 3 biopsies achieved good agreement with 95% confidence corresponding to scale-specific errors of 0.22 (0.14-0.39) and 1.87 (1.19-3.25), respectively. Of the individual histological features, erosions and ulcers had the greatest impact on the agreement statistics.

CONCLUSIONS: In the setting of active colitis, up to 3 biopsy samples per region of interest may be required to overcome microscopic heterogeneity and ensure accurate histological grading.

PMID:37075483 | DOI:10.1093/ibd/izad063

Nicotine Tob Res. 2023 Apr 19:ntad057. doi: 10.1093/ntr/ntad057. Online ahead of print.

ABSTRACT

INTRODUCTION: As smoking prevalence has decreased, there has been debate about “hardening” (smokers are more resistant to established tobacco control measures) or “softening” (smokers are more responsive to interventions) of the remaining smoking population. Despite growing evidence to reject the “hardening” hypothesis, there is lack of long-term population-based studies to test this hypothesis by educational level.

AIMS AND METHODS: Repeated cross-sectional population-based surveys during 1978-2014 and in 2018 were utilized. The target population consisted of ~5000 25-64-year-old Finns annually. The data included 109 257 respondents of which 53 351 ever-smoking individuals were included in the analyses. Response rates varied between 84% and 43%. Five hardening indicators considering smoking frequency, intensity and smoking cessation were used as the dependent variables. The main independent variable was study year (time). Statistical analyses were based on regression models using restricted cubic splines by educational level.

RESULTS: Contrary to the hardening hypothesis, hardening indicators showed softening over time among all educational groups. However, educational groups differed from each other. Compared with the highly educated, the quit ratio was lower, number of cigarettes per day (CPD) was higher, the proportions of daily smokers among current smokers and heavy smokers among daily smokers were higher among the less educated.

CONCLUSIONS: In accordance with growing evidence, also the Finnish smoking population has “softened” over time. Although the change has been predominantly in the same direction for all educational groups, the rate of change has been stronger among the highly educated, highlighting the continued burden of smoking among the less educated.

IMPLICATIONS: Even though “softening” of smoking has occurred, lighter smoking also poses health risks. Therefore, tobacco control policies and cessation services should be developed and targeted to a greater extent also for people who smoke less than daily and for those who smoke fewer CPD. Furthermore, interventions should focus on special requirements of the lower educational groups to promote health equity.

PMID:37075474 | DOI:10.1093/ntr/ntad057