Nevin Manimala

NPJ Precis Oncol. 2021 Jul 14;5(1):64. doi: 10.1038/s41698-021-00178-z.

ABSTRACT

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10^-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

PMID:34262104 | DOI:10.1038/s41698-021-00178-z

Sci Rep. 2021 Jul 14;11(1):14490. doi: 10.1038/s41598-021-93651-5.

ABSTRACT

As machine learning research in the field of cardiovascular imaging continues to grow, obtaining reliable model performance estimates is critical to develop reliable baselines and compare different algorithms. While the machine learning community has generally accepted methods such as k-fold stratified cross-validation (CV) to be more rigorous than single split validation, the standard research practice in medical fields is the use of single split validation techniques. This is especially concerning given the relatively small sample sizes of datasets used for cardiovascular imaging. We aim to examine how train-test split variation impacts the stability of machine learning (ML) model performance estimates in several validation techniques on two real-world cardiovascular imaging datasets: stratified split-sample validation (70/30 and 50/50 train-test splits), tenfold stratified CV, 10 × repeated tenfold stratified CV, bootstrapping (500 × repeated), and leave one out (LOO) validation. We demonstrate that split validation methods lead to the highest range in AUC and statistically significant differences in ROC curves, unlike the other aforementioned approaches. When building predictive models on relatively small data sets as is often the case in medical imaging, split-sample validation techniques can produce instability in performance estimates with variations in range over 0.15 in the AUC values, and thus any of the alternate validation methods are recommended.

PMID:34262098 | DOI:10.1038/s41598-021-93651-5

Sci Rep. 2021 Jul 14;11(1):14460. doi: 10.1038/s41598-021-93713-8.

ABSTRACT

The aim of this study was to explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Women who were breast cancer survivors (BCS, n = 27) and without cancer with similar characteristics (Control, n = 31) were recruited for this study. We calculated some relevant linear and nonlinear parameters of 5 min of RR interval time series such as mean RR interval (RR_ave), the corrected Poincaré index (cSD1/SD2), the sample entropy (SampEn), the long-term fractal scaling exponent (α₂) and 2UV from symbolic dynamics. Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water. We found that diverse HRV indexes and only one body composition measure showed statistical differences (p < 0.05) between the BCS and Control groups. RR_ave: 729 (648-802) vs. 795 (713-852) ms; cSD2/SD1: 3.4 (2.7-5.0) vs. 2.9 (2.3-3.5); SampEn: 1.5 (1.3-1.8) vs. 1.7 (1.5-1.8); α₂: 0.6 (0.3-0.6) vs. 0.5 (0.4-0.5); 2UV: 7.1 (4.3-11.5) vs. 10.8 (6.4-15.7) and nVFR 0.12 (0.11-0.13) vs. 0.10 (0.08-0.12) points/kg, respectively. The nVFR was strongly significantly correlated with several indexes of HRV only in the BCS group.Our findings suggest that BCS exhibit lower parasympathetic cardiac activity and changes in HRV patterns compared to Controls. A concomitant increase of visceral fat, among other factors, may contribute to cardiac autonomic disturbances and changes in HRV patterns in BCS.

PMID:34262078 | DOI:10.1038/s41598-021-93713-8

Sci Rep. 2021 Jul 14;11(1):14488. doi: 10.1038/s41598-021-93579-w.

ABSTRACT

Since its emergence, the phenomenon of SARS-CoV-2 transmission by seemingly healthy individuals has become a major challenge in the effort to achieve control of the pandemic. Identifying the modes of transmission that drive this phenomenon is a perquisite in devising effective control measures, but to date it is still under debate. To address this problem, we have formulated a detailed mathematical model of discrete human actions (such as coughs, sneezes, and touching) and the continuous decay of the virus in the environment. To take into account those discrete and continuous events we have extended the common modelling approach and employed a hybrid stochastic mathematical framework. This allowed us to calculate higher order statistics which are crucial for the reconstruction of the observed distributions. We focused on transmission within a household, the venue with the highest risk of infection and validated the model results against the observed secondary attack rate and the serial interval distribution. Detailed analysis of the model results identified the dominant driver of pre-symptomatic transmission as the contact route via hand-face transfer and showed that wearing masks and avoiding physical contact are an effective prevention strategy. These results provide a sound scientific basis to the present recommendations of the WHO and the CDC.

PMID:34262069 | DOI:10.1038/s41598-021-93579-w

Sci Rep. 2021 Jul 14;11(1):14478. doi: 10.1038/s41598-021-91644-y.

ABSTRACT

The prevalence of smokers is a major driver of lung cancer incidence in a population, though the “exposure-lag” effects are ill-defined. Here we present a multi-country ecological modelling study using a 30-year smoking prevalence history to quantify the exposure-lag response. To model the temporal dependency between smoking prevalence and lung cancer incidence, we used a distributed lag non-linear model (DLNM), controlling for gender, age group, country, outcome year, and population at risk, and presented the effects as the incidence rate ratio (IRR) and cumulative incidence rate ratio (IRR_cum). The exposure-response varied by lag period, whilst the lag-response varied according to the magnitude and direction of changes in smoking prevalence in the population. For the cumulative lag-response, increments above and below the reference level was associated with an increased and decreased IRR_cum respectively, with the magnitude of the effect varying across the lag period. Though caution should be exercised in interpretation of the IRR and IRR_cum estimates reported herein, we hope our work constitutes a preliminary step towards providing policy makers with meaningful indicators to inform national screening programme developments. To that end, we have implemented our statistical model a shiny app and provide an example of its use.

PMID:34262067 | DOI:10.1038/s41598-021-91644-y

Sci Rep. 2021 Jul 14;11(1):14450. doi: 10.1038/s41598-021-93653-3.

ABSTRACT

Mental disorders (MDs), including schizophrenia (SCZ) and bipolar disorder (BD), have attracted special attention from scientists due to their high prevalence and significantly debilitating clinical features. The diagnosis of MDs is still essentially based on clinical interviews, and intensive efforts to introduce biochemical based diagnostic methods have faced several difficulties for implementation in clinics, due to the complexity and still limited knowledge in MDs. In this context, aiming for improving the knowledge in etiology and pathophysiology, many authors have reported several alterations in metabolites in MDs and other brain diseases. After potentially fishing all metabolite biomarkers reported up to now for SCZ and BD, we investigated here the proteins related to these metabolites in order to construct a protein-protein interaction (PPI) network associated with these diseases. We determined the statistically significant clusters in this PPI network and, based on these clusters, we identified 28 significant pathways for SCZ and BDs that essentially compose three groups representing three major systems, namely stress response, energy and neuron systems. By characterizing new pathways with potential to innovate the diagnosis and treatment of psychiatric diseases, the present data may also contribute to the proposal of new intervention for the treatment of still unmet aspects in MDs.

PMID:34262063 | DOI:10.1038/s41598-021-93653-3

Nat Commun. 2021 Jul 14;12(1):4313. doi: 10.1038/s41467-021-24566-y.

ABSTRACT

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations.

PMID:34262041 | DOI:10.1038/s41467-021-24566-y

Med Sci Monit. 2021 Jul 15;27:e931102. doi: 10.12659/MSM.931102.

ABSTRACT

BACKGROUND Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, are important proteins for alternative splicing of mRNAs and are reported to promote or inhibit the progression of some tumors. However, the effects of ESRPs in breast cancer are still unknown. MATERIAL AND METHODS In this study, we detected the transcriptional level and alterations of ESRP1 in patients with breast cancer based on the Oncomine, Gene Expression Profiling Interactive Analysis, Gene Expression-Based Outcome for Breast Cancer Online, and cBioPortal databases. Using immunohistochemistry and quantitative polymerase chain reaction, the expression pattern of ESRP1 in breast cancer was analyzed. Analysis of the clinicopathological characteristics and function of ESRP1 in breast cancer were actualized through the University of Alabama Cancer database and Database for Annotation, Visualization and Integrated Discovery. Using the Kaplan-Meier plotter, the prognostic values of ESRP1 in patients with breast cancer were analyzed. The Encyclopedia of RNA Interactomes database was used to predict miRNAs that regulated ESRP1. RESULTS We found that ESRP1 was significantly overexpressed in patients with breast cancer, compared with patients without breast cancer, and had statistically significant clinicopathological characteristics. Kaplan-Meier plotter analysis indicated that the elevated expression of ESRP1 was associated with poor prognosis in patients with breast cancer. Furthermore, hsa-miR-181c-5p was identified to be potentially involved in the regulation of ESRP1. CONCLUSIONS These results suggest that ESRP1 is a valuable target for the precise treatment of breast cancer and a potential biomarker for the prognosis of patients with breast cancer.

PMID:34262011 | DOI:10.12659/MSM.931102

Med Sci Sports Exerc. 2021 Aug 1;53(8):1615-1623. doi: 10.1249/MSS.0000000000002621.

ABSTRACT

PURPOSE: This study aimed to investigate the tracking and changes of steps per day in adults and their determinants over 13 yr.

METHODS: A total of 2195 subjects (1236 women) 30-45 yr of age were randomly recruited from the ongoing Cardiovascular Risk in Young Finns Study in 2007 and were followed up in 2020. Steps per day, including both total and aerobic steps per day, were monitored for seven consecutive days with a pedometer in 2007-2008 and 2011-2012 and with an accelerometer in 2018-2020. Tracking was analyzed using Spearman’s correlation. Stability and changes of steps per day over time in both low-active and high-active groups (based on median values) were described by percentage agreements, kappa statistics, and logistic regression. Associations of sex, age, and body mass index with the initial number and changes in steps per day were analyzed using linear growth curve modeling.

RESULTS: Tracking correlations of total steps per day at 4-, 9-, and 13-yr intervals were 0.45-0.66, 0.33-0.70, and 0.29-0.60, while corresponding correlations for aerobic steps per day were 0.28-0.55, 0.23-0.52, and 0.08-0.55, respectively. Percentage agreements were higher than 54%, and kappa statistics ranged from slight to fair over time. Compared with the low-active group, the high-active group at baseline had a higher probability of being active later in adulthood. Female sex and higher age were associated directly with the initial number of steps per day and inversely with changes in the number of steps per day. Body mass index was inversely associated with the initial number of steps per day and changes in the number of total steps per day.

CONCLUSION: The 13-yr tracking of steps per day in adulthood was found to be low to moderately high. Daily ambulatory activity is essential to maintaining an active lifestyle throughout adulthood. Changes in the amount of adult steps per day vary by sex, age, and BMI.

PMID:34261992 | DOI:10.1249/MSS.0000000000002621

J Chin Med Assoc. 2021 Jul 13. doi: 10.1097/JCMA.0000000000000583. Online ahead of print.

ABSTRACT

BACKGROUND: Guyon’s canal syndrome is nerve compressive pathology which can lead to sensory and/or motor function deficits. This problem is usually difficult to distinguish from cubital tunnel syndrome and relatively less common than cubital tunnel syndrome. This study evaluated the functional results and patient-reported outcomes following decompression of the ulnar nerve in Guyon’s canal.

METHODS: Patients who were diagnosed with Guyon’s canal syndrome confirmed by electrodiagnostic studies and underwent nerve decompression surgery were included in this study. The functional improvement by examining the Froment’s sign, Wartenberg’s sign, static two-point discrimination, and Semmes Weinstein monofilament examination as physical examination scores was evaluated. The Visual Analog Scale (VAS) of satisfaction and the disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were used for the postoperative patient-reported outcome evaluation.

RESULTS: From 2003 to 2019, 38 cases had been enrolled with a mean age of 53 years, ranging from 19 to 85 years. There were seven patients with comorbidity of diabetes mellitus and 28 patients who received additional neurolysis combined with the Guyon’s release procedure. There were 19 patients with a good response to surgery and ten patients with a poor surgical outcome due to persistent paresthesia or weakness. After statistical analysis, it was revealed that several influential factors could have been related to a compromised functional outcome, including a symptom duration of more than three months, combination with additional neurolysis of ipsilateral extremity, and/or comorbidity with diabetes mellitus.

CONCLUSION: It was concluded that promising functional outcomes after surgical release of ulnar neuropathy in Guyon’s canal could be achieved if the patients did not need additional neurolysis or the symptom duration was within three months.

PMID:34261979 | DOI:10.1097/JCMA.0000000000000583