Category: Nevin Manimala

Sci Rep. 2022 Oct 26;12(1):17950. doi: 10.1038/s41598-022-22932-4.

ABSTRACT

People with type 1 diabetes have a substantially increased risk of premature death. This nationwide, register-based cohort study evaluated the significance of risk factors and previous cardiovascular disease (CVD), heart failure and chronic kidney disease (CKD), for mortality in type 1 diabetes. Nationwide, longitudinal, register-based cohort study. Patients (n = 36,303) listed in the Swedish National Diabetes Register between January 1 2015 and December 31 2017 were included and followed until December 31, 2018. Data were retrieved from national health registries through each patient’s unique identifier, to capture data on clinical characteristics, outcomes, or deaths, to describe mortality rates in risk groups. The mean follow-up time was 3.3 years, with 119,800 patient years of observation and 1127 deaths, corresponding to a crude overall mortality of 0.92% deaths/year. Statistically significant increased risk in multivariate analyzes was found in older age groups, in men, and in underweight or people with normal BMI, high HbA1c or blood pressure. A history of CVD, albuminuria and advanced stages of CKD was associated with an increased risk of mortality. Each combination of these conditions further increased the risk of mortality. These results emphasize the importance of risk factors and cardiovascular and renal diabetes complications. People with a combination of CKD, CVD, and heart failure, exhibit a markedly increased risk of dying prematurely. These findings provide strong arguments for optimized and individualized treatment of these groups of people with type 1 diabetes in clinical everyday life.

PMID:36289275 | DOI:10.1038/s41598-022-22932-4

Sci Rep. 2022 Oct 26;12(1):17945. doi: 10.1038/s41598-022-22994-4.

ABSTRACT

COVID-19 pandemic had a negative impact on the mental health and well-being (WB) of citizens. This cross-sectional study included 4 waves of data collection aimed at identifying profiles of individuals with different levels of WB. The study included a representative stratified sample of 10,013 respondents in Italy. The WHO 5-item well-being scale (WHO-5) was used for the assessment of WB. Different supervised machine learning approaches (multinomial logistic regression, partial least-square discriminant analysis-PLS-DA-, classification tree-CT-) were applied to identify individual characteristics with different WB scores, first in waves 1-2 and, subsequently, in waves 3 and 4. Forty-one percent of participants reported “Good WB”, 30% “Poor WB”, and 28% “Depression”. Findings carried out using multinomial logistic regression show that Resilience was the most important variable able for discriminating the WB across all waves. Through the PLS-DA, Increased Unhealthy Behaviours proved to be the more important feature in the first two waves, while Financial Situation gained most relevance in the last two. COVID-19 Perceived Risk was relevant, but less than the other variables, across all waves. Interestingly, using the CT we were able to establish a cut-off for Resilience (equal to 4.5) that discriminated good WB with a probability of 65% in wave 4. Concluding, we found that COVID-19 had negative implications for WB. Governments should support evidence-based strategies considering factors that influence WB (i.e., Resilience, Perceived Risk, Healthy Behaviours, and Financial Situation).

PMID:36289273 | DOI:10.1038/s41598-022-22994-4

Sci Rep. 2022 Oct 26;12(1):17936. doi: 10.1038/s41598-022-21761-9.

ABSTRACT

The U-series dating of young and ‘dirty’ speleothems is challenging due to difficulties in assessing the isotopic composition of detrital contaminants and the low-abundance of ²³⁰Th generated in situ. Here we propose a new dating approach based on the comparison of a speleothem’s paleomagnetic directions to reference curves from global paleomagnetic reconstructions. This approach is demonstrated on a stalagmite collected from the Soprador do Carvalho cave in the Central Region of Portugal. A radioisotopic age model, built using four U-series ages and three ¹⁴C, suggests relatively steady carbonate precipitation from ~ 5760 BCE until ~ 1920 CE. Forty-five 6 mm-thick subsamples were analyzed using alternating field and thermal demagnetization protocols, providing well-defined, primary magnetic directions. An age model of the stalagmite was obtained by fitting its paleomagnetic record with the reference paleosecular variation curves obtained by previous paleo-reconstruction models, applying statistical bootstrapping analysis to define their best fit. The resulting age models fit closely with the radioisotopic age model but provide a significantly higher time resolution. We reach the same conclusion when applying this approach to another stalagmite from the Algarve region of Portugal. Our approach thus appears a promising alternative to date young speleothems with high detrital contents.

PMID:36289261 | DOI:10.1038/s41598-022-21761-9

Sci Rep. 2022 Oct 26;12(1):17922. doi: 10.1038/s41598-022-19695-3.

ABSTRACT

Adult tendons are highly differentiated. In mature individuals, tendon healing after an injury occurs through fibrotic tissue formation. Understanding the intrinsic reparative properties of fetal tendons would help to understand the maturation tissue process and tendon tissue repair. The present study evaluated the evolution of histoarchitecture, cellularity and the distribution of collagens I, III and V in the posterior tibial tendon in human fetuses at different gestational ages. Morphological profiles were assessed in nine fresh spontaneously aborted fetuses (Group I: five fetuses aged between 22 and 28 weeks of gestation; Group II: four fetuses aged between 32 and 38 weeks of gestation), characterized by a combination of histology, fluorescence and immunohistochemistry. In Group I, the posterior tibial tendon showed statistically significant greater cellularity and presence of collagen III and V than in Group II tendon, which showed a predominance of collagenous I and a better organization of the extracellular matrix compared with Group I tendons. In addition, a statistically significant higher rate of CD90, a marker of mesenchymal cells, was found in Group I tendons. In fetuses with gestational age between 22 and 28 weeks, the posterior tibialis tendons showed a thin and disorganized fibrillar structure, with an increase in collagen III and V fibers and mesenchymal cells. In the posterior tibialis tendons of fetuses with gestational age between 32 and 38 weeks, the fibrillar structure was thicker with a statistically significant increase in type I collagen and decreased cellularity.

PMID:36289254 | DOI:10.1038/s41598-022-19695-3

Nat Commun. 2022 Oct 26;13(1):6369. doi: 10.1038/s41467-022-34122-x.

ABSTRACT

Volumetric defect types commonly observed in the additively manufactured parts differ in their morphologies ascribed to their formation mechanisms. Using high-resolution X-ray computed tomography, this study analyzes the morphological features of volumetric defects, and their statistical distribution, in laser powder bed fused Ti-6Al-4V. The geometries of three common types of volumetric defects; i.e., lack of fusions, gas-entrapped pores, and keyholes, are quantified by nine parameters including maximum dimension, roundness, sparseness, aspect ratio, and more. It is shown that the three defect types share overlaps of different degrees in the ranges of their morphological parameters; thus, employing only one or two parameters cannot uniquely determine a defect’s type. To overcome this challenge, a defect classification methodology incorporating multiple morphological parameters has been proposed. In this work, by employing the most discriminating parameters, this methodology has been shown effective when implemented into decision tree (>98% accuracy) and artificial neural network (>99% accuracy).

PMID:36289241 | DOI:10.1038/s41467-022-34122-x

Nat Commun. 2022 Oct 26;13(1):6380. doi: 10.1038/s41467-022-34002-4.

NO ABSTRACT

PMID:36289216 | DOI:10.1038/s41467-022-34002-4

Nat Commun. 2022 Oct 26;13(1):6360. doi: 10.1038/s41467-022-33870-0.

ABSTRACT

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies. We use primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number is associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC is statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway is independently observed in squamous lung cancer and triple negative breast cancer. In this work, we show that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.

PMID:36289203 | DOI:10.1038/s41467-022-33870-0

Blood Res. 2022 Oct 27. doi: 10.5045/br.2022.2022097. Online ahead of print.

ABSTRACT

BACKGROUND: The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation involves adding a methyl group to the carbon 5 position of cytosine. Besides comparing SOCS-1 gene methylation status between patients with multiple myeloma (MM) and healthy controls, this study also aimed to demonstrate the effect of SOCS-1 gene distribution and the effect of methylation of SOCS-1 on progression-free survival (PFS) and overall survival (OS).

MATERIALS AND METHODS: This study included 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals. The distribution of the SOCS-1 genotypes was statistically compared between MM patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined.

RESULTS: The CA/CA genotype of SOCS-1 was significantly higher in healthy controls (P=0.001), while the Del/Del genotype was significantly higher in patients with MM (P=0.034). The percent methylated reference (PMR) value of the SOCS-1 gene was significantly higher in the healthy controls (median, 43.48; range, 2.76-247.75; P=0.001). Patients with a PMR value of ≥43.48 were 3.125 times more likely to develop progression than those with a PMR value of <43.48.

CONCLUSION: The effects of SOCS-1 polymorphisms on the pathogenesis of MM and SOCS-1 methylation will further shed light on the pathophysiology of MM.

PMID:36289192 | DOI:10.5045/br.2022.2022097

Ther Innov Regul Sci. 2022 Oct 26. doi: 10.1007/s43441-022-00471-4. Online ahead of print.

ABSTRACT

The two trials paradigm plays a prominent role in drug development and has been widely and controversially discussed. Its purpose is to ensure replicability or substantiation of study results. This note investigates a simple generalization of the paradigm to more than two trials that preserves the project wise type-I error rate and power.

PMID:36289189 | DOI:10.1007/s43441-022-00471-4

Can J Anaesth. 2022 Oct 26. doi: 10.1007/s12630-022-02344-8. Online ahead of print.

ABSTRACT

PURPOSE: Awake tracheal intubation (ATI) is recommended in airway management guidelines when significant difficulty is predicted with airway management. Use of the technique may be declining, which may have implications for patient safety or for skills acquisition and maintenance. This historical cohort database study sought to determine if the use of ATI was decreasing in our adult tertiary care center.

METHODS: With institutional research ethics board approval, we queried our anesthesia information management system for cases with ATI descriptors for each year from 2014 to 2020. Records of the retrieved cases were independently reviewed by all three authors to verify they met inclusion criteria for the ATI cohort prior to analysis for the primary outcome. Secondary outcome measures included airway device and route used for ATI, first attempt and ultimate success rates, and reported adverse issues recorded in cases of failed ATI or those requiring more than one attempt.

RESULTS: A total of 692 cases of ATI were identified between 2014 and 2020. There was a statistically significant decrease in yearly ATIs over the seven-year study period (Chi square goodness of fit, P < 0.001), with ATI use decreasing by about 50%. First attempt success was significantly greater with use of flexible bronchoscopy vs video laryngoscopy to facilitate ATI (84% vs 60%; P < 0.001), while there was no difference in first attempt success with the oral vs nasal route (82% vs 82%; P = 1.0).

CONCLUSION: In this single-center historical cohort study, the use of ATI decreased significantly from 2014 to 2020. Whether this decrease will result in morbidity or mortality related to airway management is currently unclear. Regardless, it has implications for training opportunities and maintenance of competence in performing the procedure.

PMID:36289151 | DOI:10.1007/s12630-022-02344-8