Category: Statistics

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

Clin Exp Med. 2022 Oct 27. doi: 10.1007/s10238-022-00919-9. Online ahead of print.

ABSTRACT

The vitamin D receptor (VDR) is a nuclear transcription factor that acts as the main transducer in response to vitamin D (VD), regulating about 3% of the gene expression in the human genome. This study investigated the expression of VDR in the liver of patients with chronic hepatitis B virus (HBV) infection and determined its correlation with liver inflammation and fibrosis. We evaluated the effects of HBV infection on the expression of VDR in vivo and in vitro and further investigate the potential mechanism. Subsequently, the associations between hepatic VDR expression with liver inflammation and fibrosis were statistically analyzed. Results showed that hepatic VDR expression was significantly decreased in patients with chronic HBV infection as compared to healthy individuals. Similarly, in vitro experiments further confirmed that HBV infection could inhibit the expression of VDR in hepatocytes. Mechanistically, HBV was able to directly induce the expression of miR-125a which inhibited the mRNA and protein levels of VDR. Statistical analysis showed that hepatic VDR expression was significantly negatively correlated with liver inflammation and fibrosis in patients. We conclude that inhibition of hepatic vitamin D receptor expression by HBV/miR-125a is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection.

PMID:36289101 | DOI:10.1007/s10238-022-00919-9

Surg Endosc. 2022 Oct 26. doi: 10.1007/s00464-022-09712-x. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Surgical cholecystectomy is the gold standard strategy for the management of acute cholecystitis (AC). However, some patients are considered unfit for surgery due to certain comorbid conditions. As such, we aimed to compare less invasive treatment strategies such as endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) and percutaneous gallbladder drainage (PT-GBD) for the management of patients with AC who are suboptimal candidates for surgical cholecystectomy.

METHODS: A comprehensive search of multiple electronic databases was performed to identify all the studies comparing EUS-GBD versus PT-GBD for patients with AC who were unfit for surgery. A subgroup analysis was also performed for comparison of the group undergoing drainage via cautery-enhanced lumen-apposing metal stents (LAMS) versus PT-GBD. The outcomes included technical and clinical success, adverse events (AEs), recurrent cholecystitis, reintervention, and hospital readmission.

RESULTS: Eleven studies including 1155 patients were included in the statistical analysis. There was no difference between PT-GBD and EUS-GBD in all the evaluated outcomes. On the subgroup analysis, the endoscopic approach with cautery-enhanced LAMS was associated with lower rates of adverse events (RD = – 0.33 (95% CI – 0.52 to – 0.14; p = 0.0006), recurrent cholecystitis (- 0.05 RD (95% CI – 0.09 to – 0.02; p = 0.02), and hospital readmission (- 0.36 RD (95% CI-0.70 to – 0.03; p = 0.03) when compared to PT-GBD. All other outcomes were similar in the subgroup analyses.

CONCLUSIONS: EUS-GBD using cautery-enhanced LAMS is superior to PT-GBD in terms of safety profile, recurrent cholecystitis, and hospital readmission rates in the management of patients with acute cholecystitis who are suboptimal candidates for cholecystectomy. However, when cautery-enhanced LAMS are not used, the outcomes of EUS-GBD and PT-GBD are similar. Thus, EUS-GBD with cautery-enhanced LAMS should be considered the preferable approach for gallbladder drainage for this challenging population.

PMID:36289089 | DOI:10.1007/s00464-022-09712-x

Environ Manage. 2022 Oct 26. doi: 10.1007/s00267-022-01731-7. Online ahead of print.

ABSTRACT

Chromium (Cr) is a potentially toxic metal occurring in the soil as a result of natural and anthropogenic activities and is mainly found in Cr³⁺ and Cr⁶⁺. The hexavalent chromium has toxic effects on plants, animals, humans and microorganisms depending on exposure level, duration and doses. Biochar is a stable carbon-based material that has been widely documented to immobilize metals in contaminated soils and for soil remediation effectively. The present 90 days incubation study was conducted to investigate the potential use of rice stubble and sawdust-derived modified biochars on Cr⁶⁺ remediation and their effects on nutrient availability. Among the treatments, modified rice stubble biochar (RSB-M) contained the highest surface area, pore volume and CEC. The unmodified and modified biochars significantly increased soil pH, EC, CEC, and N, K availability ((p < 0.001)). Statistical analysis showed that modified rice stubble (RSB-M) and sawdust biochars (SDB-M) significantly reduced the Cr⁶⁺ with incubation days compared to unmodified biochars, possibly due to the greater porous structure and various functional groups. The submerged incubation condition also greatly impacted Cr⁶⁺ reduction since a gradual decrease (up to ~70 mg kg-1 of Cr⁶⁺) was observed in control treatments. Therefore, applying modified biochars is imperative to alleviate Cr⁶⁺ polluted soils and improve soil fertility.

PMID:36289071 | DOI:10.1007/s00267-022-01731-7