Category: Statistics

Bull Math Biol. 2021 Nov 27;84(1):8. doi: 10.1007/s11538-021-00968-3.

ABSTRACT

Kidney disease and renal disorders account for a significant proportion of health complications in mid-late adulthood worldwide. Many renal deficiencies are due to improper formation of the kidneys before birth, which are caused by disorders in the developmental process that arise from genetic and/or environmental factors. Mathematical modelling can help build on experimental knowledge to increase our understanding of the complexities of kidney organogenesis. In this paper, we present a discrete cell-based model of kidney development. Specifically, we model the tip of the developing ureteric tree to investigate the behaviours of cap mesenchyme cells which are required to sustain ureteric tip growth. We find that spatial regulation of the differentiation of cap mesenchyme cells through cellular signalling is sufficient to ensure robust ureteric tip development. Additionally, we find that increased adhesion interactions between cap mesenchyme cells and the ureteric tip surface can lead to a more stable tip-cap unit. Our analysis of the various processes on this scale highlights essential components for healthy kidney growth and provides insight into mechanisms to be studied further in order to replicate the process in vitro.

PMID:34837548 | DOI:10.1007/s11538-021-00968-3

Int J Biometeorol. 2021 Nov 27. doi: 10.1007/s00484-021-02225-7. Online ahead of print.

ABSTRACT

This study aimed to compare the peloid therapy and kinesio tape treatments in chronic lateral epicondylitis. While home exercise program and cold application were applied to the control group, peloid therapy (5 days a week for 3 weeks at 45 °C for 30 min each day, a total of 15 treatment days) was applied in addition to the first group, and kinesio taping (6 treatment days 2 times a week) was applied to the second group. Patients were evaluated with visual analog scale (VAS), grip strength with Jamar hydraulic dynamometer, Arm, Shoulder, and Hand Disabilities (DASH), quality of life in Short Form-36 (SF-36), and Patient-Rated Forearm Evaluation Questionnaire (PRFEQ) was recorded before treatment, after treatment (third week), and 1 month after the end of treatment. In this study, 156 patients with chronic lateral epicondylitis were included. In the follow-up of the patients, there was a statistically significant improvement in the hand grip strength, DASH, PRFEQ, VAS, and SF-36 scores in the 1st month follow-up after the treatment compared to the pre-treatment control in all groups (p < 0.001). At the end of the treatment, the hand grip strength (p = 0.002), DASH (p < 0.001), PRFEQ pain (p < 0.001) and function (p = 0.007), SF-36 physical health (p = 0.002) scores were statistically significant in the peloid therapy group compared to the control group. At the 1st month after the end of treatment, hand grip strength, VAS, DASH, PRFEQ pain, function, daily activities, and SF-36 physical health scores (all of p < 0.001) were statistically significant in the peloid treatment group compared to the control group. Peloid treatment was found to be more effective than kinesio taping in SF-36 physical health (p = 0.007) and PRFEQ pain (p = 0.003) scores in the 1st month follow-up after treatment. Peloid therapy in addition to exercise seems more effective in chronic lateral epicondylitis. Randomized controlled long-term studies are needed.ClinicalTrials ID: NCT04687943.

PMID:34837528 | DOI:10.1007/s00484-021-02225-7

J Cancer Res Clin Oncol. 2021 Nov 27. doi: 10.1007/s00432-021-03859-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Melanoma-associated antigen A2 (MAGE-A2) is a member of the cancer-testis antigen family differentially overexpressed in a variety of malignancies and is associated with tumor development. However, clinical significance and prognostic value of MAGE-A2 in different histological subtypes of testicular germ cell tumors (TGCTs) have not been explored.

MATERIALS AND METHODS: Here, we aimed to investigate the clinical significance and prognostic impact of MAGE-A2 expression in TGCTs compared to benign tumors as well as adjacent normal tissues and then between seminomas and non-seminomas groups using immunohistochemistry on tissue microarrays.

RESULTS: The results indicated a statistically significant difference between overexpression of MAGE-A2 and histological subtypes of TGCTs. A statistically significant association was found between a high level of nuclear expression of MAGE-A2 protein and advanced pT stage (P = 0.022), vascular invasion (P = 0.037), as well as involvement of rete testis (P = 0.022) in embryonal carcinomas. Increased nuclear expression of MAGE-A2 was observed to be associated with more aggressive behaviors and tumor progression rather than cytoplasmic expression in these cases. Further, high level nuclear expression of MAGE-A2 had shorter disease-specific survival (DSS) or progression-free survival (PFS) compared to patients with moderate and low expression of MAGE-A2, however, without a statistically significant association.

CONCLUSION: Our results confirm that increased nuclear expression of MAGE-A2 has a clinical significance in embryonal carcinomas and is associated with progression of disease. Moreover, MAGE-A2 may act as a potential predictive biomarker for the prognosis in embryonal carcinomas if follow-up period becomes longer. Further investigations for the biological function of MAGE-A2 are required in future studies.

PMID:34837545 | DOI:10.1007/s00432-021-03859-1

Graefes Arch Clin Exp Ophthalmol. 2021 Nov 27. doi: 10.1007/s00417-021-05314-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the long-term visual, refractive, tomographic, and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas.

METHODS: Charts of consecutive progressive keratoconus patients with thinnest corneal thickness less than 470 µm who underwent corneal collagen CXL with or without hypoosmolar riboflavin solution and using a standardized protocol for treatment and examinations were analyzed retrospectively. The indication for hypoosmolar riboflavin use was a central corneal thickness less than 400 µm as measured by ultrasound pachymetry after epithelial debridement and before exposure to ultraviolet A (UVA) light. Uncorrected distance visual acuity (UDVA), best spectacle-corrected distance visual acuity (CDVA), manifest refraction, slit lamp biomicroscopy, corneal tomography, corneal aberrometry, and endothelial cell counts were evaluated at baseline and yearly at all postoperative follow-up examinations until month 36. The outcomes of corneal CXL procedure performed using hypoosmolar riboflavin were compared to those performed using the standard procedure.

RESULTS: Twenty-three eyes (19 patients) were treated using hypoosmolar riboflavin application, and 30 eyes (28 patients) were treated using the standard procedure. Compared to baseline, the mean UDVA, CDVA, and keratometric readings improved statistically significantly in both groups at postoperative year 3, without any statistically significant between-group differences. Progression was not observed in any patient eye in either group. No significant endothelial cell loss and no sight threating complication were observed in any patient eye.

CONCLUSION: At 3 years follow-up, the safety and efficacy of CXL using hypoosmolar riboflavin solution seems to be similar to that of standard CXL in progressive keratoconic eyes with thin corneas. The visual, refractive, keratometric, tomographic and aberrometric outcomes of the two procedures were comparable, as well.

PMID:34837507 | DOI:10.1007/s00417-021-05314-w

Liver Transpl. 2021 Nov 27. doi: 10.1002/lt.26379. Online ahead of print.

ABSTRACT

BACKGROUND: Biliary strictures affect 4-12% of pediatric liver transplants (P-LT). Biliary strictures can contribute to graft loss if left untreated, however there remains no consensus on the best course of treatment. Study objectives included analyses of outcomes associated with biliary stricture management strategies via PTC, ERCP or surgery.

METHODS: We identified P-LT recipients (2011-2016) with biliary strictures from the Society of Pediatric Liver Transplantation (SPLIT) registry and retrieved imaging, procedural and operative reports from individual centers. Sub-analyses were performed to specifically evaluate PTC and ERCP for “Optimal Biliary Outcome” (OBO), defined as survival with stricture resolution without recurrence or surgery.

RESULTS: 113 children with median 3.9 years of follow-up had strictures diagnosed 100 days (IQR 30, 290) post LT; 81% were isolated anastomotic strictures. Stricture resolution was achieved in 92% within 101 days, more frequently with isolated anastomotic strictures (96%). 20% of strictures recurred, more commonly in association with hepatic artery thrombosis (32%). Patient and graft survival at 1- and 3-years were 99%, 98% and 94%, 92% respectively. In a subgroup analysis of 79 patients with extrahepatic strictures managed by PTC/ERCP: 59% achieved OBO following a median 4 PTC, and 75% following a median 3 ERCP (P=0.0003). Among patients with OBO, those with ERCP had longer time intervals between successive procedures (41, 47, 54, 62, 71 days) than for PTC (27, 31, 36, 41, 48 days; P=0.0006).

CONCLUSIONS: Allograft salvage was successful across all interventions. Stricture resolution was achieved in 92%, with 20% risk of recurrence. Resolution without recurrence was highest in patients with isolated anastomotic strictures and without HAT.

PMID:34837468 | DOI:10.1002/lt.26379

Horm Mol Biol Clin Investig. 2021 Nov 26. doi: 10.1515/hmbci-2021-0039. Online ahead of print.

ABSTRACT

OBJECTIVES: Studies have established a relationship between proinflammatory factors and implantation failure in IVF/ICSI cycles. Likewise, low-grade chronic inflammation is generally blamed for predisposing infertility. In the present study, we aimed to find a relationship between serum IL-6 and hs-CRP levels and IVF/ICSI cycle outcomes.

METHODS: A total of 129 patients who consented to participate and attended the IVF unit of our department for the treatment of infertility have been enrolled in this prospective cohort study. Serum levels of high sensitive C-reactive protein and interleukin 6 have been detected at the beginning of the IVF/ICSI ovulation induction cycle. Cycle outcomes have been compared between patients with and without clinical pregnancy achievement following ART treatments. IVF/ICSI cycle outcomes of these two groups were also comparable except the number of >14 mm follicles, retrieved oocytes, metaphase II oocytes, and fertilized oocytes (2 pronuclei) which were in favor of the clinical pregnancy group.

RESULTS: Mean serum hs-CRP levels were 3.08 mg/L (0.12-35.04) and 2.28 mg/L (0.09-22.52) patients with and without clinical pregnancy respectively. Mean serum IL-6 levels were 2 pg/mL (1-10.2) and 2 pg/mL (1-76.9) patients with and without clinical pregnancy respectively. Both tests were found to be statistically insignificant in predicting the success of the ART cycle in terms of implantation, clinical pregnancy, miscarriage, and live birth.

CONCLUSIONS: In the present study, we have not found any significant effect of hs-CRP and IL-6 levels in the IVF cycle. However, in the light of this and previous studies, large-scale research may prove the exact influence of these markers on IVF success.

PMID:34837488 | DOI:10.1515/hmbci-2021-0039

Mol Ecol Resour. 2021 Nov 27. doi: 10.1111/1755-0998.13557. Online ahead of print.

ABSTRACT

By capturing various patterns of the structuring of genetic variation across populations, f -statistics have proved highly effective for the inference of demographic history. Such statistics are defined as covariance of SNP allele frequency differences among sets of populations without requiring haplotype information and are hence particularly relevant for the analysis of pooled sequencing (Pool-Seq) data. We here propose a reinterpretation of the F (and D) parameters in terms of probability of gene identity and derive from this unified definition unbiased estimators for both Pool-Seq data and standard allele count data obtained from individual genotypes. We implemented these estimators in a new version of the R package poolfstat, which now includes a wide range of inference methods: (i) three-population test of admixture; (ii) four-population test of treeness; (iii) F4-ratio estimation of admixture rates; and (iv) fitting, visualization and (semi-automatic) construction of admixture graphs. A comprehensive evaluation of the methods implemented in poolfstat on both simulated Pool-Seq (with various sequencing coverages and error rates) and allele count data confirmed the accuracy of these approaches, even for the most cost-effective Pool-Seq design involving relatively low sequencing coverages. We further analyzed a real Pool-Seq data made of 14 populations of the invasive species Drosophila suzukii which allowed refining both the demographic history of native populations and the invasion routes followed by this emblematic pest. Our new package poolfstat provides the community with a user-friendly and efficient all-in-one tool to unravel complex population genetic histories from large-size Pool-Seq or allele count SNP data.

PMID:34837462 | DOI:10.1111/1755-0998.13557

Nat Rev Genet. 2021 Nov 26. doi: 10.1038/s41576-021-00434-9. Online ahead of print.

ABSTRACT

The scale of genetic, epigenomic, transcriptomic, cheminformatic and proteomic data available today, coupled with easy-to-use machine learning (ML) toolkits, has propelled the application of supervised learning in genomics research. However, the assumptions behind the statistical models and performance evaluations in ML software frequently are not met in biological systems. In this Review, we illustrate the impact of several common pitfalls encountered when applying supervised ML in genomics. We explore how the structure of genomics data can bias performance evaluations and predictions. To address the challenges associated with applying cutting-edge ML methods to genomics, we describe solutions and appropriate use cases where ML modelling shows great potential.

PMID:34837041 | DOI:10.1038/s41576-021-00434-9

Br J Cancer. 2021 Nov 26. doi: 10.1038/s41416-021-01641-1. Online ahead of print.

ABSTRACT

BACKGROUND: Aberrant activation of androgen receptor signalling following castration therapy is a common clinical observation in prostate cancer (PCa). Earlier, we demonstrated the role of MYB overexpression in androgen-depletion resistance and PCa aggressiveness. Here, we investigated MYB-androgen receptor (AR) crosstalk and its functional significance.

METHODS: Interaction and co-localization of MYB and AR were examined by co-immunoprecipitation and immunofluorescence analyses, respectively. Protein levels were measured by immunoblot analysis and enzyme-linked immunosorbent assay. The role of MYB in ligand-independent AR transcriptional activity and combinatorial gene regulation was studied by promoter-reporter and chromatin immunoprecipitation assays. The functional significance of MYB in castration resistance was determined using an orthotopic mouse model.

RESULTS: MYB and AR interact and co-localize in the PCa cells. MYB-overexpressing PCa cells retain AR in the nucleus even when cultured under androgen-deprived conditions. AR transcriptional activity is also sustained in MYB-overexpressing cells in the absence of androgens. MYB binds and promotes AR occupancy to the KLK3 promoter. MYB-overexpressing PCa cells exhibit greater tumorigenicity when implanted orthotopically and quickly regain growth following castration leading to shorter mice survival, compared to those carrying low-MYB-expressing prostate tumours.

CONCLUSIONS: Our findings reveal a novel MYB-AR crosstalk in PCa and establish its role in castration resistance.

PMID:34837075 | DOI:10.1038/s41416-021-01641-1

Sci Rep. 2021 Nov 26;11(1):23023. doi: 10.1038/s41598-021-02548-w.

ABSTRACT

SARS-CoV-2 (CoV) is the etiological agent of the COVID-19 pandemic and evolves to evade both host immune systems and intervention strategies. We divided the CoV genome into 29 constituent regions and applied novel analytical approaches to identify associations between CoV genomic features and epidemiological metadata. Our results show that nonstructural protein 3 (nsp3) and Spike protein (S) have the highest variation and greatest correlation with the viral whole-genome variation. S protein variation is correlated with nsp3, nsp6, and 3′-to-5′ exonuclease variation. Country of origin and time since the start of the pandemic were the most influential metadata associated with genomic variation, while host sex and age were the least influential. We define a novel statistic-coherence-and show its utility in identifying geographic regions (populations) with unusually high (many new variants) or low (isolated) viral phylogenetic diversity. Interestingly, at both global and regional scales, we identify geographic locations with high coherence neighboring regions of low coherence; this emphasizes the utility of this metric to inform public health measures for disease spread. Our results provide a direction to prioritize genes associated with outcome predictors (e.g., health, therapeutic, and vaccine outcomes) and to improve DNA tests for predicting disease status.

PMID:34837008 | DOI:10.1038/s41598-021-02548-w