Nevin Manimala

Mol Ecol Resour. 2023 Aug 14. doi: 10.1111/1755-0998.13856. Online ahead of print.

ABSTRACT

Hardy-Weinberg proportions (HWP) are often explored to evaluate the assumption of random mating. However, in autopolyploids, organisms with more than two sets of homologous chromosomes, HWP and random mating are different hypotheses that require different statistical testing approaches. Currently, the only available methods to test for random mating in autopolyploids (i) heavily rely on asymptotic approximations and (ii) assume genotypes are known, ignoring genotype uncertainty. Furthermore, these approaches are all frequentist, and so do not carry the benefits of Bayesian analysis, including ease of interpretability, incorporation of prior information, and consistency under the null. Here, we present Bayesian approaches to test for random mating, bringing the benefits of Bayesian analysis to this problem. Our Bayesian methods also (i) do not rely on asymptotic approximations, being appropriate for small sample sizes, and (ii) optionally account for genotype uncertainty via genotype likelihoods. We validate our methods in simulations and demonstrate on two real datasets how testing for random mating is more useful for detecting genotyping errors than testing for HWP (in a natural population) and testing for Mendelian segregation (in an experimental S1 population). Our methods are implemented in Version 2.0.2 of the hwep R package on the Comprehensive R Archive Network https://cran.r-project.org/package=hwep.

PMID:37578636 | DOI:10.1111/1755-0998.13856

Handb Exp Pharmacol. 2023 Aug 15. doi: 10.1007/164_2023_676. Online ahead of print.

ABSTRACT

Adrenoceptors are class A G-protein-coupled receptors grouped into three families (α₁-, α₂-, and β-adrenoceptors), each one including three members. All nine corresponding adrenoceptor genes display genetic variation in their coding and adjacent non-coding genomic region. Coding variants, i.e., nucleotide exchanges within the transcribed and translated receptor sequence, may result in a difference in amino acid sequence thus altering receptor function and signaling. Such variants have been intensely studied in vitro in overexpression systems and addressed in candidate-gene studies for distinct clinical parameters. In recent years, large cohorts were analyzed in genome-wide association studies (GWAS), where variants are detected as significant in context with specific traits. These studies identified two of the in-depth characterized 18 coding variants in adrenoceptors as repeatedly statistically significant genetic risk factors – p.Arg389Gly in the β₁– and p.Thr164Ile in the β₂-adrenoceptor, along with 56 variants in the non-coding regions adjacent to the adrenoceptor gene loci, the functional role of which is largely unknown at present. This chapter summarizes current knowledge on the two coding variants in adrenoceptors that have been consistently validated in GWAS and provides a prospective overview on the numerous non-coding variants more recently attributed to adrenoceptor gene loci.

PMID:37578621 | DOI:10.1007/164_2023_676

Indian J Pediatr. 2023 Aug 14. doi: 10.1007/s12098-023-04756-w. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the effect of splint on the functional duration of peripheral intravenous cannula (PIVC) in neonates.

METHODS: The trial was prospectively registered with the Clinical Trial Registry of India (CTRI/2021/09/036337). One-hundred-fifty cannulations in 71 neonates were randomized to splint (n = 75) and no-splint (n = 75) groups, respectively. The median (interquartile range, IQR) functional duration of PIVC was calculated from the time of PIVC insertion till removal due to the development of signs of PIVC failure or treatment completion. Kaplan-Meier survival analysis was used to compute the time to complication of PIVC. Complications related to PIVC were noted and multivariate Cox-proportion hazard analysis was done to find the predictors associated with PIVC failure.

RESULTS: Median (IQR) functional duration of PIVC in the splint and the no-splint group was 28 (23-48) and 30 (25-48) h, respectively (p = 0.477). PIVC duration was higher in the splint group in term neonates and the no-splint group in preterm neonates; however, the differences were not statistically significant. No difference was observed in continuous vs. intermittent infusion subgroups. Time to complication development was also comparable between the groups.

CONCLUSIONS: Splint application did not affect functional PIVC duration and its related complications in neonates.

PMID:37578610 | DOI:10.1007/s12098-023-04756-w

Environ Sci Pollut Res Int. 2023 Aug 14. doi: 10.1007/s11356-023-29121-4. Online ahead of print.

ABSTRACT

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. Metal exposure is an emerging factor affecting the risk of GDM. However, the effects of metal mixture on GDM and key metals within the mixture remain unclear. This study was aimed at investigating the association between metal mixture during early pregnancy and the risk of GDM using four statistical methods and further at identifying the key metals within the mixture associated with GDM. A nested case-control study including 128 GDM cases and 318 controls was conducted in Beijing, China. Urine samples were collected before 13 gestational weeks and the concentrations of 13 metals were measured. Single-metal analysis (unconditional logistic regression) and mixture analyses (Bayesian kernel machine regression (BKMR), quantile g-computation, and elastic-net regression (ENET) models) were applied to estimate the associations between exposure to multiple metals and GDM. Single-metal analysis showed that Ni was associated with lower risk of GDM, while positive associations of Sr and Sb with GDM were observed. Compared with the lowest quartile of Ni, the ORs of GDM in the highest quartiles were 0.49 (95% CI 0.24, 0.98). In mixture analyses, Ni and Mg showed negative associations with GDM, while Co and Sb were positively associated with GDM in BKMR and quantile g-computation models. No significant joint effect of metal mixture on GDM was observed. However, interestingly, Ni was identified as a key metal within the mixture associated with decreased risk of GDM by all three mixture methods. Our study emphasized that metal exposure during early pregnancy was associated with GDM, and Ni might have important association with decreased GDM risk.

PMID:37578585 | DOI:10.1007/s11356-023-29121-4

Environ Geochem Health. 2023 Aug 14. doi: 10.1007/s10653-023-01725-2. Online ahead of print.

ABSTRACT

Human populations are being exposed to a wide spectrum of radiation from soils as a result of the availability of radiation sources. Assessing the ecological and health effects of radionuclides in soils is crucial to support the optimal soil management practices but large-scale studies are limited. This study compiled data on radionuclides (²²⁶Ra, ²³²Th, ⁴⁰K, ²³⁸U, and ¹³⁷Cs) in soils located across the world (44 countries and 159 places) between 2008 and 2022 and applied radiological hazards indices and several multivariate statistical approaches. The average activity concentration (Bq/kg) of ²²⁶Ra, ²³²Th, ⁴⁰K, ²³⁸U, and ¹³⁷Cs were 408.56, 144.80, 508.78, 532.78, and 83.12, respectively, whereas ²²⁶Ra, ²³²Th, ⁴⁰K, and ²³⁸U exceeded the standard limits. The principal component analysis explained more than 91% of variation in soils. Based on the geoaccumulation index, ⁴⁰K posed moderately to heavy contamination whereas ²³⁸U and ²²⁶Ra posed moderate contamination in soils. Moreover, the mean values of radiological hazards evaluation such as radium equivalent activity (487.17 Bq/kg), external radiation hazard indices (1.32), internal hazard indices (2.15), absorbed dose rate (247.86 nGyh^-1), annual effective dose rate (1.82 mSvy^-1), activity utilization index (4.54) and excess lifetime cancer risk (63.84 × 10^-4) were higher than recommended limit suggesting significant radiological risks in study region soils. The findings indicated that the study area soils were contaminated by radionuclides and unsafe for hazards in terms of the health risks linked with studied radioactive contents. The study is valuable for mapping radioactivity across the globe to determine the level of radioactivity hazards.

PMID:37578560 | DOI:10.1007/s10653-023-01725-2

Int J Colorectal Dis. 2023 Aug 14;38(1):213. doi: 10.1007/s00384-023-04510-w.

ABSTRACT

BACKGROUND: Numerous factors influence healthcare resource utilization (HRU) in inflammatory bowel disease (IBD). We previously demonstrated an association between the presence of certain IBD-related symptoms and HRU. We conducted a longitudinal study to identify the clinical variables and IBD-related symptoms predictive of HRU.

METHODS: This investigation utilized clinical encounters at an IBD center within a tertiary care referral center between 10/29/2015-12/31/2019. Participants were assessed over two time points (index and follow-up office visits) separated by a minimum of 6 months. Demographics, endoscopic disease severity, totals and sub-scores of surveys assessing for IBD-related symptoms, HRU, and substance use, and IBD-related medications. HRU was defined as any IBD-related emergency room visit, hospitalization, or surgery during the 6 months prior to follow-up appointment. We identified patients exhibiting HRU (at follow-up) and computed descriptive statistics and contingency table analyses of index appointment clinical data to identify predictors of HRU. Multivariable logistic regression models were fit incorporating significant demographic and clinical factors.

RESULTS: 162 consecutively enrolled IBD patients (mean age 44.0 years; 99f:63 m; 115 Crohn’s disease [CD], 45 ulcerative colitis [UC], 2 indeterminate colitis) were included. 121 patients (74.7%) exhibited HRU (mean age 43.6 years; 73f:48 m; 84 CD, 36 UC, 1 IC) preceding follow-up appointment. Abdominal pain (OR = 2.18, 95% CI 1.04-4.35, p = 0.04) at the index appointment was the only study variable significantly associated with HRU on bivariate analysis (Table 1). However, none of the clinical factors evaluated in this study were independently associated with HRU in our multivariable logistic regression model.

CONCLUSIONS: In this longitudinal study, abdominal pain was the only clinical variable that demonstrated an association with future HRU (even when considering other symptoms and key variables such as disease activity, IBD-medications, and psychiatric comorbidities (i.e., anxious or depressed state). These findings reinforce the importance of regularly screening for and effectively treating abdominal pain in IBD.

PMID:37578543 | DOI:10.1007/s00384-023-04510-w

Eur J Appl Physiol. 2023 Aug 14. doi: 10.1007/s00421-023-05296-z. Online ahead of print.

ABSTRACT

PURPOSE: Physical activity (PA) and body fat percentage (%BF) are independently associated with arterial stiffness, but it has not been explored if there is an associative pathway among these variables. This study examined whether %BF mediates the relationship between PA or sedentary behavior levels with arterial stiffness.

METHODS: Fifty adults (1:1 men:women; age 28 ± 11 year) had carotid-femoral pulse wave velocity (CF-PWV) measured by applanation tonometry, %BF by bioelectrical impedance, and PA levels by accelerometry. Accelerometer data determined minutes per day spent in sedentary, light, moderate-to-vigorous physical activity (MVPA), and Total PA.

RESULTS: Pearson correlation indicated statistically significant associations among age, %BF, CF-PWV, MVPA, and Total PA (r = 0.34-0.65, p < 0.05). Sedentary and light PA were not associated with CF-PWV. Mediation analysis indicated significant total effects of MVPA (β = – 0.34, p = 0.044) and age (β = 0.65, p < 0.001) on CF-PWV. %BF mediated the relationship between Total PA and CF-PWV due to indirect effect of Total PA on %BF (β = – 0.34, p = 0.02) and %BF on CF-PWV (β = 0.44, p = 0.002), and partially mediated the relationship between age and CF-PWV (β = 0.54, p < 0.001). Total PA retained its significant effect on %BF (β = – 0.28, p = 0.04) and the effect of %BF on CF-PWV remained significant (β = 0.26, p = 0.03), despite age having a significant effect on both %BF (β = 0.31, p = 0.023) and CF-PWV (β = 0.54, p < 0.001).

CONCLUSIONS: %BF mediated the relationship between Total PA and arterial stiffness, even after accounting for age. Engagement in more Total PA may help to reduce %BF, resulting in decreased arterial stiffness.

PMID:37578537 | DOI:10.1007/s00421-023-05296-z

Langenbecks Arch Surg. 2023 Aug 14;408(1):307. doi: 10.1007/s00423-023-03059-0.

ABSTRACT

PURPOSE: During the COVID-19 pandemic, the new RCSEng guidelines resulted in appendicitis being more commonly managed conservatively to avoid aerosol-generating procedures. This resulted in shorter hospital stays without increased short-term complications. The 2-year outcomes of this change, specifically recurrence and re-admission rates remain unknown.

METHODS: We conducted a multicentre, prospective, observational study including all adult patients treated as appendicitis after the implementation of the new surgical guidelines during the COVID-19 pandemic. Outcomes included initial management failure, re-admission rate, appendicitis recurrence, and interval appendicectomy. A historical cohort prior to the COVID-19 pandemic was used for comparison. Patients were followed up for 2-years post index admission. Categorical and continuous variables were compared using Fisher’s exact test and Student’s T or Mann-Whitney U tests as appropriate.

RESULTS: Sixty-three and 79 patients with appendicitis were included from four NHS trusts, before (A) and after (B) the new intercollegiate guidelines respectively. Operative management was used less frequently in cohort B (28/79 vs 52/63; p<0.001). More patients re-presented in cohort B (14/79 vs 3/63; p=0.020), but not when comparing only those managed conservatively (2/11 vs 13/52; p=1.000). A similar trend was observed for appendicitis recurrence although without statistical significance (2/63 vs 9/79; p=0.112); with loss of trend when comparing those managed conservatively-only (2/11 vs 9/52; p=1.000). Among all patients, four (2.8%) were found to have underlying neoplasia of which three were initially managed conservatively (3/63; 4.8%).

CONCLUSION: Conservative management of appendicitis has previously been shown to have short-term benefits in expedited hospital discharge without early complications. The present study shows it has a higher readmission and appendicitis recurrence rates. The risks of this alongside missed/delayed management of neoplasia needs to be considered alongside the benefits including avoidance of aerosol-generating general anaesthesia and laparoscopy during the COVID-19 pandemic or similar future health crises. Small case numbers limit analysis.

PMID:37578533 | DOI:10.1007/s00423-023-03059-0

Surg Radiol Anat. 2023 Aug 14. doi: 10.1007/s00276-023-03215-7. Online ahead of print.

ABSTRACT

PURPOSE: This retrospective study aimed to determine the prevalence and morphological characteristics of accessory mandibular canals (AMCs) in an eastern Chinese population to provide clinical guidance for reducing intraoperative and postoperative complications.

METHODS: Cone beam computed tomography (CBCT) scans of 300 Chinese patients were used to identify AMCs according to a modification of Naitoh’s classification. The length of the branch (L0) and the upper and lower angles between the branch and mandibular canal were measured on sagittal images. Additionally, the branches were divided into narrow or wide types by calculating the ratio of the branch diameter to the main canal diameter. The location of the bifurcation point was characterized by measuring its distance to the buccal wall of the mandible (L1), lingual wall of the mandible (L2) and alveolar ridge (L3).

RESULTS: The prevalence rate of AMCs was 40.7% (95% CI: 35.1-46.3), and the most common type was the retromolar canal, followed by the forward canal, dental canal, trifid mandibular canals (TMCs) or others, inferior canal and buccolingual canal. Twenty-one cases of multiple branches with unusual patterns were observed in the study. The average values of L0, L1, L2 and L3 were 15.05 ± 0.63 mm, 5.79 ± 0.14 mm, 4.40 ± 0.18 mm and 14.61 ± 0.31 mm, respectively. The mean upper angle and lower angle were 141.59° ± 2.44° and 50.64° ± 2.57°, respectively. Approximately 20.8% of the branches were defined as wide type, and no statistical significance was found between different types.

CONCLUSION: AMCs are not rare anatomic variations of the mandibular canal in the eastern Chinese population; thus, CBCT examination is highly recommended for precise evaluation before surgeries involving the mandibles.

PMID:37578527 | DOI:10.1007/s00276-023-03215-7

Int J Surg. 2023 Aug 14. doi: 10.1097/JS9.0000000000000636. Online ahead of print.

ABSTRACT

BACKGROUND: The value of existing prognostic models for intrahepatic cholangiocarcinoma (ICC) is limited. The inclusion of prognostic gene mutations would enhance the predictive efficacy.

METHODS: In the screening cohorts, univariable Cox regression analysis was applied to investigate the effect of individual mutant genes on overall survival (OS). In the training set, multivariable analysis was performed to evaluate the independent prognostic roles of the clinicopathological and mutational parameters, and a prognostic model was constructed. Internal and external validations were conducted to evaluate the performance of this model.

RESULTS: Among the recurrent mutations, only TP53 and KRASG12 were significantly associated with OS across all three screening cohorts. In the training cohort, TP53 and KRASG12 mutations in combination with seven other clinical parameters (tumor size, tumor number, vascular invasion, lymph node metastasis, adjacent invasion, CA19-9, and CEA), were independent prognostic factors for OS. A mutation-annotated prognostic score (MAPS) was established based on the nine prognosticators. The C-indices of MAPS (0.782 and 0.731 in the internal and external validation cohorts, respectively) were statistically higher than those of other existing models (P<0.05). Furthermore, the MAPS model also demonstrated significant value in predicting the possible benefits of upfront surgery and adjuvant therapy.

CONCLUSIONS: The MAPS model demonstrated good performance in predicting OS of ICC patients. It may also help predict the possible benefits of upfront surgery and adjuvant therapy.

PMID:37578492 | DOI:10.1097/JS9.0000000000000636