Tag: pubmed

Clin Chem. 2022 Jan 14:hvab274. doi: 10.1093/clinchem/hvab274. Online ahead of print.

ABSTRACT

BACKGROUND: Droplet digital PCR (ddPCR) is a widely used and sensitive application for circulating tumor DNA (ctDNA) detection. As ctDNA is often found in low abundance, methods to separate low-signal readouts from noise are necessary. We aimed to characterize the ddPCR-generated noise and, informed by this, create a sensitive and specific ctDNA caller.

METHODS: We built 2 novel complimentary ctDNA calling methods: dynamic limit of blank and concentration and assay-specific tumor load estimator (CASTLE). Both methods are informed by empirically established assay-specific noise profiles. Here, we characterized noise for 70 mutation-detecting ddPCR assays by applying each assay to 95 nonmutated samples. Using these profiles, the performance of the 2 new methods was assessed in a total of 9447 negative/positive reference samples and in 1311 real-life plasma samples from colorectal cancer patients. Lastly, performances were compared to 7 literature-established calling methods.

RESULTS: For many assays, noise increased proportionally with the DNA input amount. Assays targeting transition base changes were more error-prone than transversion-targeting assays. Both our calling methods successfully accounted for the additional noise in transition assays and showed consistently high performance regardless of DNA input amount. Calling methods that were not noise-informed performed less well than noise-informed methods. CASTLE was the only calling method providing a statistical estimate of the noise-corrected mutation level and call certainty.

CONCLUSIONS: Accurate error modeling is necessary for sensitive and specific ctDNA detection by ddPCR. Accounting for DNA input amounts ensures specific detection regardless of the sample-specific DNA concentration. Our results demonstrate CASTLE as a powerful tool for ctDNA calling using ddPCR.

PMID:35030248 | DOI:10.1093/clinchem/hvab274

PLoS One. 2022 Jan 14;17(1):e0262584. doi: 10.1371/journal.pone.0262584. eCollection 2022.

ABSTRACT

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4-28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5-1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103-14 × 103]) compared to horses (4 × 102 [2 × 102-7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43-2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57-7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43-116]) compared to foals (23.2% [17.8-42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

PMID:35030228 | DOI:10.1371/journal.pone.0262584

Am J Clin Nutr. 2022 Jan 14:nqab422. doi: 10.1093/ajcn/nqab422. Online ahead of print.

ABSTRACT

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children.

OBJECTIVES: We evaluated the relationship of VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort.

METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z-scores]; serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)]; and inflammation defined as C-reactive protein (CRP ≥ 5 mg/L) and/or α1-acid glycoprotein (AGP ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. (Registered at Clinicaltrials.gov NCT02915731).

RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001) while formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each timepoint was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements.

CONCLUSIONS: Excessive TLRs due to dietary vitamin A intake and supplementation is associated with lower anthropometric measures and bone resorption decreased after supplementation. Vitamin A supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A.The Clinical Trial Registry number is NCT02915731: https://clinicaltrials.gov/ct2/show/NCT02915731.

PMID:35030234 | DOI:10.1093/ajcn/nqab422

PLoS One. 2022 Jan 14;17(1):e0262425. doi: 10.1371/journal.pone.0262425. eCollection 2022.

ABSTRACT

In this study, we examined the total bacterial community associated with ureolytic biomineralization from urine drainage systems. Biomineral samples were obtained from 11 California Department of Transportation public restrooms fitted with waterless, low-flow, or conventional urinals in 2019. Following high throughput 16S rRNA Illumina sequences processed using the DADA2 pipeline, the microbial diversity assessment of 169 biomineral and urine samples resulted in 3,869 reference sequences aggregated as 598 operational taxonomic units (OTUs). Using PERMANOVA testing, we found strong, significant differences between biomineral samples grouped by intrasystem sampling location and urinal type. Biomineral microbial community profiles and alpha diversities differed significantly when controlling for sampling season. Observational statistics revealed that biomineral samples obtained from waterless urinals contained the largest ureC/16S gene copy ratios and were the least diverse urinal type in terms of Shannon indices. Waterless urinal biomineral samples were largely dominated by the Bacilli class (86.1%) compared to low-flow (41.3%) and conventional samples (20.5%), and had the fewest genera that account for less than 2.5% relative abundance per OTU. Our findings are useful for future microbial ecology studies of urine source-separation technologies, as we have established a comparative basis using a large sample size and study area.

PMID:35030221 | DOI:10.1371/journal.pone.0262425

PLoS One. 2022 Jan 14;17(1):e0262407. doi: 10.1371/journal.pone.0262407. eCollection 2022.

ABSTRACT

Prior research has suggested that a set of unique characteristics may be associated with adult cigarette smokers who are able to quit smoking using e-cigarettes (vaping). In this cross-sectional study, we aimed to identify and rank the importance of these characteristics using machine learning. During July and August 2019, an online survey was administered to a convenience sample of 889 adult smokers (age ≥ 20) in Ontario, Canada who tried vaping to quit smoking in the past 12 months. Fifty-one person-level characteristics, including a Vaping Experiences Score, were assessed in a gradient boosting machine model to classify the status of perceived success in vaping-assisted smoking cessation. This model was trained using cross-validation and tested using the receiver operating characteristic (ROC) curve. The top five most important predictors were identified using a score between 0% and 100% that represented the relative importance of each variable in model training. About 20% of participants (N = 174, 19.6%) reported success in vaping-assisted smoking cessation. The model achieved relatively high performance with an area under the ROC curve of 0.865 and classification accuracy of 0.831 (95% CI [confidence interval] 0.780 to 0.874). The top five most important predictors of perceived success in vaping-assisted smoking cessation were more positive experiences measured by the Vaping Experiences Score (100%), less previously failed quit attempts by vaping (39.0%), younger age (21.9%), having vaped 100 times (16.8%), and vaping shortly after waking up (15.8%). Our findings provide strong statistical evidence that shows better vaping experiences are associated with greater perceived success in smoking cessation by vaping. Furthermore, our study confirmed the strength of machine learning techniques in vaping-related outcomes research based on observational data.

PMID:35030208 | DOI:10.1371/journal.pone.0262407

PLoS One. 2022 Jan 14;17(1):e0262431. doi: 10.1371/journal.pone.0262431. eCollection 2022.

ABSTRACT

BACKGROUND: Modern contraceptive method is a product or medical procedure that interferes with reproduction from acts of sexual intercourse. Globally in 2019, 44% of women of reproductive age were using a modern method of contraception but it was 29% in sub-Saharan Africa. Therefore, the main aim of this analysis was to assess the prevalence of modern contraceptive utilization and associated factors among married women in Ethiopia.

METHOD: The current study used the 2019 Ethiopia mini demographic and health survey dataset. Both descriptive and multilevel mixed-effect logistic regression analysis were done using STATA version 14. A p-value of less than 0.05 and an adjusted odds ratio with a 95% confidence interval were used to report statistically significant factors with modern contraceptive utilization.

RESULT: The overall modern contraceptive utilization among married women in Ethiopia was 38.7% (95% CI: 37.3% to 40.0%). Among the modern contraceptive methods, injectables were the most widely utilized modern contraceptive method (22.82%) followed by implants (9.65%) and pills (2.71%). Maternal age, educational level, wealth index, number of living children, number of births in the last three years, number of under 5 children in the household, religion, and geographic region were independent predictors of modern contraceptive utilization.

CONCLUSION: In the current study only four out of ten married non-pregnant women of reproductive age utilized modern contraceptive methods. Furthermore, the study has identified both individual and community-level factors that can affect the utilization of modern contraceptive methods by married women in the country. Therefore, concerned bodies need to improve access to reproductive health services, empower women through community-based approaches, and minimize region wise discrepancy to optimize the utilization.

PMID:35030213 | DOI:10.1371/journal.pone.0262431

PLoS One. 2022 Jan 14;17(1):e0262308. doi: 10.1371/journal.pone.0262308. eCollection 2022.

ABSTRACT

BACKGROUND: Food-borne diseases related to the consumption of meat and its products had public health importance worldwide. The problem became worst in Ethiopia as the result of the tradition of eating raw cattle meat. Salmonella species and Escherichia coli are important food-borne pathogens associated with meat contamination. Hence the current study aimed to assess the prevalence and antimicrobial susceptibility of Salmonella species and Extended-spectrum β-lactamase producing Escherichia coli from raw cattle meat at butcher houses in Hawassa city, Sidama regional state, Ethiopia.

METHOD: A cross-sectional study was done on the prevalence and antimicrobial susceptibility pattern of Salmonella species and Extended-spectrum β-lactamase producing E.coli from raw cattle meat at butcher houses in Hawassa city from September to December 2020. Socio-demographic data were collected using a structured questionnaire and raw cattle meat and swab samples were collected from meat cutting equipment. The collected samples transported using icebox to Hawassa University College of Medicine and Health Sciences Microbiology Laboratory for identification. Samples were grown on different culture media and antimicrobial susceptibility tests were determined by using Kirby disc diffusion method. Data were entered and analyzed into SPSS version 23. Descriptive statistics were done and P-value < 0.05 was considered as statistically significant.

RESULT: The overall prevalence of salmonella and ESBL producing E.coli among 556 samples collected from 278 butcher houses was 36 (6.47%) (95% CI: 1.68-1.79) of which 13 (2.3%) were ESBL producing E.coli and 23(4.1%) were salmonella species. Poor hand washing practice (AOR = 2.208; 95% CI: 1.249-3.904) and touching birr while selling meat (AOR = 0.75; 95% CI: (0.433-1.299) were found to be significantly associated with the prevalence of salmonella species and E.coli on cattle meat. The isolates showed moderate levels of resistance (60-70%) against Amoxicillin/ clavulanic acid and high susceptibility (85-100%) against gentamicin, cotrimoxazole, ceftazidime, and tetracycline and the overall multidrug resistance was 33.3%.

CONCLUSION: This study revealed moderately high prevalence of salmonella and E.coli due to poor hygiene and sanitation practices in the butcher shops. Furthermore, the existence of ESBL producing E.coli isolates clearly indicate the possible threat to public health. Therefore, inspection by the right agencies must be implemented in order to prevent food-borne outbreaks and antimicrobial resistance.

PMID:35030183 | DOI:10.1371/journal.pone.0262308

PLoS One. 2022 Jan 14;17(1):e0261835. doi: 10.1371/journal.pone.0261835. eCollection 2022.

ABSTRACT

This study investigates the reaction of stock markets to the Covid-19 pandemic and the Global Financial Crisis of 2008 (GFC) and compares their influence in terms of risk exposures. The empirical investigation is conducted using the modified ICSS test, DCC-GARCH, and Diebold-Yilmaz connectedness analysis to examine financial contagion and volatility spillovers. To further reveal the impact of these two crises, the statistical features of tranquil and crisis periods under different time intervals are also compared. The test results show that although the outbreak’s origin was in China, the US stock market is the source of financial contagion and volatility spillovers during the pandemic, just as it was during the GFC. The propagation of shocks is considerably higher between developed economies compared to emerging markets. Additionally, the results show that the COVID-19 pandemic induced a more severe contagious effect and risk transmission than the GFC. The study provides an extensive examination of the COVID-19 pandemic and the GFC in terms of financial contagion and volatility spillovers. The results suggest the presence of strong co-movements of world stock markets with the US equity market, especially in periods of financial turmoil.

PMID:35030202 | DOI:10.1371/journal.pone.0261835

PLoS Negl Trop Dis. 2022 Jan 14;16(1):e0010136. doi: 10.1371/journal.pntd.0010136. Online ahead of print.

ABSTRACT

BACKGROUND: As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas.

METHODS: We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165).

RESULTS: A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (convention PCR, qPCR, Digital droplet PCR and nested PCR) differed significantly, with nested PCRs showing the best performance.

CONCLUSIONS: Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals.

PMID:35030167 | DOI:10.1371/journal.pntd.0010136

Ophthalmic Plast Reconstr Surg. 2022 Jan 13. doi: 10.1097/IOP.0000000000002120. Online ahead of print.

ABSTRACT

PURPOSE: To characterize chronic orbital pain in patients who benefitted from peripheral trigeminal nerve blocks and to explore the relationship between pain etiologies and phenotypes, injection attributes, and positive response to treatment.

METHODS: In this single-center retrospective descriptive study, patients who underwent peripheral trigeminal nerve blocks for chronic orbital pain from November 2016 to May 2021 were selected. Data reviewed included inciting factors, neuropathic symptoms of orbital pain, injection composition (anesthetic alone versus anesthetic + dexamethasone), and corneal epitheliopathy grades. Primary outcomes assessed were response to injection, duration of injection effectiveness, and overall treatment efficacy. Associations between subgroups of chronic orbital pain, injection attributes, and treatment outcomes were examined.

RESULTS: Nineteen patients who underwent a total of 94 peripheral trigeminal nerve blocks for chronic orbital pain were included. During a mean follow-up period of 2.4 years after initial injection (range 7 days-4.6 years), 16 (84.2%) patients achieved either partial or complete improvement. Ocular versus nonocular origin of orbital pain or the presence of neuropathic sensory characteristics was not associated with a treatment outcome. Injections containing dexamethasone had a lower positive efficacy (relative risk, 0.88; 95% CI, 0.81-0.97) and no statistically significant association with prolonged effect. Twenty-nine (50.9%) of the 57 injections for which effect duration was recorded produced a response lasting greater than 6 weeks.

CONCLUSIONS: Modulation of trigeminal afferent nerve activity with peripheral trigeminal nerve blocks containing anesthetic with or without dexamethasone may be a promising treatment strategy for chronic orbital pain of diverse etiologies and phenotypes.

PMID:35030151 | DOI:10.1097/IOP.0000000000002120