Category: Nevin Manimala

J Clin Lab Anal. 2022 Sep;36(9):e24642. doi: 10.1002/jcla.24642. Epub 2022 Aug 10.

ABSTRACT

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.

METHODS: One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.

RESULTS: rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D’ = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p > 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).

CONCLUSIONS: Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

PMID:36082465 | DOI:10.1002/jcla.24642

J Clin Lab Anal. 2022 Sep;36(9):e24645. doi: 10.1002/jcla.24645. Epub 2022 Aug 5.

ABSTRACT

BACKGROUND: Pregnancy is a prothrombotic condition which can be abnormally exaggerated in women with thrombophilia.

METHODS: In a prospective study, patients who delivered at term, by cesarean section, between 1 October 2017 and 1 December 2021, who already had a diagnosis of thrombophilia before coming to our hospital, were included in the study group (n = 80). A similar number of nonthrombophilia patients (n = 80) without any history of thrombotic events, age- and para-matched with the study group, were included in the control group. The postpartum uterine ultrasonographic scale (PUUS) values, in the first 24-48 h, were correlated with the patients’ data.

RESULTS: The P-LCR (platelet large cell ratio), was significantly higher in the treated thrombophilia group (p = 0.042). There was no correlation between PUUS and complete blood count values, coagulation factors, maternal characteristics, or fetal outcomes, except for postpartum neutrophils (p = 0.047) and postpartum platelet count (p = 0.046).

CONCLUSIONS: Postpartum uterine involution was not significantly different, after cesarean section, between treated thrombophilia patients and nonthrombophilia patients. Involution correlated only with postpartum neutrophils and postpartum platelet count.

PMID:36082463 | DOI:10.1002/jcla.24645

Arthritis Rheumatol. 2022 Sep 9. doi: 10.1002/art.42339. Online ahead of print.

ABSTRACT

OBJECTIVES: Gout patients often have multiple comorbidities, making them susceptible to SARS-CoV-2 infection and its severe outcomes; however, few studies have examined the association between gout and the risk of SARS-CoV-2 infection and its severe sequelae, especially after COVID-19 vaccination.

METHODS: We conducted two cohort studies using The Health Improvement Network. Individuals with gout and those without gout from the general population were followed from December 8^th , 2020, to October 31^st , 2021. We estimated the rate difference (RD) and hazard ratio (HR) of SARS-CoV-2 infection and its severe outcomes (i.e., hospitalization and death over 30 days after SARS-CoV-2 infection) for individuals with gout versus those without gout using Cox proportional hazard model according to COVID-19 vaccination status. We adjusted potential confounders using overlap weighting of exposure score.

RESULTS: Among the vaccinated cohort, 1,955 cases of breakthrough infection occurred in 54,576 individuals with gout (4.68/1000 person-months) and 52,468 cases in 1,336,377 individuals without gout (3.76/1000 person-months). The adjusted RD of breakthrough infection was 0.91 (95%CI: 0.62-1.20)/1000 person-months, and the adjusted HR was 1.24 (95%CI: 1.19-1.30). Gout was also associated with an increased risk of hospitalization (adjusted HR=1.30, 95%CI: 1.10-1.53) and death (adjusted HR=1.36, 95%CI: 0.87-2.13). Women with gout showed an increased risk of hospitalization (adjusted HR 1.55, 95%CI: 1.15-2.10) and death (adjusted HR=2.46, 95%CI: 1.12-5.41). Similar associations with gout were observed in the unvaccinated cohort.

CONCLUSIONS: These general population data suggest that individuals with gout, especially women, have higher risks of both SARS-CoV-2 infection and severe sequelae, even with vaccinations. This article is protected by copyright. All rights reserved.

PMID:36082457 | DOI:10.1002/art.42339

Int J Cancer. 2022 Sep 8. doi: 10.1002/ijc.34278. Online ahead of print.

ABSTRACT

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and non-cancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28,684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P<5×10^-8 ) with their respective trait. The selected SNPs were analyzed in 2,434 MM cases and 3,446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1,955 MM cases and 1,549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147,282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR=1.22, 95%CI 1.13-1.32, P=4.81×10^-7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus. This article is protected by copyright. All rights reserved.

PMID:36082445 | DOI:10.1002/ijc.34278

Hand (N Y). 2022 Sep 8:15589447221122822. doi: 10.1177/15589447221122822. Online ahead of print.

ABSTRACT

BACKGROUND: Posterior interosseous nerve (PIN) compression in the forearm without motor paralysis is a challenging clinical diagnosis. This retrospective study evaluated the clinical assessment, diagnostic studies, and outcomes following surgical decompression of the PIN in the forearm.

METHODS: This study reviewed 182 patients’ medical charts following PIN decompression between 2000 and 2020 by a single surgeon. After exclusion of combined nerve entrapments, polyneuropathy, motor palsy, or lateral epicondylitis, the study included 14 patients. Data collected included: clinical presentation and pain drawings, provocative testing, functional outcomes, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores.

RESULTS: There were 15 PIN decompressions (14 patients, mean follow-up = 11.9 months). Clinical presentation included pain (n = 14) (proximal dorsal forearm, n = 14; distal forearm over radial sensory nerve, n = 3) and positive clinical tests (sensory collapse test over the radial tunnel, n = 8; pain with forearm pronation and compression over the radial tunnel, n = 10; Tinel sign, n = 5). Postoperatively, there were significant improvements in Visual Analog Scale pain scores (6.7 to 3.3, P = .0006), quality-of-life scores (74.7 to 32.7, P = .0001), and DASH scores (46.3 to 33.6, P = .02).

CONCLUSIONS: The PIN compression in the forearm without motor paralysis is a clinical diagnosis supported by pain drawings, pain quality, and provocative tests. Patients with persistent, therapy-resistant dorsal forearm pain should be evaluated for PIN compression. Surgical decompression provides statistically significant quantifiable improvement in pain and quality of life.

PMID:36082441 | DOI:10.1177/15589447221122822

J Cheminform. 2022 Sep 9;14(1):61. doi: 10.1186/s13321-022-00642-3.

ABSTRACT

Extraction of chemical formulas from images was not in the top priority of Computer Vision tasks for a while. The complexity both on the input and prediction sides has made this task challenging for the conventional Artificial Intelligence and Machine Learning problems. A binary input image which might seem trivial for convolutional analysis was not easy to classify, since the provided sample was not representative of the given molecule: to describe the same formula, a variety of graphical representations which do not resemble each other can be used. Considering the variety of molecules, the problem shifted from classification to that of formula generation, which makes Natural Language Processing (NLP) a good candidate for an effective solution. This paper describes the evolution of approaches from rule-based structure analyses to complex statistical models, and compares the efficiency of models and methodologies used in the recent years. Although the latest achievements deliver ideal results on particular datasets, the authors mention possible problems for various scenarios and provide suggestions for further development.

PMID:36076301 | DOI:10.1186/s13321-022-00642-3

Trials. 2022 Sep 8;23(1):762. doi: 10.1186/s13063-022-06708-9.

ABSTRACT

BACKGROUND: The HEALing (Helping to End Addiction Long-term^SM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests.

METHODS: The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups.

RESULTS: Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA).

CONCLUSIONS: Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study.

TRIAL REGISTRATION: ClinicalTrials.gov http://www.

CLINICALTRIALS: gov ; Identifier: NCT04111939.

PMID:36076295 | DOI:10.1186/s13063-022-06708-9

J Transl Med. 2022 Sep 8;20(1):412. doi: 10.1186/s12967-022-03623-0.

ABSTRACT

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology.

METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology.

RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP.

CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

PMID:36076294 | DOI:10.1186/s12967-022-03623-0

Int Breastfeed J. 2022 Sep 8;17(1):68. doi: 10.1186/s13006-022-00507-3.

ABSTRACT

BACKGROUND: Twins and late preterm (LPT) infants are at an increased risk of being breastfed to a lesser extent than term singletons. This study aimed to describe the initiation and duration of any and exclusive breastfeeding at the breast for mothers of LPT twins and term twins during the first 4 months and to explore the breastfeeding experiences of mothers of LPT twins.

METHODS: A sequential two-sample quantitative-qualitative explanatory mixed-methods design was used. The quantitative data were derived from a longitudinal cohort study in which 22 mothers of LPT twins and 41 mothers of term twins answered questionnaires at one and four months after birth (2015-2017). The qualitative data were obtained from semi-structured interviews with 14 mothers of LPT twins (2020-2021), based on results from the quantitative study and literature. Analysis included descriptive statistics of quantitative data and deductive content analysis of the qualitative data, followed by condensation and synthesis.

RESULTS: All mothers of LPT twins (100%) and most mothers of term twins (96%) initiated breastfeeding. There was no difference in any breastfeeding during the first week at home (98% versus 95%) and at 1 month (88% versus 85%). However, at 4 months, the difference was significant (44% versus 75%). The qualitative data highlighted that mothers of LPT twins experienced breastfeeding as complex and strenuous. Key factors influencing mothers’ experiences and decisions were their infants’ immature breastfeeding behaviors requiring them to express breast milk alongside breastfeeding, the burden of following task-oriented feeding regimes, and the lack of guidance from healthcare professionals. As a result, mothers started to question the worth of their breastfeeding efforts, leading to changes in breastfeeding management with diverse results. Support from fathers and grandparents positively influenced sustained breastfeeding.

CONCLUSIONS: Mothers of LPT twins want to breastfeed, but they face many challenges in breastfeeding during the first month, leading to more LPT twins’ mothers than term twins’ mothers ceasing breastfeeding during the following months. To promote and safeguard breastfeeding in this vulnerable group, care must be differentiated from routine term infant services, and healthcare professionals need to receive proper education and training.

PMID:36076279 | DOI:10.1186/s13006-022-00507-3

Int J Behav Nutr Phys Act. 2022 Sep 8;19(1):117. doi: 10.1186/s12966-022-01350-9.

ABSTRACT

BACKGROUND: Standardized validation indices (i.e., accuracy, bias, and precision) provide a comprehensive comparison of step counting wearable technologies.

PURPOSE: To expand a previously published child/youth catalog of validity indices to include adults (21-40, 41-60 and 61-85 years of age) assessed across a range of treadmill speeds (slow [0.8-3.2 km/h], normal [4.0-6.4 km/h], fast [7.2-8.0 km/h]) and device wear locations (ankle, thigh, waist, and wrist).

METHODS: Two hundred fifty-eight adults (52.5 ± 18.7 years, 49.6% female) participated in this laboratory-based study and performed a series of 5-min treadmill bouts while wearing multiple devices; 21 devices in total were evaluated over the course of this multi-year cross-sectional study (2015-2019). The criterion measure was directly observed steps. Computed validity indices included accuracy (mean absolute percentage error, MAPE), bias (mean percentage error, MPE), and precision (correlation coefficient, r; standard deviation, SD; coefficient of variation, CoV).

RESULTS: Over the range of normal speeds, 15 devices (Actical, waist-worn ActiGraph GT9X, activPAL, Apple Watch Series 1, Fitbit Ionic, Fitbit One, Fitbit Zip, Garmin vivoactive 3, Garmin vivofit 3, waist-worn GENEActiv, NL-1000, PiezoRx, Samsung Gear Fit2, Samsung Gear Fit2 Pro, and StepWatch) performed at < 5% MAPE. The wrist-worn ActiGraph GT9X displayed the worst accuracy across normal speeds (MAPE = 52%). On average, accuracy was compromised across slow walking speeds for all wearable technologies (MAPE = 40%) while all performed best across normal speeds (MAPE = 7%). When analyzing the data by wear locations, the ankle and thigh demonstrated the best accuracy (both MAPE = 1%), followed by the waist (3%) and the wrist (15%) across normal speeds. There were significant effects of speed, wear location, and age group on accuracy and bias (both p < 0.001) and precision (p ≤ 0.045).

CONCLUSIONS: Standardized validation indices cataloged by speed, wear location, and age group across the adult lifespan facilitate selecting, evaluating, or comparing performance of step counting wearable technologies. Speed, wear location, and age displayed a significant effect on accuracy, bias, and precision. Overall, reduced performance was associated with very slow walking speeds (0.8 to 3.2 km/h). Ankle- and thigh-located devices logged the highest accuracy, while those located at the wrist reported the worst accuracy.

TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

PMID:36076265 | DOI:10.1186/s12966-022-01350-9