Tag: pubmed

PLoS Genet. 2022 Dec 27;18(12):e1010557. doi: 10.1371/journal.pgen.1010557. Online ahead of print.

ABSTRACT

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 (PRIM1) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV1/FVC), and an eQTL of matrix metallopeptidase 15 (MMP15) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 (HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases.

PMID:36574455 | DOI:10.1371/journal.pgen.1010557

PLoS Negl Trop Dis. 2022 Dec 27;16(12):e0010985. doi: 10.1371/journal.pntd.0010985. Online ahead of print.

ABSTRACT

BACKGROUND: Improved education on water-related diseases in schools could help to reduce disease burden. This paper presents specific results on knowledge, attitudes and practices (KAP) of a cluster-randomized controlled trial to reduce diarrheal disease and dengue entomological risk factors in rural primary schools in Colombia. The aim was to investigate whether enhanced educational interventions on dengue and diarrheal disease in schools could improve KAP scores related to these diseases in students and teachers in rural primary schools, as well as the students’ parents.

METHODOLOGY/PRINCIPAL FINDINGS: A factorial cluster-randomized controlled trial was carried out in 35 rural primary schools in two municipalities in Cundinamarca, central Colombia. Schools were randomized into four arms: interventions related to diarrheal disease (DIA), dengue (DEN), both (DIADEN), or no interventions (control, CON). Both educational and physical interventions to reduce risk factors of dengue and diarrhea were implemented. Comprehensive teachers’ manuals were developed and deployed to guide the learning activities. The intervention was carried out over two school years. The knowledge scores of students receiving dengue interventions (DEN, DIADEN) increased by 1.16 point score (0.75-1.56, p<0.001) and those receiving diarrhea interventions (DIA, DIADEN) increased by 1.15 point score (0.67-1.63, p<0.001). The attitude and practice scores of students receiving the diarrhea interventions increased (Attitudes: 0.41 [0.11-0.71, p = 0.01]; Practices: 0.33 [0.01-0.65, p = 0.042]), but not for those receiving the dengue interventions (p = 0.31 and p = 0.08, respectively).

CONCLUSIONS/SIGNIFICANCE: There were increases in knowledge scores among students, their teachers and their parents for both diseases. However, the attitudes and practices components were not affected to the same extent. The hypothesis that the students would disseminate knowledge acquired from the educational interventions to their parents was confirmed for dengue, but not for diarrhea.

TRIAL REGISTRATION: ISRCTN40195031 The trial is registered in the Current Controlled Trials under Infections and Infestations category.

PMID:36574453 | DOI:10.1371/journal.pntd.0010985

PLoS One. 2022 Dec 27;17(12):e0279714. doi: 10.1371/journal.pone.0279714. eCollection 2022.

ABSTRACT

INTRODUCTION: The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for patients with MAC pulmonary disease. However, developing macrolide resistance was associated with poor treatment outcomes and increased mortality. In 2018, the U.S. Food and Drug Administration approved liposomal amikacin for inhalation (LAI) to treat refractory MAC pulmonary disease. The current systematic review aimed to evaluate LAI’s outcomes and adverse events in MAC pulmonary disease.

METHODS: The systematic search was performed in PubMed/Medline, EMBASE, and the Cochrane Controlled Register of Trials (CENTRAL) up to March 8, 2022. The search terms included Mycobacterium avium complex, MAC, amikacin, and liposomal amikacin.

RESULTS: After reviewing 1284 records, four papers met the inclusion criteria, including three clinical trials and one prospective cohort study. These studies showed that adding LAI to guideline-based therapies can increase sputum culture conversion rate and achieve early sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for three months after treatment) negative sputum culture. In addition, extended LAI use was a potential benefit in patients considered refractory to initial treatment. The most prevalent treatment-emergent adverse events (TEAE) reported in the LAI group were the respiratory TEAE.

CONCLUSIONS: LAI could increase the sputum culture conversion rate and achieve early sustainable, durable negative sputum culture. However, additional large-scale research is required to confirm the results.

PMID:36574432 | DOI:10.1371/journal.pone.0279714

PLoS One. 2022 Dec 27;17(12):e0279706. doi: 10.1371/journal.pone.0279706. eCollection 2022.

ABSTRACT

OBJECTIVE: Ischemic stroke (IS) with subsequent cerebrocardiac syndrome (CCS) has a poor prognosis. We aimed to investigate electrocardiogram (ECG) changes after IS with artificial intelligence (AI).

METHODS: We collected ECGs from a healthy population and patients with IS, and then analyzed participant demographics and ECG parameters to identify abnormal features in post-IS ECGs. Next, we trained the convolutional neural network (CNN), random forest (RF) and support vector machine (SVM) models to automatically detect the changes in the ECGs; Additionally, We compared the CNN scores of good prognosis (mRS ≤ 2) and poor prognosis (mRS > 2) to assess the prognostic value of CNN model. Finally, we used gradient class activation map (Grad-CAM) to localize the key abnormalities.

RESULTS: Among the 3506 ECGs of the IS patients, 2764 ECGs (78.84%) led to an abnormal diagnosis. Then we divided ECGs in the primary cohort into three groups, normal ECGs (N-Ns), abnormal ECGs after the first ischemic stroke (A-ISs), and normal ECGs after the first ischemic stroke (N-ISs). Basic demographic and ECG parameter analyses showed that heart rate, QT interval, and P-R interval were significantly different between 673 N-ISs and 3546 N-Ns (p < 0.05). The CNN has the best performance among the three models in distinguishing A-ISs and N-Ns (AUC: 0.88, 95%CI = 0.86-0.90). The prediction scores of the A-ISs and N-ISs obtained from the all three models are statistically different from the N-Ns (p < 0.001). Futhermore, the CNN scores of the two groups (mRS > 2 and mRS ≤ 2) were significantly different (p < 0.05). Finally, Grad-CAM revealed that the V4 lead may harbor the highest probability of abnormality.

CONCLUSION: Our study showed that a high proportion of post-IS ECGs harbored abnormal changes. Our CNN model can systematically assess anomalies in and prognosticate post-IS ECGs.

PMID:36574427 | DOI:10.1371/journal.pone.0279706

PLoS One. 2022 Dec 27;17(12):e0279472. doi: 10.1371/journal.pone.0279472. eCollection 2022.

ABSTRACT

The automatic sorting of construction waste (CW) is an essential procedure in the field of CW recycling due to its remarkable efficiency and safety. The classification of CW is the primary task that guides automatic and precise sorting. In our work, a new method of CW classification based on two-level fusion is proposed to promote classification performance. First, statistical histograms are used to obtain global hue information and local oriented gradients, which are called the hue histogram (HH) and histogram of oriented gradients (HOG), respectively. To fuse these visual features, a bag-of-visual-words (BoVW) method is applied to code HOG descriptors in a CW image as a vector, and this process is named B-HOG. Then, based on feature-level fusion, we define a new feature to combine HH and B-HOG, which represent the global and local visual characteristics of an object in a CW image. Furthermore, two base classifiers are used to learn the information from the color feature space and the new feature space. Based on decision-level fusion, we propose a joint decision-making model to combine the decisions from the two base classifiers for the final classification result. Finally, to verify the performance of the proposed method, we collect five types of CW images as the experimental data set and use these images to conduct experiments on three different base classifiers. Moreover, we compare this method with other extant methods. The results demonstrate that our method is effective and feasible.

PMID:36574416 | DOI:10.1371/journal.pone.0279472

PLoS One. 2022 Dec 27;17(12):e0279518. doi: 10.1371/journal.pone.0279518. eCollection 2022.

ABSTRACT

PURPOSE: To assess the rate of pseudophakic cystoid macular edema (pCME) in uneventful cataract surgery in surgeons in training vs experienced surgeons and to analyze the rate of pCME according to surgeon’s sex.

METHODS: Medical reports post phacoemulsification between 2010 and 2018 at the Department of Ophthalmology, Medical University of Graz, Austria, were reviewed for pCME. A running lifetime number of preceding cataract surgeries was used to express hands-on experience. A cut-off number of 300 surgeries was defined to distinguish between surgeons in training and experienced surgeons. Outcome parameters were incidence of pCME, patient’s sex and age, laterality of eye, coexistence of pseudoexfoliation syndrome (PEX), duration of surgery and surgeon’s sex.

RESULTS: 25.422 surgeries on 18.266 patients were included. The majority was performed by experienced surgeons (23.139, 91.0%) vs 2.283 (9.0%) by surgeons in training (25 surgeons, 9 (36%) female and 16 (64%) male). pCME occurred in 32 eyes (1.4%) following surgery by surgeons in training and in 152 eyes (0.7%) following surgery by experienced surgeons. Chance for pCME was 1.57 higher in training surgeries (95% CI 1.03-2.41, p = 0.034) and longer duration (OR = 1.04; 95% CI 1.02-1.07, p = 0.001). After excluding the first 100 surgeries for every surgeon in training similar results were observed. No difference in risk for pCME was found between female and male surgeons in both groups (training and experienced surgeons).

CONCLUSION: In conclusion, the rate for pCME after uneventful cataract surgery is significantly higher for surgeons in training but steadily decreasing and associated to surgical time. No difference in the risk for pCME was found between female and male surgeons.

PMID:36574394 | DOI:10.1371/journal.pone.0279518

PLoS One. 2022 Dec 27;17(12):e0274724. doi: 10.1371/journal.pone.0274724. eCollection 2022.

ABSTRACT

Specific microRNAs expressions may accurately characterize different stages of canine myxomatous mitral valve disease. This preliminary pilot study aimed to (1) describe the clinical and echocardiographic parameters of Cavalier King Charles Spaniels affected by myxomatous mitral valve disease at different American College of Veterinary Internal Medicine (ACVIM) stages (B1, B2 and C) and healthy control group (ACVIM A), comparing the parameters collected during the first examination (T0) and the end of the follow-up (T1); (2) assess the association between the values of echocardiographic parameters at T1 and the expression profile of miR-30b-5p at T0. Thirty-five Cavalier King Charles Spaniels (median age 4.29 years and median weight 9 Kg) in different ACVIM stages were included (7 A, 19 B1, 6 B2 and 3 C). Inverse probability weighting analysis was performed to estimate the association of the exposure variable (miR-30b-5p) with the outcome variables (clinical and echocardiographic variables). Time was included as variable. The results pointed out that high levels of plasma miR-30b-5p corresponded to lower values of left ventricular end-diastolic diameter normalized for body weight, end-diastolic and end-systolic volumes indexed for body weight, and left atrium-to aortic root ratio. Hence, higher miR-30b-5p expressions were associated with milder forms of mitral valve disease in our study population. In contrast, the results obtained for the intensity of heart murmur, the mitral regurgitation severity, and the Mitral INsufficiency Echocardiographic score) were not statistically significant. A relationship between high abundance of miR-30b-5p and myxomatous mitral valve disease that appear echocardiographically more stable over time has been demonstrated. In conclusion, Cavalier King Charles Spaniels affected by myxomatous mitral valve disease that at the first cardiologic evaluation showed an upregulation of miR-30b-5p are expected to experience lesser variations on their echocardiographic examination between T0 and T1.

PMID:36574372 | DOI:10.1371/journal.pone.0274724

PLoS One. 2022 Dec 27;17(12):e0279441. doi: 10.1371/journal.pone.0279441. eCollection 2022.

ABSTRACT

BACKGROUND: Highly connected individuals disseminate information effectively within their social network. To apply this concept to inflammatory bowel disease (IBD) care and lay the foundation for network interventions to disseminate high-quality treatment, we assessed the need for improving the IBD practices of highly connected clinicians. We aimed to examine whether highly connected clinicians who treat IBD patients were more likely to provide high-quality treatment than less connected clinicians.

METHODS: We used network analysis to examine connections among clinicians who shared patients with IBD in the Veterans Health Administration between 2015-2018. We created a network comprised of clinicians connected by shared patients. We quantified clinician connections using degree centrality (number of clinicians with whom a clinician shares patients), closeness centrality (reach via shared contacts to other clinicians), and betweenness centrality (degree to which a clinician connects clinicians not otherwise connected). Using weighted linear regression, we examined associations between each measure of connection and two IBD quality indicators: low prolonged steroids use, and high steroid-sparing therapy use.

RESULTS: We identified 62,971 patients with IBD and linked them to 1,655 gastroenterologists and 7,852 primary care providers. Clinicians with more connections (degree) were more likely to exhibit high-quality treatment (less prolonged steroids beta -0.0268, 95%CI -0.0427, -0.0110, more steroid-sparing therapy beta 0.0967, 95%CI 0.0128, 0.1805). Clinicians who connect otherwise unconnected clinicians (betweenness) displayed more prolonged steroids use (beta 0.0003, 95%CI 0.0001, 0.0006). The presence of variation is more relevant than its magnitude.

CONCLUSIONS: Clinicians with a high number of connections provided more high-quality IBD treatments than less connected clinicians, and may be well-positioned for interventions to disseminate high-quality IBD care. However, clinicians who connect clinicians who are otherwise unconnected are more likely to display low-quality IBD treatment. Efforts to improve their quality are needed prior to leveraging their position to disseminate high-quality care.

PMID:36574370 | DOI:10.1371/journal.pone.0279441

Eur J Gastroenterol Hepatol. 2023 Feb 1;35(2):212-218. doi: 10.1097/MEG.0000000000002476. Epub 2022 Nov 8.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the efficacy and safety of long-term postpartum tenofovir disoproxil fumarate (TDF) therapy in hepatitis B virus (HBV)-infected mothers with high viral load.

METHODS: In this retrospective cohort study, HBV-infected mothers with HBV DNA>2 × 105 IU/mL who initiated TDF prophylaxis treatment during pregnancy were divided into TDF continuation and discontinuation groups according to whether they stopped TDF treatment within 3 months after birth or not. Virological and biochemical markers were collected before TDF treatment, antepartum and postpartum.

RESULTS: In 131 women followed for a median of 18 months postpartum, alanine aminotransferase (ALT) abnormality rate was significantly lower in TDF continuation group vs. discontinuation group (39.4% vs. 56.9%, P = 0.045), and continuous TDF therapy in postpartum was independently associated with lower risk of ALT flares [OR = 0.308, 95% confidence interval (CI), 0.128-0.742; P = 0.009]. Long-term postpartum TDF treatment can promote the decline of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels, but the HBeAg seroconversion rate in two groups was not significant (15.5% vs. 11.7%, P = 0.541). There were no statistical differences in bone metabolism markers between two groups (P > 0.05). Compared with the TDF discontinuation group, TDF continuation group had a significantly lower estimated glomerular filtration rate level and higher creatinine level in postpartum but within normal ranges (P < 0.05).

CONCLUSIONS: For pregnant women who received prophylactic TDF treatment, long-term TDF therapy continued in postpartum can reduce the risk of ALT flares and promote the rapid decline of HBeAg and HBsAg levels.

PMID:36574312 | DOI:10.1097/MEG.0000000000002476

Eur J Gastroenterol Hepatol. 2023 Feb 1;35(2):174-180. doi: 10.1097/MEG.0000000000002486. Epub 2022 Dec 8.

ABSTRACT

OBJECTIVE: The first choice of treatment for rectal neuroendocrine tumors (R-NETs) 10 mm in size is endoscopic resection, there is still controversy concerning the optimal endoscopic treatment for resecting R-NETs. This study evaluated the efficacy and safety of multiple ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (EMR-MLUS) for R-NETs.

METHODS: We retrospectively analyzed the data of 62 patients with R-NETs ≤10 mm in size who underwent EMR-MLUS or ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (EMR-LUS) between May 2019 and April 2022, including tumor characteristics, endoscopic complete resection, pathological complete resection, the procedure time, adverse events, and follow-up were compared between the two groups of patients.

RESULTS: Of the 62 patients, 19 underwent EMR-MLUS and 43 underwent EMR-LUS. The endoscopic morphology of lesions was statistically different between group EMR-MLUS and group EMR-LUS (P = 0.015), and most of them were flat and slightly raised lesions in group EMR-MLUS. Although the pathological complete resection rate was slightly higher in the EMR-MLUS group than in the EMR-LUS group (94.74% vs. 90.70%; P = 0.290), the endoscopic complete resection rate was high in both groups. Involvement of the lateral resection margin was found four cases in the ESMR-LUS group; one case of deep resection margin involvement in the EMR-MLUS group. The mean procedure time was longer in the EMR-MLUS group than in the EMR-LUS group (12.79 ± 1.01 min vs. 11.08 ± 1.89 min; P = 0.041). In group EMR-LUS, there were two cases of immediate bleeding; in group EMR-MLUS, one case of perforation, all of them were successfully treated by endoscopy. No recurrence, progression, or metastasis was found in all patients.

CONCLUSION: EMR-MLUS is a safe and effective technique that could be considered when removing small rectal NETs, especially flat and slightly raised lesions.

PMID:36574308 | DOI:10.1097/MEG.0000000000002486