Nevin Manimala

Nat Biomed Eng. 2022 Nov 21. doi: 10.1038/s41551-022-00961-8. Online ahead of print.

ABSTRACT

Gene transcription is regulated through complex mechanisms involving non-coding RNAs (ncRNAs). As the transcription of ncRNAs, especially of enhancer RNAs, is often low and cell type specific, how the levels of RNA transcription depend on genotype remains largely unexplored. Here we report the development and utility of a machine-learning model (MENTR) that reliably links genome sequence and ncRNA expression at the cell type level. Effects on ncRNA transcription predicted by the model were concordant with estimates from published studies in a cell-type-dependent manner, regardless of allele frequency and genetic linkage. Among 41,223 variants from genome-wide association studies, the model identified 7,775 enhancer RNAs and 3,548 long ncRNAs causally associated with complex traits across 348 major human primary cells and tissues, such as rare variants plausibly altering the transcription of enhancer RNAs to influence the risks of Crohn’s disease and asthma. The model may aid the discovery of causal variants and the generation of testable hypotheses for biological mechanisms driving complex traits.

PMID:36411359 | DOI:10.1038/s41551-022-00961-8

Nat Microbiol. 2022 Nov 21. doi: 10.1038/s41564-022-01263-0. Online ahead of print.

ABSTRACT

The Klebsiella group, found in humans, livestock, plants, soil, water and wild animals, is genetically and ecologically diverse. Many species are opportunistic pathogens and can harbour diverse classes of antimicrobial resistance genes. Healthcare-associated Klebsiella pneumoniae clones that are non-susceptible to carbapenems can spread rapidly, representing a high public health burden. Here we report an analysis of 3,482 genome sequences representing 15 Klebsiella species sampled over a 17-month period from a wide range of clinical, community, animal and environmental settings in and around the Italian city of Pavia. Northern Italy is a hotspot for hospital-acquired carbapenem non-susceptible Klebsiella and thus a pertinent setting to examine the overlap between isolates in clinical and non-clinical settings. We found no genotypic or phenotypic evidence for non-susceptibility to carbapenems outside the clinical environment. Although we noted occasional transmission between clinical and non-clinical settings, our data point to a limited role of animal and environmental reservoirs in the human acquisition of Klebsiella spp. We also provide a detailed genus-wide view of genomic diversity and population structure, including the identification of new groups.

PMID:36411354 | DOI:10.1038/s41564-022-01263-0

Commun Med (Lond). 2022 Nov 21;2(1):147. doi: 10.1038/s43856-022-00215-3.

ABSTRACT

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging.

METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski’s method with a 0.05 level of significance.

RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients.

CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.

PMID:36411311 | DOI:10.1038/s43856-022-00215-3

Sci Rep. 2022 Nov 21;12(1):20008. doi: 10.1038/s41598-022-24227-0.

ABSTRACT

18F-FDG-PET/CT is standard to assess response in Hodgkin lymphoma by quantifying metabolic activity with the Deauville score. PET/CT, however, is time-consuming, cost-extensive, linked to high radiation and has a low availability. As an alternative, we investigated radiomics from non-contrast-enhanced computed tomography (NECT) scans. 75 PET/CT examinations of 43 patients on two different scanners were included. Target lesions were classified as Deauville score 4 positive (DS4+) or negative (DS4-) based on their SUVpeak and then segmented in NECT images. From these segmentations, 107 features were extracted with PyRadiomics. All further statistical analyses were then performed scanner-wise: differences between DS4+ and DS4- manifestations were assessed with the Mann-Whitney-U-test and single feature performances with the ROC-analysis. To further verify the reliability of the results, the number of features was reduced using different techniques. The feature median showed a high sensitivity for DS4+ manifestations on both scanners (scanner A: 0.91, scanner B: 0.85). It furthermore was the only feature that remained in both datasets after applying different feature reduction techniques. The feature median from NECT concordantly has a high sensitivity for DS4+ Hodgkin manifestations on two different scanners and thus could provide a surrogate for increased metabolic activity in PET/CT.

PMID:36411307 | DOI:10.1038/s41598-022-24227-0

Sci Rep. 2022 Nov 21;12(1):19997. doi: 10.1038/s41598-022-24569-9.

ABSTRACT

A fully hydroxyapatite (HA)-coated stem such as Corail stem, that compacts the cancellous bone around the stem in total hip arthroplasty (THA), is reported to have good long-term results for more than 20 years. Although various fully HA-coated stems have being used recently, it is unclear whether there are differences in the postoperative outcomes. In this study, 224 patients (234 hips) with THA using either the Corail collarless stem or the Hydra stem were enrolled. And then we performed a retrospective comparison of the data at 2 years postoperatively using propensity score matching analysis. The postoperative modified Harris hip scores in 84 hips each group were 93.6 ± 8.2 points in the Corail group and 92.8 ± 10.1 points in the Hydra group, and there was no significant difference between the two groups. However, there was significantly less stem subsidence and rate of 3rd degree or greater stress shielding in the Corail group. Although these two stems were similar collarless fully HA-coated stems and clinical outcomes were favorable results in both groups at 2 years postoperatively, radiographic evaluations showed statistically significant differences between the two groups.

PMID:36411306 | DOI:10.1038/s41598-022-24569-9

Sci Rep. 2022 Nov 21;12(1):20005. doi: 10.1038/s41598-022-20991-1.

ABSTRACT

Modern datasets are characterized by numerous features related by complex dependency structures. To deal with these data, dimensionality reduction techniques are essential. Many of these techniques rely on the concept of intrinsic dimension (id), a measure of the complexity of the dataset. However, the estimation of this quantity is not trivial: often, the id depends rather dramatically on the scale of the distances among data points. At short distances, the id can be grossly overestimated due to the presence of noise, becoming smaller and approximately scale-independent only at large distances. An immediate approach to examining the scale dependence consists in decimating the dataset, which unavoidably induces non-negligible statistical errors at large scale. This article introduces a novel statistical method, Gride, that allows estimating the id as an explicit function of the scale without performing any decimation. Our approach is based on rigorous distributional results that enable the quantification of uncertainty of the estimates. Moreover, our method is simple and computationally efficient since it relies only on the distances among data points. Through simulation studies, we show that Gride is asymptotically unbiased, provides comparable estimates to other state-of-the-art methods, and is more robust to short-scale noise than other likelihood-based approaches.

PMID:36411305 | DOI:10.1038/s41598-022-20991-1

J Feline Med Surg. 2022 Nov 21:1098612X221125573. doi: 10.1177/1098612X221125573. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the association between meningeal enhancement (MgE) and cerebrospinal fluid (CSF) analysis results, their individual association with bacteriology results from affected ear samples and whether these test results influenced clinicians’ therapeutic choice in cats with otitis media and interna (OMI).

METHODS: This was a multicentre retrospective study carried out over an 8-year period. Cats diagnosed with OMI, with or without a nasopharyngeal polyp, leading to peripheral vestibular signs were included. Only cats for which MRI with postcontrast T1-weighted sequences and CSF analyses available were included. Cats with intra-axial MRI lesions or empyema were excluded.

RESULTS: Fifty-eight cats met the inclusion criteria. MgE was reported in 26/58 cases, of which nine had an abnormal CSF result (increased total nucleated cell count [TNCC] or total protein); 32/58 cases had no MgE, of which 10 showed abnormal CSF results. There was no association between bacteriology results (external ear canal or bulla) and MgE or abnormal CSF results. CSF abnormalities were statistically significantly more common in acute cases (n = 16/37) than in chronic cases (n = 3/21; Fischer’s test P = 0.04). Prednisolone was prescribed in 10/16 cases with increased TNCC. Among the 42 cases with normal TNCC, 15 received prednisolone and 13 received non-steroidal anti-inflammatory drugs. Various antimicrobial drugs were prescribed in 53/58 cats. Duration of antimicrobial treatment was similar, regardless of positive bacterial culture (5.58 vs 4.22 weeks), abnormal CSF (5.83 vs 4.76 weeks) or MgE (5.33 vs 4.90 weeks).

CONCLUSIONS AND RELEVANCE: No association was found between the CSF and MgE results. Furthermore, no association was found between MgE, CSF or bacteriology findings. In addition, abnormal CSF results might lead the clinician to treat with corticosteroids, but they did not have any impact on duration of antimicrobial treatment. CSF abnormalities were seen significantly less frequently in chronic cases. The outcome tended to be poorer when MgE was detected on MRI.

PMID:36409551 | DOI:10.1177/1098612X221125573

JMIR Res Protoc. 2022 Nov 21;11(11):e37663. doi: 10.2196/37663.

ABSTRACT

BACKGROUND: Antimicrobial resistance is a known global public health threat. In addition, it brings serious economic consequences to agriculture. Antibiotic resistance in humans, animals, and environment is interconnected, as proposed in the tricycle surveillance by the World Health Organization. In Malaysia, research and surveillance of antimicrobial resistance are mainly performed in clinical samples, agricultural settings, and surface waters, but no surveillance of the drinking water systems has been performed yet. Hence, this policy-driven study is a combined effort of microbiologists and engineers to provide baseline data on the magnitude of antimicrobial resistance in the drinking water systems of Malaysia.

OBJECTIVE: The aim of this study was to study the baseline level of antibiotic-resistant bacteria in the drinking water distribution systems of Malaysia by collecting samples from the pretreatment and posttreatment outlets of water treatment plants in a selected state of Malaysia. We aimed to determine the prevalence of antibiotic-resistant bacteria, the occurrence of antibiotic-resistant genes, and the level of antibiotics present in the drinking water systems.

METHODS: This is a laboratory-based, cross-sectional study in a selected state of Malaysia. Water samples from 6 drinking water treatment plants were collected. Samples were collected at 3 sampling points, that is, the intake sampling station, service reservoir outlet station, and the distribution system sampling station. These were tested against 7 types of antibiotics in triplicates. Samples were screened for antibiotic-resistant bacteria and antibiotic-resistant genes and quantified for the level of antibiotics present in the drinking water treatment plants.

RESULTS: We will show the descriptive statistics of the number of bacterial colonies harvested from water samples grown on Reasoner’s 2A agar with or without antibiotics, the occurrence of antibiotic-resistant genes, and the level of antibiotics detected in the water samples. The sampling frame was scheduled to start from November 2021 and continue until December 2022. Data analysis is expected to be completed by early 2023, and the results are expected to be published in mid-2023.

CONCLUSIONS: This study provides baseline information on the status of the antimicrobial-resistant bacteria, the presence of resistance genes as contaminants, and the level of antibiotics present in the drinking water systems of Malaysia, with the aim of demonstrating to policymakers the need to consider antimicrobial resistance as a parameter in drinking water surveillance.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37663.

PMID:36409546 | DOI:10.2196/37663

Vital Health Stat 1. 2022 Nov;(196):1-20.

ABSTRACT

To evaluate the quality of web surveys, the National Center for Health Statistics’ Division of Research and Methodology has been conducting a series of studies with survey data from commercially recruited panels,referred to as the Research and Development Survey (RANDS). This report describes the propensity-score adjusted estimates from the second round of RANDS (RANDS 2) using the 2016 National Health Interview Survey (NHIS).

PMID:36409516

JAMA Netw Open. 2022 Nov 1;5(11):e2243127. doi: 10.1001/jamanetworkopen.2022.43127.

ABSTRACT

IMPORTANCE: New York City, an early epicenter of the pandemic, invested heavily in its COVID-19 vaccination campaign to mitigate the burden of disease outbreaks. Understanding the return on investment (ROI) of this campaign would provide insights into vaccination programs to curb future COVID-19 outbreaks.

OBJECTIVE: To estimate the ROI of the New York City COVID-19 vaccination campaign by estimating the tangible direct and indirect costs from a societal perspective.

DESIGN, SETTING, AND PARTICIPANTS: This decision analytical model of disease transmission was calibrated to confirmed and probable cases of COVID-19 in New York City between December 14, 2020, and January 31, 2022. This simulation model was validated with observed patterns of reported hospitalizations and deaths during the same period.

EXPOSURES: An agent-based counterfactual scenario without vaccination was simulated using the calibrated model.

MAIN OUTCOMES AND MEASURES: Costs of health care and deaths were estimated in the actual pandemic trajectory with vaccination and in the counterfactual scenario without vaccination. The savings achieved by vaccination, which were associated with fewer outpatient visits, emergency department visits, emergency medical services, hospitalizations, and intensive care unit admissions, were also estimated. The value of a statistical life (VSL) lost due to COVID-19 death and the productivity loss from illness were accounted for in calculating the ROI.

RESULTS: During the study period, the vaccination campaign averted an estimated $27.96 (95% credible interval [CrI], $26.19-$29.84) billion in health care expenditures and 315 724 (95% CrI, 292 143-340 420) potential years of life lost, averting VSL loss of $26.27 (95% CrI, $24.39-$28.21) billion. The estimated net savings attributable to vaccination were $51.77 (95% CrI, $48.50-$55.85) billion. Every $1 invested in vaccination yielded estimated savings of $10.19 (95% CrI, $9.39-$10.87) in direct and indirect costs of health outcomes that would have been incurred without vaccination.

CONCLUSIONS AND RELEVANCE: Results of this modeling study showed an association of the New York City COVID-19 vaccination campaign with reduction in severe outcomes and avoidance of substantial economic losses. This significant ROI supports continued investment in improving vaccine uptake during the ongoing pandemic.

PMID:36409495 | DOI:10.1001/jamanetworkopen.2022.43127