Tag: nevin manimala

Eur J Nutr. 2023 Oct 7. doi: 10.1007/s00394-023-03251-4. Online ahead of print.

ABSTRACT

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.

METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.

RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.

CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.

PMID:37804448 | DOI:10.1007/s00394-023-03251-4

Mamm Genome. 2023 Oct 7. doi: 10.1007/s00335-023-10019-y. Online ahead of print.

ABSTRACT

Linkage disequilibrium (LD) affects genomic studies accuracy. High-density genotyping platforms identify SNPs across animal genomes, increasing LD evaluation resolution for accurate analysis. This study aimed to evaluate the decay and magnitude of LD in a cohort of 81 crossbred dairy cattle using the GGP_HDv3_C Bead Chip. After quality control, 116,710 Single Nucleotide Polymorphisms (SNPs) across 2520.241 Mb of autosomes were retained. LD extent was assessed between autosomal SNPs within a 10 Mb range using the r² statistics. LD value declined as inter-marker distance increased. The average r² value was 0.24 for SNP pairs < 10 kb apart, decreasing to 0.13 for 50-100 kb distances. Minor allele frequency (MAF) and sample size significantly impact LD. Lower MAF thresholds result in smaller r² values, while higher thresholds show increased r² values. Additionally, smaller sample sizes exhibit higher average r² values, especially for larger physical distance intervals (> 50 kb) between SNP pairs. Effective population size and inbreeding coefficient were 150 and 0.028 for the present generation, indicating a decrease in genetic diversity over time. These findings imply that the utilization of high-density SNP panels and customized/breed-specific SNP panels represent a highly favorable approach for conducting genome-wide association studies (GWAS) and implementing genomic selection (GS) in the Bos indicus cattle breeds, whose genomes are still largely unexplored. Furthermore, it is imperative to devise a meticulous breeding strategy tailored to each herd, aiming to enhance desired traits while simultaneously preserving genetic diversity.

PMID:37804434 | DOI:10.1007/s00335-023-10019-y

Brain Struct Funct. 2023 Oct 7. doi: 10.1007/s00429-023-02714-y. Online ahead of print.

ABSTRACT

Integrating the underlying brain circuit’s structural and functional architecture is required to explore the functional organization of cognitive networks. In that regard, we recently introduced the Functionnectome. This structural-functional method combines an fMRI acquisition with tractography-derived white matter connectivity data to map cognitive processes onto the white matter. However, this multimodal integration faces three significant challenges: (1) the necessarily limited overlap between tractography streamlines and the grey matter, which may reduce the amount of functional signal associated with the related structural connectivity; (2) the scrambling effect of crossing fibers on functional signal, as a single voxel in such regions can be structurally connected to several cognitive networks with heterogeneous functional signals; and (3) the difficulty of interpretation of the resulting cognitive maps, as crossing and overlapping white matter tracts can obscure the organization of the studied network. In the present study, we tackled these problems by developing a streamline-extension procedure and dividing the white matter anatomical priors between association, commissural, and projection fibers. This approach significantly improved the characterization of the white matter involvement in the studied cognitive processes. The new Functionnectome priors produced are now readily available, and the analysis workflow highlighted here should also be generalizable to other structural-functional approaches. We improved the Functionnectome approach to better study the involvement of white matter in brain function by separating the analysis of the three classes of white matter fibers (association, commissural, and projection fibers). This step successfully clarified the activation maps and increased their statistical significance.

PMID:37804431 | DOI:10.1007/s00429-023-02714-y

Abdom Radiol (NY). 2023 Oct 7. doi: 10.1007/s00261-023-04031-8. Online ahead of print.

ABSTRACT

PURPOSE: We have long noted unique portal venous phase (PVP) imaging discordance of focal liver masses between CEUS, showing rapid marked washout, and MRI, showing progressive or sustained enhancement. We postulate association of this unique discordance with intrahepatic cholangiocarcinoma (ICC) and causal relationship to different contrast agent behavior. We investigate this unique discordance, propose its clinical significance for ICC diagnosis, and confirm further histologic associations.

METHODS: Cases were collected within our CEUS department and from pathology records over a ten-year interval. This retrospective review includes 99 patients, 73 with confirmed ICC and 26 other diagnoses, showing unique PVP discordance. The CEUS and MRI enhancement characteristics were compared for all patients.

RESULTS: Unique discordance is identified in 67/73 (92%) ICC and difference between the PVP appearance on MRI and CEUS is statistically significant (p < 0.0001). Arterial phase enhancement did not show statistically significant difference between CEUS and MRI, p > 0.05. Other diagnoses showing unique discordance include especially lymphoma (n = 7), sclerosed hemangioma (n = 6), HCC (n = 4), metastases (n = 2), and other rare entities.

CONCLUSION: ICC shows this discrepant intermodality enhancement pattern in a statistically significant number of cases and should be considered along with other LR-M features in at-risk patients. Discordance is also rarely seen in a number of other liver lesions.

PMID:37804423 | DOI:10.1007/s00261-023-04031-8

Oncol Ther. 2023 Oct 7. doi: 10.1007/s40487-023-00246-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the overall surgical outcomes of infranotch T4b oral cancers and compare them with T4a oral cancers.

METHODS: PubMed, EMBASE and Cochrane databases from 2000 to 2022 were systematically searched. Clinical studies reporting at least one outcome following curative surgery and adjuvant therapy for comparison of patients with either infranotch T4b (IN-T4b) or T4a tumour. The heterogeneity of the included studies was determined using Tau-squared, Chi-squared, and the Higgins I² test. The random effects model was used to determine the log odds ratio (logOR).

RESULTS: The systematic review comprised 11,790 patients from 16 included studies. Seven studies were included in the meta-analysis (n = 11,381). For IN-T4b patients, the pooled 2 and 5 year overall survival (OS) were 59.3% and 53.2%, 2 and 5 year disease-free survival (DFS) 57.9% and 48.4%, 2 and 5 year disease-specific survival (DSS) 72% and 68%, and 2 and 5 year local control (LC), 47% and 56%, respectively. There was no statistically significant difference in 2 year OS [logOR = 0.28 (-0.47, 1.03), p = 0.46, confidence interval (CI) = 95%], 5 year OS [logOR = 0.7 (-0.4, 1.8), p = 0.54, CI = 95%], 2 year DFS [logOR = 0.22 (-0.35, 0.79), p = 0.45, CI = 95%], 5 year DFS [logOR = 0.17 (-0.42, 0.77), p = 0.57, CI = 95%], 2 year LC [logOR = 0.47 (-0.33, 1.26), p = 0.25, CI = 95%] and 5 year LC [logOR = 0.34 (-0.31, 0.99), p = 0.31, CI = 95%] between IN-T4b and T4a oral cancers.

CONCLUSION: Results of this meta-analysis suggest that IN-T4b oral cancers have similar outcomes to T4a oral cancers, which supports down-staging IN-T4b cancers to T4a cancers.

PMID:37804420 | DOI:10.1007/s40487-023-00246-3

Drug Saf. 2023 Oct 7. doi: 10.1007/s40264-023-01353-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals.

OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process.

METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals.

RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development.

CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.

PMID:37804398 | DOI:10.1007/s40264-023-01353-w

J Comput Aided Mol Des. 2023 Oct 7. doi: 10.1007/s10822-023-00536-y. Online ahead of print.

ABSTRACT

QSAR models capable of predicting biological, toxicity, and pharmacokinetic properties were widely used to search lead bioactive molecules in chemical databases. The dataset’s preparation to build these models has a strong influence on the quality of the generated models, and sampling requires that the original dataset be divided into training (for model training) and test (for statistical evaluation) sets. This sampling can be done randomly or rationally, but the rational division is superior. In this paper, we present MASSA, a Python tool that can be used to automatically sample datasets by exploring the biological, physicochemical, and structural spaces of molecules using PCA, HCA, and K-modes. The proposed algorithm is very useful when the variables used for QSAR are not available or to construct multiple QSAR models with the same training and test sets, producing models with lower variability and better values for validation metrics. These results were obtained even when the descriptors used in the QSAR/QSPR were different from those used in the separation of training and test sets, indicating that this tool can be used to build models for more than one QSAR/QSPR technique. Finally, this tool also generates useful graphical representations that can provide insights into the data.

PMID:37804393 | DOI:10.1007/s10822-023-00536-y

Trop Anim Health Prod. 2023 Oct 7;55(6):352. doi: 10.1007/s11250-023-03736-8.

ABSTRACT

The current cross-sectional study aimed to determine the seroprevalence of Leptospira infection in bovine dairy farms in the Telangana state of India, as well as the associated risk factors, in order to implement effective preventive measures for disease control. A total of 469 blood samples were collected from 67 herds/farms in different areas, covering 20 administrative districts in the state. These samples consisted of 253 from cattle and 216 from buffaloes. Questionnaires were used to collect data on host and epidemiological factors. The collected sera were tested using the gold standard serological test, the Microscopic Agglutination Test (MAT), which employed a panel of 18 reference serovars for Leptospira exposure. The statistical analysis of epidemiological data was carried out to identify the risk factors associated with Leptospira exposure. The overall observed seroprevalence at the animal and farm levels was 41.4% and 77.6%, respectively. The most prevalent anti-leptospiral antibodies were observed against the serogroups Icterohaemorrhagiae (32.4%), Pomona (22.2%), Javanica (19.1%), Australis (17.0%), Bataviae (15.5%), Autumnalis (12.9%), Hebdomadis (12.9%), and others, in the total reacting samples. At the animal level, the significant risk factors associated with exposure to Leptospira species were breed (p = 0.03) and health status (p = 0.03). Furthermore, the multivariate statistical analysis of farm factors revealed that farm size (p = 0.05), presence of dogs (p = 0.04) and rodents (p = 0.01) on the farm, use of fodder from wet soils (p = 0.04), and proximity to water bodies (p = 0.04) were significantly associated with exposure to Leptospira in the studied region. This study provides the first report from India highlighting the important risk factors at the herd/farm and animal level associated with Leptospira infections in cattle and buffaloes. The findings contribute to strengthening the one-health strategy by facilitating the design and planning of appropriate control measures to alleviate the burden of leptospirosis in bovines.

PMID:37804390 | DOI:10.1007/s11250-023-03736-8

Clin Exp Med. 2023 Oct 7. doi: 10.1007/s10238-023-01190-2. Online ahead of print.

ABSTRACT

PD-L1 expression is known to predict the benefits of immune checkpoint inhibitor therapy for triple-negative breast cancer (TNBC). We examined whether the PD-L1 expression evaluated in biopsy specimens accurately reflects its expression in the whole tumor. Immunohistochemistry was performed on 81 biopsy and resection specimens from patients with TNBC to determine their PD-L1 status. We found PD-L1-positive tumors in 23 (28%) biopsy specimens and primarily PD-L1-negative tumors in 58 (72%). The PD-L1 status was reevaluated in matching postoperative specimens of primarily PD-L1-negative tumors. Of them, 31% (18/58) were positive, whereas 69% (40/58) were negative. Considering the pre- and postoperative analyses, 41 (51%) patients had PD-L1-positive tumors, while 40 had PD-L1-negative tumors. We found 18 (22%) more PD-L1-positive tumors while examining the resection specimens compared to biopsies, and the difference was statistically significant (p = 0.0038). Diagnostic biopsies do not fully reflect the PD-L1 expression in TNBC. Our results suggest that a significant subset of TNBC patients may be misclassified as PD-L1-negative and disqualified from anti-PD-L1 therapy.

PMID:37804360 | DOI:10.1007/s10238-023-01190-2

Knee Surg Sports Traumatol Arthrosc. 2023 Oct 7. doi: 10.1007/s00167-023-07578-7. Online ahead of print.

ABSTRACT

PURPOSE: This study reports the five-year functional outcomes from a prospective cohort study comparing robotic-arm assisted total knee arthroplasty (RO TKA) versus conventional manual total knee arthroplasty (CO TKA).

METHODS: This prospective single-surgeon study included 120 patients with symptomatic end-stage knee arthritis undergoing primary TKA. This included 60 consecutive patients undergoing CO TKA followed by 60 consecutive patients undergoing RO TKA using a semi-automated robotic device. Study patients were reviewed at one, two, and five years after surgery and the following outcomes recorded: The University of California at Los Angeles activity-level (UCLA), Knee Society Score (KSS), Oxford Knee Score (OKS) Forgotten Joint Score (FJS), and any complications.

RESULTS: There were no statistical differences between RO TKA and CO TKA in the median UCLA score (p = N.S), median KSS (p = N.S), and median OKS (p = N.S) at five-year follow-up. RO-TKA was associated with statistically significant improvements in the FJS at one (p = 0.001), two (p = 0.003), and five (p = 0.025) years of follow-up compared with CO TKA. There was no statistical difference in the incidence of knee stiffness requiring manipulation under anesthesia between the two treatment groups (p = N.S).

CONCLUSION: Patients in both treatment groups had excellent functional outcomes with comparable patient reported outcomes at five-year follow-up. RO TKA was associated with statistically significant improvements in the FJS compared with CO TKA, but these differences did not reach the minimal clinically important difference at any follow-up interval. There was no overall difference in complications between the two treatment groups at five-year follow-up.

LEVEL OF EVIDENCE: II (Prospective cohort study).

PMID:37804346 | DOI:10.1007/s00167-023-07578-7