Tag: nevin manimala

Mov Disord. 2023 Feb 14. doi: 10.1002/mds.29337. Online ahead of print.

ABSTRACT

BACKGROUND: Epidemiological studies that examined the association between Parkinson’s disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.

OBJECTIVE: We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.

METHODS: We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses.

RESULTS: We confirmed a previously reported positive genetic correlation of PD with melanoma (G_corr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G_corr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31).

CONCLUSIONS: We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

PMID:36788297 | DOI:10.1002/mds.29337

Pediatr Res. 2023 Feb 14. doi: 10.1038/s41390-023-02479-4. Online ahead of print.

ABSTRACT

Oncometabolism can be targeted for the development of less myelotoxic oncotherapeutics. Lactate dehydrogenase A (LDHA) is central to the Warburg effect, a potential oncometabolic shift in neuroblastoma (NBL). Advanced surgical, cytotoxic and cell-differentiating therapies improved survival of children with NBL. Anti-GD2 monoclonal antibodies (mAb) effectively targeting NBL are also incorporated into complex therapies. However, poor clinical outcomes of high-risk NBL require improvements. Here, we verified the pre-reported prognostic value of LDHA expression in NBL using the R2 onco-genomics platform. Kaplan-Meier curves re-demonstrated that higher tumor LDHA expression correlates with worse survival. Multivariate statistics confirmed LDHA is independent from age, stage, and MYCN amplification. In conclusion, a molecular construct is proposed with anti-GD2 mAbs utilized for the targeted delivery of liposomes containing an LDHA inhibitor, Oxamate. Development and preclinical testing of this immunoliposome may validate targeted inhibition of the Warburg effect for NBL. IMPACT: Development of therapeutics against oncometabolism. Targeted specified drug-delivery with mAb. Sparing normal tissues from profound LDHA inhibition. Immunoliposome loaded with an anti-metabolite. If preclinically successful, has translational potential.

PMID:36788290 | DOI:10.1038/s41390-023-02479-4

Sci Rep. 2023 Feb 14;13(1):2617. doi: 10.1038/s41598-023-29767-7.

NO ABSTRACT

PMID:36788260 | DOI:10.1038/s41598-023-29767-7

Nat Commun. 2023 Feb 14;14(1):832. doi: 10.1038/s41467-023-36544-7.

ABSTRACT

Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting their clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a statistical framework named X-Wing to improve predictive performance in ancestrally diverse populations. X-Wing quantifies local genetic correlations for complex traits between populations, employs an annotation-dependent estimation procedure to amplify correlated genetic effects between populations, and combines multiple population-specific PRS into a unified score with GWAS summary statistics alone as input. Through extensive benchmarking, we demonstrate that X-Wing pinpoints portable genetic effects and substantially improves PRS performance in non-European populations, showing 14.1%-119.1% relative gain in predictive R² compared to state-of-the-art methods based on GWAS summary statistics. Overall, X-Wing addresses critical limitations in existing approaches and may have broad applications in cross-population polygenic risk prediction.

PMID:36788230 | DOI:10.1038/s41467-023-36544-7

J Agromedicine. 2023 Feb 14:1-11. doi: 10.1080/1059924X.2023.2180124. Online ahead of print.

ABSTRACT

OBJECTIVES: Agriculture in the United Kingdom (UK) continues to be one of the most dangerous occupations, accounting for around a fifth of fatal workplace injuries and many other injuries, both major and minor. This study examines young farmers’ awareness of, attitude to and behaviors around safety practices on-farm.

METHOD: A survey was undertaken amongst a group of young farmers aged 16-years and over who were actively engaged in farming in Northern Ireland, focusing on attitudes and behaviors towards safety on-farm. Drawing on previous literature, this study examined whether younger farmers demonstrate a higher degree of risk tolerance and are more likely to engage in risk taking behavior when undertaking routine farming practices leading to potential injuries and lost working days. The young farmers surveyed were classified into three groups and differences in risk perception were examined.

RESULTS: The results indicate that, statistically, farmer age, intensity of farming alongside the level of farming experience contribute to incident occurrence. Our results indicate a need for attitudinal and behavioral change, particularly around risk-taking behaviors that ultimately result in farm incidents, impacting on both the performance of the farm business and individual farmer well-being.

CONCLUSION: Policies aimed at addressing perception and acceptance of risks among farmers are recommended.

PMID:36788204 | DOI:10.1080/1059924X.2023.2180124

Infection. 2023 Feb 15. doi: 10.1007/s15010-023-01995-z. Online ahead of print.

ABSTRACT

PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany.

METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants.

RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection.

CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.

PMID:36788173 | DOI:10.1007/s15010-023-01995-z

Updates Surg. 2023 Feb 14. doi: 10.1007/s13304-023-01453-3. Online ahead of print.

ABSTRACT

The aim of this study is to compare the functional, oncological, and complication outcomes of perineoscopic radical prostatectomy (PeRP) and robot-assisted radical prostatectomy (RARP) operations. Patients who underwent radical prostatectomy (RP) between October 2018 and June 2020 for localized prostate cancer (N0, < T3) were retrospectively screened. After the exclusion criteria, 56 patients who underwent PeRP and 67 patients who underwent RARP remained in the study. Demographic, perioperative, and postoperative data were collected. In functional outcomes, continence and potency status were compared at 1, 3, 6, and 12 months. The mean age of the patients was 61.3 ± 5.9 years in the PeRP group and 62.2 ± 5.7 years in the RARP group. No statistically significant differences were present between preoperative and postoperative values. Among the perioperative findings, the mean operation time was 90.4 ± 11.2 min for the PeRP group and 114.6 ± 14.7 min for the RARP group. The operation time was shorter in the PeRP group. The average hospital stay was 2 ± 0.6 days in the PeRP group and 2.3 ± 0.5 days in the RARP group. It was significantly shorter in the PeRP group. There is no statistically significant difference between the two groups in the oncological and functional results. PeRP is a surgical procedure safe in low-risk patients with medium-risk prostate cancer (PCa) who do not require lymph-node dissection. Moreover, PeRP minimizes the difficulties of perineal surgery.

PMID:36788157 | DOI:10.1007/s13304-023-01453-3

Eur J Hum Genet. 2023 Feb 15. doi: 10.1038/s41431-023-01302-2. Online ahead of print.

ABSTRACT

Age-related (AR) hearing loss (HL) is a prevalent sensory deficit in the elderly population. Several studies showed that common variants increase ARHL susceptibility. Here, we demonstrate that rare-variants play a crucial role in ARHL etiology. We analyzed exome and imputed data from white-European UK Biobank volunteers, performing both single-variant and rare-variant aggregate association analyses using self-reported ARHL phenotypes. We identified and replicated associations between ARHL and rare-variants in KLHDC7B, PDCD6, MYO6, SYNJ2, and TECTA. PUS7L and EYA4 also revealed rare-variant associations with ARHL. EYA4, MYO6, and TECTA are all known to underline Mendelian nonsyndromic HL. PDCD6, a new HL gene, plays an important role in apoptosis and has widespread inner ear expression, particularly in the inner hair cells. An unreplicated common variant association was previously observed for KHLDC7B, here we demonstrate that rare-variants in this gene also play a role in ARHL etiology. Additionally, the first replicated association between SYNJ2 and ARHL was detected. Analysis of common variants revealed several previously reported, i.e., ARHGEF28, and new, i.e., PIK3R3, ARHL associations, as well as ones we replicate here for the first time, i.e., BAIAP2L2, CRIP3, KLHDC7B, MAST2, and SLC22A7. It was also observed that the odds ratios for rare-variant ARHL associations, were higher than those for common variants. In conclusion, we demonstrate the vital role rare-variants, including those in Mendelian nonsyndromic HL genes, play in the etiology of ARHL.

PMID:36788145 | DOI:10.1038/s41431-023-01302-2

Health Commun. 2023 Feb 14:1-14. doi: 10.1080/10410236.2023.2175407. Online ahead of print.

ABSTRACT

This meta-analysis investigated the persuasive effects of temporal framing in health messaging. Our analysis included 39 message pairs from 22 studies in 20 articles (N = 4,998) that examined the effects of temporal framing (i.e. present-oriented messages vs. future-oriented messages) on attitudes, intentions, and behaviors in health contexts. We found that present-oriented messages were significantly more persuasive than future-oriented messages in terms of intentions and integrated persuasive outcomes. Effects of temporal framing on attitudes and behaviors were not statistically significant. We tested six moderators of temporal framing effects (gain vs. loss framing, temporal framing operationalization, behavior type, timing of effect assessment, age, CFC levels) but none of them was statistically significant. Implications for future temporal framing research are discussed.

PMID:36788142 | DOI:10.1080/10410236.2023.2175407

Mod Pathol. 2023 Jan 10;36(3):100051. doi: 10.1016/j.modpat.2022.100051. Online ahead of print.

ABSTRACT

An epithelial odontogenic tumor called adenoid ameloblastoma (AA) has recently been included in the new WHO classification. However, AA has considerable overlapping features with a preexisting entity, dentinogenic ghost cell tumor (DGCT). This study compared the clinical, histologic, and molecular characteristics of AA and DGCT. Eight cases of odontogenic tumors initially diagnosed as AA or DGCT were included in this study. Quantitative histologic analysis, β-catenin immunohistochemistry, and molecular profiling using next generation sequencing were performed. Additionally, accumulated clinical data of AA and DGCT were statistically analyzed. Nuclear β-catenin accumulation was detected in all cases in common, although the tumors studied histologically consisted of varying combinations of the AA-like phenotype, ghost cells, and dentinoid. However, CTNNB1 hotspot mutations were not found in any case. Instead, loss-of-function mutations in tumor suppressor genes involved in the WNT pathway, including the APC, SMURF1, and NEDD4L genes, were found regardless of histologic type. In addition, KRT13 mutations were detected in 2 cases with a high proportion of ghost cells. Finally, a literature analysis revealed clinical similarities between the previously reported cases of AA and DGCT. These findings suggest that from a clinical and molecular point of view, AA and DGCT represent a histologic spectrum of WNT pathway-altered benign odontogenic tumors rather than 2 distinct tumors. Moreover, previously unidentified keratin mutations may be associated with ghost cell formation found in specific types of odontogenic lesions.

PMID:36788106 | DOI:10.1016/j.modpat.2022.100051