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Nevin Manimala Statistics

Expanding causal genes for Parkinson’s disease via multi-omics analysis

NPJ Parkinsons Dis. 2023 Oct 21;9(1):146. doi: 10.1038/s41531-023-00591-0.

ABSTRACT

Genome‑wide association studies (GWASs) have revealed numerous loci associated with Parkinson’s disease (PD). However, some potential causal/risk genes were still not revealed and no etiological therapies are available. To find potential causal genes and explore genetically supported drug targets for PD is urgent. By integrating the expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets from multiple tissues (blood, cerebrospinal fluid (CSF) and brain) and PD GWAS summary statistics, a pipeline combing Mendelian randomization (MR), Steiger filtering analysis, Bayesian colocalization, fine mapping, Protein-protein network and enrichment analysis were applied to identify potential causal genes for PD. As a result, GPNMB displayed a robust causal role for PD at the protein level in the blood, CSF and brain, and transcriptional level in the brain, while the protective role of CD38 (in brain pQTL and eQTL) was also identified. We also found inconsistent roles of DGKQ on PD between protein and mRNA levels. Another 9 proteins (CTSB, ARSA, SEC23IP, CD84, ENTPD1, FCGR2B, BAG3, SNCA, FCGR2A) were associated with the risk for PD based on only a single pQTL after multiple corrections. We also identified some proteins’ interactions with known PD causative genes and therapeutic targets. In conclusion, this study suggested GPNMB, CD38, and DGKQ may act in the pathogenesis of PD, but whether the other proteins involved in PD needs more evidence. These findings would help to uncover the genes underlying PD and prioritize targets for future therapeutic interventions.

PMID:37865667 | DOI:10.1038/s41531-023-00591-0

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Influence of unilateral eyelid spasms and botulinum toxin treatment on intraocular pressure measured by transpalpebral tonometer

Int Ophthalmol. 2023 Oct 21. doi: 10.1007/s10792-023-02898-6. Online ahead of print.

ABSTRACT

PURPOSE: Eyelid spasms might be associated with elevated intraocular pressure (IOP) in hemifacial spasm (HFS) patients. IOP assessment using a Goldmann applanation tonometer (GAT) is often compromised by eyelid spasms. This study aimed to assess the effect of HFS on IOP measurements using the transpalpebral tonometer Diaton® before and after treatment with botulinum toxin type A (BTX-A) and compared Diaton® and GAT measurements after treatment with BTX-A.

METHODS: IOP measurements were obtained with Diaton® in 27 patients with moderate-to-severe HFS before and after treatment with BTX-A. After treatment, the IOP was also measured using GAT and the results were compared with the ones measured with a Diaton®. The patients underwent automated perimetry, OCT, and pachymetry for screening to glaucoma.

RESULTS: Mean IOP with Diaton® was 11 ± 3.42 mmHg before treatment in the affected eye and 9 ± 2.98 mmHg in the contralateral eye. This difference was statistically significant (P = 0.012). However, after treatment with BTX-A, no interocular difference was found in IOP obtained with Diaton® (P = 0.204) or GAT (P = 0.971). Comparison between GAT and Diaton® measurements showed no significant differences after BTX-A treatment between the affected (P = 0.212) and contralateral eye (P = 0.971).

CONCLUSIONS: A significant reduction in IOP measurements on the affected side of HFS patients was observed after treatment with BTX-A, demonstrating that eyelid spasms may increase the IOP. No significant difference was observed between Diaton® and GAT measurements after the application of BTX-A. No differences were found in automated perimetry, OCT, and CCT when comparing affected eyes with contralateral eyes.

PMID:37865617 | DOI:10.1007/s10792-023-02898-6

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Determinants and outcomes of acute pancreatitis in patients hospitalized for COVID-19: Early pandemic experience

Pancreatology. 2023 Oct 16:S1424-3903(23)01824-0. doi: 10.1016/j.pan.2023.10.012. Online ahead of print.

ABSTRACT

OBJECTIVES: To examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19).

METHODS: This is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05.

RESULTS: Significant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost.

CONCLUSIONS: In hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.

PMID:37865613 | DOI:10.1016/j.pan.2023.10.012

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“Selection of statistical tests influences the interpretation of a study outcome” a comment on “Giriraja KV, Bhatnagar SK, Tomlinson L, Sancilio F. An open-label, multicenter, phase 2 study of a food enriched with docosahexaenoic acid in adults with sickle cell disease. Prostaglandins Leukot Essent Fatty Acids. 2023 Jun; 193:102574. Doi: 10.1016/j.plefa.2023.102574. Epub 2023 Apr 7. PMID: 37121179”

Prostaglandins Leukot Essent Fatty Acids. 2023 Oct 12:102591. doi: 10.1016/j.plefa.2023.102591. Online ahead of print.

ABSTRACT

Parametric tests such as t-tests require a normal distribution of data. However, the determination of normal distribution may not be conclusive while dealing with a small sample size. Non-parametric tests such as Wilcoxon tests may be used in this situation, as these tests do not require normal distribution.

PMID:37865611 | DOI:10.1016/j.plefa.2023.102591

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Nevin Manimala Statistics

Emergency departments: An underutilized resource to address pediatric influenza vaccine coverage

Vaccine. 2023 Oct 19:S0264-410X(23)01222-7. doi: 10.1016/j.vaccine.2023.10.039. Online ahead of print.

ABSTRACT

BACKGROUND: Emergency department (ED) based influenza vaccine (IV) programs have been successful in adults; however, little is known about pediatric ED IV programs in terms of prevalence, feasibility, or successful implementation.

AIMS: To describe the reach and effectiveness of IV practices in pediatric EDs, and identify IV facilitators and barriers.

METHODS: We assessed, via cross-sectional survey of pediatric ED physicians, number of EDs offering IV to children, vaccines administered annually, and perceived facilitators/barriers to vaccination. The proportion of EDs offering IV is reported. Chi-square tests compared facilitators and barriers among high performers (≥50 IV/year), low performers (<50 IV/yr), and non-vaccinators. We calculated an area of missed effect for the number of children who could be vaccinated if non-vaccinating EDs offered IV.

RESULTS: Among 492 physicians from 166 EDs, 142 responded (representing 61 (37.3 %) EDs). Most EDs were in large, urban, academic, freestanding children’s hospitals (Table 1). Only twenty-six EDs (44.3 %) offer ≥ 1 IV/yr. Seventeen (65.4 %) were low performers, five (19.2 %) high performers, and four (15.4 %) were model programs. High/model performers used establish workflows more commonly than lower performers (78 % vs. 33 %), although this was not statistically significant (p = 0.077). Common facilitators included: strong provider and administration buy-in, electronic health record facilitation, storage/accessibility, and having a leadership team/champion (Fig. 1). Non-vaccinators commonly perceived lack of these factors as barriers. Many (24/61, 39.3 %) EDs expressed interested in establishing or growing IV programs. Up to 18,250 unvaccinated children could receive IV annually if non-vaccinating EDs offered IV during influenza season.

CONCLUSIONS: Over half of EDs participating in the Pediatric Emergency Medicine Collaborative Research Committee do not currently offer pediatric IV. Addressing identified barriers/facilitators to develop IV programs in EDs has potential to improve vaccination rates, especially among minority and underserved children.

PMID:37865600 | DOI:10.1016/j.vaccine.2023.10.039

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To excel at engineering design, generative AI must learn to innovate, study finds

A new study reveals the pitfalls of deep generative models when they are tasked with solving engineering design problems. The researchers say if mechanical engineers want help from AI for novel ideas and designs, they’ll have to refocus those models beyond ‘statistical similarity.’ 
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Self-inflicted burns: The Experience of a UK Regional Burns Centre

J Burn Care Res. 2023 Oct 21:irad163. doi: 10.1093/jbcr/irad163. Online ahead of print.

ABSTRACT

Self-inflicted burns (SIB) are preventable injuries that often occur due to suicidal intent or deliberate self-harm. The incidence of SIB and demographics vary across different countries. This study highlights our regional experience of SIB over almost two decades, assessing characteristics and outcomes. A retrospective chart review of all patients assessed at a UK regional burns centre, presenting with SIB, from 2003 to 2021, was performed. Subgroup analyses based on gender, the presence or absence of pre-existing psychiatric disorders and in-hospital patient mortality were undertaken. The relationship between annual mental health funding and incidence of SIB was assessed. Over the study period 285 SIB cases, with a median age of 42.84 years, presented to our centre. The majority of patients were male (63.2%) and had a pre-existing psychiatric disorder (74.7%). Flame burns were the most frequent type of injury (82.1%) and the median total body surface area (TBSA) was 10.25%. The average length of hospital stay was 10 days and inpatient mortality rate 20.7%, significantly great than the mortality of the rest of the cohort (3.7%, p<0.01). SIB survivors were younger and had less severe burns, relative to non-survivors. There was no statistically significant correlation between the incidence of self-inflicted burns and mental health funding. Self-inflicted burns account for a minority of referrals to our regional burns centre. Adequately funded regional and national measures should be implemented to reduce the incidence and impact of these injuries, alongside appropriate mental health support.

PMID:37864840 | DOI:10.1093/jbcr/irad163

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Does diabetes mellitus affect the development of fetal brain structures and spaces including corpus callosum, subarachnoid space, insula, and parieto-occipital fissure?

J Clin Ultrasound. 2023 Oct 21. doi: 10.1002/jcu.23597. Online ahead of print.

ABSTRACT

PURPOSE: We investigated the impact of pregestational and gestational diabetes mellitus (PGDM and GDM) on the development of fetal intracranial structures and spaces.

METHODS: This prospective cross-sectional study involved singleton pregnancies between 20 and 32 weeks of gestation. The study comprised a control group (n = 65) of healthy pregnant women without diabetes mellitus (DM); a PGDM group (n = 43) of pregnant women having type 2 DM in a controlled diabetic state; and a GDM group (n = 26) of pregnant women with GDM diagnosed with 2-h 75-g oral glucose tolerance test and received intervention to reduce the diabetic impact on fetus. During neurosonographic evaluation, the simultaneous measurements of corpus callosum (CC) width and depth in the midsagittal image; and lateral craniocortical and posterior craniocortical widths of the subarachnoid space and insular and parieto-occipital fissure depths in the axial image were performed. Before statistical analysis, these values were carefully adjusted for the occipitofrontal diameter.

RESULTS: The DM groups displayed substantially higher frequencies of family history of DM and obstetric history of GDM compared to the control group (p < 0.05). Regarding the neurosonographic parameters, the CC length and insular and parieto-occipital fissure depths were significantly increased in the GDM group but not in the PGDM group (p < 0.05). No significant difference was found among the study groups regarding other neurosonographic parameters (p > 0.05).

CONCLUSION: The results of neurosonographical evaluation of fetal brain structures and spaces reveal that diabetic impact may not be seen in the presence of PGDM, especially in pregnant women receiving prenatal interventions to reduce or avoid diabetic adverse effects on fetal brain development. The effect of GDM on neurosonographically assessed fetal brain development should be evaluated in further studies with subjects matched for gestational weeks and antenatal care conditions.

PMID:37864816 | DOI:10.1002/jcu.23597

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Mapping Kenyon cell inputs in Drosophila using dye electroporation

STAR Protoc. 2023 Oct 20;4(4):102478. doi: 10.1016/j.xpro.2023.102478. Online ahead of print.

ABSTRACT

Here, we describe a technique for charting the inputs of individual Kenyon cells in the Drosophila brain. In this technique, a single Kenyon cell per brain hemisphere is photo-labeled to visualize its claw-like dendritic terminals; a dye-filled electrode is used to backfill the projection neuron connected to each claw. This process can be repeated in hundreds of brains to build a connectivity matrix. Statistical analyses of such a matrix can reveal connectivity patterns such as random input and biased connectivity. For complete details on the use and execution of this protocol, please refer to Hayashi et al. (2022).1.

PMID:37864788 | DOI:10.1016/j.xpro.2023.102478

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A Visit to the Pediatrician as a Part of Comprehensive Prenatal Care?

Matern Child Health J. 2023 Oct 21. doi: 10.1007/s10995-023-03791-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend that expectant parents receive a preventive visit with a pediatrician in the prenatal period (a pediatric prenatal visit, or PPV). Discussing newborn health topics in the prenatal period tends to be more effective than immediately postpartum, and research suggests, for example, that the PPV increases timely childhood immunizations. However, only 22% of expectant parents have these visits, and there are significant disparities by race and income.

METHODS: A 2-min online survey with open-ended questions was emailed to 304 eligible obstetrics providers in Rochester, NY. Simple descriptive statistics and chisquare analysis were applied to survey responses. Responses were organized within the framework of knowledge, attitudes, and practices to identify barriers to guideline adherence resulting in chronic under-utilization of the PPV.

RESULTS: Ninety obstetric providers completed the survey. 66 reported awareness of the PPV, and 45 reported referring patients for a PPV. However, in open-ended questions, respondents expressed confusion between the PPV and a “meet and greet” visit with a pediatrician. Some respondents believed that the PPV is not covered by insurance, even though these visits are covered by Medicaid and marketplace insurance. Providers who had personally received one as a parent expressed positive attitudes.

DISCUSSION: These findings indicate that unfamiliarity with the PPV is one barrier to referral. Educating providers about the guideline recommendations, evidence base, and insurance coverage could overcome this barrier. Doing so could reduce disparities in utilization of the pediatric prenatal visit.

PMID:37864772 | DOI:10.1007/s10995-023-03791-5