Tag: nevin manimala

Genet Epidemiol. 2023 Feb 19. doi: 10.1002/gepi.22519. Online ahead of print.

ABSTRACT

The application of causal mediation analysis (CMA) considering the mediation effect of a third variable is increasing in epidemiological studies; however, this requires fitting strong assumptions on confounding bias. To address this limitation, we propose an extension of CMA combining it with Mendelian randomization (MRinCMA). We applied the new approach to analyse the causal effect of obesity and diabetes on pancreatic cancer, considering each factor as potential mediator. To check the performance of MRinCMA under several conditions/scenarios, we used it in different simulated data sets and compared it with structural equation models. For continuous variables, MRinCMA and structural equation models performed similarly, suggesting that both approaches are valid to obtain unbiased estimates. When noncontinuous variables were considered, MRinCMA presented, overall, lower bias than structural equation models. By applying MRinCMA, we did not find any evidence of causality of obesity or diabetes on pancreatic cancer. With this new methodology, researchers would be able to address CMA hypotheses by appropriately accounting for the confounding bias assumption regardless of the conditions used in their studies in different settings.

PMID:36807329 | DOI:10.1002/gepi.22519

Sex Transm Dis. 2023 Feb 20. doi: 10.1097/OLQ.0000000000001783. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of sexually transmitted infections (STIs) is at an all-time high. Direct-to-consumer STI testing services may help alleviate this undue health burden. These products are sold online and rarely require interaction with a healthcare professional (HCP). Vendors offer STI self-collection kits or prescriptions for HCP specimen collection. The objective was to understand the scope of direct-to-consumer STI testing services offered and provide recommendations for consumers and industry.

METHODS: Seven volunteers searched for “STD tests” on Google from February 1 through March 31, 2021 and shared their top three results. The study team extracted data from consumer-facing information on each website. Descriptive statistics and thematic qualitative analyses were performed.

RESULTS: Twenty vendors were identified. Most vendors (95%) used Clinical Laboratory Improvement Amendments (CLIA)-certified or College of American Pathologists (CAP) accredited laboratories. Analyses distinguished between STI self-collection kits (n = 9) using independent laboratories and HCP specimen collection (n = 10) which used commercial laboratories (n = 1 offered both). The STI self-collection kits were cheaper per test and bundle on average (eg, $79.00 vs $106.50 for chlamydia/gonorrhea), and more closely aligned with clinical recommendations compared with the HCP specimen collection options. Websites often contained inaccurate or misleading information (n = 13), often promoting testing outside of the recommendations.

CONCLUSIONS: Direct-to-consumer STI testing services are part of an emerging market lacking regulation. Consumers should select vendors offering prescriptions for HCP specimen collection at CAP accredited and CLIA-certified laboratories. Vendors should provide a screening tool to assess individual patient risk prior to test purchase.

PMID:36807311 | DOI:10.1097/OLQ.0000000000001783

Biometrics. 2023 Feb 17. doi: 10.1111/biom.13843. Online ahead of print.

ABSTRACT

Bayesian networks have been widely used to generate causal hypotheses from multivariate data. Despite their popularity, the vast majority of existing causal discovery approaches make the strong assumption of a (partially) homogeneous sampling scheme. However, such assumption can be seriously violated, causing significant biases when the underlying population is inherently heterogeneous. To this end, we propose a novel causal Bayesian network model, termed BN-LTE, that embeds heterogeneous samples onto a low-dimensional manifold and builds Bayesian networks conditional on the embedding. This new framework allows for more precise network inference by improving the estimation resolution from population level to observation level. Moreover, while causal Bayesian networks are in general not identifiable with purely observational, cross-sectional data due to Markov equivalence, with the blessing of causal effect heterogeneity, we prove that the proposed BN-LTE is uniquely identifiable under relatively mild assumptions. Through extensive experiments, we demonstrate the superior performance of BN-LTE in causal structure learning as well as inferring observation-specific gene regulatory networks from observational data. This article is protected by copyright. All rights reserved.

PMID:36807295 | DOI:10.1111/biom.13843

Nurse Educ. 2023 Feb 17. doi: 10.1097/NNE.0000000000001379. Online ahead of print.

ABSTRACT

BACKGROUND: An interprofessional clinical education model operating student-led, faculty-guided clinics partnered with rural Midwest American communities lacking health care access.

PURPOSE: To evaluate how an internship, guided by the Theory of Cultural Humility, during the COVID-19 pandemic supported development of cultural humility in interprofessional health profession students.

APPROACH: Nursing, exercise science, public health, and social work participants completed an internship during early phases of the COVID-19 pandemic, despite many experiences being suspended. Quantitative evaluation using pre-/postadministration of Foronda’s Cultural Humility Scale was completed across 3 periods measuring change in cultural humility.

RESULTS: Total scores of Foronda’s Cultural Humility Scale increased for all 3 periods (n = 11, n = 74, and n = 44), demonstrated by aggregate data and statistical analysis. The largest change occurred in the first period.

CONCLUSIONS: Engaging interprofessional students in experiential learning during real-life, real-time public health events creates reflection of complex practice issues while developing cultural humility.

PMID:36807285 | DOI:10.1097/NNE.0000000000001379

Acta Cytol. 2023 Feb 20. doi: 10.1159/000529769. Online ahead of print.

ABSTRACT

INTRODUCTION: Cytological samples from cutaneous melanoma (CM) metastases may be the only biomaterial available for diagnostic and predictive purpose in the clinical practice. BRAF evaluation from cytological samples actually implies the loss of one or more diagnostic smears, or the execution of one or more passes to obtain dedicated cytological samples. We tested BRAF molecular evaluation in CM metastases on cell suspension obtained from fine needle aspiration cytology (FNAC) needle rinses.

METHODS: Forty-two patients with lymph node enlargements and a previous CM were enrolled. Patients were submitted to FNAC, and direct smears and cell-block were prepared for diagnostic purpose. The needle was carefully flushed in a vial containing 350μL of nuclease-free water and a cell suspension was obtained for BRAF molecular evaluation. Molecular evaluation was also performed on histological samples for statistics.

RESULTS: The series included 35 CM metastases and 7 reactive lymphadenopathies. Three cases resulted inadequate and adequacy was 92.9%. BRAF V600E/Ec mutations were found in 7 out of 32 (21.9%) CM metastases cases. BRAF mutations other than V600E/Ec were found in 2 out of 32 (6.25%) cases. Sensitivity, specificity, positive predictive value, and negative predictive value resulted 100%.

CONCLUSION: BRAF molecular evaluation in CM metastases on cell suspension obtained from FNAC needle rinses is a time-sparing and accurate technique allowing to spare biomaterial in the clinical setting.

PMID:36807248 | DOI:10.1159/000529769

Clin Genet. 2023 Feb 19. doi: 10.1111/cge.14312. Online ahead of print.

ABSTRACT

Hereditary deafness and retinal dystrophy are each genetically heterogenous and clinically variable. Three small unrelated families segregating the combination of deafness and retinal dystrophy were studied by exome sequencing (ES). The proband of Family 1 was found to be compound heterozygous for NM_004525.3: LRP2: c.5005A>G, p.(Asn1669Asp) and c.149C>G, p.(Thr50Ser). In Family 2, two sisters were found to be compound heterozygous for LRP2 variants, p.(Tyr3933Cys) and an experimentally confirmed c.7715+3A>T consensus splice-altering variant. In Family 3, the proband is compound heterozygous for a consensus donor splice site variant LRP2: c.8452_8452+1del and p.(Cys3150Tyr). In mouse cochlea, LRP2 is expressed abundantly in the stria vascularis marginal cells demonstrated by smFISH, single-cell and single-nucleus RNAseq, suggesting that a deficiency of LRP2 may compromise the endocochlear potential, which is required for hearing. LRP2 variants have been associated with Donnai-Barrow syndrome and other multisystem pleiotropic phenotypes different from the phenotypes of the four cases reported herein. Our data expand the phenotypic spectrum associated with pathogenic variants in LRP2 warranting their consideration in individuals with a combination of hereditary hearing loss and retinal dystrophy. This article is protected by copyright. All rights reserved.

PMID:36807241 | DOI:10.1111/cge.14312

Lasers Med Sci. 2023 Feb 20;38(1):76. doi: 10.1007/s10103-023-03736-y.

ABSTRACT

To investigate the effect of low-level laser therapy (LLLT) on orthodontic tooth movement during maxillary molar distalization over a 12-week observation period. Twenty patients were enrolled in this clinical trial. On the 0th, 3rd, 7th, 14th, 21st, 42nd, and 63rd days following the initial activation of the distalization appliance, laser therapy was applied in a total of 16 different points of the first and second molars for 10 s per point to the randomly determined molar region of the individuals in the intervention group. The amount of molar distalization was measured using digital scans of the three-dimensional (3D) digital models obtained during the 3rd, 6th, 9th, and 12th weeks. The amount of tooth movement on the laser-applied side of subjects in the intervention group was significantly greater than those in the contralateral and control groups at all time intervals (p < 0.001). The amount of tooth movement between the contralateral side of the intervention group and the control group was determined to be statistically insignificant (p > 0.05) at all time intervals. The laser-treated molars of the subjects in the intervention group moved 1.22 times more than the molars in the contralateral side and in the control group in 12 weeks. The rate of tooth movement in the laser, contralateral, and control groups was 0.033, 0.027, and 0.027 mm/day, respectively. Although LLLT was found to be statistically significant in terms of accelerating tooth movement, the effect of LLLT is not considered to be clinically significant. This trial was retrospectively registered (September 22, 2022) at Clinical-Trials.gov (Ref no: NCT05550168).

PMID:36807215 | DOI:10.1007/s10103-023-03736-y

J Neurosurg. 2023 Feb 17:1-11. doi: 10.3171/2023.1.JNS221452. Online ahead of print.

ABSTRACT

OBJECTIVE: This study sought to characterize resting-state functional MRI (fMRI) connectivity patterns of the posterior hypothalamus (pHTH) and the nucleus basalis of Meynert (NBM) in surgical patients with mesial temporal lobe epilepsy (mTLE), and to investigate potential correlations between functional connectivity of these arousal regions and neurocognitive performance.

METHODS: The study evaluated resting-state fMRI in 60 patients with preoperative mTLE and in 95 healthy controls. The authors first conducted voxel-wise connectivity analyses seeded from the pHTH, combined anterior and tuberal hypothalamus (atHTH; i.e., the rest of the hypothalamus), and the NBM ipsilateral (ipsiNBM) and contralateral (contraNBM) to the epileptogenic zone. Based on these results, the authors included the pHTH, ipsiNBM, and frontoparietal neocortex in a network-based statistic (NBS) analysis to elucidate a network that best distinguishes patients from controls. The connections involving the pHTH and ipsiNBM from this network were included in age-corrected pairwise region of interest (ROI) analysis, along with connections between arousal structures, including the pHTH, ipsiNBM, and brainstem arousal regions. Finally, patient functional connectivity was correlated with clinical neurocognitive testing scores for IQ as well as attention and concentration tests.

RESULTS: The voxel-wise analysis demonstrated that the pHTH, when compared with the atHTH, showed more widespread functional connectivity decreases in surgical mTLE patients when compared with controls. It was also observed that the ipsiNBM, but not the contraNBM, showed decreased functional connectivity in mTLE. The NBS analysis uncovered a perturbed network of frontoparietal regions, the pHTH, and ipsiNBM that distinguishes patients from controls. Age-corrected ROI analysis revealed functional connectivity decreases between the pHTH and bilateral superior frontal gyri, medial orbitofrontal cortices, rostral anterior cingulate cortices, and inferior parietal cortices in mTLE when compared with controls. For the ipsiNBM, there was reduced connectivity with bilateral medial orbitofrontal and rostral anterior cingulate cortices. Age-corrected ROI analysis also demonstrated upstream connectivity decreases from controls between the pHTH and the brainstem arousal regions, cuneiform/subcuneiform (CSC) nuclei, and ventral tegmental area, as well as the ipsiNBM and CSC nuclei. Reduced functional connectivity was also detected between the pHTH and ipsiNBM. Lastly, neurocognitive test scores for attention and concentration were found to be positively correlated with the functional connectivity between the pHTH and ipsiNBM, suggesting worse performance associated with connectivity perturbations.

CONCLUSIONS: This study demonstrated perturbed resting-state functional connectivity of arousal regions in surgical mTLE and is one of the first investigations to demonstrate decreased functional connectivity of the pHTH with frontoparietal regions and other arousal regions. Connectivity disturbances in arousal regions may contribute to neurocognitive deficits in surgical mTLE patients.

PMID:36807210 | DOI:10.3171/2023.1.JNS221452

Int Psychogeriatr. 2023 Feb 20:1-7. doi: 10.1017/S1041610223000066. Online ahead of print.

ABSTRACT

OBJECTIVE: Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure.

DESIGN: Cross-sectional study.

SETTING: Academic Health Center.

PARTICIPANTS: Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust).

MEASUREMENT: LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0-5), classifying subjects as robust (0), prefrail (1-2), and frail (3-5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM).

RESULTS: We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = -26,-11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large.

CONCLUSION: We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression-frailty phenotype in older adults.

PMID:36803400 | DOI:10.1017/S1041610223000066

BMC Med Genomics. 2023 Feb 20;16(1):30. doi: 10.1186/s12920-023-01456-4.

ABSTRACT

BACKGROUND: Osteosarcoma has been the most common primary bone malignant tumor in children and adolescents. Despite the considerable improvement in the understanding of genetic events attributing to the rapid development of molecular pathology, the current information is still lacking, partly due to the comprehensive and highly heterogeneous nature of osteosarcoma. The study is to identify more potential responsible genes during the development of osteosarcoma, thus identifying promising gene indicators and aiding more precise interpretation of the disease.

METHODS: Firstly, from GEO database, osteosarcoma transcriptome microarrays were used to screen the differential expression genes (DEGS) in cancer comparing to normal bone samples, followed by GO/KEGG interpretation, risk score assessment and survival analysis of the genes, for the purpose of selecting a credible key gene. Further, the basic physicochemical properties, predicted cellular location, gene expression in human cancers, the association with clinical pathological features and potential signaling pathways involved in the key gene’s regulation on osteosarcoma development were in succession explored.

RESULTS: Based on the selected GEO osteosarcoma expression profiles, we identified the differential expression genes in osteosarcoma versus normal bone samples, and the genes were classified into four groups based on the difference level, further genes interpretation indicated that the high differently level (> 8 fold) genes were mainly located extracellular and related to matrix structural constituent regulation. Meanwhile, module function analysis of the 67 high differential level (> 8 fold) DEGS revealed a 22-gene containing extracellular matrix regulation associated hub gene cluster. Further survival analysis of the 22 genes revealed that STC2 was an independent prognosis indicator in osteosarcoma. Moreover, after validating the differential expression of STC2 in cancer vs. normal tissues using local hospital osteosarcoma samples by IHC and qRT-PCR experiment, the gene’s physicochemical property revealed STC2 as a cellular stable and hydrophilic protein, and the gene’s association with osteosarcoma clinical pathological parameters, expression in pan-cancers and the probable biological functions and signaling pathways it involved were explored.

CONCLUSION: Using multiple bioinformatic analysis and local hospital samples validation, we revealed the gain of expression of STC2 in osteosarcoma, which associated statistical significantly with patients survival, and the gene’s clinical features and potential biological functions were also explored. Although the results shall provide inspiring insights into further understanding of the disease, further experiments and detailed rigorous clinical trials are needed to reveal its potential drug-target role in clinical medical use.

PMID:36803385 | DOI:10.1186/s12920-023-01456-4