Category: Statistics

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

Expert Opin Drug Saf. 2023 Feb 18. doi: 10.1080/14740338.2023.2182284. Online ahead of print.

ABSTRACT

BACKGROUND: Anaplastic lymphoma kinases (ALK) tyrosine kinase inhibitors (TKIs) are targeted therapies used in advanced ALK-positive non-small cell lung cancers (NSCLC) which showed excellent efficacy and safety. However, ALK TKIs-associated cardiovascular toxicities [cardiac disorders, venous thromboembolic events (VTEs), and hypertension] have been raising more attention and remain incompletely characterized. We conducted the first meta-analysis to investigate the cardiovascular toxicities associated with ALK TKIs in patients with ALK-positive NSCLC.

RESEARCH DESIGN AND METHODS: To determine the relative risks (RRs) of cardiovascular toxicities associated with these agents, we carried out a meta-analysis comparing ALK TKIs with chemotherapy and a meta-analysis comparing crizotinib with second- and third-generation ALK TKIs. Statistical analysis was conducted to calculate the RRs and 95% confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of the included studies.

RESULTS: A total of 11 studies (2855 patients) were included in our study. Compared with chemotherapy, ALK TKIs ranked to have more severe cardiovascular toxicities (RR 5.03, 95% CI 1.97-12.84, P=0.0007), which was mainly reflected in cardiac disorders (RR 8.38, 95% CI 5.06-13.87, P<0.00001). Compared with second- and third-generation ALK TKIs, increased risks of cardiac disorders and VTEs associated with crizotinib were found (cardiac disorders RR 1.75, 95% CI 1.07-2.86, P=0.03; risk of VTEs RR 3.97, 95% CI 1.69-9.31, P=0.002; respectively).

CONCLUSION: ALK TKIs were associated with higher risks of cardiovascular toxicities. In particular, special attention should be given to the risks of cardiac disorders and VTEs related to crizotinib therapy.

PMID:36803384 | DOI:10.1080/14740338.2023.2182284

Hum Fertil (Camb). 2023 Feb 20:1-6. doi: 10.1080/14647273.2023.2179896. Online ahead of print.

ABSTRACT

The purpose of this study was to evaluate the incidence of unbalanced chromosome rearrangement in blastocyst-stage embryos from carriers of pericentric inversion of chromosome 1 (PEI-1). A total of 98 embryos from 22 PEI-1 carriers were tested for unbalanced rearrangements, originating from inversion carriers, and overall aneuploidy. Logistic regression analysis indicated that the ratio of inverted segment size to chromosome length was a statistically significant risk factor for unbalanced chromosome rearrangement from PEI-1 carriers (p = 0.003). The optimal cut-off values to predict the risk of unbalanced chromosome rearrangement was 36%, with the incidence being 2.0% in the <36% group and 32.7% in the ≥36% group. The unbalanced embryo rate was 24.4% in male carriers compared to 12.3% in female carriers. Inter-chromosomal effect analysis was performed using 98 blastocysts from PEI-1 carriers and 116 blastocysts from age-matched controls. PEI-1 carriers had similar sporadic aneuploidy rates compared to those of age-matched controls at 32.7 vs. 31.9%, respectively. In conclusion, the risk of unbalanced chromosome rearrangement is affected by inverted segment size in PEI-1 carriers.

PMID:36803371 | DOI:10.1080/14647273.2023.2179896

Expert Rev Anti Infect Ther. 2023 Feb 20. doi: 10.1080/14787210.2023.2181789. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about the duration of antibiotic use in hospital settings. We evaluated the duration of hospital antibiotic therapy (as a quality indicator proxy) for four commonly prescribed antibiotics (amoxicillin, co-amoxiclav, doxycycline and flucloxacillin) including the assessment of COVID-19 impact.

METHODS: A repeated, cross-sectional study using the Hospital Electronic Prescribing and Medicines Administration system (January/2019-March/2022). Monthly median duration of therapy/duration categories were calculated, stratified by routes of administration, age and sex. Impact of COVID-19 was assessed using segmented time-series analysis.

RESULTS: There were significant variations in the median duration of therapy across routes of administration (P<0.05), with the highest value among those antibiotic courses comprised of both oral and IV antibiotics (“Both” group). Significantly higher proportions of prescriptions within the “Both” group had a duration of > 7 days compared to oral or IV. Duration of therapy overall differed significantly by age. Some small statistically significant changes in the level/trends of duration of therapy were observed in the post- COVID-19 period.

CONCLUSIONS: No evidence for prolonged duration of therapy were observed, even during COVID-19 pandemic. Duration of IV therapy was relatively short suggesting timely clinical review and consideration of IV to oral switch. Longer duration of therapy was observed among older patients.

PMID:36803370 | DOI:10.1080/14787210.2023.2181789

BMC Med Educ. 2023 Feb 17;23(1):118. doi: 10.1186/s12909-023-04071-0.

ABSTRACT

BACKGROUND: The purpose of this article is to discuss the statistical methods for agreement analysis used in Richelle’s article (BMC Med Educ 22:335, 2022). The authors investigated the attitudes of final-year medical students regarding substance use during pregnancy and identified the factors that influence these attitudes.

METHODS: We found that Cohen’s kappa value for measuring the agreement between these medical students’ attitudes towards drugs/alcohol use during pregnancy was questionable. In addition, we recommend using weighted kappa instead of Cohen’s kappa for agreement analysis at the presence of three categories.

RESULTS: The agreement improved from “good” (Cohen’s kappa) to “very good” (weighted kappa) for medical students’ attitudes towards drugs/alcohol use during pregnancy.

CONCLUSION: To conclude, we recognize that this does not significantly alter the conclusions of the Richelle et al. paper, but it is necessary to ensure that the appropriate statistical tools are used.

PMID:36803351 | DOI:10.1186/s12909-023-04071-0

J Clin Child Adolesc Psychol. 2023 Feb 20:1-13. doi: 10.1080/15374416.2023.2169924. Online ahead of print.

ABSTRACT

OBJECTIVE: Depression disparities between heterosexual youth and lesbian, gay, bisexual, queer, and other non-heterosexual (LGBQ+) youth are robust and linked to discrimination in schools. Advocacy by school-based Gender-Sexuality Alliances (GSAs) to raise awareness of LGBQ+ issues and to counteract discrimination may reduce these disparities within schools, yet has not been investigated schoolwide. We considered whether GSA advocacy over the school year moderated sexual orientation differences in depressive symptoms at the school year’s end for students in the general school population (i.e., students who were not members of the GSA).

METHOD: Participants were 1,362 students (M_age = 15.68; 89% heterosexual; 52.6% female; 72.2% White) in 23 Massachusetts secondary schools with GSAs. Participants reported depressive symptoms at the beginning and end of the school year. Separately, GSA members and advisors reported their GSA’s advocacy activities during the school year and other GSA characteristics.

RESULTS: LGBQ+ youth reported higher depressive symptoms than heterosexual youth at the school year’s beginning. However, after adjusting for initial depressive symptoms and multiple covariates, sexual orientation was a weaker predictor of depressive symptoms at the school year’s end for youth in schools whose GSAs engaged in more advocacy. Depression disparities were significant in schools whose GSAs reported lower advocacy, but were statistically non-significant in schools whose GSAs reported higher advocacy.

CONCLUSION: Advocacy could be a means by which GSAs achieve school-wide impacts, benefiting LGBQ+ youth who are not GSA members. GSAs may therefore be a key resource for addressing the mental health needs of LGBQ+ youth.

PMID:36803346 | DOI:10.1080/15374416.2023.2169924