Nevin Manimala

Clin Oral Investig. 2023 Nov 13. doi: 10.1007/s00784-023-05321-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare differences in outcome in skeletal and dental parameters in hypo- and hyperdivergent Class II patients after extraction of upper first premolars and comprehensive orthodontic treatment.

MATERIALS AND METHODS: 37 Class-II-patients with dental camouflage treatment were divided into a hypo- (n = 18) or a hyperdivergent (n = 19) group depending on the mandibular plane angle (hypo: < 34° or hyper: ≥ 34°). Lateral cephalograms were available before (T1) and after (T2) treatment and were analyzed with customized measurements. Data from a growth survey served as a control and were used to calculate the actual treatment effect. Data were analyzed by one-sample Student’s t-tests and independent Student’s t-tests. Statistical significance was set at p < 0.05.

RESULTS: The measurements showed similar changes in both groups. The effects were mainly dentoalveolar. Hypodivergent patients showed an almost equal increase in anterior and posterior facial height, while hyperdivergent patients only showed an increase in anterior facial height.

CONCLUSIONS: In hyperdivergent patients, the anterior facial height increases despite camouflage treatment. This indicates a tendency towards bite opening and backward rotation of the mandible. Hypodivergent patients do not experience deepening of the bite.

CLINICAL RELEVANCE: In hyperdivergent patients with upper first premolars extraction the anterior facial height increased differently than in hypodivergent patients. This should be considered if a bite opening is a possible contraindication to treatment.

PMID:37953326 | DOI:10.1007/s00784-023-05321-7

Nucleic Acids Res. 2023 Nov 11:gkad1035. doi: 10.1093/nar/gkad1035. Online ahead of print.

ABSTRACT

The versatility of cellular response arises from the communication, or crosstalk, of signaling pathways in a complex network of signaling and transcriptional regulatory interactions. Understanding the various mechanisms underlying crosstalk on a global scale requires untargeted computational approaches. We present a network-based statistical approach, MuXTalk, that uses high-dimensional edges called multilinks to model the unique ways in which signaling and regulatory interactions can interface. We demonstrate that the signaling-regulatory interface is located primarily in the intermediary region between signaling pathways where crosstalk occurs, and that multilinks can differentiate between distinct signaling-transcriptional mechanisms. Using statistically over-represented multilinks as proxies of crosstalk, we infer crosstalk among 60 signaling pathways, expanding currently available crosstalk databases by more than five-fold. MuXTalk surpasses existing methods in terms of model performance metrics, identifies additions to manual curation efforts, and pinpoints potential mediators of crosstalk. Moreover, it accommodates the inherent context-dependence of crosstalk, allowing future applications to cell type- and disease-specific crosstalk.

PMID:37953325 | DOI:10.1093/nar/gkad1035

Nucleic Acids Res. 2023 Nov 11:gkad1005. doi: 10.1093/nar/gkad1005. Online ahead of print.

ABSTRACT

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

PMID:37953324 | DOI:10.1093/nar/gkad1005

Nucleic Acids Res. 2023 Nov 11:gkad957. doi: 10.1093/nar/gkad957. Online ahead of print.

ABSTRACT

The Nucleic Acid Knowledgebase (nakb.org) is a new data resource, updated weekly, for experimentally determined 3D structures containing DNA and/or RNA nucleic acid polymers and their biological assemblies. NAKB indexes nucleic acid-containing structures derived from all major structure determination methods (X-ray, NMR and EM), including all held by the Protein Data Bank (PDB). As the planned successor to the Nucleic Acid Database (NDB), NAKB’s design preserves all functionality of the NDB and provides novel nucleic acid-centric content, including structural and functional annotations, as well as annotations from and links to external resources. A variety of custom interactive tools have been developed to enable rapid exploration and drill-down of NAKB’s content.

PMID:37953312 | DOI:10.1093/nar/gkad957

Thyroid Res. 2023 Nov 13;16(1):43. doi: 10.1186/s13044-023-00186-0.

ABSTRACT

BACKGROUND: Subclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over.

METHODS: This project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage.

DISCUSSION: There needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population.

TRIAL REGISTRATION: Not applicable.

PMID:37953303 | DOI:10.1186/s13044-023-00186-0

Transl Psychiatry. 2023 Nov 13;13(1):346. doi: 10.1038/s41398-023-02649-2.

ABSTRACT

It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls. Data on genetics and depressive disorders were retrieved from neonatal biobanks and the Psychiatric Central Research Register. PGSs were calculated from both individual-level genetic data and meta-analysis summary statistics from the Psychiatric Genomics Consortium. Conditional logistic regression was used to calculate the odds ratio (OR), accounting for the selection-related reproductive behavior. After adjustment for covariates, higher PGSs for severe mental disorders were associated with increased ORs of both PPD and MDD. Compared with MDD cases, MDD PGS and attention-deficit/hyperactivity disorder PGS were marginally but not statistically higher for PPD cases, with the OR of PPD versus MDD being 1.12 (95% CI: 0 .97-1.29) and 1.11 (0.97-1.27) per-standard deviation increase, respectively. The ORs of PPD versus MDD did not statistically differ by PGSs of bipolar disorder, schizophrenia, or autism spectrum disorder. Our findings suggest that relying on PGS data, there was no clear evidence of distinct genetic make-up of women with depression occurring during or outside postpartum, after taking the selection-related reproductive behavior into account.

PMID:37953300 | DOI:10.1038/s41398-023-02649-2

J Orthop Surg Res. 2023 Nov 13;18(1):858. doi: 10.1186/s13018-023-04347-7.

ABSTRACT

BACKGROUND: The new Knee Society Knee Scoring System (KSS) has been widely used to assess the symptoms, satisfaction, expectations, and physical activities of patients who undergo total knee arthroplasty (TKA). KSS has been translated and validated into many languages but not Persian. The aim of this study was to translate and evaluate the validity and reliability of the Persian version of the new KSS.

METHODS: The Persian version of the new KSS was translated and culturally adapted according to international guidelines, including translation, back-translation, pre-testing, and expert committee review. A total of 142 patients scheduled to undergo TKA were included in this study and were asked to complete the Persian-KSS, Oxford Knee Score (OKS), and the Visual Analogue Scale (VAS) index both two weeks before the surgery and 6 months after the surgery. Face, content, and construct validity were evaluated to assess the validity of Persian-KSS.

RESULTS: The Persian-KSS was comprehensive, indicating that the Persian version of KSS was clear and easy to understand for Persian-speaking patients undergoing TKA. The reliability of the Persian-KSS, assessed by Cronbach’s alpha, was 0.894 and 0.800 for the pre- and post-operative stages, respectively. The intraclass correlation coefficient (ICC) assessed the test-retest reliability, which was 0.766 and 0.796 for the pre- and post-operative stages, respectively. The construct validity analysis of Persian-KSS demonstrated a statistically significant correlation between Persian-KSS and the OKS (r = – 0.935, p-value = 0.000 for the pre-operative stage, and r = – 0.809, p-value = 0.000 for the post-operative stage) and VAS index (r = – 0.401, p-value = 0.001 for the pre-operative stage and r = – 0.259, p-value = 0.029 for the post-operative stage).

CONCLUSION: The Persian-KSS, developed after the translation and cross-cultural adaptation process, was proven to be a reliable and valid assessment measure for those who undergo TKA.

PMID:37953297 | DOI:10.1186/s13018-023-04347-7

Microsc Microanal. 2023 Nov 10:ozad121. doi: 10.1093/micmic/ozad121. Online ahead of print.

ABSTRACT

Electron backscatter diffraction (EBSD) images of extruded pure aluminum were statistically analyzed to investigate creep-induced subgrain structures after applying two different levels of creep stress, corresponding to the power law (PL) and power-law breakdown (PLB) regimes. Kernel average misorientation analysis of EBSD measurements revealed 2D morphologies, which were subdivided by a multi-step segmentation procedure into subgranular arrangements. Various descriptors were employed to characterize the “subgrains” quantitatively, including their size, shape, spatial arrangement, and crystallographic orientation. In particular, the analysis of the orientations of subgrains was conducted by neglecting rotations around the loading axis. This approach facilitated the individual investigation of the {001} and {111} subgrain families with respect to the loading axis for two investigated stress levels plus a reference specimen. For the PL regime, the statistical analysis of subgrain descriptors computed from segmented image data revealed a similar degree of strain accumulation for {111} and {001} subgrains. In contrast, for the PLB regime, the analyzed descriptors indicate that {111} subgrains tend to accumulate significantly more strain than {001} ones. These observations suggest that the mechanisms leading to PLB may be associated with strain localization dependent on intergranular stress, hindering the recovery process within {111} grains.

PMID:37953284 | DOI:10.1093/micmic/ozad121

BMC Public Health. 2023 Nov 13;23(1):2228. doi: 10.1186/s12889-023-17052-1.

ABSTRACT

INTRODUCTION: Dolutegravir (DTG)-based regimen was included in the expanded formulary of China’s National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China.

METHODS: A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis.

RESULTS: Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses.

CONCLUSIONS: DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.

PMID:37953277 | DOI:10.1186/s12889-023-17052-1

Nutr Res. 2023 Oct 19;120:99-114. doi: 10.1016/j.nutres.2023.10.002. Online ahead of print.

ABSTRACT

The influence of dietary saturated fatty acids intake on human health and cardiovascular disease (CVD) remains debated. The aim of this study was to explore the association between dietary saturated fatty acid consumption and all-cause and CVD mortality among the elderly population. Data for the participants in this study were obtained from the National Health and Nutrition Examination Survey dataset spanning the years 2003 through 2008. Information regarding mortality and the follow-up duration were extracted from the 2019 public-use linked mortality files provided by the National Center for Health Statistics. A total of 3404 participants were included in this study. The ratio of dietary saturated fatty acids to total fat was associated with the mortality from all-cause, heart disease, and cerebrovascular disease after adjusting confounding factors (P < .05). For every 10% increase in the saturated fatty acids to total fat ratio, all-cause mortality increased by 24% (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.37), the heart disease mortality increased by 26% (HR, 1.26; 95% CI, 1.05-1.52), and the cerebrovascular disease mortality increased by 67% (HR, 1.67; 95% CI, 1.14-2.45) at 10 years’ follow-up. In addition, low dietary saturated fatty acids intake was associated with reduced mortality because of all-cause and heart disease after adjusting confounding factors (P < .05). In conclusion, in this elderly population, dietary saturated fatty acid intake was associated with all-cause mortality, heart disease mortality, and cerebrovascular disease mortality. Reducing saturated fatty acid intake in the diet may extend the survival rate for the elderly population. However, the difference of the effects of specific dietary saturated fatty acids with different chain lengths on mortality needs further study.

PMID:37952265 | DOI:10.1016/j.nutres.2023.10.002