A Soft-Tissue Driven Bone Remodeling Algorithm for Mandibular Residual Ridge Resorption Based on Patient CT Image Data.

The role of the biomechanical stimulation generated from soft tissue has not been well quantified or separated from the self-regulated hard tissue remodeling governed by Wolff's Law. Prosthodontic overdentures, commonly used to restore masticatory functions, can cause localized ischemia and inflammation as they often compress patients' oral mucosa and impede local circulation. This biomechanical stimulus in mucosa is found to accelerate the self-regulated residual ridge resorption (RRR), posing ongoing clinical challenges. Based on the dedicated long-term clinical datasets, we developed an in-silico framework with a combination of techniques, including advanced image post-processing, patient-specific finite element models and unsupervised machine learning Self-Organizing map algorithm, to identify the soft tissue induced residual ridge resorption and quantitatively elucidate the governing relationship between the RRR and hydrostatic pressure in mucosa. The proposed governing equation has not only enabled a predictive simulation for RRR as showcased in this study, providing a biomechanical basis for optimizing prosthodontic treatments, but also extended our understanding of the mechanobiological responses in the soft-hard tissue interfaces and the role in bone remodeling. This article is protected by copyright. All rights reserved.

Association of categorical diagnoses and psychopathologies with quality of life in patients with depression, anxiety, and somatic symptoms: A cross-sectional study.

OBJECTIVE: Major depressive disorder (MDD), anxiety disorders, and somatic symptom disorder (SSD) are associated with quality of life (QoL) reduction. This cross-sectional study investigated the relationship between these conditions as categorical diagnoses and related psychopathologies with QoL, recognizing their frequent overlap. METHODS: We recruited a total of 403 clinical patients and healthy individuals, administering diagnostic interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. QoL and psychopathologies were assessed using the WHO Quality of Life-BREF (WHOQOL-BREF) and several self-administered questionnaires, respectively. Multiple linear regression analyses examined the associations between psychiatric diagnoses, psychopathologies, and QoL. RESULTS: SSD and MDD were independently associated with impaired global (ß = -0.318 and - 0.287) and all QoL domains (ß = -0.307, -0.150, -0.125, and - 0.133, in physical, psychological, social, and environmental domains respectively for SSD; ß = -0.278, -0.344, -0.275, and - 0.268 for MDD). The Beck Depression Inventory-II score showed pervasive associations with QoL (ß = -0.390, -0.408, -0.685, -0.463, and - 0.420, in global, physical, psychological, social, and environmental domains). The Patient Health Questionnaire-15 and Health Anxiety Questionnaire scores were associated with global (ß = -0.168 and - 0.181) and physical (ß = -0.293 and - 0.121) QoL domain, while the Cognitions About Body and Health Questionnaire score was only associated with environmental QoL domain (ß = -0.157). CONCLUSION: SSD and MDD were independently associated with QoL impairment. Depressive symptoms were associated with all QoL domains, whereas somatic symptom burden and health anxiety primarily affected the physical QoL domain. Clinicians should consider concomitant psychopathologies when managing patients with depression, anxiety, or somatic symptoms.

Associations of early retirement and mortality risk: a population-based study in Taiwan.

BACKGROUND: Early retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors. METHODS: Using Taiwan's National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45-64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score). RESULTS: The analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45-54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders. CONCLUSIONS: This study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles.

Do the benefits of homeownership on mental health vary by race and poverty status? An application of doubly robust estimation for causal inference.

While empirical studies have observed that homeownership is associated with improved mental health conditions, research indicates that this relationship might vary by race. Moreover, such a White-Black disparity in the impacts of homeownership on mental health could be complexed by poverty status, as maintaining one's homeownership could be a financial burden for people living in poverty status, defined by the US official poverty threshold. We add to the existing literature by analyzing the impacts of homeownership on psychological distress, simultaneously disaggregating by race and poverty status using survey data from the Panel Study on Income Dynamics from the 2017 and 2019 waves (N = 7059). Propensity score weighting and doubly robust estimation are applied to estimate causal inference for the impact of 2017 homeownership on 2019 psychological distress using negative binomial models. First, we found the impacts of homeownership on reducing psychological distress are significant for White Americans, not for Black Americans. Second, we found such a White-Black disparity is only observable for populations not living in poverty. On the other hand, for populations living in poverty, homeownership no longer lowers psychological distress for either race. Findings suggest that financial support and mental health support are needy to address inequality in the impacts of homeownership on mental health, which could simultaneously vary by poverty status and race. Implications are discussed.

Radiological Verification for the Suitability of Using the Quadriceps Angle to Represent Orientation of the Quadriceps Femoris.

OBJECTIVES: The orientation of the quadriceps femoris can be represented by the quadriceps angle (Q-angle) has not yet been approved because of the high incidence of patellar instability. In this study, the correlations among components of the quadriceps femoris and the Q-angle using the plain radiographic technique were assessed. This retrospective study aims to use the radiographic technique to clarify these doubts from anatomic viewpoints. METHODS: One hundred consecutive young adult patients (50 men and 50 women; aged, 34 ± 5 and 33 ± 6 years, respectively) who sustained chronic unilateral lower extremity injuries (unilateral femoral, tibial nonunions or malunions) were enrolled. The contralateral intact lower extremity was used for the study. The full-length standing scanogram (FLSS) was used to evaluate the rectus Q-angle (R-Q angle), vastus Q-angle (V-Q angle), and clinical Q-angle (C-Q angle; i.e., known as the Q-angle). The three Q-angles were compared statistically. The Mann-Whitney U test and the Kruskal-Wallis test were used for comparison among groups. The Spearman rank correlation coefficient was used to evaluate the degree of relationship between two groups. RESULTS: The C-Q angle or the V-Q angle was statistically different from the R-Q angle (p < 0.001). The C-Q angle between sexes was not different (p = 0.25). High correlation occurred among the C-Q angle, the R-Q angle, and the V-Q angles (correlation coefficient, 0.886-0.979). The multiple linear regression revealed of C-Q angle = 0.72; R-Q angle, p < 0.001 + 0.21; and V-Q angle, (p = 0.009) + 2.61° in 100 patients. CONCLUSION: Orientation of the quadriceps femoris can be represented by the Q-angle. Compared to the rectus femoris, the three vastus muscles of the quadriceps femoris are more correlated to the Q-angle.

Isolable Spirocyclic Silylone: π-Delocalized Spiro[3.3]heptasila-2,6-diylidone.

Strained cyclic tetrylones are important synthons due to various synthetic applications. Connecting two cyclic tetrylone rings through a single shared quaternary group 14 element atom to form a spirocyclic molecule has been unexplored both theoretically and experimentally. The formation of a spirocyclic motif has been a synthetic challenge. In contrast, the reaction of amidinato disilicon(I) 1, (Me3P)2SiCl4, and KC8 afforded π-delocalized spiro[3.3]heptasila-2,6-diylidone2 and tetrasilacyclobutadiene byproducts 3 and 4. Compound 2 is the smallest spirocyclic tetrylone derivative, which is composed of a σ-type lone pair and delocalized π bond in each all-silicon spirocyclic ring. The electronic property is supported by its coordination with a W(CO)5 moiety.

Cytotoxicity effect and transcriptome analysis of PCV3-infected cells revealed potential viral pathogenic mechanisms.

Porcine circovirus type 3 (PCV3) has become an important pathogen in the global swine industry and poses a threat to pig health, but its pathogenic mechanism remains unknown. In this study, we constructed an innovative, linear infectious clone of PCV3 for rescuing the virus, and explored the transcriptome of infected cells to gain insights into its pathogenic mechanisms. Subsequently, an in vivo experiment was conducted to evaluate the pathogenicity of the rescued virus in pig. PCV3 nucleic acid was distributed across various organs, indicating systemic circulation via the bloodstream and viremia. Immunohistochemical staining also revealed a significant presence of PCV3 antigens in the spleen, lungs, and lymph nodes, indicating that PCV3 had tropism for these organs. Transcriptome analysis of infected ST cells revealed differential expression of genes associated with apoptosis, immune responses, and cellular metabolism. Notably, upregulation of genes related to the hypoxia-inducible factor-1 pathway, glycolysis, and the AGE/RAGE pathway suggests activation of inflammatory responses, ultimately leading to onset of disease. These findings have expanded our understanding of PCV3 pathogenesis, and the interplay between PCV3 and host factors.

Induction of Petite Colonies in Candida glabrate via Rose Bengal-Mediated Photodynamic Therapy.

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.

Lung adenocarcinoma with EGFR L858R-K860I and L858R-L861F doublet mutations from which the L858R mutation is undetectable through the cobas EGFR mutation test v2.

In East Asia, epidermal growth receptor factor (EGFR) mutations are the most prevalent and important biomarkers for treating patients with advanced lung cancer. However, as L858R doublet mutations are rare, commercially available EGFR tests may yield false-negative results. To determine whether the L858R mutation of the L858R-K860I and L858R-L861F doublet mutations could be identified using different types of EGFR detection tests and to describe the clinical response of patients with lung cancer with L858R doublet mutations to EGFR tyrosine kinase inhibitors (TKI). Information and samples from four patients with L858R doublet mutations, including three with L858R-K860I and one with L858R-L861F, were retrospectively collected from the archives of our department. For each case, the clinical response to EGFR-TKI was retrieved from the medical records. Archived formalin-fixed paraffin-embedded blocks were subjected to Sanger sequencing, the cobas and Idylla EGFR tests, the IntelliPlex-LCP-DNA assay, and AmoyDx PLC panel. L858R mutations were all detected by Sanger sequencing and the Idylla EGFR test but missed by the cobas assay. The AmoyDx PLC detected L858R only in cases with L858R-K860I while the IntelliPlex-LCP-DNA assay detected L858R in the case with L858R-L861F. Additionally, three of the patients, who had measurable tumors, showed partial responses to afatinib and osimertinib. The L858R mutation associated with L858R-K860I and L858R-L861F doublet mutations could be detected using Idylla but not cobas EGFR tests. Using next-generation sequencing analysis should be considered after initial negative reports from the cobas test, because patients with L858R doublet mutations may benefit from EGFR-TKIs.

Carbon dioxide capture and functionalization by bis(N-heterocyclic carbene)-borylene complexes.

Derivatives of free monocoordinated borylenes have attracted considerable interest due to their ability to exhibit transition-metal-like reactivity, in particular small molecules capture. However, such complexes are rare as the formation is either endergonic, or the resulting adduct is a transient intermediate that is prone to reaction. Here, we present the synthesis of two bis(N-heterocyclic carbene)-borylene complexes capable of capturing and functionalizing carbon dioxide. The capture and subsequent functionalization of CO2 by the bis(NHC)-disilylamidoborylene 1 is demonstrated by the formation of the bis(NHC)-isocyanatoborylene-carbon dioxide complex 3. Reversible capture of CO2 is observed using the bis(NHC)-mesitylborylene 2, and the persistent bis(NHC)-mesitylborylene-carbon dioxide adduct 4 can be stabilized by hydrogen bonding with boric acid. The reactions of 4 with ammonia-borane and aniline demonstrate that the captured CO2 can be further functionalized.

HPN328, a Trispecific T Cell-activating Protein Construct Targeting DLL3-Expressing Solid Tumors.

Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive and limited therapeutic options lead to poor prognosis for patients. HPN328 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro concomitant with T cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T cell engagers. HPN328 exhibited linear pharmacokinetic in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3 expressing malignancies.

Patient Location and Disparities in Access to Fertility Preservation for Women With Gynecologic or Breast Cancer.

OBJECTIVE: To assess the effect of geographic factors on fertility-sparing treatment or assisted reproductive technology (ART) utilization among women with gynecologic or breast cancers. METHODS: We conducted a cohort study of reproductive-aged patients (18-45 years) with early-stage cervical, endometrial, or ovarian cancer or stage I-III breast cancer diagnosed between January 2000 and December 2015 using linked data from the California Cancer Registry, the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. Generalized linear mixed models were used to evaluate associations between distance from fertility and gynecologic oncology clinics, as well as California Healthy Places Index score (a Census-level composite community health score), and ART or fertility-sparing treatment receipt. RESULTS: We identified 7,612 women with gynecologic cancer and 35,992 women with breast cancer. Among all patients, 257 (0.6%) underwent ART. Among patients with gynecologic cancer, 1,676 (22.0%) underwent fertility-sparing treatment. Stratified by quartiles, residents who lived at increasing distances from gynecologic oncology or fertility clinics had decreased odds of undergoing fertility-sparing treatment (gynecologic oncology clinics: Q2, odds ratio [OR] 0.76, 95% CI, 0.63-0.93, P =.007; Q4, OR 0.72, 95% CI, 0.56-0.94, P =.016) (fertility clinics: Q3, OR 0.79, 95% CI, 0.65-0.97, P =.025; Q4, OR 0.67, 95% CI, 0.52-0.88, P =.004), whereas this relationship was not observed among women who resided within other quartiles (gynecologic oncology clinics: Q3, OR 0.81 95% CI, 0.65-1.01, P =.07; fertility clinics: Q2, OR 0.87 95% CI, 0.73-1.05, P =.15). Individuals who lived in communities with the highest (51 st -100 th percentile) California Healthy Places Index scores had greater odds of undergoing fertility-sparing treatment (OR 1.29, 95% CI, 1.06-1.57, P =.01; OR 1.66, 95% CI, 1.35-2.04, P =.001, respectively). The relationship between California Healthy Places Index scores and ART was even more pronounced (Q2 OR 1.9, 95% CI, 0.99-3.64, P =.05; Q3 OR 2.86, 95% CI, 1.54-5.33, P <.001; Q4 OR 3.41, 95% CI, 1.83-6.35, P <.001). CONCLUSION: Geographic disparities affect fertility-sparing treatment and ART rates among women with gynecologic or breast cancer. By acknowledging geographic factors, health care systems can ensure equitable access to fertility-preservation services.

Widowhood and mortality risk in Taiwan: a population-based matched cohort study.

BACKGROUND: Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood. METHODS: This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204 010 widowed men and 596 136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816 040 comparison men and 2 384 544 comparison women were selected. RESULTS: Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection. CONCLUSIONS: The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.

Clinical dose rationale of tislelizumab in patients with solid or hematological advanced tumors.

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune-mediated AEs, and infusion-related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure-response (E-R) analyses by logistic regression using data from study BGB-A317-001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E-R relationship. Overall, the totality of data, including efficacy, safety, and E-R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

Morphology and chemical composition of Taiwan oil millet (Eccoilopus formosanus) epicuticular wax.

MAIN CONCLUSION: Taiwan oil millet has two types of epicuticular wax: platelet wax composed primarily of octacosanol and filament wax constituted essentially by the singular compound of octacosanoic acid. Taiwan oil millet (TOM-Eccoilopus formosanus) is an orphan crop cultivated by the Taiwan indigenous people. It has conspicuous white powder covering its leaf sheath indicating abundant epicuticular waxes, that may contribute to its resilience. Here, we characterized the epicuticular wax secretion in TOM leaf blade and leaf sheath using various microscopy techniques, as well as gas chromatography to determine its composition. Two kinds of waxes, platelet and filaments, were secreted in both the leaf blades and sheaths. The platelet wax is secreted ubiquitously by epidermal cells, whereas the filament wax is secreted by a specific cell called epidermal cork cells. The newly developed filament waxes were markedly re-synthesized by the epidermal cork cells through papillae protrusions on the external periclinal cell wall. Ultrastructural images of cork cell revealed the presence of cortical endoplasmic reticulum (ER) tubules along the periphery of plasma membrane (PM) and ER-PM contact sites (EPCS). The predominant wax component was a C28 primary alcohol in leaf blade, and a C28 free fatty acid in the leaf sheath, pseudopetiole and midrib. The wax morphology present in distinct plant organs corresponds to the specific chemical composition: platelet wax composed of alcohols exists mainly in the leaf blade, whereas filament wax constituted mainly by the singular compound C28 free fatty acids is present abundantly in leaf sheath. Our study clarifies the filament wax composition in relation to a previous study in sorghum. Both platelet and filament waxes comprise a protection barrier for TOM.

A colonial serrated polyp classification model using white-light ordinary endoscopy images with an artificial intelligence model and TensorFlow chart.

In this study, we implemented a combination of data augmentation and artificial intelligence (AI) model-Convolutional Neural Network (CNN)-to help physicians classify colonic polyps into traditional adenoma (TA), sessile serrated adenoma (SSA), and hyperplastic polyp (HP). We collected ordinary endoscopy images under both white and NBI lights. Under white light, we collected 257 images of HP, 423 images of SSA, and 60 images of TA. Under NBI light, were collected 238 images of HP, 284 images of SSA, and 71 images of TA. We implemented the CNN-based artificial intelligence model, Inception V4, to build a classification model for the types of colon polyps. Our final AI classification model with data augmentation process is constructed only with white light images. Our classification prediction accuracy of colon polyp type is 94%, and the discriminability of the model (area under the curve) was 98%. Thus, we can conclude that our model can help physicians distinguish between TA, SSA, and HPs and correctly identify precancerous lesions such as TA and SSA.