Assortative mating across nine psychiatric disorders is consistent and persistent over cultures and generations.

Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.

Comparison of Demographic and Clinical Characteristics of Taiwan Biobank Participants with Nonparticipants.

BACKGROUND: This study investigated fundamental demographic variables within the Taiwan Biobank (TWBB) and compared them with national demographic statistics. Additionally, a matched cohort analysis compared TWBB participants with nonparticipants to uncover disparities in sociodemographic and clinical characteristics. METHODS: A total of 128,663 individuals aged 30 to 70 without cancer were recruited within the TWBB, and 514,652 nonparticipants matched by age and sex were randomly selected from the National Health Insurance claims database. Sociodemographic variables, healthcare utilization metrics, underlying medical conditions, and subsequent mortality and cancer risk were analyzed. RESULTS: TWBB participants were more likely to be female, older, married, higher educated, with higher incomes, and urban residency. Healthcare utilization metrics showed minimal differences. Pre-cohort entry, TWBB participants had a higher prevalence of certain medical conditions, such as peptic ulcer disease, osteoarthritis, osteoporosis, and uterine leiomyoma in females. During follow-up periods, elevated mortality rates were observed among TWBB participants but decreased cancer risk. CONCLUSION: The TWBB cohort exhibits disparities in sociodemographic and health-related attributes compared to the general population, comprising older, females, married, higher educated, higher income, and predominantly in urban areas. While mortality rates are slightly elevated within the TWBB cohort, cancer incidence rates are lower. Despite limitations in representativeness, the TWBB's size and exposure measures offer valuable insights into associations between exposures and health conditions.

Oral Administration of Lactococcus lactis Expressing Mite and Cockroach Major Allergens Alleviates Progression of Atopic March in a Mouse Model.

PURPOSE: Atopic march is defined as the development of atopic dermatitis in early childhood. We recently developed an atopic march mouse model through skin sensitization with aeroallergens from house dust mites and cockroaches. Using this model, this study aimed to evaluate the oral immunotherapy efficacy of Lactococcus lactis harboring specific antigens on the progression of atopic march. METHODS: Dust mite major allergen Der p 2 and cockroach Per a 2-372 were expressed in L. lactis as a fusion recombinant clone (D2P2). L. lactis-D2P2 was administered intragastrically to Aeroallergen patch-sensitized mice once a day for a total of 35 times. The immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of lungs and skin were evaluated. RESULTS: Our data showed that L. lactis-D2P2 significantly lowered total immunoglobulin E levels, decreased scratch bouts, and relieved AHR compared with the control mice. Histological analysis of the skin and lung tissue demonstrated the therapeutic effects of L. lactis-D2P2 to modulate immune responses via decreased eosinophil infiltration and reduced expression of key cytokines, interleukin (IL)-31 and IL-13, respectively. CONCLUSIONS: The results imply that mucosal allergen-specific immunotherapy of L. lactis-D2P2 is a more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. This study provides a promising platform for the development of novel oral protein-based vaccines in the early prevention of allergies.

Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.

In utero and early childhood infections have been associated with an increased risk of neurodevelopmental disorders; however, the observed associations may be confounded by familial predispositions. This study examined the neurodevelopmental disorders attributable to maternal infections during pregnancy and early childhood infections during the first year of life, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), tic disorders, and mental retardation (MR). We performed population and sibling comparison analyses to account for unmeasured familial confounding factors. We conducted a register-based cohort study with 2,885,662 individuals (comprising 1,864,660 full siblings) born in Taiwan between 2001 and 2018 and followed up until 2021. We employed Cox regression analysis to assess the association between in utero and early childhood infections requiring hospitalization and the subsequent risk of neurodevelopmental disorders. In the population analyses, an offspring exposed to maternal infection had an increased risk for ASD (hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.13-1.26), ADHD (HR = 1.14, 95% CI: 1.11-1.18), and MR (HR = 1.21, 95% CI: 1.13-1.30). These associations attenuated toward null in the sibling analyses. Individuals exposed to early childhood infection had an increased risk for ASD (HR = 1.13, 95% CI: 1.10-1.16), ADHD (HR = 1.16, 95% CI: 1.15-1.18), tic disorders (HR = 1.12, 95% CI: 1.09-1.15), and MR (HR = 1.64, 95% CI: 1.60-1.69) in the population analyses; these associations were also significant for ASD (HR = 1.14, 95% CI: 1.07-1.21) and MR (HR = 1.52, 95% CI: 1.44-1.62) in the sibling analyses. The association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors. Conversely, infection in early childhood may be attributable to it being a sensitive period and may play a role in the subsequent risk of ASD and MR.

Comparative Risk of Neuropsychiatric Adverse Events Associated With Leukotriene-Receptor Antagonists Versus Inhaled Corticosteroids.

BACKGROUND: Leukotriene-receptor antagonists (LTRA) and inhaled corticosteroids (ICS) are common controller medications for asthma, but limited studies examine their comparative risks on neuropsychiatric adverse events (NAEs) in patients with asthma. OBJECTIVE: To investigate the comparative risks of LTRA versus ICS on 7 distinct categories of NAEs in patients with asthma at a nationwide level. METHODS: We conducted a nationwide cohort study during 2010-2021. Incident NAEs and their clinical subgroups (eg, psychotic disorders, anxiety disorders, movement disorders, behavioral and emotional disorders, mood disorders, sleep-related disorders, and personality disorders) were assessed. Cox proportional hazards regressions were used to quantify the comparative risks. RESULTS: There were 1,249,897 patients with asthma aged 6 to 64 years. Incidence rates for NAEs were 25.10 per 1000 person-years among patients treated with LTRA and 23.46 per 1000 person-years among those treated with ICS. The incidence rate difference was 1.64 (95% confidence interval [CI]: 0.30-2.98) per 1000 person-years. Positive associations of NAEs and 3 clinical subgroups were found in patients treated with LTRA compared with ICS (hazard ratios [HR]: 1.06 [95% CI: 1.00-1.12] for NAEs; HR: 1.88 [95% CI: 1.24-2.84] for psychotic disorders; HR: 1.10 [95% CI: 1.01-1.20] for anxiety disorders; and HR: 1.27 [95% CI: 1.02-1.58] for behavioral and emotional disorders), but not for movement disorders, mood disorders, sleep-related disorders, and personality disorders. CONCLUSIONS: This nationwide cohort study identified heightened risks, ranging from 6% to 88%, of NAEs and 3 clinical subgroups in patients with asthma treated with LTRA compared with ICS. These findings underscore the necessity for clinicians to communicate with patients regarding potential neuropsychiatric harms when prescribing LTRA.

Cancer diagnosis during pregnancy is associated with severe maternal and neonatal morbidity.

BACKGROUND: Data on maternal and fetal outcomes in patients diagnosed with cancer during pregnancy are limited. Given expected increase in patients diagnosed with cancer during pregnancy, there is a growing need to evaluate clinical outcomes. OBJECTIVE: To evaluate obstetric outcomes among women with early-stage gynecologic or breast cancer who were diagnosed during pregnancy compared to women without cancer in a population-based cohort. METHODS: We performed a population-based study of women aged 18-45 years with stage I gynecologic or stage I-III breast cancer reported to the California Cancer Registry for the years 2000-2012. Data were linked to the 2000-2012 California birth data to produce a database with cancer characteristics and obstetric outcomes. We included patients who had a delivery within the 10 months following cancer diagnosis. The primary outcome was severe maternal morbidity (SMM). Secondary outcomes included pre-term birth (PTB) and neonatal morbidity. Propensity scores were used to match similar controls to cases in a 2:1 ratio based on demographic attributes and medical comorbidities included in the Obstetric Comorbidity Index (OB-CMI). Logistic regressions were used to evaluate outcomes. RESULTS: The cohort consisted of 503 women with cancer in pregnancy (319 breast, 125 ovarian, 59 cervical), and 1,006 matched controls. Cancer during pregnancy was associated with higher odds of SMM (6.8% vs <1.1%; odds ratio [OR] 8.03, 95% CI 3.82-16.88), PTB between 32-36 weeks (32.6% vs 8.3%, OR 5.38, 95% CI 4.02-7.20), and neonatal morbidity (12.5% vs 6.1%; OR 2.22, 95% CI 1.53-3.21) compared to matched controls. In sub-analysis of SMM indicators, hysterectomy and sepsis were significantly associated with cancer during pregnancy (4.8% vs <1.1%, P<.001; <2.2% vs 0.0%, P=.037, respectively). CONCLUSION: Cancer during pregnancy is associated with increased risk of maternal and neonatal morbidity. These findings highlight the need for careful management and consideration of obstetric outcomes in these patients.

The Anti-Inflammatory Effect of Lactococcus lactis-Ling-Zhi 8 on Ameliorating Atherosclerosis and Nonalcoholic Fatty Liver in High-Fat Diet Rabbits.

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD.

Detection in Orchards of Predominant Azole-Resistant Candida tropicalis Genotype Causing Human Candidemia, Taiwan.

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Retirement Transition Sequences and Well-Being Among Older Workers Focusing on Gender Differences.

This study examines retirement transition patterns and well-being in later life, focusing on gender differences using data from the 2004-2016 Health and Retirement Study (HRS) with 1,653 older workers. Sequence analysis identifies key retirement patterns, showing that men predominantly transitioned from full-time to mid-time voluntary retirement, while women experienced more gradual involuntary retirement. Involuntary retirees, both men and women, had precarious work histories and poorer mental health. The findings highlight gender-specific implications for social policy and emphasize the need for support in promoting successful aging and reducing social inequities among involuntary retirees.

Outcomes of Post-Immunotherapy Durable Responders of Advanced Hepatocellular Carcinoma- with Emphasis on Locoregional Therapy for Oligoprogression.

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and >3 lesions, respectively. Results: A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1-58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p < 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794). Conclusion: Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression.

Bilateral optic disc edema and serous retinal detachment as initial ocular manifestations of systemic lymphoma: A case report and literature review.

This report describes a unique case of systemic diffuse large B-cell lymphoma (DLBCL) with initial ocular manifestations of bilateral optic disc edema and serous retinal detachment (SRD). A 29-year-old man presented with altered color vision in the left eye, mild fever, weakness, and headache, followed by bilaterally reduced visual acuity. Anterior segment and vitreous examinations showed no inflammation with sluggish response of light reflex. His fundus examination revealed bilateral multiple SRDs and optic disc swelling with choroidal thickening. On fluorescein angiography, pinpoint hyperfluorescence, associated dye pooling, and optic disc staining with leakage were found bilaterally. Laboratory studies revealed elevated C-reactive protein and mild leukocytosis with neutrophil predominance. He was provisionally diagnosed with probable Vogt-Koyanagi-Harada syndrome and received methylprednisolone pulse therapy. Five days later, his systemic condition deteriorated following initial ocular symptom improvement. Whole-body computerized tomography revealed clustered lymphadenopathies, which were interpreted as DLBCL after lymph node biopsy. His ocular condition improved after DLBCL chemotherapy. We hope to promote early recognition with appropriate workups through this case and literature review.

Financial toxicity in breast cancer patients receiving regional nodal irradiation: Variation by cancer subtype.

BACKGROUND: We evaluated sociodemographic and clinical predictors of financial toxicity (FT) among patients with breast cancer with higher risk clinical factors warranting regional nodal irradiation (RNI). METHODS: Among 183 participants in a clinical trial of conventional vs. hypofractionated treatment with RNI, 125 (68 %) completed a pilot survey of FT measured using the validated Economic Strain and Resilience in Cancer (ENRICh) instrument, scored from 0 (minimal) to 10 (severe) FT. Associations with predictors were evaluated using Pearson correlation coefficients and Kruskal Wallis, Mann-Whitney U, and Jonckheere-Terpstra tests. Predictors of severe FT (ENRICh≥5) were tested using multivariable logistic regression with odds ratios converted to relative risks (RR). RESULTS: Of the sample, all received RNI, 92 % chemotherapy, 67 % axillary dissection, 26 % mastectomy without reconstruction, and 32 % mastectomy with reconstruction. At a median follow up of 1.48 years, median FT score was 2.13 (IQR 0.93-4.6), with 20.8 % of patients experiencing severe FT. Unadjusted worse FT score was associated with younger age (P = 0.003), Hispanic ethnicity (P = 0.006), lower income (P = 0.02), shorter interval from diagnosis to FT assessment (P = 0.02), and chemotherapy receipt (P = 0.05), but not with breast surgery type (P = 0.42), axillary surgery type (P = 0.33), or pathologic T (P = 0.68) or N stage (P = 0.47). In multivariable analysis, triple negative subtype was the sole clinical factor predicting severe FT (RR = 3.38; 95 % CI 1.48-4.99; P = 0.01). CONCLUSION: Among patients with breast cancer receiving RNI, triple negative subtype was associated with severe FT, suggesting that tumor receptor subtype may help identify a key breast cancer subpopulation for early FT intervention.

Trends in the use of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and recently diagnosed colorectal, lung, or prostate cancer.

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer. METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately. RESULTS: We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3 years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3 months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer). CONCLUSIONS: Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3 months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease.

Distinct characteristics of various autoimmune liver diseases: A 22-year hospital-based study in Taiwan.

BACKGROUND AND AIM: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia. METHODS: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled. RESULTS: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases. CONCLUSIONS: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

A population-based study of familial coaggregation and shared genetic etiology of psychiatric and gastrointestinal disorders.

BACKGROUND: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear. METHODS: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa. RESULTS: Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively. CONCLUSIONS: There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.

It has been proposed that people with psychiatric disorders such as depression could have an increased chance of developing gastrointestinal disorders such as irritable bowel syndrome. We looked at whether this was the case in a large number of people from Taiwan. We found that people with a psychiatric disorder, or with relatives having a psychiatric disorder, were more likely to have gastrointestinal disorders, and vice versa. These findings suggest that people who have psychiatric disorders or have psychiatric disorder-affected relatives should be monitored for gastrointestinal disorders, and vice versa, to enable them to benefit from all the treatments they might need to improve their health.

Survival After Simple Compared With Radical Hysterectomy for Patients With Early-Stage Cervical Cancer.

OBJECTIVE: To assess the effect on overall survival of simple hysterectomy with lymph node staging compared with radical hysterectomy with lymph node staging for patients with early-stage cervical cancer. METHODS: We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with early cervical carcinoma of 2 cm or smaller (stage IA1 with lymphovascular space invasion through IIA1, International Federation of Gynecology and Obstetrics staging) from 2010 to 2019. After 1:1 propensity score matching, we compared patients who underwent simple hysterectomy with lymph node staging and those with radical hysterectomy with lymph node staging. The variables used for matching were age, tumor size, race and ethnicity, lymphovascular space invasion, year of diagnosis, Charlson-Deyo comorbidity score, histology, and surgical approach. The primary outcome was overall survival at the end of follow-up. Secondary outcomes included 30-day readmission rate and 30- and 90-day mortality rates. RESULTS: In total, 4,167 patients met the inclusion criteria, of whom 2,637 patients (63.3%) underwent radical hysterectomy and lymph node staging and 1,530 patients (36.7%) underwent simple hysterectomy and lymph node staging. After propensity score matching, 1,529 patients in each group were included. There was no statistically significant difference in overall survival between patients who underwent simple hysterectomy and those who underwent radical hysterectomy (hazard ratio 1.25, 95% CI, 0.91-1.73, P=.17). Subgroup analysis by histology, lymphovascular space invasion, tumor size, and surgical approach did not reveal statistically significant differences in overall survival according to hysterectomy type. The hysterectomy groups also did not significantly differ in 30-day readmission rate (4.6% vs 4.2%, P=.73), 30-day mortality rate (0.1% vs 0%, P=.14), or 90-day mortality rate (0.1% vs 0.1%, P=.93). CONCLUSION: Patients with low-risk cervical cancer could undergo less radical surgery without a negative effect on their oncologic outcomes.

A simple and cost-effective strategy for electrochemiluminescence spectral determination.

BACKGROUND: Electrochemiluminescence (ECL), as a unique and powerful analytical technique, has been widely used in various fields. The determination of ECL spectra plays a crucial role in understanding ECL reaction mechanisms and conducting spectra-resolved ECL analysis. ECL intensity is typically detected using a photomultiplier tube, which offers high sensitivity for detecting extremely weak light signals but does not allow for spectral identification. Due to the time-dependent variation of ECL intensity caused by the applied potential and electrochemical reaction processes, it is challenging to perform ECL spectral detection using conventional wavelength-scanning spectrometers. RESULTS: In this study, we present a straightforward and cost-effective ECL spectral detection strategy by incorporating an automatically controlled tunable optical filter device between a commonly used PMT detector and a specially designed ECL reaction cell. The effectiveness of this approach was confirmed through initial validation, where the spectrum of a green LED spotlight was measured and compared with a commercial spectrometer. In a dynamic system with stable ECL signals, the ECL spectrum of the typical Ru(bpy)32+/TPA system was rapidly acquired by adjusting the bandpass filters. To account for time-varying ECL signals in practical measurements, time-based correction algorithms were implemented to rectify variations in ECL intensity. By integrating time-based correction algorithms and an automatically controlled tunable optical filter device into a commonly utilized PMT detector, the rapid and sensitive ECL spectra determination was achieved. Experimental results demonstrated the reliability of the proposed strategy. SIGNIFICANCE: This strategy is based on the widely used high-sensitivity PMT detection component, enabling the rapid and sensitive measurement of ECL spectra without altering the ECL detection hardware. It is simple, fast, efficient, and cost-effective, with the potential to be widely used for rapid ECL spectral detection and spectra-resolved ECL analysis.

Estimating expected years of life lost of psychiatric disorders in Taiwan: A Nationwide cohort study.

OBJECTIVES: This study employed a national longitudinal cohort to assess expected years of life lost (EYLL) in newly diagnosed psychiatric patients. METHODS: Data from Taiwan's National Death Registry and Health Insurance Research Database were scrutinized to identify patients with various psychiatric disorders. Disorders were ranked hierarchically, and age groups were categorized as young, middle-aged, and older adults. We utilized the semiparametric survival extrapolation method to estimate life expectancy (LE) and EYLL. Modifying effect of comorbid conditions and socioeconomic characteristics were also explored. RESULTS: Among the 5,757,431 cases, young adults with dementia, alcohol use disorder, schizophrenia, and bipolar disorder experienced an excess of 15 years of EYLL. Middle-aged adults faced approximately 9 years or more of EYLL, while older adults had lower EYLL values. Comorbid conditions, low income levels, and living in rural areas were associated with higher EYLL. CONCLUSIONS: This study underscores the substantial EYLL among young adults with psychiatric disorders and the significant impact of specific disorders on EYLL. Early intervention, tailored support, and healthcare system readiness are imperative for improved outcomes. Resource allocation and targeted interventions focusing on early detection and comprehensive treatment can alleviate the economic burden.

Automated, Real-Time Integration of Biometric Data From Wearable Devices With Electronic Medical Records: A Feasibility Study.

PURPOSE: A major barrier to the incorporation of biometric data into clinical practice is the lack of device integration with electronic medical records (EMRs). We developed infrastructure to transmit biometric data from an Apple Watch into the EMR for physician review. The study objective was to test feasibility of using this infrastructure for patients undergoing radiotherapy. METHODS: The study included patients with breast or prostate cancer receiving ≥3 weeks of radiotherapy who reported owning an Apple Watch. Daily resting heart rate (HR), HR variability, step count, and exercise minutes were automatically transferred to our EMR using a custom app installed on each patient's iPhone. Biometric data were presented to the treating radiation oncologist for review on a weekly basis during creation of the on-treatment note. Feasibility was defined a priori as physician review of biometric data for at least 90% of patients. Time trends in biometric data were tested using the Jonckheere-Terpstra test. Patient satisfaction was assessed using the System Usability Scale (SUS), with scores above 80 considered above-average user experience. RESULTS: Of the 20 patients enrolled, biometric data were successfully transmitted to the EMR and reviewed by the radiation oncologist for 95% (n = 19) of patients, thus meeting the a priori feasibility threshold. For patients with radiation courses ≥4 weeks, exercise minutes decreased over time (P = .01) and daily mean HR variability increased over time (P = .02). The median SUS was 82.5 (IQR, 70-87.5). CONCLUSION: Our study demonstrates the feasibility of real-time integration of biometric data collected from an Apple Watch into the EMR with subsequent physician review. The high rates of physician review and patient satisfaction provide support for further development of large-scale collection of wearable device data.

Spirocyclopropanes and Substituted Furans by Controlling Reactivity of 1,3-Enynoates: γ- and δ-Addition of Phosphines to Conjugate Acceptors.

In the Morita-Baylis-Hillman (MBH) reaction, a nucleophile undergoes ß-addition to activated alkenes or alkynes, forming reactive intermediates for subsequent carbon-carbon or carbon-hetero bond formation. By using a π-conjugated acceptor, however, an unprecedented reactivity of 1,3-enynoates and indane-1,3-diones was uncovered in the presence of phosphines. When indan-1,3-diones were used, Î³-addition of phosphines to 1,3-enynoates was observed for the first time; moderate to good yields were obtained for 14 substances containing the prominent spirocyclopropane scaffold with 100% retention of (Z)-alkene. When 2-methyl-indan-1,3-diones were used, di(tri)-substituted furans were produced through the δ-addition pathway, with 20 substances and a yield of up to 88% being achieved. Control experiments and density functional theory calculations were conducted to obtain insights into the unconventional γ-addition reaction pathway.