Defect Induced Structural Transition and Lipase Immobilization in Mesoporous Aluminum Metal-Organic Frameworks.

The transition from disorder to order and structural transformation are distinctive metal-organic framework (MOF) features. How to adapt or control both behaviors in MOF has rarely been studied. In this case, we demonstrate that our successful synthesis of [Al(OH)(PDA)]n (AlPDA-53-DEF, AlPDA-53-H, and AlPDA-68) with H2PDA=4,4'-[1,4-phenylenebis(ethyne-2,1-diyl)]-di benzoic acid has shown the intricate world of Aluminum Metal-Organic Frameworks (Al-MOFs). It offers profound insights into defect structures to order and transformations. AlPDA-53-DEF, in particular, revealed a fascinating interplay of various pore sizes within both micro and mesoporous regions, unveiling a unique lattice rearrangement phenomenon upon solvent desorption. Defects and disorders emerged as crucial impacts of transforming AlPDA-53-DEF, with its initially imperfect crystallinity, into the highly crystalline, hierarchically porous AlPDA-53-H.

Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

OBJECTIVES: Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD). METHODS: The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. RESULTS: Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD. CONCLUSIONS: This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5 years.

The effects of swLORETA Z-score neurofeedback for patients comorbid with major depressive disorder and anxiety symptoms.

BACKGROUND: Patients with major depressive disorder (MDD) exhibit atypical brain activities in the frontal, temporal, and parietal lobes. The study aimed to investigate the effects of standardized weighted low-resolution electromagnetic tomography Z-score neurofeedback (swLZNFB) on symptoms of depression and anxiety, electroencephalography (EEG) parameters, and deep brain activities in patients with MDD. METHOD: Forty-eight patients with MDD comorbid with anxiety symptoms were assigned to the swLZNFB group and the control group. Participants completed the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) and a 5-minute resting EEG at the pre-and post-tests. The swLZNFB group received ten sessions of one-hour treatment twice weekly. The control group received treatment as usual. The scores for BDI-II and BAI, number of EEG abnormalities, percentage of EEG abnormalities, and current source density (CSD) measured in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and amygdala were compared at pre-and post-tests between the two groups. RESULTS: There were decreased scores of BDI-II and BAI, number of EEG abnormalities, and percentage of EEG abnormalities at post-test compared with pre-test in the swLZNFB group, and lower scores of BDI-II and BAI at post-test in the swLZNFB group compared with the control group. Moreover, decreased CSD of beta1 and beta3 in the PFC, ACC, PCC, and amygdala at post-test compared to pre-test in the swLZNFB group. LIMITATIONS: Not a randomized controlled trial. CONCLUSION: Ten sessions of swLZNFB reduced clinical symptoms and atypical brain activities, it serves as a potential psychological intervention for patients with MDD.

Recent advances in the biological depolymerization and upcycling of polyethylene terephthalate.

Polyethylene terephthalate (PET) is favored for its exceptional properties and widespread daily use. This review highlights recent advancements that enable the development of biological tools for PET decomposition, transforming PET into valuable platform chemicals and materials in upcycling processes. Enhancing PET hydrolases' catalytic activity and efficiency through protein engineering strategies is a priority, facilitating more effective PET waste management. Efforts to create novel PET hydrolases for large-scale PET depolymerization continue, but cost-effectiveness remains challenging. Hydrolyzed monomers must add additional value to make PET recycling economically attractive. Valorization of hydrolysis products through the upcycling process is expected to produce new compounds with different values and qualities from the initial polymer, making the decomposed monomers more appealing. Advances in synthetic biology and enzyme engineering hold promise for PET upcycling. While biological depolymerization offers environmental benefits, further research is needed to make PET upcycling sustainable and economically feasible.

Machine Learning and Radiomics of Bone Scintigraphy: Their Role in Predicting Recurrence of Localized or Locally Advanced Prostate Cancer.

BACKGROUND: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. METHODS: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. RESULTS: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. CONCLUSIONS: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS.

Harnessing split fluorescent proteins in modular protein logic for advanced whole-cell detection.

Whole-cell biosensors have demonstrated promising capabilities in detecting target molecules. However, their limited selectivity and precision can be attributed to the broad substrate tolerance of natural proteins. In this study, we aim to enhance the performance of whole-cell biosensors by incorporating of logic AND gates. Specifically, we utilize the HrpR/S system, a widely employed hetero-regulation module from Pseudomonas syringae in synthetic biology, to construct an orthogonal AND gate in Escherichia coli. To accomplish this, we compare the HrpR/S system with self-associating split fluorescent proteins using the Spy Tag/Spy Catcher system. Our objective is to selectively activate a reporter gene in the presence of both IPTG and Hg(II) ions. Through systematic genetic engineering and evaluation of various biological parts under diverse working conditions, our research demonstrates the utility of self-associating split fluorescent proteins in developing high-performance whole-cell biosensors. This approach offers advantages such as engineering simplicity, reduced basal activity, and improved selectivity. Furthermore, the comparison with the HrpR/S system serves as a valuable control model, providing insights into the relative advantages and limitations of each approach. These findings present a systematic and adaptable strategy to overcome the substrate tolerance challenge faced by whole-cell biosensors.

Exploring the potential of iron-based metal-organic frameworks as peroxidase nanozymes for glucose detection with various secondary building units.

Finding materials in biosensing that balance enzyme-like reactivity, stability, and affordability is essential for the future. Because of their unique peroxidase properties, including variable pore size, surface area, and Lewis acid active sites, iron-based metal-organic frameworks (MOFs) have evolved as viable possibilities. In this study, we constructed a Fe-MOF and tested its peroxidase-like activity and responsiveness toward H2O2 colorimetric techniques. Using encapsulation, we incorporated glucose oxidase into the ZIF-90 PVP MOF and conducted a sequential reaction with the Fe-MOF to detect glucose. The results showed better peroxidase catalytic activity of the MIL-88B(Fe) (1,4-NDC) MOF and similar secondary building unit (SBU) Fe-MOFs were studied in other peroxidase nanozyme studies. When combined with an enzyme-encapsulating ZIF-90 PVP MOF, they could be sequentially employed for glucose detection purposes. This study highlights the potential of nanozymes as an alternative to natural enzymes, with promising applications in biosensing and beyond.

Symbiotic UCYN-A strains co-occurred with El Niño, relaxed upwelling, and varied eukaryotes over 10 years off Southern California.

Biological nitrogen fixation, the conversion of N2 gas into a bioavailable form, is vital to sustaining marine primary production. Studies have shifted beyond traditionally studied tropical diazotrophs. Candidatus Atelocyanobacterium thalassa (or UCYN-A) has emerged as a focal point due to its streamlined metabolism, intimate partnership with a haptophyte host, and broad distribution. Here, we explore the environmental parameters that govern UCYN-A's presence at the San Pedro Ocean Time-series (SPOT), its host specificity, and statistically significant interactions with non-host eukaryotes from 2008-2018. 16S and 18S rRNA gene sequences were amplified by "universal primers" from monthly samples and resolved into Amplicon Sequence Variants, allowing us to observe multiple UCYN-A symbioses. UCYN-A1 relative abundances increased following the 2015-2016 El Niño event. This "open ocean ecotype" was present when coastal upwelling declined, and Ekman transport brought tropical waters into the region. Network analyses reveal all strains of UCYN-A co-occur with dinoflagellates including Lepidodinium, a potential predator, and parasitic Syndiniales. UCYN-A2 appeared to pair with multiple hosts and was not tightly coupled to its predominant host, while UCYN-A1 maintained a strong host-symbiont relationship. These biological relationships are particularly important to study in the context of climate change, which will alter UCYN-A distribution at regional and global scales.

Trade-Offs between Competitive Ability and Resistance to Top-Down Control in Marine Microbes.

Trade-offs between competitive ability and resistance to top-down control manifest the "kill-the-winner" hypothesis that explains how mortality caused by protists and viruses can promote bacterial diversity. However, the existence of such trade-offs has rarely been investigated in natural marine bacterial communities. To address this question, we conducted on-board dilution experiments to manipulate top-down control pressure (protists only or protists plus viruses [protists+viruses] combined) and then applied 16S rRNA gene high-throughput sequencing techniques to assess the responses of each bacterial taxon. Dilution experiments enabled us to measure the top-down-control-free growth rate as the competitive ability and top-down-control-caused mortality as the reverse of resistance to top-down control. Overall, bacterial taxa with higher top-down-control-free growth rates were accompanied by lower top-down-control-caused resistance. Furthermore, competition-resistance trade-offs were stronger and more consistent when top-down control was caused by protists+viruses combined than by protists only. When protists+viruses were diluted, the bacterial rank abundance distribution became steepened and evenness and richness were decreased. However, when protists were diluted, only richness decreased. Our results indicate the existence of competition-resistance trade-offs in marine microbes and demonstrate the positive impacts of such trade-offs on bacterial diversity. Regardless, the strength of the competition-resistance trade-offs and the impacts on bacterial diversity were contingent on whether top-down control was caused by protists+viruses combined or protists only. IMPORTANCE We addressed the "kill-the-winner" hypothesis from the perspective of its principle (the competition-resistance trade-off) in marine bacterial communities incubated in situ. Our results supported the existence of competition-resistance trade-offs and the positive effect on bacterial community diversity. The study linked theoretical expectations and complex natural systems and provided new knowledge regarding how top-down controls and competition trade-offs shaped natural bacterial communities.

The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia.

PURPOSE: The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function. MATERIALS AND METHODS: Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated. RESULTS: Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms. CONCLUSIONS: We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.

A bioinspired copper-based coordination polymer for the detection of pheochromocytoma biomarkers.

Oxidase-mimicking (catechol oxidase/laccase) nanozymes provide outstanding specificity in the detection of epinephrine (Epi) for the assessment of pheochromocytoma; however, epinephrine (Epi) and norepinephrine (NE) co-existing in the same systems will reduce the selectivity of the biosensor. In the current study, we synthesized copper-based coordination polymer (Cu-CP) nanozymes capable of accelerating the oxidation of Epi with high specificity. Furthermore, the Cu-CP is able to detect Epi over a wide linear range of 0.5-100 µM with a low detection limit of 0.36 µM while providing excellent stability and recyclability. Furthermore, we employed colorimetric and fluorescence signals for sequential detection of the coexistence of Epi and NE for use in tracking the treatment outcomes of patients with pheochromocytoma. Experiments using artificial urine further confirmed the efficacy of the proposed system.

Effects of phytoplankton, viral communities, and warming on free-living and particle-associated marine prokaryotic community structure.

Free-living and particle-associated marine prokaryotes have physiological, genomic, and phylogenetic differences, yet factors influencing their temporal dynamics remain poorly constrained. In this study, we quantify the entire microbial community composition monthly over several years, including viruses, prokaryotes, phytoplankton, and total protists, from the San-Pedro Ocean Time-series using ribosomal RNA sequencing and viral metagenomics. Canonical analyses show that in addition to physicochemical factors, the double-stranded DNA viral community is the strongest factor predicting free-living prokaryotes, explaining 28% of variability, whereas the phytoplankton (via chloroplast 16S rRNA) community is strongest with particle-associated prokaryotes, explaining 31% of variability. Unexpectedly, protist community explains little variability. Our findings suggest that biotic interactions are significant determinants of the temporal dynamics of prokaryotes, and the relative importance of specific interactions varies depending on lifestyles. Also, warming influenced the prokaryotic community, which largely remained oligotrophic summer-like throughout 2014-15, with cyanobacterial populations shifting from cold-water ecotypes to warm-water ecotypes.

Association between Self-Stigma and Suicide Risk in Individuals with Schizophrenia: Moderating Effects of Self-Esteem and Perceived Support from Friends.

This cross-sectional study assessed the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk in individuals with schizophrenia. We included 300 participants (267 with schizophrenia and 33 with schizoaffective disorder). Suicide risk was assessed using items adopted from the suicide module of the Mini-International Neuropsychiatric Interview; self-stigma was assessed using the Self-Stigma Scale-Short; perceived support from friends was assessed using the Friend Adaptation, Partnership, Growth, Affection, and Resolve Index; and self-esteem was assessed using the Rosenberg Self-Esteem Scale. A moderation analysis was performed to examine the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk. The results indicated that self-stigma was positively associated with suicide risk after the effects of other factors were controlled for. Both perceived support from friends and self-esteem significantly reduced the magnitude of suicide risk in participants with self-stigma. Our findings highlight the value of interventions geared toward ameliorating self-stigma and enhancing self-esteem in order to reduce suicide risk in individuals with schizophrenia.

Validation and Comparison of the Informant-Rated and Self-Rated Versions of the Mild Behavioral Impairment Checklist.

BACKGROUND: The Mild Behavioral Impairment Checklist (MBI-C) has been developed to assess mild behavioral impairment (MBI). However, no study has validated the use of MBI-C using a promising translation method in Taiwan. Thus, consistency and discrepancy between informant-rated and self-rated scores have not been extensively researched. OBJECTIVE: This study validated and compared the informant- and self-rated versions of the MBI-C among community-dwelling people in Taiwan. METHOD: We recruited 202 pairs of individuals without dementia aged ≥50 years and their cohabitating informants. The participants completed the MBI-C (MBI-C-self), and the informants completed the MBI-C (MBI-C-informant) and the Neuropsychiatric Inventory Questionnaire (NPI-Q) independently. Internal consistency, inter-rater reliability, and convergent validity were examined. RESULTS: Both MBI-C-self and MBI-C-informant exhibited satisfactory Cronbach's α values (0.92 and 0.88, respectively). The MBI-C-informant total scorewas correlated with the NPI-Q total score (r = 0.83, p < 0.001). Inter-rater reliability between the two versions, as represented by the inter-rater correlation coefficient, was 0.57 (p < 0.001). The prevalence of MBI based on the MBI-C-informant scores was 1.5% higher than that based on the MBI-C-self scores according to the suggested cut-off score of 8.5. The affective dysregulation domain score of MBI-C-informant was significantly lower than that of MBI-C-self. CONCLUSION: MBI-C-informant exhibited both high reliability and validity. Discrepancies between MBI-C-informant and MBI-C-self related to the detection rates and affective dysregulation domain scores were noted. The level of consistency and discrepancy between these two versions provide implications for the use of MBI-C in clinical practice and future research.

Clinical Outcomes of Metastatic Breast Cancer in Patients Having Imaging Liver Pseudocirrhosis with or without Evident Varices.

BACKGROUND: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis-related portal hypertension (pHTN). This study defined evident pHTN by the presence of esophageal or gastric varices and compared patients' outcomes of metastatic breast cancer with imaging-diagnosed pseudocirrhosis with or without varices. METHODS: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Survival outcomes were compared based on endoscopic evidence of esophageal or gastric varices. RESULTS: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Eighty-one (76%) had initial metastases in both hepatic lobes, and 32 (30%) had esophageal or gastric varices. The median overall survival (OS) was 5 and 13 months in patients with and without varices (P = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative subtype was 16, 9, and 2 months, respectively (P = .001). Patients with varices usually had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with varices had OS exceeding 1 year. In multivariate analysis, evident varices (P = .007) and triple-negative subtype (P = .013) were associated with poor OS. CONCLUSIONS: Patients with pseudocirrhosis and evident varices had a significantly shorter median OS, and were usually associated with clinical cirrhosis-related complications. To maximize OS, early identification and meticulous supportive care are warranted.

The Clinical Implication of Serogroup Distribution and Drug Resistance of Non-Typhoidal Salmonella in Children: A Single Center Study in Southern Taiwan during 2004-2019.

Background: A regional antibiotic susceptibility database of certain pathogens is crucial for first-line physicians in terms of providing clinical judgement and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiological data of Salmonella serogroups and drug resistance in pediatric patients. Methods: This is a single-center retrospective study enrolling patients aged from 0 to 18 years who were hospitalized with cultured proven non-typhoidal Salmonella (NTS) infection from 2004 to 2019. The isolates were collected and the demographic data, serogroups of Salmonella and antimicrobial susceptibilities were further analyzed. Results: A total of 1583 isolates of NTS were collected. Serogroup C2 was prone to cause invasive non-typhoidal salmonellosis (iNTS), especially bacteremia. Patients aged < 2 years were associated with serogroups B and C2 infection, while those aged ≥ 2 years were associated with serogroups D and E infection. The prevalence of serogroup B declined with simultaneous increase in prevalence of serogroups D and E. Serogroups B and E were associated with ceftriaxone resistance, while Serogroup D was less drug-resistant than the others. The prevalence of ceftriaxone-resistant Salmonella had not increased, although more ciprofloxacin-resistant isolates were found in iNTS infection. Conclusions: Age < 2 years is a risk factor of iNTS for children, and the distribution of serogroup changes should be closely monitored. Ceftriaxone is still the drug of choice for treating pediatric iNTS infection, and although no increase was observed in the prevalence of ceftriaxone-resistant strains in this study, continuing surveillance of such cases is warranted.

Cu-PyC MOF with oxidoreductase-like catalytic activity boosting colorimetric detection of Cr(VI) on paper.

Hexavalent chromium ions (Cr(VI)) are highly toxic and prone to bioaccumulation in the natural environment. This study sought to develop a facile and cost-effective approach to on-site monitoring Cr(VI) content in diverse environmental samples. We synthesized copper-based MOF nanozymes (Cu-PyC MOF) and developed a simple colorimetric method by which to detect Cr(VI) on paper-based devices. The colorimetric product is obtained using the MOF nanozyme as a catalyst, Cr(VI) as an oxidant, 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate to produce a bluish-green color observable by the naked eye or a UV-visible spectrophotometer. After Cu-PyC MOF was suspended in an acidic buffer, it remained stable and showed oxidoreductase-like catalytic activity, which in turn boosts Cr(VI) reduction. The proposed scheme enables the detection of Cr(VI) within 3 min over a linear range of 0.5-50 µM with a low detection limit of 0.051 µM. The proposed nanozyme-based colorimetric method exhibits excellent reusability and selectivity over other 27 interference ions and can be used in real sample analysis.

Comparing the Psychometric Properties among Three Versions of the UCLA Loneliness Scale in Individuals with Schizophrenia or Schizoaffective Disorder.

The UCLA Loneliness Scale (Version 3; UCLA-LSV3) is widely used for assessing loneliness. Nevertheless, the validity of this scale for assessing loneliness in individuals with schizophrenia or schizoaffective disorder has not been determined. Additionally, studies validating the eight-item and three-item versions of UCLA-LSV3 have not included individuals with severe mental illness; therefore, whether the short versions are comparable to the full 20-item version of UCLA-LSV3 for this population is unclear. The present study examined the unidimensional structure, internal consistency, concurrent validity, and test-retest reliability of the Chinese versions of UCLA-LSV3 (i.e., 20-item, 8-item, and 3-item versions) to determine which version is most appropriate for assessing loneliness in individuals with schizophrenia or schizoaffective disorder in Taiwan. A total of 300 participants (267 with schizophrenia and 33 with schizoaffective disorder) completed the scales, comprising UCLA-LSV3, the Center for Epidemiological Studies Depression Scale (CES-D), the suicidality module of the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E), and the family and peer Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) index. Construct validity was evaluated through confirmatory factor analysis. The three versions of UCLA-LSV3 were compared with the CES-D, the suicidality module of the K-SADS-E, and the family and peer APGAR index to establish concurrent validity. The results indicated that all three versions of UCLA-LSV3 exhibited acceptable to satisfactory psychometric properties in terms of unidimensional constructs, concurrent validity, and test-retest reliability. The full version of UCLA-LSV3 had the best performance, followed by the eight-item version and the three-item version. Moreover, the three versions had relatively strong associations with each other. Therefore, when deliberating which version of UCLA-LSV3 is the best choice for assessing loneliness in individuals with schizophrenia or schizoaffective disorder, healthcare providers and therapists should consider time availability and practicality.

Statins were not associated with hepatocellular carcinoma after controlling for time-varying confounders in patients with diabetes.

BACKGROUND AND OBJECTIVES: We examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods. METHODS: This retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure. RESULTS: Over a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79-0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87-1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94-1.31) using the MSM approach. CONCLUSION: Statin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.

Cardiac Autonomic and Cardiac Vagal Control During and After Depressive and Happiness Autobiographical Memories in Patients With Major Depressive Disorder.

Background: Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are indices of cardiac autonomic and cardiac vagal control (CVC), both of which are markers of emotional regulation and physical health. This study examined (1) the differences in cardiac autonomic regulation and CVC during baseline, depressive, and happiness autobiographical memory tasks between participants with major depressive disorder (MDD group) and healthy controls (HC group); (2) the associations between depressive symptoms and cardiac autonomic and CVC; and (3) the reactivity and recovery of cardiac autonomic and CVC between the MDD and HC groups. Methods: A total of 168 and 178 participants were included in the MDD and HC groups, respectively. Demographic data and the Beck Depression Inventory-II were collected before the experimental procedure. Lead II electrocardiograph (ECG) was measured during baseline, depressive, and happiness autobiographical memory tasks, and then interbeat intervals from ECG were converted to the time and frequency domains of HRV and RSA. Results: The participants in the MDD group showed lower HRV (including standard deviation of normal to normal intervals, low frequency, the natural logarithm of low frequency, and the natural logarithm of high frequency) and CVC (RSA and lnRSA) than those in the HC group. Depressive symptoms were positively correlated with heart rate and negatively correlated with the indices of cardiac autonomic and CVC. There was significantly increased reactivity and recovery of cardiac autonomic and CVC during and after depressive and happiness autobiographical memory tasks in the HC group, but not in the MDD group. Discussion: Participants with MDD had cardiac autonomic and CVC dysregulation, decreased reactivity, and did not recover to baseline after emotional provocations. These results can be the theoretical basis for clinical intervention by using HRV biofeedback to restore cardiac autonomic regulation and CVC during and after emotional events in the future.