Unique influences of pregnancy and anticipated parenting on cigarette smoking: results and implications of a within-person, between-pregnancy study.

Not all pregnant individuals want to become parents and "parenting intention" can also vary within individuals during different pregnancies. Nevertheless, the potential impact of parenting intention on health-related behavior during pregnancy has been heavily underexplored. In this study, we employed a within-person between pregnancy design to estimate the effect of parenting-specific influences on smoking, separate from pregnancy-specific and individual-level influences. We quantified within-mother differences in smoking during pregnancies of infants they reared (n = 84) versus pregnancies of infants they placed for adoption at birth (n = 65) using multivariate mixed-effects Poisson regression models. Mean cigarettes/day declined as the pregnancy progressed regardless of whether infants were reared or placed. However, participants smoked fewer cigarettes/day during reared pregnancies. Relative to "adopted" pregnancies, smoking during "reared" pregnancies was lower by 24%, 41%, and 54% in first (95% CI 0.64-0.90; p = 0.001), second (95% CI 0.48-0.72; p < 0.001), and third trimesters (95% CI 0.36-0.59; p < 0.001), respectively, independent of between-pregnancy differences in maternal age, fetal sex, parity, and pregnancy complications. Female sex and nulliparity were protective. Parenting intention was associated with a protective effect on pregnancy smoking independent of pregnancy-specific influences and individual characteristics. Failure to consider the impact of parenting intention on health-related behavior during pregnancy could perpetuate an unrealistic expectation to "do what's best for the baby" and stigmatize women with unintended or unwanted pregnancies.

Wearable Loop Sensor for Bilateral Knee Flexion Monitoring.

We have previously reported wearable loop sensors that can accurately monitor knee flexion with unique merits over the state of the art. However, validation to date has been limited to single-leg configurations, discrete flexion angles, and in vitro (phantom-based) experiments. In this work, we take a major step forward to explore the bilateral monitoring of knee flexion angles, in a continuous manner, in vivo. The manuscript provides the theoretical framework of bilateral sensor operation and reports a detailed error analysis that has not been previously reported for wearable loop sensors. This includes the flatness of calibration curves that limits resolution at small angles (such as during walking) as well as the presence of motional electromotive force (EMF) noise at high angular velocities (such as during running). A novel fabrication method for flexible and mechanically robust loops is also introduced. Electromagnetic simulations and phantom-based experimental studies optimize the setup and evaluate feasibility. Proof-of-concept in vivo validation is then conducted for a human subject performing three activities (walking, brisk walking, and running), each lasting 30 s and repeated three times. The results demonstrate a promising root mean square error (RMSE) of less than 3° in most cases.

A Programmable CRISPR/Cas9 Toolkit Improves Lycopene Production in Bacillus subtilis.

Bacillus subtilis has been widely used and generally recognized as a safe host for the production of recombinant proteins, high-value chemicals, and pharmaceuticals. Thus, its metabolic engineering attracts significant attention. Nevertheless, the limited availability of selective markers makes this process difficult and time-consuming, especially in the case of multistep biosynthetic pathways. Here, we employ CRISPR/Cas9 technology to build an easy cloning toolkit that addresses commonly encountered obstacles in the metabolic engineering of B. subtilis, including the chromosomal integration locus, promoter, terminator, and guide RNA (gRNA) target. Six promoters were characterized, and the promoter strengths ranged from 0.9- to 23-fold that of the commonly used strong promoter P43. We characterized seven terminators in B. subtilis, and the termination efficiencies (TEs) of the seven terminators are all more than 90%. Six gRNA targets were designed upstream of the promoter and downstream of the terminator. Using a green fluorescent protein (GFP) reporter, we confirmed integration efficiency with the single-locus integration site is up to 100%. We demonstrated the applicability of this toolkit by optimizing the expression of a challenging but industrially important product, lycopene. By heterologous expression of the essential genes for lycopene synthesis on the B. subtilis genome, a total of 13 key genes involved in the lycopene biosynthetic pathway were manipulated. Moreover, our findings showed that the gene cluster ispG-idi-dxs-ispD could positively affect the production of lycopene, while the cluster dxr-ispE-ispF-ispH had a negative effect on lycopene production. Hence, our multilocus integration strategy can facilitate the pathway assembly for production of complex chemicals and pharmaceuticals in B. subtilis. IMPORTANCE We present a toolkit that allows for rapid cloning procedures and one-step subcloning to move from plasmid-based expression to stable chromosome integration and expression in a production strain in less than a week. The utility of the customized tool was demonstrated by integrating the MEP (2C-methyl-d-erythritol-4-phosphate) pathway, part of the pentose phosphate pathway (PPP), and the hetero-lycopene biosynthesis genes by stable expression in the genome. The tool could be useful to engineer B. subtilis strains through diverse recombination events and ultimately improve its potential and scope of industrial application as biological chassis.

Heterologous Expression of Jatropha curcas Fatty Acyl-ACP Thioesterase A (JcFATA) and B (JcFATB) Affects Fatty Acid Accumulation and Promotes Plant Growth and Development in Arabidopsis.

Plant fatty acyl-acyl carrier protein (ACP) thioesterases terminate the process of de novo fatty acid biosynthesis in plastids by hydrolyzing the acyl-ACP intermediates, and determine the chain length and levels of free fatty acids. They are of interest due to their roles in fatty acid synthesis and their potential to modify plant seed oils through biotechnology. Fatty acyl-ACP thioesterases (FAT) are divided into two families, i.e., FATA and FATB, according to their amino acid sequence and substrate specificity. The high oil content in Jatropha curcas L. seed has attracted global attention due to its potential for the production of biodiesel. However, the detailed effects of JcFATA and JcFATB on fatty acid biosynthesis and plant growth and development are still unclear. In this study, we found that JcFATB transcripts were detected in all tissues and organs examined, with especially high accumulation in the roots, leaves, flowers, and some stages of developing seeds, and JcFATA showed a very similar expression pattern. Subcellular localization of the JcFATA-GFP and JcFATB-GFP fusion protein in Arabidopsis leaf protoplasts showed that both JcFATA and JcFATB localized in chloroplasts. Heterologous expression of JcFATA and JcFATB in Arabidopsis thaliana individually generated transgenic plants with longer roots, stems and siliques, larger rosette leaves, and bigger seeds compared with those of the wild type, indicating the overall promotion effects of JcFATA and JcFATB on plant growth and development while JcFATB had a larger impact. Compositional analysis of seed oil revealed that all fatty acids except 22:0 were significantly increased in the mature seeds of JcFATA-transgenic Arabidopsis lines, especially unsaturated fatty acids, such as the predominant fatty acids of seed oil, 18:1, 18:2, and 18:3. In the mature seeds of the JcFATB-transgenic Arabidopsis lines, most fatty acids were increased compared with those in wild type too, especially saturated fatty acids, such as 16:0, 18:0, 20:0, and 22:0. Our results demonstrated the promotion effect of JcFATA and JcFATB on plant growth and development, and their possible utilization to modify the seed oil composition and content in higher plants.

Lasting effects of residential mobility during childhood on psychopathology among Chinese University students.

BACKGROUND: Residential mobility during childhood increases risk of psychopathology in adulthood and is a common experience among Chinese children. This study investigated associations between number and age of first move, etiological risk factors for psychopathology, and common mental disorders in adolescence and early adulthood. METHODS: The sample included 39,531 undergraduates (84.5% completion rate) age 15-34 years in their first year at a Chinese comprehensive university in annual cross-sectional surveys during 2014-2018. Common mental disorders measured using standardised self-report instruments. Data analysed using logistic regression models and interaction analysis. RESULTS: Half of all students experienced one or more moves of residence before age 15 years. Outcomes of Depression, Somatisation, Obsessive-compulsive disorder, Hallucinations and Delusions, and Suicide attempts showed dose-response relationships with increasing number of moves. Other etiological risk factors, including childhood disadvantage and maltreatment, showed similar dose response relationships but did not confound associations with mobility. We found interactions between reporting any move and being a left-behind child on depression and somatisation; number of moves and younger age at first move on depression, somatisation, suicide attempts and hallucinations and delusions. CONCLUSIONS: Residential mobility in childhood is associated with psychopathology in adulthood and this association increases with increasing number of moves. Mobility is also associated with childhood disadvantage and maltreatment but associations with psychopathology are independent of these factors. Multiplicative effects were shown for multiple moves starting at a younger age and if the participant had been a left-behind child.

Interpersonal violence in a deprived Scottish urban area with aggregations of physical health risks and psychiatric morbidity: an ecological study.

BACKGROUND: Glasgow, Scotland, has previously shown exceptional levels of violence among young men, shows aggregations of health conditions, with shortened life expectancy. Health conditions can be both causes and consequences of violence, of shared community-level socio-economic risk factors, and can result from large-scale social forces beyond the control of populations with high levels of violence. The aim of the study was to provide an in depth understanding of the Public Health problem of violence among young adult men in Glasgow East. METHOD: Ecological investigation of violence and its associations with health conditions in areas of contrasting socioeconomic deprivation. National survey of 1916 British men aged 18-34 years, augmented by a sub-sample of 765 men in Glasgow East (GE). Participants completed questionnaires covering current physical and sexual health, psychiatric symptoms, substance misuse, lifestyle, and crime and violence. RESULTS: The 5-year prevalence of violence was similar in both surveys but fights involving weapons (AOR 3.32, 95% CI 2.29-4.79), gang fights (AOR 2.30, 95% CI 1.77-2.98), and instrumental violence supporting criminal lifestyles were more common in GE, where 1 in 9 men had been in prison. Violent men in both samples reported poorer physical and sexual health and all types of psychiatric morbidity except depression, with multiple high-risk behaviours for both future poor health and violence. Associations between drug and alcohol dependence and violence in GE could not be entirely explained by deprivation. CONCLUSION: Violence in deprived urban areas is one among many high-risk behaviours and lifestyle factors leading to, as well as resulting from, aggregations of both psychiatric and physical health conditions. Poverty partly explained raised levels of violence in GE. Other factors such as drug and alcohol misuse and macho attitudes to violence, highly prevalent among men in this socially excluded community, also contributed. Multi-component preventive interventions may be needed in deprived areas and require future investigations into how multiple co-existing risk factors produce multimorbidity, including psychiatric disorders, substance misuse, poor physical health and violence.

Epidemiology of knife carrying among young British men.

PURPOSE: Knife carrying has caused considerable public concern in the UK. But little is known of the epidemiology and characteristics of men who carry knives. We investigated associations with socioeconomic deprivation, area-level factors, and psychiatric morbidity. METHODS: Cross-sectional surveys of 5005 British men, 18-34 years, oversampling Black and Minority Ethnic (BME) men, lower social grades, and in London Borough of Hackney and Glasgow East. Participants completed questionnaires covering violent behaviour and psychiatric morbidity using standardised self-report instruments. Socioeconomic deprivation measured at small area level. RESULTS: Prevalence of knife carrying was 5.5% (4.8-6.9) and similar among white and BME subgroups. However, prevalence was twice the national rate in Glasgow East, and four times higher among Black men in Hackney, both areas with high levels of background violence and gang activity. Knife carrying was associated with multiple social problems, attitudes encouraging violence, and psychiatric morbidity, including antisocial personality disorder (AOR 9.94 95% CI 7.28-13.56), drug dependence (AOR 2.96 95% CI 1.90-4.66), and paranoid ideation (AOR 6.05 95% CI 4.47-8.19). There was no evidence of a linear relationship with socioeconomic deprivation. CONCLUSION: Men who carry knives represent an important public health problem with high levels of health service use. It is not solely a criminal justice issue. Rates are increased in areas where street gangs are active. Contact with the criminal justice system provides opportunity for targeted violence prevention interventions involving engagement with integrated psychiatric, substance misuse, and criminal justice agencies.

Exosomes Play an Important Role in the Progression of Plasma Cell Mastitis via the PI3K-Akt-mTOR Signaling Pathway.

BACKGROUND: Plasma cell mastitis (PCM) is one of the most frequently encountered inflammatory diseases of the nonlactating breast. However, its pathogenesis has remained unknown. METHODS: In this study, we observed the ultrastructure changes of PCM by a transmission electron microscope. The transcriptome expression difference of exosomes was detected by RNA-Seq; then, we confirmed the key difference genes by western blot and immunohistochemistry. Finally, we established the mouse PCM model by tissue homogenate injection to validate the role of exosomes on the progression of PCM. RESULTS: The analysis of the exosomal transcriptome expression difference between PCM and normal mammary tissues using RNA-Seq showed the differential genes and enrichment pathways involved in the course of PCM. The decreased HSP90AA1 and EEF2, excessive production of p-AKT, and p-mTOR were consistent with clinical specimens. Inhibition of exosome secretion significantly inhibited inflammatory cell infiltration, and the mammary duct had maintained a better structure in the PCM mouse model. CONCLUSION: Our results revealed the role of exosomes acting as critical signal introduction facilitators in the progression of plasma cell mastitis and identified potential key genes in the regulation of this process. These results will help to dissect the molecular mechanism of PCM and provide therapeutic targets.

Comparison between percutaneous and open reduction for treating paediatric talar neck fractures.

BACKGROUND: The purpose of the study was to introduce percutaneous reduction and fixation of paediatric talar neck fractures. The study also included a comparison between the technique and the conventional open surgery. METHODS: From October 2003 to May 2013, 23 children (group A) with closed two-part talar neck fractures were treated with percutaneous reduction. For comparison, another group of 26 children (group B) were treated with the conventional open surgery. A p value < 0.05 was considered statistically significant. RESULTS: In group A, bone healing was achieved in all cases at a mean of eight weeks. At the mean follow-up of 27 months, mean plantar flexion and dorsiflexion reached 96% of the opposite, normal, side. There were 20 excellent and three good results. In group B, bone healing occurred in 21 of 26 cases at a mean of 11 weeks. Nonunion was noted in five patients, among whom three were combined with avascular necrosis of the talar body. Mean follow-up was 29 months; mean plantar flexion and dorsiflexion reached 94% of the opposite normal side. There were 13 excellent, six good, two fair and five unsatisfactorily results. There were significant differences in the time to bone healing and in ankle-joint motion and function (p < 0.05). CONCLUSIONS: Percutaneous reduction is a successful technique for paediatric talar neck fractures. Compared with conventional open surgery, the mini-invasive procedure may produce rapid bone healing and better functional results. LEVEL OF EVIDENCE: Therapeutic study, Level Ia (perspective study).

Correction to: Comparison between percutaneous and open reduction for treating paediatric talar neck fractures.

In the original publication of this paper, the author name was incorrectly presented.

Wearable Loop Sensors for Knee Flexion Monitoring: Dynamic Measurements on Human Subjects.

Goals: We have recently introduced a new class of wearable loop sensors for joint flexion monitoring that overcomes limitations in the state-of-the-art. Our previous studies reported a proof-of-concept on a cylindrical phantom limb, under static scenarios and with a rigid sensor. In this work, we evaluate our sensors, for the first time, on human subjects, under dynamic scenarios, using a flexible textile-based prototype tethered to a network analyzer. An untethered version is also presented and validated on phantoms, aiming towards a fully wearable design. Methods: Three dynamic activities (walking, brisk walking, and full flexion/extension, all performed in place) are used to validate the tethered sensor on ten (10) adults. The untethered sensor is validated upon a cylindrical phantom that is bent manually at random speed. A calibration mechanism is developed to derive the sensor-measured angles. These angles are then compared to gold-standard angles simultaneously captured by a light detection and ranging (LiDAR) depth camera using root mean square error (RMSE) and Pearson's correlation coefficient as metrics. Results: We find excellent correlation (≥ 0.981) to gold-standard angles. The sensor achieves an RMSE of 4.463° ± 1.266° for walking, 5.541° ± 2.082° for brisk walking, 3.657° ± 1.815° for full flexion/extension activities, and 0.670° ± 0.366° for the phantom bending test. Conclusion: The tethered sensor achieves similar to slightly higher RMSE as compared to other wearable flexion sensors on human subjects, while the untethered version achieves excellent RMSE on the phantom model. Concurrently, our sensors are reliable over time and injury-safe, and do not obstruct natural movement. Our results set the ground for future improvements in angular resolution and for realizing fully wearable designs, while maintaining the abovementioned advantages over the state-of-the-art.

Two-year outcomes of anterior versus posterior scleral application of mitomycin C-soaked sponge in trabeculectomy.

PURPOSE: To compare the safety and efficacy of two different application methods of mitomycin C (MMC)-soaked sponge in trabeculectomy. STUDY DESIGN: Retrospective study. METHODS: We included 71 eyes of 71 patients that had undergone trabeculectomy. In the anterior scleral application group, 36 eyes were treated using the long side of the MMC-soaked sponge placed parallel to the limbus. The efficacy and safety in these eyes were compared with eyes treated with the posterior scleral application group, consisting of 35 eyes treated with the long side of the MMC-soaked sponge placed perpendicular to the limbus. The follow-up period was 2 years. The safety of the procedure, including bleb morphology and complications, was the primary outcome, while the success rate was the secondary outcome. RESULTS: The cumulative success rate at 2 years postoperatively was 94.4% in the anterior and and 94.3% in the posterior scleral application group (P = 1.000). However, with the posterior scleral application of the MMC-soaked sponge, blebs were more low-lying (P = 0.048), less in extent (P < 0.001), more normally vascularized (P = 0.027) and more posteriorly directed (P < 0.001). Furthermore, the incidence of thin-walled cystic bleb (P = 0.028) and bleb leakage (P = 0.025) was significantly lower in the posterior scleral application group than in the anterior group. CONCLUSION: Although there were similar success rates, the posterior scleral application of MMC-soaked sponge with trabeculectomy was safer with a better bleb morphology than the anterior scleral application.

Clinical features and prognosis of parotid metastasis of breast cancer: retrospective analysis of 57 cases.

Purpose: Parotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate. Methods: A comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators. Results: The primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy. Conclusion: Parotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Enhancing Suicide Risk Prediction With Polygenic Scores in Psychiatric Emergency Settings: Prospective Study.

BACKGROUND: Despite growing interest in the clinical translation of polygenic risk scores (PRSs), it remains uncertain to what extent genomic information can enhance the prediction of psychiatric outcomes beyond the data collected during clinical visits alone. OBJECTIVE: This study aimed to assess the clinical utility of incorporating PRSs into a suicide risk prediction model trained on electronic health records (EHRs) and patient-reported surveys among patients admitted to the emergency department. METHODS: Study participants were recruited from the psychiatric emergency department at Massachusetts General Hospital. There were 333 adult patients of European ancestry who had high-quality genotype data available through their participation in the Mass General Brigham Biobank. Multiple neuropsychiatric PRSs were added to a previously validated suicide prediction model in a prospective cohort enrolled between February 4, 2015, and March 13, 2017. Data analysis was performed from July 11, 2022, to August 31, 2023. Suicide attempt was defined using diagnostic codes from longitudinal EHRs combined with 6-month follow-up surveys. The clinical risk score for suicide attempt was calculated from an ensemble model trained using an EHR-based suicide risk score and a brief survey, and it was subsequently used to define the baseline model. We generated PRSs for depression, bipolar disorder, schizophrenia, suicide attempt, and externalizing traits using a Bayesian polygenic scoring method for European ancestry participants. Model performance was evaluated using area under the receiver operator curve (AUC), area under the precision-recall curve, and positive predictive values. RESULTS: Of the 333 patients (n=178, 53.5% male; mean age 36.8, SD 13.6 years; n=333, 100% non-Hispanic and n=324, 97.3% self-reported White), 28 (8.4%) had a suicide attempt within 6 months. Adding either the schizophrenia PRS or all PRSs to the baseline model resulted in the numerically highest discrimination (AUC 0.86, 95% CI 0.73-0.99) compared to the baseline model (AUC 0.84, 95% Cl 0.70-0.98). However, the improvement in model performance was not statistically significant. CONCLUSIONS: In this study, incorporating genomic information into clinical prediction models for suicide attempt did not improve patient risk stratification. Larger studies that include more diverse participants are required to validate whether the inclusion of psychiatric PRSs in clinical prediction models can enhance the stratification of patients at risk of suicide attempts.

Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes.

Importance: Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts. Objective: To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting. Design, Setting, and Participants: This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024. Exposures: Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder. Main Outcomes and Measures: Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables. Results: Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interaction: OR, 0.83 [95% CI, 0.74-0.94]). Conclusions and Relevance: Sexual trauma and mental health polygenic scores, while correlated with one another, were independent and joint risk factors for severe mental illness in a large, diverse hospital biobank population. Furthermore, associations of schizophrenia and bipolar disorder polygenic scores with respective diagnoses were greater in those without disclosures, suggesting that genetic predisposition to mental illness as measured by polygenic scores may be less impactful in the presence of this severe environmental risk factor.

Genetic Heterogeneity Across Dimensions of Alcohol Use Behaviors.

OBJECTIVE: Increasingly large samples in genome-wide association studies (GWASs) for alcohol use behaviors (AUBs) have led to an influx of implicated genes, yet the clinical and functional understanding of these associations remains low, in part because most GWASs do not account for the complex and varied manifestations of AUBs. This study applied a multidimensional framework to investigate the latent genetic structure underlying heterogeneous dimensions of AUBs. METHODS: Multimodal assessments (self-report, interview, electronic health records) were obtained from approximately 400,000 UK Biobank participants. GWAS was conducted for 18 distinct AUBs, including consumption, drinking patterns, alcohol problems, and clinical sequelae. Latent genetic factors were identified and carried forward to GWAS using genomic structural equation modeling, followed by functional annotation, genetic correlation, and enrichment analyses to interpret the genetic associations. RESULTS: Four latent factors were identified: Problems, Consumption, BeerPref (declining alcohol consumption with a preference for drinking beer), and AtypicalPref (drinking fortified wine and spirits). The latent factors were moderately correlated (rg values, 0.12-0.57) and had distinct patterns of associations, with BeerPref in particular implicating many novel genomic regions. Patterns of regional and cell type-specific gene expression in the brain also differed between the latent factors. CONCLUSIONS: Deep phenotyping is an important next step to improve understanding of the genetic etiology of AUBs, in addition to increasing sample size. Further effort is required to uncover the genetic heterogeneity underlying AUBs using methods that account for their complex, multidimensional nature.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae. PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle Closure Glaucoma Without Cataract: 1-Year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6 and 18 mm Hg with at least a 20% reduction compared with baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACGs were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P =0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P =0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Cost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China.

Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.