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Alexandra Capellini,1,* Matthew Williams,1,* Kenan Onel,1– 3 Kuan-Lin Huang1– 3 1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA; 2Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA; 3Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, USA, New York, NY, 10029, USA*These authors contributed equally to this workCorrespondence: Kenan Onel; Kuan-Lin HuangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, Box 1498, New York, NY, 10029, USATel +1 212-824-6134Email kenan.onel@mssm.edu; kuan-lin.huang@mssm.eduAbstract: The canonical model for hereditary cancer predisposition is a cancer predisposition gene (CPG) that drives either one or both of two fundamental hallmarks of cancer, defective genomic integrity and deregulated cell proliferation, ultimately resulting in the accumulation of mutations within cells. Thus, the genes most commonly associated with cancer-predisposing genetic syndromes are tumor suppressor genes that regulate DNA repair (eg, BRCA1, BRCA2, MMR genes) and/or cell cycle (eg, APC, RB1). In recent years, however, the spectrum of high-penetrance CPGs has expanded considerably to include genes in non-canonical pathways such as oncogenic signaling, metabolism, and protein translation. We propose here that, given the variety of pathways that may ultimately affect genome integrity and cell proliferation, the model of cancer genetic predisposition needs to be expanded to account for diverse mechanisms. This synthesis calls for modeling and multi-omic studies applying novel experimental and computational approaches to understand cancer genetic predisposition.Keywords: cancer, genetics, predisposition, multi-omics, genomics, oncogenesis

Cheng-Yi Wang,1,* Yin-Lan Hu,2,* Ya-Hui Wang,3 Cheng-Hsin Chen,1 Chih-Cheng Lai,4 Kun-Lun Huang51Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu-jen Catholic University, New Taipei City, Taiwan; 2Department of Dentistry, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 3Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 5Division of Pulmonary Medicine, Tri-service General Hospital, Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan*These authors contributed equally to this workBackground: Latent tuberculosis infection (LTBI) is a precursor of active tuberculosis diseases and an important issue in the United States and worldwide. The association between vitamin D deficiency and LTBI is poorly understood.Methods: From 2011 to 2012, the National Health and Nutrition Examination Survey (NHANES) assessed LTBI (according to tuberculin skin testing and QuantiFERON®,-TB Gold In-Tube) and measured serum levels of vitamin D. We evaluated the association between LTBI and vitamin D using multivariate logistic regression models adjusted for known confounders.Results: The LTBI group had a lower 25-hydroxyvitamin D [25(OH)D] level than the non-LTBI group (p=0.0012). The adjusted risk of LTBI was significantly higher among participants with serum 25(OH)D levels

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Study Objectives: We compared the clinical characteristics and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed to define the role of serum cryptococcal antigen (sCRAG) and radiographs during a follow-up period of up to 1 year.Design: Retrospective cohort study.Setting: University hospital.Patients: The clinical records, chest radiographs, and CT scan findings of 13 immunocompetent and 16 immunocompromised patients with a diagnosis based on cerebrospinal fluid (CSF) culture, sCRAG titers, and cytologic or histologic confirmation of the presence of pulmonary cryptococcosis were reviewed during the course of the study. Two thoracic radiologists reviewed chest radiographs and CT scans for morphologic characteristics and the distribution of parenchymal abnormalities, and a final reading was reached by consensus. The correlation between serial radiographs and sCRAG titers was examined in 9 immunocompetent and 10 immunocompromised patients.Measurements: Serum or CSF cryptococcal antigen.Results: The most common clinical symptom was cough, which was present in 24 patients (82.8%). Pulmonary nodules were the most frequent radiologic abnormality. Cavitation within nodules and parenchymal consolidation were significantly less common in immunocompetent patients compared to immunocompromised patients (p = 0.02 and p = 0.05, respectively). Immunocompromised patients tended to have a larger extent of pulmonary involvement than immunocompetent patients, the changes seen on their serial radiographs were more variable, and their corresponding sCRAG titers were higher (> 1:256). In the immunocompetent patients, the radiographic characteristics of lesions usually improved with a corresponding decrease in sCRAG titers over time.Conclusions: Our study suggests that pulmonary cryptococcosis usually follows a benign clinical course in immunocompetent patients. Immunocompromised patients often undergo an evolution to cavitary lesions that represent a more aggressive disease nature. Serial radiographic changes and changes in sCRAG titers reliably reflect disease progression and the response to therapy. [ABSTRACT FROM AUTHOR]

Numerous herbivore-induced plant volatiles (HIPVs) play important roles in plant defense. In tea plants (Camellia sinensis), (Z)-3-hexenyl acetate (3-HAC) has been characterized as associated with resistance to herbivores. To date, how tea plants biosynthesize and regulate 3-HAC to resist herbivores remain unclear. Based on transcriptomes assembled from Ectropis obliqua-fed leaves, a cDNA encoding BAHD acyltransferase, namely CsCHAT1, was highly induced in leaves fed with E. obliqua. Enzymatic assays showed that CsCHAT1 converted (Z)-3-hexenol into 3-HAC. Further suppression of CsCHAT1 expression reduced the accumulation of 3-HAC and lowered the resistance of tea plants to E. obliqua, while 3-HAC replenishment rescued the reduced resistance of CsCHAT1-silenced tea plants against E. obliqua. Two transcription factors (TFs), CsNAC30 and CsTCP11, were co-expressed with CsCHAT1. An integrative approach of biochemistry, DNA-protein interaction, gene silencing, and metabolic profiling revealed that the two TFs positively regulated the expression of CsCHAT1. The suppression of either one decreased the production of 3-HAC and eliminated the resistance of tea plants to E. obliqua. Notably, the suppression of either one considerably impaired JA-induced 3-HAC biosynthesis in tea plant. The proposed pathway can be targeted for innovative agro-biotechnologies protecting tea plants from damage by E. obliqua., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

The essential Drosophila RNA-binding protein Brain Tumor (Brat) represses specific genes to control embryogenesis and differentiation of stem cells. In the brain, Brat functions as a tumor suppressor that diminishes neural stem cell proliferation while promoting differentiation. Though important Brat-regulated target mRNAs have been identified in these contexts, the full impact of Brat on gene expression remains to be discovered. Here, we identify the network of Brat-regulated mRNAs by performing RNA sequencing (RNA-seq) following depletion of Brat from cultured cells. We identify 158 mRNAs, with high confidence, that are repressed by Brat. De novo motif analysis identified a functionally enriched RNA motif in the 3' untranslated regions (UTRs) of Brat-repressed mRNAs that matches the biochemically defined Brat binding site. Integrative data analysis revealed a high-confidence list of Brat-repressed and Brat-bound mRNAs containing 3'UTR Brat binding motifs. Our RNA-seq and reporter assays show that multiple 3'UTR motifs promote the strength of Brat repression, whereas motifs in the 5'UTR are not functional. Strikingly, we find that Brat regulates expression of glycolytic enzymes and the vacuolar ATPase complex, providing new insight into its role as a tumor suppressor and the coordination of metabolism and intracellular pH., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

Objective: To evaluate the residual placental volume and correlated factors using three-dimensional ultrasound (3D) in patients with placenta accreta spectrum (PAS) after conservative management., Materials and Methods: From January 2005 to December 2023, we retrospectively reviewed patients with PAS who underwent prophylactic transcatheter arterial embolization and retained the placenta in situ. The residual placental volume was assessed using 3D ultrasound equipped with virtual organ computer-aided analysis. We determined the resorption rate of the residual placenta (RRRP) and analyzed correlated factors., Results: Eighteen patients with PAS were included. The mean RRRP was 152.64 ± 147.97 cm 3 /month. The median natural resorption time was 5.5 months. According to Spearman's correlation, only the initial placental volume was significantly associated with RRRP (p = 0.001, correlation coefficient = 0.701). Initial placental volume was not associated with postpartum hemorrhage, postpartum infection, resume of menstruation, subsequent pregnancy, or mean white blood cell count., Conclusion: 3D ultrasound is useful for measuring the volume of residual placenta. A larger initial placental volume was associated with a higher RRRP., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier B.V.)

Background: Pseudohyperkalemia (falsely elevated serum potassium) must be distinguished from true hyperkalemia to avoid unnecessary treatment. Some case reports suggest that pneumatic tube transportation may increase the risk of pseudohyperkalemia, but comprehensive research on the topic is lacking. Here, we aimed to assess the association between WBC levels, pneumatic tube transport, and pseudohyperkalemia prevalence., Methods: We analyzed 1188 samples collected from 240 patients between 2019 and 2022. Samples with elevated WBC counts (≥ 100 × 10 3 /μL) and potassium levels were included in this study. The method of specimen transportation was documented., Results: Pseudohyperkalemia was observed (7/390) in specimens transported using pneumatic tubes. No pseudohyperkalemia was identified with manually transported specimens (0/132). Every increase in WBC count by 100 × 10 3 /μL in the specimens multiplied the odds ratio of pseudohyperkalemia by 3.75 when delivered with pneumatic tube. The prevalence of pseudohyperkalemia increased as WBC count increased, especially at WBC counts greater than 200 × 10 3 /μL., Conclusion: Pneumatic tube transport poses a risk for pseudohyperkalemia in patients with extreme leukocytosis. Physicians should anticipate odd potassium levels when interpreting blood test results. Redrawing of blood samples, manual specimen transportation, or point-of-care testing are suggested to prevent further misdiagnosis., (© 2024. Japanese Society of Hematology.)

Aim: Evidence suggests an association between maternal hypothyroidism and risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in offspring. We examined the risk of ASD and ADHD in individuals with congenital hypothyroidism (CHT)., Methods: A nationwide population-based cohort study enrolled a total of 1260 children younger than 12 years with a confirmed diagnosis of CHT and no prior diagnosis of any neurodevelopmental disorders, selected from the National Health Insurance Research Database of Taiwan between 1998 to 2013. In addition, 12,600 controls matched for sex, age, and residence were selected. Cox proportional hazards analysis was used to investigate the association among CHT, ASD, and ADHD., Results: Children with CHT were associated with a higher incidence of ASD (7.1‰ vs 1.3‰, P < 0.001) and ADHD (39.7‰ vs 18.7‰, P < 0.001) than the control group. Cox regression analyses demonstrated that children with CHT were associated with elevated risks of ASD (hazard ratio [HR], 4.72 [95% confidence interval (CI), 2.08-10.70]) and ADHD (HR, 2.03 [95% CI, 1.49-2.77]), after adjusting for demographic data and family history of major psychiatric disorders, compared with the control group., Conclusion: Children with CHT were associated with approximately a two-fold increased risk of ADHD and a four-fold increased risk of ASD than the control group. Our study highlights the need for future research to elucidate the potential pathophysiology among CHD, ASD, and ADHD., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Background: Arterial cannulation sites for the surgical repair of type A aortic dissection (AAD) have evolved from right axillary artery (AA) cannulation to bilateral carotid artery (CA) based of femoral artery (FA) cannulation. Postoperative descending aorta remodeling is closely linked to the false lumen area ratio (FLAR), defined as false lumen area/aortic area, as well as to the incidence of renal replacement therapy (RRT)., Aim: To investigate the effect of the updated arterial cannulation strategy on descending aortic remodeling., Methods: A total of 443 AAD patients who received FA combined cannulation between March 2015 and March 2023 were included in the study. Of these, 209 received right AA cannulation and 234 received bilateral CA cannulation. The primary outcome was the change in FLAR, as calculated from computed tomography angiography in three segments of the descending aorta: Thoracic (S1), upper abdominal (S2), and lower abdominal (S3). Secondary outcomes were the incidence of RRT and the serum inflammation response, as observed by the levels of high sensitivity C reaction protein (hs-CRP) and Interleukin-6 (IL-6)., Results: The postoperative/preoperative ratio of FLAR in S2 and S3 was higher in the AA group compared to the CA group (S2: 0.80 ± 0.08 vs 0.75 ± 0.07, P < 0.001; S3: 0.57 ± 0.12 vs 0.50 ± 0.12, P < 0.001, respectively). The AA group also had a significantly higher incidence of RRT (19.1% vs 8.5%, P = 0.001; odds ratio: 2.533, 95%CI: 1.427-4.493) and higher levels of inflammation cytokines 24 h after the procedure [hr-CRP: 117 ± 17 vs 104 ± 15 mg/L; IL-6: 129 (103, 166) vs 83 (69, 101) pg/mL; both P < 0.001] compared to the CA group., Conclusion: The CA cannulation strategy was associated with better abdominal aorta remodeling after AAD repair compared to AA cannulation, as observed by a greater change in FLAR and lower incidence of RRT., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This paper investigates the fixed-time cluster formation tracking (CFT) problem for networked perturbed robotic systems (NPRSs) under directed graph information interaction, considering parametric uncertainties, external perturbations, and actuator input deadzone. To address this complex problem, a novel hierarchical fixed-time neural adaptive control algorithm is proposed based on a hierarchical fixed-time framework and a neural adaptive control strategy. The objective of this study is to achieve accurate CFT of NPRSs within a fixed time. Specifically, we design a distributed observer algorithm to estimate the states of the virtual leader within a fixed time accurately. By using these observers, a neural adaptive fixed-time controller is developed in the local control layer to ensure rapid and reliable system performance. Through the use of the Lyapunov argument, we derive sufficient conditions on the control parameters to guarantee the fixed-time stability of NPRSs. The theoretical results are eventually validated through numerical simulations, demonstrating the effectiveness and robustness of the proposed approach., (© 2024. The Author(s).)

Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline BRCA1 and BRCA2 (gBRCA1/2) carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors. gBRCA1/2 -driven hereditary and sporadic tumors undergo convergent evolution to develop a similar set of driver deletions, and deletions explain the elevated cancer risk of gBRCA1/2 -carriers. Orthogonal mutation timing analysis identifies deletions of chromosome 17 and 13q as early, recurrent events. Single-cell analyses confirmed deletion rate differences in gBRCA1/2 vs. non-carrier tumors as well as cells engineered to harbor gBRCA1/2 . The centrality of deletion-associated chromosomal instability to tumorigenesis shapes interpretation of the somatic evolution of non-malignant tissue and guides strategies for precision prevention and early detection., Competing Interests: COMPETING FINANCIAL INTERESTS K.H. is a co-founder and board member of a not-for-profit organization, Open Box Science, where he does not receive any compensation. P.C.B. sits on the scientific advisory boards of BioSymetrics, Inc. and Intersect Diagnostics, Inc. and previously sat on that of Sage Bionetworks. All other authors declare no competing financial interests.

Cancer cells are heterogeneous, each harboring distinct molecular aberrations and are dependent on different genes for their survival and proliferation. While successful targeted therapies have been developed based on driver DNA mutations, many patient tumors lack druggable mutations and have limited treatment options. Here, we hypothesize that new precision oncology targets may be identified through "expression-driven dependency", whereby cancer cells with high expression of a targeted gene are more vulnerable to the knockout of that gene. We introduce a Bayesian approach, BEACON, to identify such targets by jointly analyzing global transcriptomic and proteomic profiles with genetic dependency data of cancer cell lines across 17 tissue lineages. BEACON identifies known druggable genes, e.g., BCL2, ERBB2, EGFR, ESR1, MYC , while revealing new targets confirmed by both mRNA- and protein-expression driven dependency. Notably, the identified genes show an overall 3.8-fold enrichment for approved drug targets and enrich for druggable oncology targets by 7 to 10-fold. We experimentally validate that the depletion of GRHL2 , TP63 , and PAX5 effectively reduce tumor cell growth and survival in their dependent cells. Overall, we present the catalog of express-driven dependency targets as a resource for identifying novel therapeutic targets in precision oncology.

Background: Coronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients., Methods: This study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT., Results: Most post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1 s to forced vital capacity ratio (<70%) was initially 2% in Group 4, it increased to 29% after MCT. No significant differences in allergic history or underlying diseases were observed between the groups., Conclusions: These findings provide comprehensive insights into the AHR and respiratory symptoms of post-COVID-19 individuals, highlighting the characteristics and potential exacerbations in patients with positive MCT results. This emphasises the need of MCT to address respiratory dynamics in post-COVID-19 individuals., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to declare., (Copyright ©The authors 2024.)

Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15-29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients' suicidal symptoms was based on Item 10 of the Montgomery-Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD., (© 2024. The Author(s).)

Background: As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear., Methods: Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up., Results: Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86)., Conclusions: Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation., Impact: ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI). Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group. TBI requiring hospitalization occurred more in the sibling group than in the proband group. TBI risk should be closely monitored among unaffected siblings of patients with ADHD., (© 2024. The Author(s).)

Water treatment faces significant challenges due to the increasing complexity of pollutants and the need for more efficient, sustainable treatment methods. However, current adsorbent materials often struggle with issues such as low adsorption capacity, slow kinetics, and poor reusability, limiting their practical application. In this study, we developed a novel hierarchical porous hybrid gel (HPHG) for water treatment to address the limitations of conventional adsorbents. The HPHG features a multi-level porous structure (from 48 ± 28 nm to 4385 ± 823 nm) that significantly enhances its porosity and specific surface area. We systematically investigated the relationship between the material's structure and its adsorption performance. Kinetic studies revealed a tendency towards a pseudo-second-order adsorption model, attributed to the material's unique structural features that facilitate rapid mass exchange channels inside HPHG and provide abundant active sites for pollutant adsorption. Reusability tests demonstrated that the material retained 85.4% of its initial adsorption capacity after five adsorption-desorption cycles, highlighting its potential for practical applications. This study provides valuable insights into structure-performance relationships in advanced water treatment materials, offering a promising approach for designing next-generation adsorbents with superior efficiency and sustainability., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Amyloid plaques, implicated in Alzheimer's disease, exhibit a spatial propagation pattern through interconnected brain regions, suggesting network-driven dissemination. This study utilizes PET imaging to investigate these brain connections and introduces an innovative method for analyzing the amyloid network. A modified version of a previously established method is applied to explore distinctive patterns of connectivity alterations across cognitive performance domains. PET images illustrate differences in amyloid accumulation, complemented by quantitative network indices. The normal control group shows minimal amyloid accumulation and preserved network connectivity. The MCI group displays intermediate amyloid deposits and partial similarity to normal controls and AD patients, reflecting the evolving nature of cognitive decline. Alzheimer's disease patients exhibit high amyloid levels and pronounced disruptions in network connectivity, which are reflected in low levels of global efficiency (Eg) and local efficiency (Eloc). It is mostly in the temporal lobe where connectivity alterations are found, particularly in regions related to memory and cognition. Network connectivity alterations, combined with amyloid PET imaging, show potential as discriminative markers for different cognitive states. Dataset-specific variations must be considered when interpreting connectivity patterns. The variability in MCI and AD overlap emphasizes the heterogeneity in cognitive decline progression, suggesting personalized approaches for neurodegenerative disorders. This study contributes to understanding the evolving network characteristics associated with normal cognition, MCI, and AD, offering valuable insights for developing diagnostic and prognostic markers., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Setting: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB)., Objective: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care., Design: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation., Results: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB ( n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs., Conclusion: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)

Objectives: Previous studies have demonstrated poor oral hygiene in children with attention deficit hyperactivity disorder (ADHD). However, the association between ADHD and periodontitis is still unclear., Methods: In all, 16,211 adolescents with ADHD and 162,110 age- and sex-matched controls participated in the study between 2001 and 2011. To identify the occurrence of periodontitis, the participants were followed up till the end of 2011. Confounding factors, including smoking, diabetes, and depressive disorder, were assessed and adjusted in the Cox regression models., Results: Adolescents with ADHD ( HR : 2.29) were more likely to develop periodontitis later in life than controls. We additionally observed the beneficial effect of atomoxetine ( HR : 0.42) on the periodontitis risk among adolescents with ADHD. However, this finding should be interpreted cautiously given the small sample ( n  = 290) of children taking atomoxetine in the present study., Conclusions: ADHD is an independent risk factor for subsequent periodontitis development. Oral health should be closely monitored in adolescents with ADHD. Future investigation of the shared pathomechanisms between periodontitis and ADHD is warranted., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Monomethyl fumarate (MMF), a potent anti-inflammatory agent used to treat multiple sclerosis, has demonstrated efficacy in various inflammatory and ischemia/reperfusion (IR) models; however, its impact on IR-induced acute lung injury (ALI) has not been explored. We investigated, for the first time, whether MMF attenuates lung IR injury through inhibition of the GAPDH/Siah1 signaling pathway. Rats were subjected to IR injury using an isolated perfused lung model, and proximity ligation assays were employed to evaluate the presence and distribution of the GAPDH/Siah1 complex. In vitro studies involved pretreating human primary alveolar epithelial cells (HPAECs) with MMF and/or inducing GAPDH overexpression or silencing, followed by exposure to hypoxia-reoxygenation. The findings revealed significantly reduced lung damage indicators, including edema, proinflammatory cytokines, oxidative stress and apoptosis, in MMF-treated rats. Notably, MMF treatment inhibited GAPDH/Siah1 complex formation and nuclear translocation, indicating that disruption of the GAPDH/Siah1 cascade was the primary cause of these improvements. Our in vitro studies on pretreated HPAECs corroborate these in vivo findings, further strengthening this interpretation. Our study results suggest that the protective effects of MMF against lung IR injury may be attributed, at least in part, to its ability to disrupt the GAPDH/Siah1 signaling cascade, thereby attenuating inflammatory and apoptotic responses. Given these encouraging results, MMF has emerged as a promising therapeutic candidate for the management of lung IR injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

INTS11 and CPSF73 are metal-dependent endonucleases for Integrator and pre-mRNA 3'-end processing, respectively. Here, we show that the INTS11 binding partner BRAT1/CG7044, a factor important for neuronal fitness, stabilizes INTS11 in the cytoplasm and is required for Integrator function in the nucleus. Loss of BRAT1 in neural organoids leads to transcriptomic disruption and precocious expression of neurogenesis-driving transcription factors. The structures of the human INTS9-INTS11-BRAT1 and Drosophila dIntS11-CG7044 complexes reveal that the conserved C terminus of BRAT1/CG7044 is captured in the active site of INTS11, with a cysteine residue directly coordinating the metal ions. Inspired by these observations, we find that UBE3D is a binding partner for CPSF73, and UBE3D likely also uses a conserved cysteine residue to directly coordinate the active site metal ions. Our studies have revealed binding partners for INTS11 and CPSF73 that behave like cytoplasmic chaperones with a conserved impact on the nuclear functions of these enzymes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Structural features of proteins capture underlying information about protein evolution and function, which enhances the analysis of proteomic and transcriptomic data. Here, we develop Structural Analysis of Gene and protein Expression Signatures (SAGES), a method that describes expression data using features calculated from sequence-based prediction methods and 3D structural models. We used SAGES, along with machine learning, to characterize tissues from healthy individuals and those with breast cancer. We analyzed gene expression data from 23 breast cancer patients and genetic mutation data from the Catalog of Somatic Mutations In Cancer database as well as 17 breast tumor protein expression profiles. We identified prominent expression of intrinsically disordered regions in breast cancer proteins as well as relationships between drug perturbation signatures and breast cancer disease signatures. Our results suggest that SAGES is generally applicable to describe diverse biological phenomena including disease states and drug effects., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Cerebral air embolism (CAE) is considered as a rare complication during the routine medical procedures in the literature review. We reported a very rare complication of CAE after the percutaneous kyphoplasty (PKP) for the treatment of acute vertebral compression fracture.

Placebo effects are notable demonstrations of mind-body interactions 1,2 . During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia 3-6 . However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics 7 , the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain., (© 2024. The Author(s).)

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca 2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca 2+ . WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Research Question: What differences exist in the phenotypes of pre-eclampsia, perinatal outcomes and neonatal echocardiography between pregnancies conceived naturally and through IVF?, Design: Six hundred and ten women diagnosed with pre-eclampsia between January 2002 and December 2022 were included in this study. This research was conducted within the IVF and Maternal-Fetal Medicine Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan. Participants were divided into two groups: those who achieved pregnancy through IVF, and those who conceived naturally. The phenotypes of pre-eclampsia and perinatal outcomes were assessed using a propensity-matched sample (n = 218), along with neonatal echocardiography., Results: After conducting propensity score matching, the natural conception group had a higher prevalence of early-onset pre-eclampsia (53.9% versus 37.7%, P = 0.04) and exhibited more severe features of pre-eclampsia (89.1% versus 69.8%, P = 0.01) compared with the IVF group. Regarding perinatal outcomes, neonates in the IVF group had higher placental weights compared with the natural conception group (580 versus 480 g, P = 0.031). The prevalence of abnormal findings on neonatal echocardiography was similar between the groups. Multivariate analysis showed that greater gestational age at delivery reduced the likelihood of abnormal findings on echocardiography [adjusted risk ratio (aRR) 0.950, P = 0.001], while pregestational diabetes mellitus increased the likelihood of abnormal findings (aRR 1.451, P = 0.044). Septal defects were the most common type of defect, occurring in 16.1% of infants., Conclusion: The impact of IVF conception on the severity of pre-eclampsia is not as expected. Neonatal echocardiography revealed a higher prevalence of abnormalities in offspring of women with pre-eclampsia compared with the general population. However, these issues were not linked to the method of conception, suggesting the existence of undisclosed factors that could influence the clinical features and perinatal outcomes of pre-eclampsia., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Circulating biomarkers play a pivotal role in personalized medicine, offering potential for disease screening, prevention, and treatment. Despite established associations between numerous biomarkers and diseases, elucidating their causal relationships is challenging. Mendelian Randomization (MR) can address this issue by employing genetic instruments to discern causal links. Additionally, using multiple MR methods with overlapping results enhances the reliability of discovered relationships. Here, we report an MR study using multiple methods, including inverse variance weighted, simple mode, weighted mode, weighted median, and MR-Egger. We use the MR-base resource (v0.5.6) from Hemani et al. 2018 to evaluate causal relationships between 212 circulating biomarkers (curated from UK Biobank analyses by Neale lab and from Shin et al. 2014, Roederer et al. 2015, and Kettunen et al. 2016 and 99 complex diseases (curated from several consortia by MRC IEU and Biobank Japan). We report novel causal relationships found by four or more MR methods between glucose and bipolar disorder (Mean Effect Size estimate across methods: 0.39) and between cystatin C and bipolar disorder (Mean Effect Size: -0.31). Based on agreement in four or more methods, we also identify previously known links between urate with gout and creatine with chronic kidney disease, as well as biomarkers that may be causal of cardiovascular conditions: apolipoprotein B, cholesterol, LDL, lipoprotein A, and triglycerides in coronary heart disease, as well as lipoprotein A, LDL, cholesterol, and apolipoprotein B in myocardial infarction. This Mendelian Randomization study not only corroborates known causal relationships between circulating biomarkers and diseases but also uncovers two novel biomarkers associated with bipolar disorder that warrant further investigation. Our findings provide insight into understanding how biological processes reflecting circulating biomarkers and their associated effects may contribute to disease etiology, which can eventually help improve precision diagnostics and intervention.

Objectives: Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD., Methods: We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays., Results: The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups., Conclusion: The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

We introduce Get Free Copy (https://getfreecopy.com), a web-based platform designed to streamline the search for biomedical literature across major repositories like arXiv, bioRxiv, medRxiv, and PubMed Central (PMC). Addressing challenges posed by paywalls and fragmented databases, it offers a unified interface for efficient retrieval of free, legitimate copies of biomedical literature. The platform's implementation involves a Node.js backend and dynamic front-end display, enhancing accessibility and research efficiency. As an open-source project, Get Free Copy represents a significant contribution to the open-access movement, inviting global researcher collaboration for further development., Competing Interests: KH is a co-founder and board member of a not-for-profit organization, Open Box Science, where he does not receive any compensation. All other authors declare no competing interests., (© The Author(s) 2024.)

Background: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown., Methods: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified., Results: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02-1.44), especially daughters (HR: 1.30, 95% CI: 1.06-1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29-1.67) compared with those having no parents with severe mental disorders., Discussion: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group., (© 2024. The Author(s).)

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP ( n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Viral disruption of innate immune signaling is a critical determinant of productive infection. The Human Cytomegalovirus (HCMV) UL26 protein prevents anti-viral gene expression during infection, yet the mechanisms involved are unclear. We used TurboID-driven proximity proteomics to identify putative UL26 interacting proteins during infection to address this issue. We find that UL26 forms a complex with several immuno-regulatory proteins, including several STAT family members and various PIAS proteins, a family of E3 SUMO ligases. Our results indicate that UL26 prevents STAT phosphorylation during infection and antagonizes transcriptional activation induced by either interferon α (IFNA) or tumor necrosis factor α (TNFα). Additionally, we find that the inactivation of PIAS1 sensitizes cells to inflammatory stimulation, resulting in an anti-viral transcriptional environment similar to ΔUL26 infection. Further, PIAS1 is important for HCMV cell-to-cell spread, which depends on the presence of UL26, suggesting that the UL26-PIAS1 interaction is vital for modulating intrinsic anti-viral defense., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ciesla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated., Patients and Methods: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS)., Results: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score., Conclusions: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP., Competing Interests: Conflicts of interest sources of funding: T.C.Y. owns equity in APRINOIA Therapeutics. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Although a growing number of studies have investigated the relationship between psychosocial factors and periodontitis, studies investigating the association between bipolar disorder (BD) and periodontitis are lacking. Using the Taiwan National Health Insurance Research Database, 4251 adolescents with BD and 17,004 age- and sex-matched controls were included. They were followed up from enrollment to the end of 2011 or death. Periodontitis was diagnosed during the follow-up. Cox regression analysis indicated that adolescents with BD had a higher risk of periodontitis (hazard ratio [HR]: 2.96, 95% confidence interval [CI] 2.77-3.17) than did controls. Subanalyses stratified by sex revealed a higher risk of periodontitis in male (HR: 2.83, 95% CI 2.56-3.14) and female (HR: 3.01, 95% CI 2.74-3.30) adolescents with BD than their respective controls. The long-term use of mood stabilizers was associated with a higher risk of periodontitis (HR: 1.19, 95% CI 1.06-1.35) in the BD cohort. Our study highlighted an increased risk of periodontitis in adolescents with BD compared with controls during the follow-up. We recommend that more attention should be paid to the prevention of periodontitis in adolescents with BD, especially those who are female or receiving mood stabilizers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Tau pathology plays a crucial role in neurodegeneration diseases including Alzheimer's disease (AD) and non-AD diseases such as progressive supranuclear palsy. Tau positron emission tomography (PET) is an in-vivo and non-invasive medical imaging technique for detecting and visualizing tau deposition within a human brain. In this work, we aim to investigate the biodistribution of the dosimetry in the whole body and various organs for the [ 18 F]Florzolotau tau-PET tracer. A total of 12 healthy controls (HCs) were enrolled at Chang Gung Memorial Hospital. All subjects were injected with approximately 379.03 ± 7.03 MBq of [ 18 F]Florzolotau intravenously, and a whole-body PET/CT scan was performed for each subject. For image processing, the VOI for each organ was delineated manually by using the PMOD 3.7 software. Then, the time-activity curve of each organ was acquired by optimally fitting an exponential uptake and clearance model using the least squares method implemented in OLINDA/EXM 2.1 software. The absorbed dose for each target organ and the effective dose were finally calculated., Results: From the biodistribution results, the elimination of [ 18 F]Florzolotau is observed mainly from the liver to the intestine and partially through the kidneys. The highest organ-absorbed dose occurred in the right colon wall (255.83 μSv/MBq), and then in the small intestine (218.67 μSv/MBq), gallbladder wall (151.42 μSv/MBq), left colon wall (93.31 μSv/MBq), and liver (84.15 μSv/MBq). Based on the ICRP103, the final computed effective dose was 34.9 μSv/MBq with CV of 10.07%., Conclusions: The biodistribution study of [ 18 F]Florzolotau demonstrated that the excretion of [ 18 F]Florzolotau are mainly through the hepatobiliary and gastrointestinal pathways. Therefore, a routine injection of 370 MBq or 185 MBq of [ 18 F]Florzolotau leads to an estimated effective dose of 12.92 or 6.46 mSv, and as a result, the radiation exposure to the whole-body and each organ remains within acceptable limits and adheres to established constraints., Trial Registration: Retrospectively Registered at Clinicaltrials.gov (NCT03625128) on 12 July, 2018, https://clinicaltrials.gov/study/NCT03625128 ., (© 2024. The Author(s).)

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (β = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Congenital cleft lip and palate (CCLP) may be associated with major psychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder., Methods: From the Taiwan National Health Insurance Research Database, 1,158 children and adolescents with CCLP and 11,580 age/sex-matched controls without CCLP were included in this study between 2001 and 2010; they were followed up until the end of 2011 to identify the aforementioned major psychiatric disorders., Results: After adjustment for age, sex, income, residence, and family history, the Cox regression model revealed a positive relationship of CCLP with subsequent schizophrenia (hazard ratio [HR]: 7.60, 95% confidence interval [CI]: 2.03-28.54), ASD (HR: 6.03, 95% CI: 1.76-20.61), and ADHD (HR: 7.33, 95% CI: 5.01-10.73)., Discussion: These findings suggest that clinicians should be attentive to the presence or emergence of mental health conditions in patients with CCLP. Further studies are necessary to investigate the pathogenesis between CCLP and major psychiatric disorders., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma., Case Presentation: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion., Conclusion: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload., (© 2024. The Author(s).)

Background: Dementia care is challenging due to the divergent trajectories in disease progression and outcomes. Predictive models are needed to flag patients at risk of near-term mortality and identify factors contributing to mortality risk across different dementia types., Methods: Here, we developed machine-learning models predicting dementia patient mortality at four different survival thresholds using a dataset of 45,275 unique participants and 163,782 visit records from the U.S. National Alzheimer's Coordinating Center (NACC). We built multi-factorial XGBoost models using a small set of mortality predictors and conducted stratified analyses with dementiatype-specific models., Results: Our models achieved an area under the receiver operating characteristic curve (AUC-ROC) of over 0.82 utilizing nine parsimonious features for all 1-, 3-, 5-, and 10-year thresholds. The trained models mainly consisted of dementia-related predictors such as specific neuropsychological tests and were minimally affected by other age-related causes of death, e.g., stroke and cardiovascular conditions. Notably, stratified analyses revealed shared and distinct predictors of mortality across eight dementia types. Unsupervised clustering of mortality predictors grouped vascular dementia with depression and Lewy body dementia with frontotemporal lobar dementia., Conclusions: This study demonstrates the feasibility of flagging dementia patients at risk of mortality for personalized clinical management. Parsimonious machine-learning models can be used to predict dementia patient mortality with a limited set of clinical features, and dementiatype-specific models can be applied to heterogeneous dementia patient populations., (© 2024. The Author(s).)

A 36-year-old woman, gravida 3, para 1 (previous cesarean section), with one medical abortion, and no history of systemic diseases presented an unremarkable medical history during prenatal visits. The final prenatal ultrasound at 38 weeks of gestation showed a vertex presentation, a weight of 2600 g, a normal amniotic fluid level, and the placenta located on the posterior wall of the uterus. Fetal cardiotocography conducted before delivery reported a reactive heart rate without decelerations. The Doppler wave analysis of the fetal umbilical artery was normal (the ratio of peak-systolic flow velocity to the end-diastolic flow velocity was 2.5) without the absence or reversal of end-diastolic velocity. The total score of the fetal biophysical profile by ultrasound was 8. The night before the scheduled cesarean section, she experienced heightened anxiety and was unable to sleep, noting "crazy" fetal movements throughout the night. During the cesarean section, it was discovered that the umbilical cord was wrapped around the newborn's legs, resembling ankle shackles. The fetal weight was 2740 g, and Apgar scores were 9 at the first minute and 10 at the fifth minute. The motility of the neonatal legs was normal without cyanosis or neurological adverse outcomes.

It remains unclear how major psychiatric comorbidities and parental psychiatric disorders differ in males and females with autism spectrum disorder (ASD). Between 2001 and 2011, 17,627 children and 5071 adolescents with ASD (ICD-9-CM code: 299) were identified from Taiwan's National Health Insurance Research Database and assessed for major psychiatric comorbidities and parental psychiatric disorders. Compared with females with ASD, males with ASD were more likely to be diagnosed as having attention deficit hyperactivity disorder (relative risk [RR], 95% confidence interval [CI] 1.63, 1.51-1.75) and disruptive behavior disorder (1.38, 1.17-1.62) and less likely to be diagnosed as having schizophrenia (0.45, 0.36-0.56), bipolar disorder (0.58, 0.45-0.74), or intellectual disability (0.53, 0.49-0.58). Furthermore, compared with women, having a parental history of schizophrenia (RR, 95% CI 0.66, 0.49-0.89) or intellectual disability (0.34, 0.19-0.61) was less associated with ASD among men. However, the difference in ASD diagnosis between ICD-9-CM and ICD-10/11-CM systems may reflect the different, but surely overlapping, entity of ASD, which may limit the generalization of our results. Additional studies should be performed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.