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1.
Neurospine ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575113

RESUMO

Objective: To demonstrate the non-inferiority of the novel hemostatic agent, Hemofence® (BMI Korea Co. Ltd., Jeju Korea, thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. Methods: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For non-inferiority test, a 97.5% one-sided confidence interval was used; the test group was deemed non-inferior if the lower limit exceeded -10%. Results: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% confidence interval (-4.90%, 7.44%) confirmed the test drug's non-inferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.0000, p=0.2427, and p=0.9663, respectively). Conclusion: A novel hemostatic agent, Hemofence®, demonstrated an efficacy and safety profile comparable to that of Floseal.

2.
Bioinformatics ; 40(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38490256

RESUMO

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations. AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available at https://github.com/UW-GAC/admix-kit_workflow.


Assuntos
Software , Genótipo , Fenótipo
3.
Gland Surg ; 13(1): 19-31, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323228

RESUMO

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

4.
Chemosphere ; 353: 141537, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408568

RESUMO

Despite the great potential of electrochemical nitrate reduction as a hydroxylamine production method, this strategy has not been sufficiently examined, and the effects of electrode material type on the selectivity and efficiency of this reduction remain underexplored. To bridge this gap, the present study evaluated six metals (Ag, Cu, Ni, Sn, Ti, and Zn) as cathode materials for the electrochemical reduction of nitrate to hydroxylamine, showing that the selectivity of hydroxylamine production was maximal for Sn, while the corresponding faradaic and energy utilization efficiencies were maximal for Ti. Although all tested materials favored nitrate reduction over hydrogen evolution, the disparity in the onset potentials of these reactions did not adequately explain the variations in nitrate removal efficiency, which was found to be influenced by material resistance and charge-transfer properties. The rate constants of elementary nitrate reduction steps determined from the time-dependent concentrations of nitrate and its reduction products (nitrous acid, hydroxylamine, and ammonium) were used to calculate the selectivity and efficiency of hydroxylamine production for each electrode. In turn, these selectivities and efficiencies were correlated with the density functional theory-computed adsorption energies of a key hydroxylamine precursor on different electrodes to afford a volcano-type plot with Ti and Sn at its pinnacle. Thus, this study introduces valuable descriptors and methods for the further screening of electrocatalysts for hydroxylamine generation and the establishment of more environmentally friendly hydroxylamine production techniques utilizing sustainable electricity.


Assuntos
Nitratos , Titânio , Nitratos/química , Hidroxilamina , Titânio/química , Metais , Hidroxilaminas , Eletrodos
5.
Water Res ; 253: 121343, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38422888

RESUMO

A dye-sensitized photocatalysis system was developed for degrading persistent organic contaminants using solid waste (i.e., red mud, RM) and peroxymonosulfate (PMS) under visible light. Complete degradation of acid orange 7 (AO7) was achieved in RM suspension with PMS, where the co-existence of amorphous FeO(OH)/α-Fe2O3 was the key factor for PMS activation. The experimental results obtained from photochemical and electrochemical observations confirmed the enhanced PMS activation due to the Fe-OH phase in RM. DFT calculations verified the acceleration of PMS activation due to the high adsorption energy of PMS on FeO(OH) and low energy barrier for generating reactive radicals. Compared to the control experiment without AO7 showing almost no degradation of other organic contaminants (phenol, bisphenol A, 4-chlorophenol, 4-nitrophenol, and benzoic acid), photo-sensitized AO7* enhanced electron transfer in the FeIII/FeII cycle, dramatically enhancing the degradation of organic contaminants via radical (•OH, SO4•-, and O2•-) and non-radical (dye*+ and 1O2) pathways. Therefore, the novel finding of this study can provide new insights for unique PMS activation by heterogeneous Fe(III) containing solid wastes and highlight the importance of sensitized dye on the interaction of PMS with Fe charge carrier for the photo-oxidation of organic contaminants under visible light.


Assuntos
Compostos Azo , Benzenossulfonatos , Compostos Férricos , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Peróxidos , Luz
6.
JAMA Netw Open ; 7(2): e2355331, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38334998

RESUMO

Importance: Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. Objective: To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. Design, Setting, and Participants: This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. Main Outcomes and Measures: The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Results: Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. Conclusions and Relevance: This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Receptores Proteína Tirosina Quinases/uso terapêutico , Receptores ErbB
7.
Exp Clin Transplant ; 22(1): 35-42, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284373

RESUMO

OBJECTIVES: Machine perfusion of liver grafts has gained popularity for its abilities to preserve liver grafts,reduce cold storage damage, and evaluate graft viability before transplant. However, debate persists regarding the optimal solutions, logistics, and biomarkers for assessing graft quality. To shed light on the lengthy debates surrounding the use of machine perfusion in liver graft preservation,this study utilized bibliometric analysis to evaluate the status and development trends of main research areas. MATERIALS AND METHODS: On December 10th, 2022, we conducted a literature search using the Web of Science database to identify articles related to liver machine perfusion. The search included only original studies and reviews and excluded meeting abstracts, letters, notes, editorials, short surveys, book chapters, and errata. We identified the number of citations and encompassed various aspects, such as annual trends, countries, institutions, authors, journals, and key words. We used VOSviewer version 1.6.18 to generate tables and figures. RESULTS: After manually removing irrelevant papers, we included 264 articles (89 reviews; remaining were original studies). The articles were cited 5743 times, averaging 21.92 per article. We found that the United Kingdom (n = 76) was the country that produced the most articles,followed by theUnited States (66 articles). Most papers in our search were published in Liver Transplantation (n = 31) and Transplantation (n = 16). CONCLUSIONS: Bibliometric analysis provided insights into debates and advancements in liver graft preservation using machine perfusion. The analysis showed leading countries and key research areas in the field. This overview serves as a valuable resource for researchers, offering a foundation for further exploration and guiding future investigations in the field of machine perfusion for liver graft preservation.


Assuntos
Transplante de Fígado , Perfusão , Humanos , Criopreservação , Bases de Dados Factuais , Reino Unido
8.
J Hazard Mater ; 465: 133525, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38237436

RESUMO

Copper (Cu) is an effective antimicrobial material; however, its activity is inhibited by oxidation. Titanium dioxide (TiO2) photocatalysis prevents Cu oxidation and improves its antimicrobial activity and stability. In this study, the virucidal efficacy of Cu-doped TiO2 nanoparticles (Cu-TiO2) with three different oxidation states of the Cu dopant (i.e., zero-valent Cu (Cu0), cuprous (CuI), and cupric (CuII) oxides) was evaluated for the phiX174 bacteriophage under visible light illumination (Vis/Cu-TiO2). CuI-TiO2 exhibited superior virucidal activity (5 log inactivation in 30 min) and reusability (only 11 % loss of activity in the fifth cycle) compared to Cu0-TiO2 and CuII-TiO2. Photoluminescence spectroscopy and photocurrent measurements showed that CuI-TiO2 exhibited the highest charge separation efficiency and photocurrent density (approximately 0.24 µA/cm2) among the three materials, resulting in the most active redox reactions of Cu. Viral inactivation tests under different additives and viral particle integrity analyses (i.e., protein oxidation and DNA damage analyses) revealed that different virucidal species played key roles in the three Vis/Cu-TiO2 systems; Cu(III) was responsible for the viral inactivation by Vis/CuI-TiO2. The Vis/CuI-TiO2 system exhibited substantial virucidal performance for different viral species and in different water matrices, demonstrating its potential practical applications. The findings of this study offer valuable insights into the design of effective and sustainable antiviral photocatalysts for disinfection.


Assuntos
Anti-Infecciosos , Nanopartículas , Iluminação , Luz , Nanopartículas/química , Oxirredução , Titânio/química , Catálise
9.
Chemosphere ; 349: 140897, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070613

RESUMO

Biodegradable cellulose acetate (CA) nanofibers containing Rose Bengal (RB) dye were fabricated by electrospinning technique. RB dye, an anionic photosensitizer, has been used in photodynamic therapy due to its excellent biocompatibility and ability to absorb light to generate reactive oxygen species (ROS), but has a decisive disadvantage of water solubility on infection prevention. Firstly, water-insoluble RB dye was synthesized through complexation with cationic ionic liquid (IL) for antiviral agents. The synthesized water-insoluble RB dyes were embedded into biodegradable CA nanofibers by electrospinning. The electrospun nanofibers passed both antiviral test for φx174 virus under visible light irradiation and biodegradability-test using enzymes. The fabricated RB nanofibers absorbed light and generated ROS to inactivate the virus. As a result, the log reduction (-Log10(N/N0)) of φx174 titer under visible light reached a detection limit of 5.00 within 30 min. Also, the fabricated nanofibers were degraded up to 34 wt % in 9 weeks by lipase and cellulase enzymes compared with non-biodegradable nanofibers.


Assuntos
Nanofibras , Rosa Bengala , Rosa Bengala/farmacologia , Corantes , Espécies Reativas de Oxigênio , Luz , Água , Antivirais
10.
Artigo em Inglês | MEDLINE | ID: mdl-38082711

RESUMO

During liver transplantation, ischemia-reperfusion injury (IRI) is inevitable and decreases the overall success of the surgery. While guidelines exist, there is no reliable way to quantitatively assess the degree of IRI present in the liver. Our recent study has shown a correlation between the bile-to-plasma ratio of FDA-approved sodium fluorescein (SF) and the degree of hepatic IRI, presumably due to IRI-induced decrease in the activity of the hepatic multidrug resistance-associated protein 2 (MRP2); however, the contribution of SF blood clearance via the bile is still convoluted with other factors, such as renal clearance. In this work, we sought to computationally model SF blood clearance via the bile. First, we converted extant SF fluorescence data from rat whole blood, plasma, and bile to concentrations using calibration curves. Next, based on these SF concentration data, we generated a "liver-centric", physiologically-based pharmacokinetic (PBPK) model of SF liver uptake and clearance via the bile. Model simulations show that SF bile concentration is highly sensitive to change in the activity of hepatic MPR2. These simulations suggest that SF bile clearance along with the PBPK model can be used to quantify the effect of IRI on the activity of MRP2.Clinical Relevance- This study establishes the theory necessary to generate a model for predicting the degree of IRI during liver transplantation.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Ratos , Animais , Fígado , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/metabolismo
11.
bioRxiv ; 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37873338

RESUMO

Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic study of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.

12.
J Transplant ; 2023: 8858320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795130

RESUMO

Background: As the field of transplantation has expanded, so have the quantity and variety of articles published on the topic. Evaluation of publications and journals is crucial to the expansion of transplant research. This study investigated the research output and journal metrics of the leading solid organ transplant journals published between 2011 and 2021 based on estimations of the trends in the category CiteScore from the Scopus database. Materials and Methods: We obtained data on the listed journals from the Scopus Source List. We then filtered the list for "Transplantation" journals. Only the top quartiles or quartile 1 (Q1) journals were placed in this category. This study focused specifically on transplantation journals and did not include other journals related to diseases of transplanted organs such as the kidney, liver, heart, and lungs. Results: The number of transplantation journals increased by 42.8% in the last ten years, from 28 in 2011 to 40 in 2021. Between 2011 and 2021, nine transplantation journals ranked in the highest quartile (Q1). The American Journal of Transplantation was the top journal in both years, with a 150% increase in citations and an 11.2% increase in articles published. Open access (OA) transplant journals rose from 3 in 2011 to 10 in 2021. In 2021, OA journals earned 8,555 citations, a 125% increase from 2011. Despite this increase, non-OA journals received more citations than OA in 2021 (p value 0.026). Conclusion: Solid organ transplantation advances lead to more publications and citations. Regular journals and publications evaluation benefits academics and policymakers by promoting the growth of research. This study examined solid organ transplantation journals and gave a global perspective on transplant journal rankings and compared their status in 2011 and 2021.

13.
Cureus ; 15(7): e42150, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37602076

RESUMO

INTRODUCTION: ChatGPT (OpenAI, San Francisco, California, United States) is a chatbot powered by language-based artificial intelligence (AI). It generates text based on the information provided by users. It is currently being evaluated in medical research, publishing, and healthcare. However, there has been no prior study on the evaluation of its ability to help in kidney transplant research. This feasibility study aimed to evaluate the application and accuracy of ChatGPT in the field of kidney transplantation. METHODS: On two separate dates, February 21 and March 2, 2023, ChatGPT 3.5 was questioned regarding the medical treatment of kidney transplants and related scientific facts. The responses provided by the chatbot were compiled, and a panel of two specialists reviewed the correctness of each answer. RESULTS: We demonstrated that ChatGPT possessed substantial general knowledge of kidney transplantation; however, they lacked sufficient information and had inaccurate information that necessitates a deeper understanding of the topic. Moreover, ChatGPT failed to provide references for any of the scientific data it provided regarding kidney transplants, and when requested for references, it provided inaccurate ones. CONCLUSION: The results of this short feasibility study indicate that ChatGPT may have the ability to assist in data collecting when a particular query is posed. However, caution should be exercised and it should not be used in isolation as a supplement to research or decisions regarding healthcare because there are still challenges with data accuracy and missing information.

14.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37446313

RESUMO

Mechanical unloading during microgravity causes skeletal muscle atrophy and impairs mitochondrial energetics. The elevated production of reactive oxygen species (ROS) by mitochondria and Nox2, coupled with impairment of stress protection (e.g., SIRT1, antioxidant enzymes), contribute to atrophy. We tested the hypothesis that the SIRT1 activator, SRT2104 would rescue unloading-induced mitochondrial dysfunction. Mitochondrial function in rat gastrocnemius and soleus muscles were evaluated under three conditions (10 days): ambulatory control (CON), hindlimb unloaded (HU), and hindlimb-unloaded-treated with SRT2104 (SIRT). Oxidative phosphorylation, electron transfer capacities, H2O2 production, and oxidative and antioxidant enzymes were quantified using high-resolution respirometry and colorimetry. In the gastrocnemius, (1) integrative (per mg tissue) proton LEAK was lesser in SIRT than in HU or CON; (2) intrinsic (relative to citrate synthase) maximal noncoupled electron transfer capacity (ECI+II) was lesser, while complex I-supported oxidative phosphorylation to ECI+II was greater in HU than CON; (3) the contribution of LEAK to ECI+II was greatest, but cytochrome c oxidase activity was lowest in HU. In both muscles, H2O2 production and concentration was greatest in SIRT, as was gastrocnemius superoxide dismutase activity. In the soleus, H2O2 concentration was greater in HU compared to CON. These results indicate that SRT2104 preserves mitochondrial function in unloaded skeletal muscle, suggesting its potential to support healthy muscle cells in microgravity by promoting necessary energy production in mitochondria.


Assuntos
Antioxidantes , Sirtuína 1 , Ratos , Animais , Antioxidantes/farmacologia , Sirtuína 1/metabolismo , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Músculo Esquelético/metabolismo , Oxirredução , Atrofia Muscular/metabolismo , Mitocôndrias/metabolismo , Membro Posterior/metabolismo , Biologia
15.
Child Adolesc Psychiatry Ment Health ; 17(1): 71, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37309007

RESUMO

BACKGROUND: The frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear. METHODS: We included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4-18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive-Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26. RESULTS: Tic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70). CONCLUSIONS: The IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD. Trial registration This study retrospectively registered participants.

16.
Diabetologia ; 66(7): 1273-1288, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37148359

RESUMO

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).


Assuntos
Diabetes Mellitus Tipo 2 , Saúde da População , Humanos , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/genética , Medicina de Precisão , Genótipo , Hispânico ou Latino/genética , Polimorfismo de Nucleotídeo Único/genética
17.
Transpl Infect Dis ; 25(3): e14027, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36762493

RESUMO

BACKGROUND: Abdominal solid organ transplant (SOT) programs have been hit hard by the COVID-19 pandemic, which was officially declared as such on March 11, 2020. Over two years, the tightening and softening of limitations in response to the "waves" of infection and COVID-19 fluctuations have provided distinct issues for waitlisted patients, transplant recipients, and transplant organizations. METHOD: We searched Scopus using the terms "transplant" and "transplantation," and organ-related phrases like "intestin*," "liver," "kidney," "hepatic," "renal," and "pancrea*," as well as COVID-19 terms such as "COVID-19," "coronavirus," and "SARS-CoV-2." We included articles, reviews, conference papers, letters, notes, editorials, brief surveys, book chapters, and errata and studied nations, institutions, authors, journals, keywords, and articles. VOSviewer 1.6.18 and Excel were used to create tables and figures. RESULTS: We included 1,251 of 1,256 studies. Among them, 289 (23.1%), 489 (39.1%), and 473 (37.8%) papers were published in 2020, 2021, and 2022, with mean (SD) citations of 30.3 (53.3), 14.3 (26.8), and 4.79 (6.38), respectively. Compared to other abdominal organs, the field of kidney transplants had the highest number of articles describing the impact of COVID-19. The United States contributed the most articles, and the American Journal of Transplantation published the most articles. CONCLUSION: To our knowledge, this is the first bibliometric investigation of the impact of COVID-19 on SOT. This report provides an overview of the research conducted on SOT and COVID-19. There is potential for this bibliometric analysis to serve as a beneficial and practical resource for ongoing and future research.


Assuntos
COVID-19 , Transplante de Órgãos , Humanos , Estados Unidos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Transplante de Órgãos/efeitos adversos , Bibliometria
18.
Soa Chongsonyon Chongsin Uihak ; 34(1): 30-36, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36636495

RESUMO

Objectives: This study examined the changes in anxiety and depressive symptoms in the parents of Korean adults with autism spectrum disorder (ASD) after participating in the Korean version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA-K). Methods: Forty-six parents were enrolled (mean age 54.7 years; 22 fathers and 24 mothers), of whom 27 participated in the PEERS®- YA-K as social coaches. Participants completed self-report scales, including the Test of Young Adult Social Skills Knowledge (TYASSK), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Symptom Check-List-90-R (SCL-90-R). The scales were administered three times: before and after the 16-week program and 4 months after the program ended. Differences between participant variables at pretreatment, post-treatment, and follow-up were analyzed using paired-sample t-tests. Results: Participants showed a significant improvement in their social skills knowledge (TYASSK) (p<0.01). There was a significant improvement in the BAI and BDI scores of parents with severe depressive and anxiety symptoms at the baseline (p<0.05). Paternal paranoia and maternal hostility results also significantly improved on the SCL-90-R. Conclusion: This study suggests that PEERS®-YA-K can reduce parental anxiety and depressive symptoms. To the best of our knowledge, this is the first to compare the degree of depression and anxiety after PEERS®-YA-K in parents of adults with ASD.

19.
Antimicrob Agents Chemother ; 67(1): e0045222, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36515544

RESUMO

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).


Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , Guanidinas , Ésteres , Método Duplo-Cego , Resultado do Tratamento
20.
J Microbiol Biotechnol ; 33(1): 114-122, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36474320

RESUMO

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (ß-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.


Assuntos
Doenças Neurodegenerativas , Via de Sinalização Wnt , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Células HEK293 , Metaboloma , Metabolômica
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