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1.
bioRxiv ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38948755

RESUMO

Huntington's disease (HD), due to expansion of a CAG repeat in HTT , is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5'-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.

2.
Sci Adv ; 10(28): eade4454, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38985861

RESUMO

The laser system is the most complex component of a light-pulse atom interferometer (LPAI), controlling frequencies and intensities of multiple laser beams to configure quantum gravity and inertial sensors. Its main functions include cold-atom generation, state preparation, state-selective detection, and generating a coherent two-photon process for the light-pulse sequence. To achieve substantial miniaturization and ruggedization, we integrate key laser system functions onto a photonic integrated circuit. Our study focuses on a high-performance silicon photonic suppressed-carrier single-sideband (SC-SSB) modulator at 1560 nanometers, capable of dynamic frequency shifting within the LPAI. By independently controlling radio frequency (RF) channels, we achieve 30-decibel carrier suppression and unprecedented 47.8-decibel sideband suppression at peak conversion efficiency of -6.846 decibels (20.7%). We investigate imbalances in both amplitudes and phases between the RF signals. Using this modulator, we demonstrate cold-atom generation, state-selective detection, and atom interferometer fringes to estimate gravitational acceleration, g ≈ 9.77 ± 0.01 meters per second squared, in a rubidium (87Rb) atom system.

3.
Saf Health Work ; 15(2): 151-157, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39035809

RESUMO

Background: Replacement drivers represent a significant portion of platform labor in the Republic of Korea, often facing night shifts and the demands of emotional labor. Research on replacement drivers is limited due to their widespread nature. This study examined the levels of presenteeism and absenteeism among replacement drivers in comparison to those of paid male workers in the Republic of Korea. Methods: This study collected data for replacement drivers and used data from the 6th Korean Working Conditions Survey for paid male workers over the age of 20 years. Propensity score matching was performed to balance the differences between paid workers and replacement drivers. Multivariable logistic regression was used to estimate the adjusted odds ratio (OR) and 95% confidence intervals for presenteeism and absenteeism by replacement drivers. Stratified analysis was conducted for age groups, educational levels, income levels, and working hours. The analysis was adjusted for variables including age, education, income, working hours, working days per week, and working duration. Results: Among the 1,417 participants, the prevalence of presenteeism and absenteeism among replacement drivers was 53.6% (n = 210) and 51.3% (n = 201), respectively. The association of presenteeism and absenteeism (adjusted OR [95% CI] = 8.42 [6.36-11.16] and 20.80 [95% CI = 14.60-29.62], respectively) with replacement drivers being significant, with a prominent association among the young age group, high educational, and medium income levels. Conclusion: The results demonstrated that replacement drivers were more significantly associated with presenteeism and absenteeism than paid workers. Further studies are necessary to establish a strategy to decrease the risk factors among replacement drivers.

4.
Brain Commun ; 6(4): fcae213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007039

RESUMO

The frequency of the apolipoprotein E ɛ4 allele and vascular risk factors differs among ethnic groups. We aimed to assess the combined effects of apolipoprotein E ɛ4 and vascular risk factors on brain age in Korean and UK cognitively unimpaired populations. We also aimed to determine the differences in the combined effects between the two populations. We enrolled 2314 cognitively unimpaired individuals aged ≥45 years from Korea and 6942 cognitively unimpaired individuals from the UK, who were matched using propensity scores. Brain age was defined using the brain age index. The apolipoprotein E genotype (ɛ4 carriers, ɛ2 carriers and ɛ3/ɛ3 homozygotes) and vascular risk factors (age, hypertension and diabetes) were considered predictors. Apolipoprotein E ɛ4 carriers in the Korean (ß = 0.511, P = 0.012) and UK (ß = 0.302, P = 0.006) groups had higher brain age index values. The adverse effects of the apolipoprotein E genotype on brain age index values increased with age in the Korean group alone (ɛ2 carriers × age, ß = 0.085, P = 0.009; ɛ4 carriers × age, ß = 0.100, P < 0.001). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ2 carriers × age × ethnicity, ß = 0.091, P = 0.022; ɛ4 carriers × age × ethnicity, ß = 0.093, P = 0.003). The effects of apolipoprotein E on the brain age index values were more pronounced in individuals with hypertension in the Korean group alone (ɛ4 carriers × hypertension, ß = 0.777, P = 0.038). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ4 carriers × hypertension × ethnicity, ß=1.091, P = 0.014). We highlight the ethnic differences in the combined effects of the apolipoprotein E ɛ4 genotype and vascular risk factors on accelerated brain age. These findings emphasize the need for ethnicity-specific strategies to mitigate apolipoprotein E ɛ4-related brain aging in cognitively unimpaired individuals.

5.
Front Neurosci ; 18: 1411334, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846713

RESUMO

Background: Deep-learning-based brain age estimation using magnetic resonance imaging data has been proposed to identify abnormalities in brain development and the risk of adverse developmental outcomes in the fetal brain. Although saliency and attention activation maps have been used to understand the contribution of different brain regions in determining brain age, there has been no attempt to explain the influence of shape-related cortical structural features on the variance of predicted fetal brain age. Methods: We examined the association between the predicted brain age difference (PAD: predicted brain age-chronological age) from our convolution neural networks-based model and global and regional cortical structural measures, such as cortical volume, surface area, curvature, gyrification index, and folding depth, using regression analysis. Results: Our results showed that global brain volume and surface area were positively correlated with PAD. Additionally, higher cortical surface curvature and folding depth led to a significant increase in PAD in specific regions, including the perisylvian areas, where dramatic agerelated changes in folding structures were observed in the late second trimester. Furthermore, PAD decreased with disorganized sulcal area patterns, suggesting that the interrelated arrangement and areal patterning of the sulcal folds also significantly affected the prediction of fetal brain age. Conclusion: These results allow us to better understand the variance in deep learning-based fetal brain age and provide insight into the mechanism of the fetal brain age prediction model.

6.
Intern Emerg Med ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907758

RESUMO

The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a robust and reliable instrument for discerning delirium within the specific context of the intensive care unit (ICU). Nonetheless, the CAM-ICU is burdened by various limitations, including a protracted learning curve and the need for frequent daily administration. The 4 A's Test (4AT) was formulated to assess delirium in hospitalized patients and may have distinct advantages over the CAM-ICU, particularly regarding practical applicability within the ICU bundle. This study was performed to assess the utility of the 4AT in detecting delirium in critically ill patients. This multicenter prospective observational study involved critically ill patients at four academic tertiary care hospitals in South Korea from June 2021 to September 2022. In total, 274 patients (median age, 64 years; 56.9% men) were included, and 75 (27.4%) developed delirium. The 4AT showed good performance in detecting ICU delirium (area under the curve, 0.879; P < 0.001). The 4AT showed a sensitivity of 74.0%, specificity of 95.4%, positive predictive value of 77.5%, negative predictive value of 94.6%, and accuracy of 91.7% for ICU detection of delirium. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CAM-ICU for detecting ICU delirium were 71.3%, 97.1%, 83.8%, 94.1%, and 92.6%, respectively. The 4AT showed acceptable reliability and validity for detecting ICU delirium in critically ill patients. Because the 4AT is simpler and easier to learn, this scale could be a useful alternative to the CAM-ICU for detecting delirium in critically ill patients.

7.
Life (Basel) ; 14(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38929650

RESUMO

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and <14 Gy). The results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8%, respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (p = 0.628), while Group 2 (<14 Gy) exhibited significantly lower PTE (p = 0.039). This study concludes that SRS with a radiation dose < 14 Gy demonstrates comparable tumor control with reduced toxicity, advocating consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

8.
J Pers Med ; 14(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929831

RESUMO

Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.

9.
PLoS One ; 19(6): e0305360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38935680

RESUMO

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.


Assuntos
Neoplasias do Endométrio , Miométrio , Gradação de Tumores , Invasividade Neoplásica , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Miométrio/patologia , Miométrio/cirurgia , Pessoa de Meia-Idade , Adulto , República da Coreia/epidemiologia , Estudos Prospectivos , Idoso , Período Pré-Operatório , Imageamento por Ressonância Magnética , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia
10.
Elife ; 122024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869243

RESUMO

An expanded CAG repeat in the huntingtin gene (HTT) causes Huntington's disease (HD). Since the length of uninterrupted CAG repeat, not polyglutamine, determines the age-at-onset in HD, base editing strategies to convert CAG to CAA are anticipated to delay onset by shortening the uninterrupted CAG repeat. Here, we developed base editing strategies to convert CAG in the repeat to CAA and determined their molecular outcomes and effects on relevant disease phenotypes. Base editing strategies employing combinations of cytosine base editors and guide RNAs (gRNAs) efficiently converted CAG to CAA at various sites in the CAG repeat without generating significant indels, off-target edits, or transcriptome alterations, demonstrating their feasibility and specificity. Candidate BE strategies converted CAG to CAA on both expanded and non-expanded CAG repeats without altering HTT mRNA and protein levels. In addition, somatic CAG repeat expansion, which is the major disease driver in HD, was significantly decreased in the liver by a candidate BE strategy treatment in HD knock-in mice carrying canonical CAG repeats. Notably, CAG repeat expansion was abolished entirely in HD knock-in mice carrying CAA-interrupted repeats, supporting the therapeutic potential of CAG-to-CAA conversion strategies in HD and potentially other repeat expansion disorders.


Assuntos
Edição de Genes , Proteína Huntingtina , Doença de Huntington , Expansão das Repetições de Trinucleotídeos , Doença de Huntington/genética , Doença de Huntington/terapia , Animais , Edição de Genes/métodos , Camundongos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Expansão das Repetições de Trinucleotídeos/genética , Modelos Animais de Doenças , Humanos , Mutação , Técnicas de Introdução de Genes
11.
Int J Pharm ; 660: 124315, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38852747

RESUMO

The compendial USP〈701〉 disintegration test method offers a crucial pass/fail assessment for immediate release tablet disintegration. However, its single end-point approach provides limited insight into underlying mechanisms. This study introduces a novel calorimetric approach, aimed at providing comprehensive process profiles beyond binary outcomes. We developed a novel disintegration reaction calorimeter to monitor the heat release throughout the disintegration process and successfully obtained enthalpy change profiles of placebo tablets with various porosities. The formulation comprised microcrystalline cellulose (MCC), anhydrous lactose, croscarmellose sodium (CCS), and magnesium stearate (MgSt). An abrupt temperature rise was observed after introducing the disintegration medium to tablets, and the relationship between the heat rise time and the tablet's porosity was investigated. The calorimeter's sensitivity was sufficient to discern distinct heat changes among individual tablets, and the analysis revealed a direct correlation between the two. Higher porosity corresponded to shorter heat rise time, indicating faster disintegration rates. Additionally, the analysis identified a concurrent endothermic process alongside the anticipated exothermic phenomenon, potentially associated with the dissolution of anhydrous lactose. Since lactose is the only soluble excipient within the blend composition, the endothermic process can be attributed to the absorption of heat as lactose molecules dissolve in water. The findings from this study underscore the potential of utilising calorimetric methods to quantify the wettability of complex compounds and, ultimately, optimise tablet formulations.


Assuntos
Calorimetria , Celulose , Excipientes , Temperatura Alta , Lactose , Ácidos Esteáricos , Comprimidos , Lactose/química , Celulose/química , Excipientes/química , Porosidade , Ácidos Esteáricos/química , Calorimetria/métodos , Solubilidade , Carboximetilcelulose Sódica/química , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Composição de Medicamentos/métodos
12.
Eur J Surg Oncol ; 50(9): 108484, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38901293

RESUMO

OBJECTIVE: To identify the effects of subcutaneous drain insertion on wound dehiscence and infection in patients who underwent gynecological midline laparotomy. METHODS: This analysis identified the secondary endpoints of the KGOG 4001 study, a prospective, multicenter, non-blind, randomized controlled trial. Patients scheduled to undergo midline laparotomy for gynecological diseases and, with body mass index<35 kg/m2, were randomized (1:1) to treatment (with subcutaneous drain) and control (without subcutaneous drain) groups from February 2021 to December 2021. We compared the incidence rate of wound dehiscence 4 weeks post-surgery and the cumulative incidence rate of wound dehiscence and infection up to 4 weeks post-surgery between the two groups. RESULTS: Of 174 patients randomized to the treatment (n = 84) and control (n = 90) groups, 12 were excluded owing to loss to follow-up; finally, 162 patients (treatment, n = 79; control, n = 83) were included in intention-to-treat analysis. The frequency of cancer surgery (79.7 % vs. 77.1 %, p = 0.683), mean surgery time (227.7 vs. 226.7 min, p = 0.960), and mean wound length (24.2 vs. 24.3 cm, p = 0.933) were comparable between two groups. No significant differences were observed in the incidence rate of wound dehiscence 4 weeks post-surgery (1.3 % vs. 2.4 %, p > 0.999), cumulative incidence rate of wound dehiscence (8.9 % vs. 6.0 %, p = 0.491), and cumulative incidence rate of wound infection (1.3 % vs. 0.0 %, p = 0.488) up to 4 weeks post-surgery between the two groups. CONCLUSION: Subcutaneous drain insertion is not associated with a significant improvement in the incidence of wound dehiscence and infection in patients who undergo gynecological midline laparotomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643197.

13.
Biomater Sci ; 12(13): 3321-3334, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38812375

RESUMO

Keloid is a type of scar formed by the overexpression of extracellular matrix substances from fibroblasts following inflammation after trauma. The existing keloid treatment methods include drug injection, surgical intervention, light exposure, cryotherapy, etc. However, these methods have limitations such as recurrence, low treatment efficacy, and side effects. Consequently, studies are being conducted on the treatment of keloids from the perspective of inflammatory mechanisms. In this study, keloid models are created to understand inflammatory mechanisms and explore treatment methods to address them. While previous studies have used animal models with gene mutations, chemical treatments, and keloid tissue transplantation, there are limitations in fully reproducing the characteristics of keloids unique to humans, and ethical issues related to animal welfare pose additional challenges. Consequently, studies are underway to create in vitro artificial skin models to simulate keloid disease and apply them to the development of treatments for skin diseases. In particular, herein, scaffold technologies that implement three-dimensional (3D) full-thickness keloid models are introduced to enhance mechanical properties as well as biological properties of tissues, such as cell proliferation, differentiation, and cellular interactions. It is anticipated that applying these technologies to the production of artificial skin for keloid simulation could contribute to the development of inflammatory keloid treatment techniques in the future.


Assuntos
Queloide , Pele Artificial , Queloide/terapia , Humanos , Animais , Modelos Biológicos , Engenharia Tecidual , Alicerces Teciduais/química , Pele/metabolismo , Pele/patologia
14.
Small ; : e2401546, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705853

RESUMO

The design of high-energy facets in electrocatalysts has attracted significant attention due to their potential to enhance electrocatalytic activity. In this review, the significance of high-energy facets in various electrochemical reactions are highlighted, including oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), nitrogen reduction reaction (NRR), and carbon dioxide reduction reaction (CRR). Their importance in various electrochemical reactions and present strategies for constructing high-energy facets are discussed, including alloying, heterostructure formation, selective etching, capping agents, and coupling with substrates. These strategies enable control over crystallographic orientation and surface morphology, fine-tuning electrocatalytic properties. This study also addresses future directions and challenges, emphasizing the need to better understand fundamental mechanisms. Overall, high-energy facets offer exciting opportunities for advancing electrocatalysis.

15.
PLoS One ; 19(5): e0299205, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38805507

RESUMO

OBJECTIVE: To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. METHODS: A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. RESULTS: A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68-2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67-2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85-2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28-3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10-3.36, p = 0.023) affects adversely on OS. CONCLUSION: Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies.


Assuntos
Linfonodos , Neoplasias Ovarianas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Metástase Linfática , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Idoso de 80 Anos ou mais
16.
BMC Pulm Med ; 24(1): 259, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797852

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic. METHODS: This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors. RESULTS: Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors. CONCLUSIONS: In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Neoplasias Hematológicas , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Hematológicas/complicações , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/epidemiologia , Idoso , Mortalidade Hospitalar , SARS-CoV-2 , Fatores de Risco , Incidência , Adulto , Hospitalização/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/complicações
17.
Nat Commun ; 15(1): 3182, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609352

RESUMO

Huntington's disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin's polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.


Assuntos
Doença de Huntington , Humanos , Doença de Huntington/genética , Éxons/genética , Perfilação da Expressão Gênica , Heterozigoto , Homozigoto , Proteínas MutL , Proteínas de Neoplasias
18.
Nano Lett ; 24(14): 4224-4232, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557115

RESUMO

In this study, we identify the local structures of ex-solved nanoparticles using machine-learned potentials (MLPs). We develop a method for training machine-learned potentials by sampling local structures of heterointerface configurations as a training set with its efficacy tested on the Ni/MgO system, illustrating that the error in interface energy is only 0.004 eV/Å2. Using the developed scheme, we train an MLP for the Ni/La0.5Ca0.5TiO3 ex-solution system and identify the local structures for both exo- and endo-type particles. The established model aligns well with the experimental observations, accurately predicting a nucleation size of 0.45 nm. Lastly, the density functional theory calculations on the established atomistic model verify that the kinetic barrier for the dry reforming of methane are substantially reduced by 0.49 eV on the ex-solved catalysts compared to that on the impregnated catalysts. Our findings offer insights into the local structures, growth mechanisms, and underlying origin of the catalytic properties of ex-solved nanoparticles.

19.
J Korean Soc Radiol ; 85(2): 434-436, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38617863
20.
J Korean Soc Radiol ; 85(2): 308-326, 2024 Mar.
Artigo em Coreano | MEDLINE | ID: mdl-38617866

RESUMO

A comprehensive evaluation of cardiac function includes information in relation to cardiac output and systemic venous return. The heart is composed of four chambers: two atria and two ventricles, each with its own unique mechanical function. These four cardiac chambers, their valves, and the pulmonary circulation system are inter-related as they preload or afterload on each other. Cardiac dysfunction is a failure of global cardiac function, resulting in typical clinical manifestations. To investigate the underlying cause of cardiac dysfunction, a step-by-step evaluation of cardiac blood flow tracks is necessary. In this context, imaging markers showing details of the cardiac structures have an important role in assessing cardiac function. An image-based evaluation allows for investigation of function in terms of individual cardiac components. Evaluation of cardiac function using cardiac CT has recently been validated. This review aimed to discuss cardiac CT-based imaging markers for comprehensive and detailed cardiac function assessment.

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