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1.
ACS Nano ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990779

RESUMO

Use of a template triggers an epitaxial interaction with the depositing material during synthesis. Recent studies have demonstrated that two-dimensional tellurium (tellurene) can be directionally oriented when grown on transition metal dichalcogenide (TMD) templates. Specifically, employing a T-phase TMD, such as WTe2, restricts the growth direction even further due to its anisotropic nature, which allows for the synthesis of well-oriented tellurene films. Despite this, producing large-area epitaxial films still remains a significant challenge. Here, we report the continuous synthesis of a 1T'-MoTe2 template via chemical vapor deposition and tellurene via vapor transport. The interaction between helical Te and the 1T'-MoTe2 template facilitates the Te chains to collapse into ribbon shapes, enhancing lateral growth at a rate approximately 6 times higher than in the vertical direction, as confirmed by scanning electron microscopy and atomic force microscopy. Interestingly, despite the predominance of the lateral growth, cross-sectional transmission electron microscopy analysis of the tellurene ribbons revealed a consistent 60-degree incline at the edges. This suggests that the edges of the tellurene ribbons, where they contact the template surface, are favorable sites for additional Te absorption, which then stacks along the incline angle to expand. Furthermore, controlling the synthesis temperature, duration, and preheating time has facilitated the successful synthesis of tellurene films. The resultant tellurene exhibited hole mobility as high as ∼400 cm2/V s. After removing the underlying metallic template with plasma treatment, the film showed a current on/off ratio of ∼103. This ratio was confirmed by two-terminal field-effect transistor measurements and supported by near-field terahertz (THz) spectroscopy mapping.

2.
Ann Surg Oncol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954089

RESUMO

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

3.
Sci Rep ; 14(1): 15466, 2024 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965336

RESUMO

This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.


Assuntos
Fezes , Microbioma Gastrointestinal , Probióticos , Desmame , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Suínos , Projetos Piloto , Probióticos/administração & dosagem , Fezes/microbiologia , Salmonelose Animal/microbiologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Lactobacillaceae , Salmonella typhimurium/efeitos dos fármacos
4.
Comput Methods Programs Biomed ; 254: 108302, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38996805

RESUMO

BACKGROUND AND OBJECTIVE: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients. METHODS: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024. RESULTS: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores). CONCLUSIONS: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health.

5.
Transpl Int ; 37: 12657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38845757

RESUMO

This study aimed to assess the lung transplantation (LT) outcomes of patients with right ventricular dysfunction (RVD), focusing on the impact of various extracorporeal membrane oxygenation (ECMO) configurations. We included adult patients who underwent LT with ECMO as a bridge-to-transplant from 2011 to 2021 at a single center. Among patients with RVD (n = 67), veno-venous (V-V) ECMO was initially applied in 79% (53/67) and maintained until LT in 52% (35/67). Due to the worsening of RVD, the configuration was changed from V-V ECMO to veno-arterial (V-A) ECMO or a right ventricular assist device with an oxygenator (Oxy-RVAD) in 34% (18/67). They showed that lactic acid levels (2-6.1 mmol/L) and vasoactive inotropic score (6.6-22.6) increased. V-A ECMO or Oxy-RVAD was initiated and maintained until LT in 21% (14/67) of cases. There was no significant difference in the survival rates among the three configuration groups (V-V ECMO vs. configuration changed vs. V-A ECMO/Oxy-RVAD). Our findings suggest that the choice of ECMO configuration for LT candidates with RVD should be determined by the patient's current hemodynamic status. Vital sign stability supports the use of V-V ECMO, while increasing lactic acid levels and vasopressor needs may require a switch to V-A ECMO or Oxy-RVAD.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Disfunção Ventricular Direita , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Disfunção Ventricular Direita/terapia , Disfunção Ventricular Direita/cirurgia , Adulto , Resultado do Tratamento , Coração Auxiliar , Idoso
6.
Artigo em Inglês | MEDLINE | ID: mdl-38866622

RESUMO

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

7.
Commun Chem ; 7(1): 146, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942965

RESUMO

Pyridine, an essential structure in drug development, shows a wide array of bioactivities according to its substitution patterns. Among the bioactive pyridines, meta-substituted pyridines suffer from limited synthetic approaches despite their significance. In this study, we present a condensation-based synthetic method enabling the facile incorporation of biologically relevant functional groups at the meta position of pyridine. This methodology unveiled the concealed reactivity of 3-formyl(aza)indoles as diformylmethane analogs for synthesizing dissymmetric di-meta-substituted pyridines without ortho and para substitutions. Furthermore, we uncovered resonance-assisted hydrogen bonding (RAHB) as the requirement for the in situ generation of enamines, the key intermediates of this transformation. Successful development of the designed methodology linked to wide applications-core remodeling of natural products, drug-natural product conjugation, late-stage functionalization of drug molecules, and synthesis of the regioisomeric CZC24832. Furthermore, we discovered anti-inflammatory agents through the functional evaluation of synthesized bi-heteroaryl analogs, signifying the utility of this methodology.

8.
JAMA Cardiol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922632

RESUMO

Importance: The appropriate follow-up surveillance strategy for patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains unknown. Objective: To assess clinical outcomes in patients with and without ACS who have undergone high-risk PCI according to a follow-up strategy of routine stress testing at 12 months after PCI vs standard care alone. Design, Setting, and Participants: The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented vs Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial was a randomized clinical trial that compared follow-up strategies of routine functional testing vs standard care alone 12 months after high-risk PCI. Patients were categorized as presenting with or without ACS. Patients were enrolled in the trial from November 2017 through September 2019, and patients were randomized from 11 sites in South Korea; data analysis was performed in 2022. Intervention: Patients categorized as presenting with or without ACS were randomized to either a routine functional testing or standard care alone follow-up strategy 12 months after high-risk PCI. Main Outcomes and Measures: The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years following randomization. Kaplan-Meier event rates through 2 years and Cox model hazard ratios (HRs) were generated, and interactions were tested. Results: Of 1706 included patients, 350 patients (20.5%) were female, and the mean (SD) patient age was 64.7 (10.3) years. In total, 526 patients (30.8%) presented with ACS. Compared with those without ACS, patients with ACS had a 55% greater risk of the primary outcome (HR, 1.55; 95% CI, 1.03-2.33; P = .03) due to higher event rates in the first year. The 2-year incidences of the primary outcome were similar between strategies of routine functional testing or standard care alone in patients with ACS (functional testing: 16 of 251 [6.6%]; standard care: 23 of 275 [8.5%]; HR, 0.76; 95% CI, 0.40-1.44; P = .39) and in patients without ACS (functional testing: 30 of 598 [5.1%]; standard care: 28 of 582 [4.9%]; HR, 1.04; 95% CI, 0.62-1.74; P = .88) (P for interaction for ACS = .45). Although a landmark analysis suggested that the rates of invasive angiography and repeat revascularization were higher after 1 year in the routine functional testing group, the formal interactions between ACS status and either invasive angiography or repeat revascularization were not significant. Conclusion and Relevance: Despite being at higher risk for adverse clinical events in the first year after PCI than patients without ACS, patients with ACS who had undergone high-risk PCI did not derive incremental benefit from routine surveillance stress testing at 12 months compared with standard care alone during follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT03217877.

9.
bioRxiv ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38853868

RESUMO

Lipid transfer through membrane contact has been implicated to support vesicular transport, but a mechanistic understanding of this process remains to be achieved. Here, examining Coat Protein I (COPI) transport, we find that phosphatidylcholine (PC) with short acyl chains (sPC), which is needed to support COPI vesicle fission, is delivered through membrane contact from the endoplasmic reticulum (ER) to the Golgi complex at sites of COPI vesicle formation. Phosphatidylinositol transfer protein beta (PITPß) plays a central role in this delivery by not only catalyzing PC transfer, but also forming membrane contact. By combining cell-based studies with reconstitution approaches, we achieve spatial and temporal detail in explaining how sPC delivery occurs. Our findings advance the mechanistic understanding of how membrane contact is needed for vesicular transport in a model pathway and shed new insights into how PITPß acts.

10.
Korean Circ J ; 54(7): 398-406, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38859644

RESUMO

BACKGROUND AND OBJECTIVES: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. METHODS: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. RESULTS: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16-4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98-3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75-3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51-2.50 for stroke). CONCLUSIONS: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03554837.

11.
Clin Orthop Surg ; 16(3): 461-469, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827764

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that frequently causes forefoot deformities. Arthrodesis of the first metatarsophalangeal joint is a common surgery for severe hallux valgus. However, joint-preserving surgery can maintain the mobility of the joint. This study aimed to investigate the clinical and radiographic outcomes of distal chevron metatarsal osteotomy (DCMO) for correcting hallux valgus deformity associated with RA. Methods: Between August 2000 and December 2018, 18 consecutive patients with rheumatoid forefoot deformities (24 feet) underwent DCMO for hallux valgus with/without lesser toe surgery. Radiological evaluations were conducted, assessing the hallux valgus angle, the intermetatarsal angle between the first and second metatarsals, and the Sharp/van der Heijde score for erosion and joint space narrowing. Clinical outcomes were quantified using a visual analog scale for pain and the American Orthopaedic Foot and Ankle Society forefoot scores to measure function and alignment. Results: The mean hallux valgus angle decreased from 38.0° (range, 25°-65°) preoperatively to 3.5° (range, 0°-17°) at the final follow-up (p < 0.05). The mean intermetatarsal angle decreased from 14.9° (range, 5°-22°) preoperatively to 4.3° (range, 2°-11°) at the final follow-up. (p < 0.05). Regarding the Sharp/van der Heijde score, the mean erosion score (0-10) showed no significant change, decreasing from 3.83 (range, 0-6) preoperatively to 3.54 (range, 0-4) at the final follow-up (p = 0.12). Recurrent hallux valgus was observed in 1 patient and postoperative hallux varus deformity was observed in 2 feet. Spontaneous fusion of the metatarsophalangeal joint developed in 1 case. Conclusions: DCMO resulted in satisfactory clinical and radiographic outcomes for correcting RA-associated hallux valgus deformity.


Assuntos
Artrite Reumatoide , Hallux Valgus , Osteotomia , Humanos , Hallux Valgus/cirurgia , Hallux Valgus/diagnóstico por imagem , Artrite Reumatoide/cirurgia , Artrite Reumatoide/complicações , Feminino , Pessoa de Meia-Idade , Osteotomia/métodos , Masculino , Idoso , Adulto , Estudos Retrospectivos
12.
World Neurosurg ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838936

RESUMO

OBJECTIVE: Elderly patients undergoing spinal surgery are at an increased risk of morbidity and mortality. Evaluating frailty and preoperative status is crucial for predicting postoperative outcomes. This study aimed to assess the predictive value of the modified Frailty Index (mFI), sarcopenia, Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index (GNRI) in determining postoperative complications in patients undergoing oblique lumbar interbody fusion (OLIF) over 60 years. METHODS: Preoperative risk factors were assessed using 11 variables, including mFI, PNI, GNRI. Complication rates were compared among nonfrail (mFI = 0; n = 50), prefrail (mFI = 0.09-0.18; n = 144), and frail (mFI ≥0.27; n = 80) patients. Demographic and perioperative variables were compared between the complication and noncomplication groups. The incidence of complications was the primary outcome measure. RESULTS: Complications occurred in 36 of 274 patients (13.1%). The frail group exhibited a significantly higher incidence of pneumonia than the nonfrail and prefrail groups. The complication group displayed significant differences in several variables, including age, fusion level, albumin level, lymphocyte count, platelet count, creatinine level, and estimated blood loss. Moreover, mFI, PNI, and GNRI differed significantly between the complication and noncomplication groups. CONCLUSION: MFI, PNI, and GNRI can be useful for predicting postoperative morbidity and mortality in patients undergoing OLIF. These comprehensive assessment methods enable the identification of high-risk patients and the formulation of tailored strategies to enhance postoperative outcomes. Integrating mFI, PNI, and GNRI into the preoperative evaluation process can help healthcare providers proactively manage high-risk patients, thus improving the overall quality of care for elderly individuals undergoing OLIF.

13.
Clin Exp Reprod Med ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38711333

RESUMO

Objective: Bis-[4-chlorophenyl]-1,1,1-trichloroethane (DDT), one of the most widely used synthetic pesticides, is an endocrine-disrupting chemical with the potential to interfere with the human reproductive system. The effects of DDT and one of its metabolites, p,p'-DDT, on human endometrial stromal cells (ESCs) and health outcomes remain unknown. In this study, we investigated whether p,p'-DDT induces an imbalance in cell proliferation and apoptosis in human ESCs via oxidative stress. Methods: We assessed apoptosis in ESCs by quantifying the expression of markers associated with both intrinsic and extrinsic pathways. Additionally, we measured levels of reactive oxygen species (ROS), antioxidant enzyme activity, and estrogen receptors (ERs). We also examined changes in signaling involving nuclear factor kappa-light-chain-enhancer of activated B cells. Results: Following treatment with 1,000 pg/mL of p,p'-DDT, we observed an increase in Bax expression, a decrease in Bcl-2 expression, and increases in the expression of caspases 3, 6, and 8. We also noted a rise in the generation of ROS and a reduction in glutathione peroxidase expression after treatment with p,p'-DDT. Additionally, p,p'-DDT treatment led to changes in ER expression and increases in the protein levels of phosphatidylinositol 3-kinase (PI3K), phospho-protein kinase B (phospho-AKT), and phospho-extracellular signal-regulated kinase (phospho-ERK). Conclusion: p,p'-DDT was found to induce apoptosis in human ESCs through oxidative stress and an ER-mediated pathway. The activation of the PI3K/AKT and ERK pathways could represent potential mechanisms by which p,p'-DDT prompts apoptosis in human ESCs and may be linked to endometrial pathologies.

14.
Ann Thorac Med ; 19(2): 131-138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766373

RESUMO

BACKGROUND: Standard antibiotic treatment for nontuberculous mycobacteria pulmonary disease (NTMPD) has unsatisfactory success rates. Pulmonary resection is considered adjunctive therapy for patients with refractory disease or severe complications, but surgical indications and extent of resection remain unclear. We present surgical treatment outcomes for NTMPD and analyzes risk factors for unfavorable outcomes. METHODS: We conducted a retrospective investigation of medical records for patients diagnosed with NTMPD who underwent surgical treatment at Asan Medical Center between 2007 and 2021. We analyzed clinical data including microbiological and surgical outcomes. RESULTS: A total of 71 NTMPD patients underwent thoracic surgery. Negative conversion of acid-fast bacillus (AFB) culture following pulmonary resection was observed in 51 (73.9%) patients. In terms of long-term outcomes, negative conversion was sustained in 38 cases (55.1%). Mortality occurred in 7 patients who underwent pulmonary resections for NTMPD. Statistically significant associations with factors for recurrence or non-negative conversion of AFB culture were found in older age (odds ratio [OR] =1.093, 95% confidence interval [CI]: 1.029-1.161, P = 0.004), male sex (OR = 0.251, 95% CI: 0.071-0.892, P = 0.033), and extensive NTMPD lesions involving three lobes or more (OR = 5.362, 95% CI: 1.315-21.857, P = 0.019). Interstitial lung disease (OR = 13.111, 95% CI: 1.554-110.585, P = 0.018) and pneumonectomy (OR = 19.667, 95% CI: 2.017-191.797, P = 0.018) were statistically significant risk factors for postoperative mortality. CONCLUSION: Pulmonary resection can be an effective adjuvant treatment option for NTMPD patients, with post-operative antibiotic treatment as the primary treatment. Careful patient selection is crucial, considering the associated risk factors and resectability due to complications and recurrence.

15.
Nat Cell Biol ; 26(6): 903-916, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702503

RESUMO

Dynamic changes in mechanical microenvironments, such as cell crowding, regulate lineage fates as well as cell proliferation. Although regulatory mechanisms for contact inhibition of proliferation have been extensively studied, it remains unclear how cell crowding induces lineage specification. Here we found that a well-known oncogene, ETS variant transcription factor 4 (ETV4), serves as a molecular transducer that links mechanical microenvironments and gene expression. In a growing epithelium of human embryonic stem cells, cell crowding dynamics is translated into ETV4 expression, serving as a pre-pattern for future lineage fates. A switch-like ETV4 inactivation by cell crowding derepresses the potential for neuroectoderm differentiation in human embryonic stem cell epithelia. Mechanistically, cell crowding inactivates the integrin-actomyosin pathway and blocks the endocytosis of fibroblast growth factor receptors (FGFRs). The disrupted FGFR endocytosis induces a marked decrease in ETV4 protein stability through ERK inactivation. Mathematical modelling demonstrates that the dynamics of cell density in a growing human embryonic stem cell epithelium precisely determines the spatiotemporal ETV4 expression pattern and, consequently, the timing and geometry of lineage development. Our findings suggest that cell crowding dynamics in a stem cell epithelium drives spatiotemporal lineage specification using ETV4 as a key mechanical transducer.


Assuntos
Diferenciação Celular , Linhagem da Célula , Células-Tronco Embrionárias Humanas , Proteínas Proto-Oncogênicas c-ets , Fatores de Transcrição , Humanos , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Endocitose , Proliferação de Células , Integrinas/metabolismo , Integrinas/genética , Transdução de Sinais , Mecanotransdução Celular
18.
Artigo em Inglês | MEDLINE | ID: mdl-38748520

RESUMO

Depth-aware Video Panoptic Segmentation (DVPS) is a challenging task that requires predicting the semantic class and 3D depth of each pixel in a video, while also segmenting and consistently tracking objects across frames. Predominant methodologies treat this as a multi-task learning problem, tackling each constituent task independently, thus restricting their capacity to leverage interrelationships amongst tasks and requiring parameter tuning for each task. To surmount these constraints, we present Slot-IVPS, a new approach employing an object-centric model to acquire unified object representations, thereby facilitating the model's ability to simultaneously capture semantic and depth information. Specifically, we introduce a novel representation, Integrated Panoptic Slots (IPS), to capture both semantic and depth information for all panoptic objects within a video, encompassing background semantics and foreground instances. Subsequently, we propose an integrated feature generator and enhancer to extract depth-aware features, alongside the Integrated Video Panoptic Retriever (IVPR), which iteratively retrieves spatial-temporal coherent object features and encodes them into IPS. The resulting IPS can be effortlessly decoded into an array of video outputs, including depth maps, classifications, masks, and object instance IDs. We undertake comprehensive analyses across four datasets, attaining state-of-the-art performance in both Depth-aware Video Panoptic Segmentation and Video Panoptic Segmentation tasks. Codes will be available at https://github.com/SAITPublic/.

20.
J Prosthet Dent ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38797573

RESUMO

STATEMENT OF PROBLEM: Interest is growing in immediately loading definitive implant-supported prostheses. However, it appears that implant protocols are evolving faster than their scientific validation. PURPOSE: The purpose of this scoping review was to identify the current trends, feasibility, and clinical outcomes of a specific clinical loading scenario (type A), where a single definitive implant-retained restoration is delivered within 3 days. The focus question was "In partially edentulous patients requiring an implant-retained prosthesis (population), is immediate loading with a definitive restoration (concept) a viable treatment option (context)?" MATERIAL AND METHODS: An electronic search was conducted in the PubMed, CENTRAL, Scopus, Embase, and Web of Science databases. Two authors independently reviewed the studies, screened titles and abstracts, and performed full-text analysis. Cross-reference checks within the bibliography of included studies, relevant reviews, and guideline were conducted. Bibliometric information and study details were extracted. RESULTS: The search identified 2568 titles after removing duplicates. Four studies involving 91 participant and 100 implant-retained restorations were included in this scoping review. The selected articles were a randomized controlled trial (RCT), a prospective clinical study, and the remaining 2 were case series. The follow-up periods investigated ranged from 6 to 26 months. All studies evaluated marginal bone loss as a primary outcome, and only 1 implant failure was reported. Patient-reported outcome measures were favorable, and no major biological or technical complications were reported in any study. CONCLUSIONS: Immediate loading with a definitive restoration within 3 days appears to be a suitable approach in specific clinical situations.

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