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1.
Immunology ; 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36708143

RESUMO

The NLRP3 inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC-0160 or pioglitazone, increased NLRP3 inflammasome activation and IL-1ß secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP-associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sensitizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU-induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3-related autoinflammatory diseases. This article is protected by copyright. All rights reserved.

2.
Environ Pollut ; 321: 121096, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657513

RESUMO

Microplastics are ubiquitous and affect all environments, including rivers. In recent years the number of studies about microplastics in rivers has strongly increased. But still many questions exist regarding sources, pathways, and the role of land use patterns. In this study the relationship between microplastics abundance and anthropogenic factors (population density, urbanization, land use types), as well as the potential role of storm sewers as pathways in tributaries of the Wu River in Taichung, central Taiwan, were studied. Two river catchments of the Dali River were studied in greater detail to investigate the influence of land use on microplastics abundance along an urban-rural gradient, and to observe the change of microplastics abundance in the transition from rural to urban areas. Samples were taken from 41 different locations in urban and rural areas using a manta net with a mesh size of 0.3 mm. Results show abundances ranging from 0 pcs/m³ in unpopulated rural areas up to 230 pcs/m³ in densely populated urban centers, and are positively correlated with population density. Remarkably, a sharp increase in microplastics abundance was observed at the transition from rural to urban areas, which coincides with the appearance of storm sewers. Land use analysis revealed that microplastics abundance positively correlates with the size of industrial, residential and traffic areas in the catchment areas, and negatively correlates with the size of forest areas. Source areas for microplastics in the studied rivers are likely residential and commercial areas. Furthermore, the results of this study show that correlations between microplastics abundances and population density or land use patterns along urban-rural gradients are not trivial. Strength of correlations can depend on local factors or how well urban-rural gradients are developed. Absence of correlations need to be considered carefully, as existing correlations might be masked by the above-mentioned factors.

3.
Nat Sci Sleep ; 15: 1-12, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660440

RESUMO

Purpose: To compare peripapillary and macular vascular densities (PVDs and MVDs) between patients with obstructive sleep apnea/hypopnea syndrome (OSA) and control subjects with symptoms of sleep-related breathing disorders only by swept-source optical coherence tomography angiography (OCTA). Participants and Methods: In this prospective study, 192 participants underwent a full-night polysomnography to determine OSA severity and subsequently received OCTA measurements as well as AngioTool software analysis. Results: A total of 146 patients with OSA (51 mild, 43 moderate, 52 severe) and 24 control subjects (apnea/hypopnea index, AHI <5) were enrolled. PVDs and MVDs in the superficial and choroidal layers were significantly different among the four groups. When participants with simple snoring/mild OSA (AHI <15) were grouped together and compared with moderate/severe OSA (AHI ≥15), PVDs were significantly lower for the latter group in the superficial layer (p = 0.0003), deep layer (p = 0.004), and choroidal layer (p = 0.003). MVDs were also lower for the moderate/severe OSA group in the superficial (p = 0.012) and choroidal layer (p = 0.004). Negative correlations were identified between AHI and PVDs in the superficial layer (ρ = -0.257, p = 0.0007), deep layer (ρ = -0.197, p = 0.0102) and choroidal layer (ρ = -0.220, p = 0.0039) and between AHI and MVDs in the superficial layer (ρ = -0.199, p = 0.0094) and choroid layer (ρ = -0.186, p = 0.0152). Conclusion: PVDs and MVDs were significantly lower in patients with moderate/severe OSA as compared to subjects with simple snoring/mild OSA. Furthermore, decreased PVDs and MVDs significantly correlated with OSA severity.

4.
Ann Med ; 55(1): 168-174, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36519679

RESUMO

INTRODUCTION: Red blood cell (RBC) storage solution is used for suspending and preserving RBCs for later use in in vitro immunohematology testing. Proper RBC preservation is crucial for obtaining accurate results in RBC phenotyping and pretransfusion antibody screening tests. Haemolysis or RBC antigen degradation during storage can result in inaccurate RBC phenotyping, thereby decreasing the sensitivity of pretransfusion antibody screening and identification assays. The conventional RBC storage solutions usually contain adenosine, adenine, and antibiotics. We designed an RBC storage solution and determined whether it could preserve RBC integrity for 70 days. MATERIALS AND METHODS: The new storage solution has a different formula from that of the conventional solution-in particular, it is strengthened with polyethylene glycol (PEG). The extent of haemolysis and hemagglutination reactivity of the RBC antigen systems, Rh, Duffy, Kidd, Lewis, MNS, P1, and the rare antigen Mia (which has a low prevalence antigen in most parts of the world but a higher prevalence in Taiwan), in the new RBC storage solution was compared with that of the conventionally preserved RBC storage solution. RESULTS: The RBCs preserved in the new solution for 70 days retained a similar haemolysis grade as those preserved in the control solution for 28 days. Although both solutions largely preserved RBC antigenicity, the decline in RBC hemagglutination scores in new solution often occurred later than that in the control solution in most antigen phenotyping assays, especially labile antigens such as D, P1, and M. CONCLUSION: The new solution reduces haemolysis more effectively and preserves antigenicity throughout the 70-day storage period. Moreover, Mia antigen is more stable in the experimental group.


Assuntos
Preservação de Sangue , Hemólise , Humanos , Preservação de Sangue/métodos , Eritrócitos/metabolismo , Adenina/metabolismo , Taiwan
5.
J Biomed Mater Res B Appl Biomater ; 110(3): 527-534, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492134

RESUMO

For cardiopulmonary bypass, the polyvinyl chloride (PVC) circuit which can initiate the activation of platelets and the coagulation cascade after blood cell contacting is the possible detrimental effect. Surface coating of the PVC tubing system can be an effective approach to enhance circuit's hemocompatibility. In this study, aluminum oxide (Al2 O3 ) thin films were deposited through thermal atomic layer deposition (T-ALD) or plasma-enhanced ALD (PE-ALD) on PVC samples, and the anticoagulation of the Al2 O3 -coated PVC samples was demonstrated. The results revealed that Al2 O3 deposition through ALD increased surface roughness, whereas T-ALD had a relative hydrophilicity compared with blank PVC and PE-ALD. Whole blood immersion tests showed that blood clots formed on blank PVC and that a large amount of red blood cells was found on PE-ALD substrates, whereas less blood cells were noted in T-ALD samples. Both T-ALD and PE-ALD Al2 O3 films did not cause activation of blood cells, as evidenced in CD3+ /CD4+ /CD8+ , CD61+ /CD62P+ , and CD45+ /CD42b+ populations. Analysis of serum coagulation factors showed that a lower amount of prothrombin was absorbed on T-ALD Al2 O3 samples than that on blank PVC. For albumin and fibrinogen immersion tests, immunostaining and scanning electron microscopy further revealed that a thin albumin layer was absorbed on T-ALD Al2 O3 substrates but not on PVC samples. This study revealed that deposition of Al2 O3 films by T-ALD can improve anticoagulation of the PVC tubing system.


Assuntos
Óxido de Alumínio , Cloreto de Polivinila , Óxido de Alumínio/farmacologia , Anticoagulantes , Ponte Cardiopulmonar
6.
Mol Genet Metab Rep ; 33: 100942, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36466970

RESUMO

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an autosomal recessive urea cycle disorder with varying presentations. Patients with a neonatal-onset phenotype are initially healthy but develop severe hyperammonemia days after birth and often have poor or lethal outcomes, while patients who present later in life may exhibit less severe clinical manifestations. CPS1 deficiency is rarely found on newborn screening because most states do not screen for this disease due to the technical difficulties. We report a case of an 11-year-old, previously healthy girl who presented with hyperammonemia and acute psychosis after eating large amounts of meat at summer camp. A diagnosis of carbamoyl phosphate synthetase type 1 deficiency was suspected by biochemical profiles and confirmed by molecular analysis. Subsequent follow up lab results revealed ammonia to be only 25-39 µmol/L shortly after glutamine reached levels as high as 770-1432 µmol/L with concurrent alanine elevations, highlighting the compensating mechanisms of the human body. Her initial hospital course also demonstrated the importance of continuous renal replacement therapy (CRRT) in avoiding rebound hyperammonemia and high glutamine and the benefits of intracranial pressure (ICP) monitoring, providing 3% hypertonic saline and temperature control to avoid fever in treating cerebral edema. Carglumic acid was not considered helpful in this case, with BUN levels ranging between 2 and 4 mg/dL after administration.

7.
Nanomaterials (Basel) ; 12(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36558265

RESUMO

The SrZrTiO3 (SZT) thin film prepared by sol-gel process for the insulator of resistive random-access memory (RRAM) is presented. Al was embedded in the SZT thin film to enhance the switching characteristics. Compared with the pure SZT thin-film RRAM, the RRAM with the embedded Al in SZT thin film demonstrated outstanding device parameter improvements, such as a resistance ratio higher than 107, lower operation voltage (VSET = -0.8 V and VRESET = 2.05 V), uniform film, and device stability of more than 105 s. The physical properties of the SZT thin film and the embedded-Al SZT thin-film RRAM devices were probed.

8.
Asia Pac Psychiatry ; : e12525, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36584983

RESUMO

INTRODUCTION: The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019. METHODS: PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased. DISCUSSIONS: Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required.

9.
Sci Rep ; 12(1): 21139, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36477410

RESUMO

Coriander (Coriandrum sativum L.) contains abundant antioxidants and essential oils which can provide antibacterial, antifungal, and antioxidant activities in the pharmaceutical, health and food production industry. To improve the economic values of coriander, the relationships between optimal light treatments for maximizing both plant growth and the antioxidant and essential oil content of coriander leaves need to be determined. Plants were exposed to five light-emitting diodes spectral color mixtures, high blue light (BL) intensity induced the levels of reducing power response. The light treatments were then adjusted for the analysis of secondary metabolite compounds of coriander leaves. Among 30 identified compounds, the amounts of decamethyl-cyclopentasiloxane and dodecane were significantly reduced in the R80 + G50 + B50 condition, whereas dodecamethyl-cyclohexasiloxane level was significantly reduced in R50 + G50 + B80 condition. Various light quality and intensity combinations influenced the accumulations of chlorophyll and phytochemical contents, mediated antioxidative properties, and secondary metabolites of coriander leaves, which may be useful in developing a new LED lighting apparatus optimized for coriander production in plant factories.


Assuntos
Coriandrum , Antioxidantes
10.
Adv Mater ; : e2201058, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36414399

RESUMO

Interest in topological materials continues to grow unabated in view of their conceptual novelties as well as their potential as platforms for transformational new technologies. Electronic states in a topological material are robust against perturbations and support unconventional electromagnetic responses. The first-principles band-theory paradigm has been a key player in the field by providing successful prediction of many new classes of topological materials. This perspective presents a cross section through the recent work on understanding the role of geometry and topology in generating topological states and their responses to external stimuli, and as a basis for connecting theory and experiment within the band theory framework. In this work, effective strategies for topological materials discovery and impactful directions for future topological materials research are also commented.

11.
J Chin Med Assoc ; 85(11): 1038-1043, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343271

RESUMO

In mid-2022, the COVID-19 cases have reached close to 562 million, but its overall infection rate is hard to confirm. Even with effective vaccines, break-through infections with new variants occur, and safe and reliable testing still plays a critical role in isolation of infected individuals and in control of an outbreak of a COVID-19 pandemic. In response to this urgent need, the diagnostic tests for COVID-19 are rapidly evolving and improving these days. The health authorities of many countries issued requirements for detecting SARS-CoV-2 diagnosis tests during the pandemic and have timely access to these tests to ensure safety and effectiveness. In this study, we compared the requirements of EUA in Taiwan, Singapore, and the United States. For the performance evaluations of nucleic acid extraction, inclusivity, limit of detection (LoD), cross-reactivity, interference, cutoff, and stability, the requirements are similar in the three countries. The use of natural clinical specimens is needed for clinical evaluation in Taiwan and the United States. However, carry-over and cross-contamination studies can be exempted in Taiwan and the United States but are required in Singapore. This review outlines requirements and insight to guide the test developers on the development of IVDs. Considering the rapidly evolving viruses and severe pandemic of COVID-19, timely and accurate diagnostic testing is imperative to the management of diseases. As noted above, the performance requirements for SARS-CoV-2 nucleic acid tests are similar between Taiwan, Singapore and the United States. The differences are mainly in two points: the recommended microorganisms for cross-reactivity study, and the specimen requirement for clinical evaluation. This study provides an overview of current requirements of SARS-CoV-2 nucleic acid tests in Taiwan, Singapore, and the United States.


Assuntos
COVID-19 , Ácidos Nucleicos , Estados Unidos , Humanos , COVID-19/diagnóstico , Pandemias , SARS-CoV-2 , Teste para COVID-19 , Saúde Pública , Taiwan/epidemiologia , Singapura/epidemiologia
12.
BMC Sports Sci Med Rehabil ; 14(1): 194, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397168

RESUMO

BACKGROUND: Core exercise is often adopted as an adjunct in maintaining musculoskeletal health in rehabilitation; we previously showed that standing core rotational exercise improves femoral blood flow after training. This study aimed to investigate the effects of different rotational cadences on circulatory and hemodynamic responses after acute standing core exercise. METHODS: Sixteen healthy male adults (22 ± 1 yrs) were randomly assigned to participate in two 30-min standing core exercises of fast (75 rpm, FC) and slow cadence (20 rpm, SC) sessions after completing an acute bout of seated knee extension exercise session (KE) (80% of 1 repetition maximum × 12 repetitions × 3 sets). Impedance cardiography-derived circulatory responses and femoral hemodynamics by ultrasound imaging were measured pre- and 30, and 60 min post-exercise. RESULTS: KE acutely increased post-exercise cardiac output at 30 min (p = 0.008) and heart rate at 30 min (p = 0.04) and 60 min (p = 0.01), yet brachial blood pressure did not change. Systemic vascular resistance was significantly lower after FC and KE at 30 min (p = 0.008) and 60 (p = 0.04) min, respectively, compared with the baseline. In addition, KE acutely decreased post-exercise arterial stiffness (p = 0.05) at 30 min, increased femoral conductance (p = 0.03, p < 0.001), and blood flow (p = 0.009, p < 0.001) at 30 and 60 min. No significant changes were observed in absolute femoral blood flow after FC and SC, except that FC significantly increased relative femoral blood flow (p = 0.007) and conductance (p = 0.005). Post-exercise femoral diameter significantly increased in KE at 30 (p = 0.03) and 60 min (p = 0.01), but not in core exercise. CONCLUSION: Our results suggest that standing core exercise elicits circulatory and hemodynamic changes only when the rotational cadence is set at a faster cadence, which provides preliminary scientific evidence for its use in exercise programs.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36367914

RESUMO

Spasticity is a common complication for patients with stroke, but only few studies investigate the relation between spasticity and voluntary movement. This study proposed a novel automatic system for assessing the severity of spasticity (SS) of four upper-limb joints, including the elbow, wrist, thumb, and fingers, through voluntary movements. A wearable system which combined 19 inertial measurement units and a pressure ball was proposed to collect the kinematic and force information when the participants perform four tasks, namely cone stacking (CS), fast flexion and extension (FFE), slow ball squeezing (SBS), and fast ball squeezing (FBS). Several time and frequency domain features were extracted from the collected data, and two feature selection approaches based on recursive feature elimination were adopted to select the most influential features. The selected features were input into five machine learning techniques for assessing the SS for each joint. The results indicated that using CS task to assess the SS of elbow and fingers and using FBS task to assess the SS of thumb and wrist can reach the highest weighted-average F1-score. Furthermore, the study also concluded that FBS is the optimal task for assessing all the four upper-limb joints. The overall result shown that the proposed automatic system can assess four upper-limb joints through voluntary movements accurately, which is a breakthrough of finding the relation between spasticity and voluntary movement.

14.
Eur J Oncol Nurs ; 61: 102225, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332455

RESUMO

PURPOSE: This study aimed to assess the 5-year survival, quality of life for cancer- and lung-specific symptoms, and to identify predictive factors of quality of life during a 12-month period after video-assisted thoracic surgery (VATS) for early-stage lung adenocarcinoma. METHODS: A convenience sample of 53 patients who had undergone VATS for lung cancer was used for this longitudinal, prospective study. All participants provided responses to the cancer-specific quality-of-life European Organization for Research and Treatment of Cancer questionnaire as well as a questionnaire for lung cancer-specific symptoms using structured interviews at baseline (T0) and 3-, 6-, 9-, and 12-months post-surgery (T1, T2, T3, and T4, respectively). Generalized estimating equation models were used to investigate whether quality of life scores improved from baseline measures and to determine characteristics associated with changes in scores for quality-of-life post-surgery. RESULTS: The mean age of participants was 58.5 years (SD = 8.76), and most were female (64.2%). Participants received either a wedge or sublobular lobectomy (47.2%) or a lobectomy (52.8%). The size of the primary tumour for most participants was <2 cm (78.7%). The five-year survival rate was 90%. Lung-specific symptoms of insomnia were worse at T1 compared with baseline. Significant improvements in scores for function and cancer symptoms were seen at T4 compared with scores at T0. Age, marital status, smoking, alcohol consumption, and a history of previous cancer were significantly associated with quality of life. CONCLUSIONS: Surgical resection with VATS resulted in good 5-year survival rates and long-term improvements in quality of life. Our findings suggest VATS for patients with early-stage lung adenocarcinoma should be considered as a means of improving long-term survival and quality of life.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Qualidade de Vida , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Pneumonectomia/métodos , Estudos Longitudinais , Estudos Prospectivos , Estadiamento de Neoplasias , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia
15.
Cells ; 11(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36428973

RESUMO

Arterial stiffness is a reliable independent predictor of cardiovascular events. Exercise training might enhance arterial compliance through improved metabolic health status. Different modes of exercise may have different effects on arterial stiffness. However, the interactions among different modes of exercise on endothelial senescence, the development of arterial vascular stiffness, and the associated molecular mechanisms are not completely understood. In this narrative review, we evaluate the current evidence focusing on the effects of various exercise modes on arterial stiffness and vascular health, and the known underlying physiological mechanisms are discussed as well. Here, we discuss the most recent evidence of aerobic exercise, high-intensity interval training (HIIT), and resistance exercise (RE) on arterial stiffness and endothelial senescence in physiological and cellular studies. Indeed, aerobic, HIIT, and progression RE-induced arterial compliance may reduce arterial stiffness by effectively promoting nitric oxide (NO) bioavailability and reducing endothelial senescence. However, the transient increase in inflammation and sympathetic activation may contribute to the temporary elevation in arterial stiffness following whole-body high-intensity acute resistance exercise.


Assuntos
Rigidez Vascular , Exercício Físico , Artérias , Nível de Saúde , Senescência Celular
16.
Nat Commun ; 13(1): 6046, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266271

RESUMO

In one-dimensional (1D) systems, electronic interactions lead to a breakdown of Fermi liquid theory and the formation of a Tomonaga-Luttinger Liquid (TLL). The strength of its many-body correlations can be quantified by a single dimensionless parameter, the Luttinger parameter K, characterising the competition between the electrons' kinetic and electrostatic energies. Recently, signatures of a TLL have been reported for the topological edge states of quantum spin Hall (QSH) insulators, strictly 1D electronic structures with linear (Dirac) dispersion and spin-momentum locking. Here we show that the many-body interactions in such helical Luttinger Liquid can be effectively controlled by the edge state's dielectric environment. This is reflected in a tunability of the Luttinger parameter K, distinct on different edges of the crystal, and extracted to high accuracy from the statistics of tunnelling spectra at tens of tunnelling points. The interplay of topology and many-body correlations in 1D helical systems has been suggested as a potential avenue towards realising non-Abelian parafermions.

17.
Curr Oncol ; 29(10): 6956-6967, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36290824

RESUMO

(1) Background: To investigate the contralateral neck failure (cRF) rates and outcomes among patients with well-lateralized locally advanced oral cavity squamous cell carcinoma (OSCC) with/without ipsilateral or bilateral neck adjuvant irradiation. (2) Methods: Patients with lateralized OSCC diagnosed between 2007 and 2017 were retrospectively enrolled. Patients who had undergone curative surgery with pathologically proven pT3/4 or pN0-2b without distant metastasis were included, while those with cross-midline, neck-level 1a involvement and positive extra-nodal extension (ENE) were excluded. The primary endpoint was the cumulative incidence of 5-year cRF as the first site of failure. The secondary endpoints included cancer-specific survival (CSS), local-regional recurrence-free survival (LRRFS), distant-metastasis-free survival (DMFS), and contralateral-regional recurrence-free survival (cRRFS). (3) Results: In total, 149 patients were analyzed with a median follow-up time of 5.2 years (range, 2.91-7.83). Pathological stages T3 and T4 were 22.7% and 56.8%, respectively. Pathologically negative and positive lymph nodes were 61.4% and 38.6%, respectively. The cumulative 5-year cRF rate was 3.6% (95% CI, 1.3-7.7%). No significant differences in the 5-year CSS, LRRFS, DMFS, and cRRFS were observed among those undergoing unilateral or bilateral neck irradiation. Five patients (3.4%) had contralateral neck recurrence, all simultaneously with local recurrence. No isolated contralateral neck recurrence was identified. (4) Conclusions: The cRF rate was acceptably low in patients with well-lateralized advanced OSCC with the initially uninvolved contralateral neck. Omitting contralateral neck irradiation with active surveillance could be considered without compromising the cure rate in locally advanced OSCC patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Estudos Retrospectivos , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia
18.
Nat Struct Mol Biol ; 29(11): 1043-1055, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36303034

RESUMO

It is estimated that 10%-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, systematic diagnosis or prediction of splicing variants is yet to be established, especially for the near-exon intronic splice region. The major challenge lies in the redundant and ill-defined branch sites and other splicing motifs therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants that overlapped with branch sites and collected 5,884 variants across the 5' splice region. We found that strong splice sites and exonic features preserve splicing from intronic sequence variation. Whereas the splice-altering mechanism of the 3' intronic variants is complex, that of the 5' is mainly splice-site destruction. Statistical learning combined with these molecular features allows precise prediction of altered splicing from an intronic variant. This statistical model provides the identity and ranking of biological features that determine splicing, which serves as transferable knowledge and out-performs the benchmarking predictive tool. Moreover, we demonstrated that intronic splicing variants may associate with disease risks in the human population. Our study elucidates the mechanism of splicing response of intronic variants, which classify disease-associated splicing variants for the promise of precision medicine.


Assuntos
Processamento Alternativo , Sítios de Splice de RNA , Humanos , Íntrons/genética , Splicing de RNA/genética , Éxons/genética , Mutação
19.
Clin Med Insights Oncol ; 16: 11795549221123617, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36134036

RESUMO

Background: Palliative chemotherapy is the preferred standard of care for patients with metastatic gastric cancer (mGC). It remains uncertain whether older patients with mGC would benefit from palliative chemotherapy. This study aimed to investigate the clinical impact of palliative chemotherapy in older patients with mGC. Methods: This single-institute, retrospective, and real-world study included 428 patients with mGC between January 2009 and December 2019. Among them, 306 who received palliative chemotherapy were further stratified into 2 groups according to age: ≤70 (n = 236) and >70 (n = 70) years. The clinical demographics, outcomes, and hematologic toxicities of chemotherapy were compared between the 2 groups. Prognostic factors were determined using the Cox proportional hazards model. Results: Of the screened 428 patients, older patients had worse overall survival (OS) than younger patients. Among patients who received chemotherapy (n = 306), patients aged >70 and ⩽70 years had comparable progression-free survival (PFS) and OS. The incidence of severe hematologic toxicity was similar between the 2 groups. The Eastern Cooperative Oncology Group performance status of 2 or more metastatic sites, elevated carbohydrate antigen 19-9 level, high neutrophil-to-lymphocyte ratio (NLR), and undergoing palliative gastrectomy were independent prognostic factors for OS. Notably, age >70 years was not a significant factor for poor OS. Conclusions: Older age of >70 years might not be considered an obstacle to administering palliative chemotherapy to patients with mGC.

20.
Nanomaterials (Basel) ; 12(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36145040

RESUMO

We enhanced the device uniformity for reliable memory performances by increasing the device surface roughness by exposing the HfO2 thin film surface to argon (Ar) plasma. The results showed significant improvements in electrical and synaptic properties, including memory window, linearity, pattern recognition accuracy, and synaptic weight modulations. Furthermore, we proposed a non-identical pulse waveform for further improvement in linearity accuracy. From the simulation results, the Ar plasma processing device using the designed waveform as the input signals significantly improved the off-chip training and inference accuracy, achieving 96.3% training accuracy and 97.1% inference accuracy in only 10 training cycles.

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