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1.
Lancet Reg Health West Pac ; 47: 101096, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38808021

RESUMO

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods: This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 × 109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50 × 109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50 × 109/L or ≥100 × 109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30 × 109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings: From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT ≥50 × 109/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50 × 109/L or ≥100 × 109/L or an increase twice more than baseline as well as ≥30 × 109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates. Interpretation: This study preliminarily confirmed that 100 mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. Funding: National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

2.
J Pharm Biomed Anal ; 245: 116162, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38678857

RESUMO

Ritonavir, an excellent inhibitor of CYP3A4, has recently been combined with nirmatrelvir to form Paxlovid for the treatment of severe acute respiratory syndrome coronavirus 2 infections. The root of Scutellaria baicalensis Georgi (S. baicalensis), a traditional Chinese medicinal (TCM) herb commonly used to treat heat/inflammation in the lung and digestive tracts, which are major organs targeted by viral infections, contains flavones that can influence the CYP3A metabolism pathway. To investigate the ability of ritonavir to cross the bloodbrain barrier (BBB) and its potential herb-drug interactions with an equivalent TCM clinical dose of S. baicalensis, multisite microdialysis coupled with an LCMS/MS system was developed using rat model. Pretreatment with S. baicalensis extract for 5 days, which contains less flavones than those used in previous studies, had a significant influence on ritonavir, resulting in a 2-fold increase in the total concentration of flavones in the blood and brain. Treatment also boosted the maximum blood concentration of flavones by 1.5-fold and the maximum brain concentration of flavones by 2-fold, all the while exerting no noticeable influence on the transfer ratio across the bloodbrain barrier. These experimental results demonstrated that the use of a typical traditional Chinese medicinal dose of S. baicalensis is sufficient to influence the metabolic pathway and synergistically increase the concentration of ritonavir in rats.


Assuntos
Antivirais , Barreira Hematoencefálica , Interações Ervas-Drogas , Microdiálise , Extratos Vegetais , Ratos Sprague-Dawley , Ritonavir , Scutellaria baicalensis , Animais , Ritonavir/farmacocinética , Ritonavir/farmacologia , Scutellaria baicalensis/química , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Ratos , Microdiálise/métodos , Masculino , Antivirais/farmacocinética , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem/métodos , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem
4.
Clin Lymphoma Myeloma Leuk ; 24(6): e257-e266, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461040

RESUMO

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.


Assuntos
Dasatinibe , Mesilato de Imatinib , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Dasatinibe/uso terapêutico , Dasatinibe/farmacologia , Mesilato de Imatinib/uso terapêutico , Mesilato de Imatinib/farmacologia , Adulto , Idoso , Pirimidinas/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Resultado do Tratamento , Adulto Jovem , Adolescente , Benzamidas/uso terapêutico , Idoso de 80 Anos ou mais , Aminopiridinas
5.
Opt Lett ; 49(3): 550-553, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300056

RESUMO

Femtosecond laser filament-induced plasma spectroscopy (FIPS) demonstrates great potential in remote sensing for identifying atmospheric pollutant molecules. Due to the widespread aerosols in the atmosphere, remote detection based on FIPS would be affected by both the excitation and the propagation of fingerprint fluorescence, which still remain elusive. Here the physical model of filament-induced aerosol fluorescence is established to reveal the combined effect of Mie scattering and amplification spontaneous emission, which is subsequently proven by experimental results, the dependence of the backward fluorescence on the interaction length between filaments and aerosols. These findings provide an insight into the complicated aerosol effect in the overall physical process of FIPS including propagation, excitation, and emission, paving the way to its practical application in atmospheric remote sensing.

6.
Lancet Oncol ; 25(1): 117-125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092009

RESUMO

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.


Assuntos
Linfoma de Células T Periférico , Adulto , Humanos , Masculino , Feminino , Adolescente , Pessoa de Meia-Idade , Linfoma de Células T Periférico/tratamento farmacológico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Progressão da Doença , Janus Quinase 1/genética , Tirosina/uso terapêutico
7.
J Biochem Mol Toxicol ; 38(1): e23590, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037286

RESUMO

Polo-like kinase 1 (PLK1) inhibitor NMS-P937 is a targeted therapeutic agent with good preclinical efficacy in various human cancers, and its therapeutic effect on nasopharyngeal carcinoma (NPC) remains to be determined. Here, to explore biological activity of NMS-P937 in NPC, multiple types of NPC cells were utilized. We tested IC50 values, carried out flow cytometry, western blot analysis analysis, immunofluorescence, and constructed subcutaneous xenograft mouse models. We found that treatment with NMS-P937 increased the proportion of G2/M phase NPC cells, where CyclinB1 expression was upregulated and CyclinE1 expression was downregulated. Besides, NMS-P937 treatment-induced NPC cell apoptosis with increased cleavage of PARP and caspase-3. Mechanistically, NMS-P937 treatment led to aberrant mitosis, causing increased reactive oxygen species (ROS) levels. ROS scavenger N-acetylcysteine partially reversed ROS levels induced by NMS-P937. Furthermore, NMS-P937 administration restrained NPC xenografts growth in nude mice. Overall, NMS-P937 suppressed NPC cell proliferation and increased ROS levels, causing cell cycle abnormalities and apoptosis. NMS-P937 holds great promise as a therapeutic agent for treating nasopharyngeal carcinoma.


Assuntos
Neoplasias Nasofaríngeas , Quinase 1 Polo-Like , Pirazóis , Quinazolinas , Humanos , Camundongos , Animais , Carcinoma Nasofaríngeo/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Nasofaríngeas/metabolismo , Apoptose
8.
Oncol Ther ; 12(1): 131-145, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38104036

RESUMO

INTRODUCTION: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. METHODS: Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. RESULTS: Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group. CONCLUSIONS: Overcoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05092048.

9.
Biomed Pharmacother ; 170: 116077, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38154274

RESUMO

Hepatitis D virus (HDV), which co-infects or superinfects patients with hepatitis B virus, is estimated to affect 74 million people worldwide. Chronic hepatitis D is the most severe form of viral hepatitis and can result in liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Currently, there are no efficient HDV-specific drugs. Therefore, there is an urgent need for novel HDV therapies that can achieve a functional cure or even eliminate the viral infection. In the HDV life cycle, agents targeting the entry step of HDV infection preemptively reduce the intrahepatic viral RNA. Human sodium taurocholate co-transporting polypeptide (hNTCP), a transporter of bile acids on the plasma membrane of hepatocytes, is an essential entry receptor of HDV and is a promising molecular target against HDV infection. Here, we investigated the effect of ergosterol peroxide (EP) on HDV infection in vitro and in vivo. EP inhibited HDV infection of hNTCP-expressing dHuS-E/2 hepatocytes by interrupting the early fusion/endocytosis step of HDV entry. Furthermore, molecular modeling suggested that EP hinders LHBsAg binding to hNTCP by blocking access to S267 and V263. In addition, we generated hNTCP-expressing transgenic (Tg) C57BL/6 mice using the Cre/loxP system for in vivo study. EP reduced the liver HDV RNA level of HDV-challenged hNTCP-Cre Tg mice. Intriguingly, EP downregulated the mRNA level of liver IFN-γ. We demonstrate that EP is a bona fide HDV entry inhibitor that acts on hNTCP and has the potential for use in HDV therapies.


Assuntos
Carcinoma Hepatocelular , Hepatite D , Neoplasias Hepáticas , Simportadores , Camundongos , Animais , Humanos , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos C57BL , Hepatite D/tratamento farmacológico , Hepatite D/patologia , Vírus da Hepatite B/fisiologia , Hepatócitos , Camundongos Transgênicos , Simportadores/metabolismo
10.
Int J Mol Sci ; 24(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38068895

RESUMO

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.


Assuntos
Endotoxemia , Kadsura , Lignanas , Piper , Camundongos , Animais , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Kadsura/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Interleucina-6/genética , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Lignanas/uso terapêutico
11.
J Orthop Surg Res ; 18(1): 945, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071288

RESUMO

BACKGROUND: Controversies regarding the optimal internal fixation method for posterior sternoclavicular dislocation (SCD) exist. Therefore, this study aimed to investigate the clinical efficacy of a new type of sternoclavicular hook plate for treating posterior SCD. METHODS: Eleven patients (eight men and three women) with posterior SCD who underwent treatment with the new sternoclavicular hook plate from June 2011 to January 2022 were retrospectively analyzed. The patients' ages ranged from 33 to 71 years (54.91 ± 13.58 years). Operation time, blood loss, length of hospital stay, and postoperative complications were recorded. Postoperative joint reduction and healing were evaluated using radiography and computed tomography. The Constant-Murley and Rockwood sternoclavicular joint scores were used to evaluate the functional recovery of the affected limb 12 months after surgery. RESULTS: All 11 patients were followed up for 12-24 months (18.00 ± 3.74 months). All incisions healed by first intention. The healing time ranged from 9 to 13 days (10.82 ± 1.54 days), and the joint healing time was 3-4 months (3.55 ± 0.52 months). The operation time was 45-75 min (59.55 ± 11.06 min), intraoperative blood loss was 22-58 mL (39.91 ± 11.07 mL), and the length of hospitalization was 6-14 days (9.91 ± 3.27 days). There were no complications such as infections, internal fixation failure, or nerve injury. The Constant-Murley score was 93.64 ± 9.01 at 12 months postoperatively. The Rockwood score was 13.36 ± 1.86, of which nine cases were excellent, one case was good, and one case was fair. CONCLUSION: The novel sternoclavicular hook plate is effective for the treatment of posterior SCD. This novel device can facilitate early joint functional exercises and good functional recovery.


Assuntos
Articulação Acromioclavicular , Luxações Articulares , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Fixação Interna de Fraturas/métodos , Placas Ósseas , Resultado do Tratamento
12.
Opt Express ; 31(17): 28586-28595, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710909

RESUMO

In this work, sub-ppb aerosol detection is achieved by femtosecond laser filament with a single pulse energy of 4 mJ at a distance of 30 m. A concave mirror with an open aperture of 41.4 cm is employed in an off-axis optical system to focus the femtosecond laser beam and collect the fluorescence of NaCl aerosol. The simulation and experimental results show that the astigmatism can be greatly reduced when femtosecond laser beam is incident non-symmetrically on the concave mirror. Compared with the case that femtosecond laser strikes at the center of the concave mirror, the intensity of acoustic signal emitted from the optical filament is increased by 69.5 times, and the detection of limit of sodium element in aerosol is reduced by 86%, which is down to 0.32 ppb. The improved excitation scheme in this work utilizes the nonsymmetrical beam spot on the concave mirror to compensate the non-symmetry induced by the off-axis setup, reducing the astigmatism of the focusing laser beam and decreasing the sodium chloride aerosol's detection of limit.

14.
Nanoscale ; 15(31): 12907-12914, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37435813

RESUMO

Deep-subwavelength features have a minimal impact on wave transport in all dielectric systems; thus the homogenization approach was commonly adopted. Recently, the breakdown of effective medium theory (EMT) for the incident wave near the total reflection (TR) angle was demonstrated in a deep-subwavelength dielectric multilayer. Additionally, anomalous transmission was reported at angles exceeding the TR angle when introducing disorder and was attributed to Anderson localization. Here we firstly demonstrated that the alleged anomalous transmission also occurs in the disorder-free case, illustrating that attributing anomalous transmission to Anderson localization deserves a more in-depth study. To clarify the underlying physics of this asserted anomalous transmission, Anderson localization and broken EMT, the incident angle dependent reflectivity and modes for ordered and disordered deep-subwavelength multilayers were investigated systematically. Actually, the EMT is still convincing and the anomalous transmission is reasonable after a simple correction. However, the anomalous transmission is more accessible and the permittivity correction is more imperative in the disordered system due to the Anderson localization. These findings can be expanded to other wave systems such as acoustic waves and matter waves, providing insight into EMT and deepening our understanding of the intriguing transport phenomena in deep subwavelength systems.

15.
Leuk Lymphoma ; 64(8): 1458-1464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37282611

RESUMO

The experience of a physician at a clinical center is among the critical factors in managing chronic myeloid leukemia (CML) during its treatment with tyrosine kinase inhibitors (TKIs). The authors conducted a cross-sectional questionnaire to investigate barriers to physician use of published evidence-based guidelines in CML management in a real-world setting. Among the participating physicians (N = 407), 99.8% of physicians reported that CML guidelines were useful; however, only 62.9% of physicians reported that they follow guidelines in real-time. Although 90.7% of physicians prefer second-generation TKIs as the first-line treatment, imatinib (88.2%) remains the most widely administered TKI in the first-line setting. Only 50.6% of physicians switched the treatment when patients failed to achieve early molecular response (at 3 months), whereas 70.3% of physicians switched the treatment when patients' response to TKI was inadequate at 6 months and/or 12 months. Moreover, only 43.5% of physicians considered treatment-free remission (TFR) as one of the top 3 goals for their patients. The major concern to obtain TFR was patients' adherence. This study demonstrated that CML management was generally in line with the current guidelines, but some of the details at the point of care are needed to be improved in CML.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Transversais , Fidelidade a Diretrizes , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
17.
Opt Express ; 31(6): 9224-9235, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157496

RESUMO

This paper reports a multi-functional terahertz (THz) metamaterial based on a nano-imprinting method. The metamaterial is composed of four layers: 4 L resonant layer, dielectric layer, frequency selective layer, and dielectric layer. The 4 L resonant structure can achieve broadband absorption, while the frequency selective layer can achieve transmission of specific band. The nano-imprinting method combines electroplating of nickel mold and printing of silver nano-particle ink. Using this method, the multilayer metamaterial structures can be fabricated on ultrathin flexible substrates to achieve visible light transparency. For verification, a THz metamaterial with broadband absorption in low frequency and efficient transmission in high frequency is designed and printed. The sample's thickness is about 200 µm and area is 65 × 65 mm2. Moreover, a fiber-based multi-mode terahertz time-domain spectroscopy system was built to test its transmission and reflection spectra. The results are consistent with the expectations.

19.
Opt Express ; 31(4): 6464-6474, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36823901

RESUMO

An optimized remote material detection scheme based on the laser filament-induced plasma spectroscopy and light detection and ranging (FIPS-LIDAR) is proposed in this work. The elemental composition and concentration of aerosol are measured by FIPS-LIDAR. By focusing the femtosecond laser with a large aperture (Φ41 cm) concave mirror and coaxial fluorescence collection scheme, the remote detection of aerosol in air at µg/m3 level has been realized at a distance of 30 m. The limit of detection for Na+ in aerosol droplets is 8 ppm (3 µg/m3 in air), which is the lowest detection limit that has been reported using millijoule femtosecond laser pulse (4.4 mJ). Furthermore, using spectral preprocessing and optimization of the proposed significance of peak (SOP) algorithm, feature peak signals are extracted from weak signals and the limit of detection can be further decreased to 1.4 µg/m3.

20.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36592062

RESUMO

Recent studies have revealed that long noncoding RNAs (lncRNAs) are closely linked to several human diseases, providing new opportunities for their use in detection and therapy. Many graph propagation and similarity fusion approaches can be used for predicting potential lncRNA-disease associations. However, existing similarity fusion approaches suffer from noise and self-similarity loss in the fusion process. To address these problems, a new prediction approach, termed SSMF-BLNP, based on organically combining selective similarity matrix fusion (SSMF) and bidirectional linear neighborhood label propagation (BLNP), is proposed in this paper to predict lncRNA-disease associations. In SSMF, self-similarity networks of lncRNAs and diseases are obtained by selective preprocessing and nonlinear iterative fusion. The fusion process assigns weights to each initial similarity network and introduces a unit matrix that can reduce noise and compensate for the loss of self-similarity. In BLNP, the initial lncRNA-disease associations are employed in both lncRNA and disease directions as label information for linear neighborhood label propagation. The propagation was then performed on the self-similarity network obtained from SSMF to derive the scoring matrix for predicting the relationships between lncRNAs and diseases. Experimental results showed that SSMF-BLNP performed better than seven other state of-the-art approaches. Furthermore, a case study demonstrated up to 100% and 80% accuracy in 10 lncRNAs associated with hepatocellular carcinoma and 10 lncRNAs associated with renal cell carcinoma, respectively. The source code and datasets used in this paper are available at: https://github.com/RuiBingo/SSMF-BLNP.


Assuntos
RNA Longo não Codificante , Humanos , Algoritmos , Biologia Computacional/métodos , RNA Longo não Codificante/genética , Software , Carcinoma Hepatocelular/genética , Carcinoma de Células Renais/genética , Neoplasias Hepáticas/genética , Neoplasias Renais/genética
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