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1.
Front Plant Sci ; 15: 1320109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444529

RESUMO

Introduction: Soybean pod count is one of the crucial indicators of soybean yield. Nevertheless, due to the challenges associated with counting pods, such as crowded and uneven pod distribution, existing pod counting models prioritize accuracy over efficiency, which does not meet the requirements for lightweight and real-time tasks. Methods: To address this goal, we have designed a deep convolutional network called PodNet. It employs a lightweight encoder and an efficient decoder that effectively decodes both shallow and deep information, alleviating the indirect interactions caused by information loss and degradation between non-adjacent levels. Results: We utilized a high-resolution dataset of soybean pods from field harvesting to evaluate the model's generalization ability. Through experimental comparisons between manual counting and model yield estimation, we confirmed the effectiveness of the PodNet model. The experimental results indicate that PodNet achieves an R2 of 0.95 for the prediction of soybean pod quantities compared to ground truth, with only 2.48M parameters, which is an order of magnitude lower than the current SOTA model YOLO POD, and the FPS is much higher than YOLO POD. Discussion: Compared to advanced computer vision methods, PodNet significantly enhances efficiency with almost no sacrifice in accuracy. Its lightweight architecture and high FPS make it suitable for real-time applications, providing a new solution for counting and locating dense objects.

2.
Opt Express ; 31(25): 42464-42477, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087620

RESUMO

In ptychography, the translation position error will cause the periodic grid deviation and tremendously decrease the reconstruction quality. It is crucial to attain the precise translation position of the probe with respect to the object. The current correction methods may fall into a local optimal value, and miss the better results. An accurate method based on the quantum particle swarm optimization is proposed to globally correct the translation position error and add the randomness to avoid trapping in local optimum. In our proposed method, particles in a quantum bound state can appear at any point in the solution space with a certain probability density. In order words, the corrected translation position can be spread over the searching space, which can acquire the possibility of jumping out of the local optimum. Experiments are conducted to verify that our proposed method can be used to enhance the correction accuracy of the translation position error as well as avoid local optimum.

3.
Opt Express ; 31(22): 36754-36769, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017819

RESUMO

This paper proposes a high-precision phase retrieval method based on deep learning to extract the Zernike coefficients from a single-frame interferogram with an irregular-shaped aperture. Once the Zernike coefficients are obtained, the phase distribution can be retrieved directly using the Zernike polynomials. For many apertures, the root mean square (RMS) of the residual wavefront between the true and estimated wavefronts reached the order of 10-3 λ. Simulations were conducted under different noise conditions, indicating that the proposed method has high measurement accuracy and robustness. Experiments demonstrated that the accuracy achieved by this method was comparable to that of commercial phase-shifting interferometers. We believe that this method is useful for measuring optical surfaces with irregular apertures.

4.
Opt Express ; 31(18): 28954-28962, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710704

RESUMO

Orbital angular momentum (OAM) interferometers have attracted great attention in metrology. However, OAM interferometers usually have large sizes and are difficult to align. OAM-based wavefront-splitting interferometer (WSI-OAM) can achieve nano-displacement measurement with compact size and easy to align. In this manuscript, we propose and demonstrate a nano-displacement measurement system based on WSI-OAM. A resolution of 0.1 nm with an uncertainty of 0.013 nm is achieved with measurement accuracy higher than 99.87% and linearity close to 99%. This work offers a practical approach to miniaturize and integrate OAM interferometers in metrology.

5.
Sci Rep ; 13(1): 4311, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922519

RESUMO

B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan-Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/patologia , Carcinoma de Células Escamosas/patologia , Prognóstico
6.
Curr Stem Cell Res Ther ; 18(8): 1056-1068, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36597604

RESUMO

Mesenchymal stem cells (MSCs) are getting attention in the field of cancer immunotherapy. The main effects of MSCs on tumors are homing and regulation of inflammatory and immune responses. Indeed, cancer immunotherapy has become a promising treatment and MSCs play a potential role in regulating the efficacy of immunotherapy. In addition, MSCs are an ideal carrier for immunomodulatory protein transmission. As such MSCs combined with immunotherapy drugs could act synergistically against tumors, throwing a great impact on cancer therapy. And MSCs may have potential in the treatment of cytokine storm or cytokine release syndrome (CRS). It is assumed that MSCs can form chimeric antigen receptor MSCs (CAR-MSCs). Whether CAR-MSCs can provide a new idea of cancer immunotherapy is unknown. It is a prime time to review the latest progress of MSCs in cancer immunotherapy, in order to clarify to fully understand the role of MSCs in cancer therapy in clinical practice.


Assuntos
Células-Tronco Mesenquimais , Neoplasias , Humanos , Imunoterapia , Imunomodulação , Neoplasias/terapia , Neoplasias/metabolismo , Síndrome da Liberação de Citocina , Células-Tronco Mesenquimais/metabolismo , Imunoterapia Adotiva
7.
Artigo em Inglês | MEDLINE | ID: mdl-36503447

RESUMO

BACKGROUND: Immune cell infiltration is an important component of nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to explore novel genes associated with immune infiltration in the progression of NAFLD. METHODS: CIBERSORT was used to evaluate the abundance of immune infiltration in the human NAFLD via a high-throughput sequencing dataset. Further weighted gene co-expression network analysis (WGCNA) was performed to search for the susceptibility gene module and hub genes associated with differential immune cells. The expression of hub genes in different liver non-parenchymal cell clusters and NAFLD-associated hepatocellular carcinoma (HCC) was also explored. RESULTS: Four hub genes (ITGBL1, SPINT1, COL1A2, and THBS2) were ultimately identified, which may be associated with immune infiltration, fibrosis progression, and activity score. The receiver operating characteristic curve (ROC) analysis suggested that these genes had good predictive value for NASH and advanced fibrosis. A single-cell analysis showed that COL1A2 was highly expressed in hepatic stellate cells (HSCs), especially in the later stage, while SPINT1 was highly expressed in cholangiocytes (Cho). In addition, ITGBL1, COL1A2, and THBS2 might be associated with transforming from nonalcoholic steatohepatitis (NASH) to HCC. Our findings identified several novel genes that might be related to immune infiltration in NAFLD. CONCLUSION: These genes may serve as potential markers for the assessment of immune infiltration as well as therapeutic targets for NAFLD. More studies are needed to elucidate the biological mechanism of these genes in the occurrence and development of NAFLD.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Fibrose , Integrina beta1
8.
Blood Adv ; 6(24): 6263-6270, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36083121

RESUMO

Chronic graft-versus-host disease (cGVHD) of the lung, or bronchiolitis obliterans syndrome (BOS), is a high-risk disease manifestation associated with poor outcomes. Currently available treatments have demonstrated limited clinical efficacy in this setting. Belumosudil is a novel oral selective rho-associated coiled-coil-containing protein kinase-2 inhibitor that was recently approved by the US Food and Drug Administration in the treatment of cGVHD. We identified 59 subjects with BOS who were enrolled and treated in 2 prospective clinical trials of belumosudil. Patients with BOS had a percentage predicted forced expiratory volume in 1 second (FEV1) of ≤79% at enrollment and clinician attribution of lung disease owing to cGVHD. The National Institutes of Health (NIH) cGVHD lung scores at enrollment were 1 (n = 30, 59%), 2 (n = 23, 39%), or 3 (n = 6, 10%). According to NIH response criteria, the best overall response rate (ORR) for lung cGVHD was 32% (partial response: 17%; complete response: 15%). Response rates were inversely proportional to baseline NIH GVHD lung score at enrollment (lung score 1: ORR 50%; lung score 2: ORR 17%, lung score 3: ORR 0%) (P = .006). In multivariable analysis, male sex, lower baseline NIH cGVHD lung score, and partial response to previous line of cGVHD therapy before enrollment were associated with higher rates of lung-specific response. No significant correlation was identified between pulmonary function evaluations and measures of patient symptoms (NIH lung symptom score or Lee Symptom Scale score for lung). In conclusion, belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease. Optimization of treatment response evaluations remains a challenge in patients with BOS.


Assuntos
Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Prospectivos
9.
Sci Rep ; 12(1): 13887, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974063

RESUMO

To explore the effect of prior thyroid cancer on the survival of primary liver cancer (PLC). Eligible PLC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2016. Propensity score matching (PSM) was used to create a highly comparable control group that PLC patients without prior thyroid cancer. All PLC patients were divided into three groups based on the survival information: (1) PLC-specific death; (2) death due to other causes; (3) alive. The effect sizes were presented by the corresponding hazard ratio (HR) and 95% confidence intervals (CI). Totally, 142 PLC patients with prior thyroid cancer and 1420 PLC patients without prior thyroid cancer were included. During the follow-up period, 714 (45.71%) PLC patients died of liver cancer while 638 (40.85%) PLC patients were alive. Median survival time for PLC patients was 11.00 months, respectively. PLC patients with prior thyroid cancer have a lower risk of death (HR = 0.64; 95% CI: 0.48-0.86). Subgroup analyses stratified by gender displayed the similar relation in female patients with PLC. Prior thyroid cancer may be a protective factor for liver cancer death in PLC patients, especially in female patients.


Assuntos
Neoplasias Hepáticas , Neoplasias da Glândula Tireoide , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Programa de SEER , Neoplasias da Glândula Tireoide/epidemiologia
10.
Endocrine ; 78(2): 270-279, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35976509

RESUMO

PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic ß cells. The goal of this study was to explore potential biological biomarkers for T1DM. METHODS: Two microarray datasets (GSE55098 and GSE156035) about human peripheral blood mononuclear cells (PBMCs) were systematically extracted from the Gene Expression Omnibus (GEO) database. Common genes were identified from the perspective of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) respectively, and hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis. We also observed the expression of these hub genes in some common autoimmune diseases and predicted transcription factors (TFs) that might be associated with these genes. RESULTS: Seven hub genes (DDIT4, ESCO2, SH3BP4, PRICKLE1, EPM2AIP1, KCNJ15 and GRM8) were finally identified. Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of T1DM. Gene set enrichment analysis (GSEA) suggested that most of these hub genes may be mainly involved in the changes of biological functions such as inflammation, infection, immunity, cancer, and apoptosis. Further, compared with the control group, the expression levels of these hub genes also changed in some other autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), etc., indicating that they might be the common targets of these autoimmune diseases. CONCLUSIONS: The present study identified novel genes associated with T1DM from the PBMCs perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of T1DM.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Humanos , Leucócitos Mononucleares/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Redes Reguladoras de Genes , Biologia Computacional , Perfilação da Expressão Gênica , Biomarcadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Acetiltransferases/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo
11.
Transplant Cell Ther ; 28(10): 700.e1-700.e6, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35781099

RESUMO

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT) owing to both the disease itself and the immunosuppressive agents used for treatment. Response criteria endorsed by the National Institutes of Health (NIH) Consensus Conference on Clinical Trials in chronic GVHD include both clinician-documented measures and patient-reported outcomes (PROs) since both are considered clinical benefits by the Food and Drug Administration. The correlation between clinically assessed responses in organs and PRO improvements in organ-specific symptoms has not been investigated in depth. We used data from 2 published studies of belumosudil, an oral rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor, for chronic GVHD to test the correlation between clinical and PRO outcomes. Participants completed PROs at enrollment and every 1 to 2 cycles according to the study design. Individual organ responses (complete plus partial response) and clinically meaningful changes in PROs were defined according to published methods. Generalized estimating equation methods were used to correlate changes in PROs associated with clinical responses according to NIH criteria, accounting for missing information and repeated measures. Data from all doses in both trials were included without stratification. The liver and genital tract were not included owing to a lack of site-specific PROs. Our pooled analysis of clinical and PRO data included 170 patients enrolled in 2 belumosudil studies (NCT02841995, n = 54; NCT03640481, n = 132) for whom we had baseline PROs, at least 1 follow-up PRO, and at least 1 response assessment. There was a strong positive correlation between complete and partial organ and overall responses and changes in PRO symptom scores, as well as clinically meaningful improvements. For all organs except joints, esophagus, and lower gastrointestinal tract, there was at least 1 PRO statistically correlated with NIH organ response. These data support the use of PROs for response assessment to document clinically meaningful benefit in chronic GVHD clinical trials.


Assuntos
Doença Enxerto-Hospedeiro , Acetamidas , Doença Crônica , Estudos Clínicos como Assunto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Proteínas Quinases
12.
Opt Express ; 30(9): 14088-14102, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473160

RESUMO

The application of large-aperture telescopes requires the support of co-phase measurement techniques for segmented mirrors. This paper proposes a novel method to detect the co-phase state of segmented mirrors by applying a dual-wavelength phase-shifting interferometer based on optical vortex. Theory and experiments indicate that the wrapped phase map edges obtained by phase-shifting interference of the vortex beam are distributed in the form of a Fermat spiral. The piston error of the segmented mirrors corresponds to the rotation of the standard Fermat spiral center. In contrast, the tip/tilt error corresponds to the alteration of the center position of the deformed Fermat spiral. The rotation angle and the center position of the spiral are obtained by curve fitting, and the co-phase errors can be inversely solved. The experiments achieved an accuracy of approximately 4.04 nm in the piston and 0.16″ in the tip/tilt. The method avoids using complex lens arrays and devices, has an extended measurement range, high accuracy, and allows the co-phase errors between all sub-mirrors to be obtained in real-time. This study provides a novel and general method for detecting co-phase errors in a segmented primary mirror.

13.
Adv Sci (Weinh) ; 9(14): e2105331, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35233960

RESUMO

Flexible transparent electrodes (FTEs) with embedded metal meshes play an indispensable role in many optoelectronic devices due to their excellent mechanical stability and environmental adaptability. However, low-cost, simple, efficient, and environmental friendly integrated manufacturing of high-performance embedded metal meshes remains a huge challenge. Here, a facile and novel fabrication method is proposed for FTEs with an embedded metal mesh via liquid substrateelectric-field-driven microscale 3D printing process. This direct printing strategy avoids tedious processes and offers low-cost and high-volume production, enabling the fabrication of high-resolution, high-aspect ratio embedded metal meshes without sacrificing transparency. The final manufactured FTEs with 80 mm × 80 mm embedded metal mesh offers excellent optoelectronic performance with a sheet resistance (Rs ) of 6 Ω sq-1 and a transmittance (T) of 85.79%. The embedded metal structure still has excellent mechanical stability and good environmental suitability under different harsh working conditions. The practical feasibility of the FTEs is successfully demonstrated with a thermally driven 4D printing structure and a resistive transparent strain sensor. This method can be used to manufacture large areas with facile, high-efficiency, low-cost, and high-performance FTEs.

14.
J Clin Pharmacol ; 62(9): 1059-1078, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35303368

RESUMO

Cancer immunotherapy with immune checkpoint inhibitors has revolutionized traditional cancer therapy. Although many patients have achieved long-term survival benefits from treatment with immune checkpoint inhibitors, there are still some patients who develop rapid tumor progression after immunotherapy, known as HPD. Here, we summarize the current knowledge on HPD after treatment with immune checkpoint inhibitors to promote a more thorough understanding of the disease. This review focuses on multiple aspects of HPD, especially the tumor microenvironment, with the hope that more reliable biomarkers and therapeutics will be established for HPD in the future.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Progressão da Doença , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
15.
Small ; 18(17): e2107811, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35224846

RESUMO

Transparent glass with metal mesh is considered a promising strategy for high performance transparent glass heaters (TGHs). However, the realization of simple, low-cost manufacture of high performance TGHs still faces great challenges. Here, a technique for the fabrication of high performance TGHs is proposed using liquid sacrificial substrate electric-field-driven (LS-EFD) microscale 3D printing of thick film silver paste. The liquid sacrificial substrate not only significantly improves the aspect ratio (AR) of silver mesh, but also plays a positive role in printing stability. The fabricated TGHs with a line width of 35 µm, thickness of 12.3 µm, and pitch of 1000 µm exhibit a desirable optoelectronic performance with sheet resistance (Rs ) of 0.195 Ω sq-1 and transmittance (T) of 88.97%. A successful deicing test showcases the feasibility and practicality of the manufactured TGHs. Moreover, an interface evaporator is developed for the coordination of photothermal and electrothermal systems based on the high performance TGHs. The vapor generation rate of the device reaches 10.69 kg m-2 h-1 with a voltage of 2 V. The proposed technique is a promising strategy for the cost-effective and simple fabrication of high performance TGHs.

16.
Appl Opt ; 61(1): 60-68, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35200806

RESUMO

Metalenses exhibit excellent performance as a new type of optical element; mid-infrared devices based on metalenses are advantageous to numerous applications in biomedical, military and industrial fields. The demand for large-area and high-efficiency mid-infrared metalenses has increased in recent years. However, the current processing methods for metalens production introduce different types of processing errors. Therefore, qualitative analyses of various errors that may exist in the processing of metalenses should be performed. In this study, we use the finite-difference time-domain calculation method and introduce various typical errors into a transmission phase-based mid-infrared metalens for simulation and analysis. The simulation results show that the defects caused by these processes affect focusing efficiency, and that some defects affect the quality of light. Subsequently, we prepare a metalens within the allowable error range and test its optical performances. The experiment confirms the excellent imaging performance of our metalens. Our study can help manufacturers identify defects to improve manufacturing processes, thereby enabling the incorporation of metalenses in industrial applications.

18.
Blood ; 138(22): 2278-2289, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34265047

RESUMO

Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.


Assuntos
Acetamidas/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento , Adulto Jovem , Quinases Associadas a rho/antagonistas & inibidores
19.
Opt Express ; 29(8): 12049-12065, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33984973

RESUMO

The existence of vector solitons that arise from the birefringence nature of optical fibers has been increasingly of interest for the stability of mode-locked fiber lasers, particularly for those operating in the high-fundamental-repetition-rate regime, where a large amount of fiber birefringence is required to restore the phase relation between the orthogonally polarized vector solitons, resulting in stable mode-locking free of polarization rotation. These vector solitons can exhibit diverse time-varying polarization dynamics, which prevent industrial and scientific applications requiring stable and uniform pulse trains at high fundamental repetition rates. This pressing issue, however, has so far been rarely studied. To this end, here we theoretically and experimentally dissect the formation of vector solitons in a GHz-repetition-rate fiber laser and investigate effective methods for suppressing roundtrip-to-roundtrip polarization dynamics. Our numerical model can predict both dynamic and stable regimes of high-repetition-rate mode-locking by varying the amount of fiber birefringence, resulting in the polarization rotation vector soliton (PRVS) and linearly polarized soliton (LPS), respectively. These dynamic behaviors are further studied by using an analytical approach. Interestingly, our theoretical results indicate a cavity-induced locking effect, which can be a complementary soliton trapping mechanism for the co-propagating solitons. Finally, these theoretical predications are experimentally verified, and we obtain both PRVS and LPS by adjusting the intracavity fiber birefringence.

20.
J Clin Oncol ; 39(17): 1888-1898, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33877856

RESUMO

PURPOSE: The rho-associated coiled-coil-containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD). PATIENTS AND METHODS: A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). The primary end point was overall response rate (ORR). RESULTS: The median time from cGVHD diagnosis to enrollment was 20 months. Seventy-eight percent of patients had severe cGVHD, 50% had ≥ 4 organs involved, 73% had cGVHD refractory to their last LOT, and 50% had received ≥ 3 prior LOTs. With an overall median follow-up of 29 months, the ORR (95% CI) with belumosudil 200 mg once daily, 200 mg twice daily, and 400 mg once daily was 65% (38% to 86%), 69% (41% to 89%), and 62% (38% to 82%), respectively. Responses were clinically meaningful, with a median duration of response of 35 weeks, and were associated with quality-of-life improvements and corticosteroid (CS) dose reductions. CS treatment was discontinued in 19% of patients. The failure-free survival rate was 76% (62% to 85%) and 47% (33% to 60%) at 6 and 12 months, respectively. The 2-year overall survival rate was 82% (69% to 90%). Belumosudil was well-tolerated, with low rates of cytopenia. There were no unexpected adverse events and no apparent increased risk of infection, including cytomegalovirus infection and reactivation. CONCLUSION: Belumosudil treatment resulted in a high ORR and overall survival rate and demonstrated quality-of-life improvements, CS dose reductions, and limited toxicity. Data from the study indicated that belumosudil may prove to be an effective therapy for patients with treatment-refractory cGVHD.


Assuntos
Acetamidas/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Quinases Associadas a rho/antagonistas & inibidores , Acetamidas/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Adulto Jovem
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