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1.
Blood ; 142(16): 1359-1370, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37339586

RESUMO

This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, and follicular lymphoma. We report the results in cases of cHL. Adult patients with RR cHL who had received ≥1 prior lines of therapy and were ineligible for transplantation were treated in a dose-escalation cohort with 2 dose levels (DLs) and then on an expansion cohort at the recommended phase 2 dose (RP2D) in 21-day cycles. Vorinostat 100 mg twice a day (DL1) and 200 mg twice a day (DL2) was administered orally from days 1 to 5 and 8 to 12; all patients received pembrolizumab 200 mg IV every 3 weeks. The primary end point was safety and determination of RP2D. In total, 32 patients with cHL were enrolled, including 30 at DL2 (RP2D); 78% had received prior anti-programmed cell death 1 (anti-PD-1) therapy, and 56% were PD-1 refractory. Grade ≥3 adverse events (AEs) included hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Immune-related AEs included grade 1 or 2 thyroiditis (13%), grade 1 rash (6%), and grade 3 esophagitis/duodenitis (3%). The overall response rate (ORR) was 72% and complete response (CR) rate was 34%. Patients refractory to prior PD-1 blockade (n = 18) had ORR and CR rates of 56% and 11%, respectively. Pembrolizumab and vorinostat was well tolerated with a high ORR rate in RR cHL including in anti-PD-1-refractory disease. This trial was registered at www.clinicaltrials.gov as #NCT03150329.


Assuntos
Anticorpos Monoclonais Humanizados , Doença de Hodgkin , Adulto , Humanos , Doença de Hodgkin/tratamento farmacológico , Vorinostat , Receptor de Morte Celular Programada 1/uso terapêutico , Recidiva Local de Neoplasia
2.
Opt Express ; 32(6): 9562-9572, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571187

RESUMO

We demonstrated a high-performance partially corrugated waveguide distributed feedback (PCW-DFB) laser with high output power, low relative intensity noise (RIN) and narrow linewidth. By introducing offset quantum-well structure that provides enough threshold gain difference for single transverse mode operation, the laser can achieve single mode behavior with an 8-µm-wide ridge waveguide. The laser has been designed by the simulation model based on the coupled wave equations, and the fabricated PCW-DFB laser with the cavity length of 1.3 mm exhibited an output power higher than 190 mW. Stable single mode characteristics have been achieved with a side-mode suppression-ratio (SMSR) over 55 dB. The RIN was less than -160.5 dB/Hz at an injection current of 470 mA, and the linewidth reached 45 kHz.

3.
Opt Express ; 32(3): 3123-3137, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297541

RESUMO

This study investigates the thermal compensation mechanism in dual-mode Si3N4 microresonators that demonstrates the ease of generation of single-solitons with nearly octave-wide spectral bandwidth. The deterministic creation of soliton frequency combs is achieved by merely switching the wavelength of a tunable laser or a semiconductor diode laser in a single step. The pump frequency detuning range that can sustain the soliton state is 30 gigahertz (GHz), which is approximately 100 times the resonance linewidth. Interestingly, these dual-mode resonators also support the coexistence of primary combs and solitons, enabling their utilization as functional microwave synthesizers. Furthermore, these resonators readily facilitate the generation of diverse multi-solitons and soliton crystals. This work presents a simplified system to access high-performance and versatile Kerr solitons, with wide-ranging applications in optical metrology, microwave photonics, and LiDAR.

4.
Glob Chang Biol ; 30(2): e17182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348761

RESUMO

Biodiversity is considered important to the mitigation of global change impacts on ecosystem multifunctionality in terrestrial ecosystems. However, potential mechanisms through which biodiversity maintains ecosystem multifunctionality under global change remain unclear. We grew 132 plant communities with two levels of plant diversity, crossed with treatments based on 10 global change factors (nitrogen deposition, soil salinity, drought, plant invasion, simulated grazing, oil pollution, plastics pollution, antibiotics pollution, heavy metal pollution, and pesticide pollution). All global change factors negatively impacted ecosystem multifunctionality, but negative impacts were stronger in high compared with low diversity plant communities. We explored potential mechanisms for this unexpected result, finding that the inhibition of selection effects (i.e., selection for plant species associated with high ecosystem functioning) contributed to sensitivity of ecosystem multifunctionality to global change. Specifically, global change factors decreased the abundance of novel functional plants (i.e., legumes) in high but not low diversity plant communities. The negative impacts of global change on ecosystem multifunctionality were also mediated by increased relative abundance of fungal plant pathogens (identified from metabarcoding of soil samples) and their negative relationship with the abundance of novel functional plants. Taken together, our experiment highlights the importance of protecting high diversity plant communities and legumes, and managing fungal pathogens, to the maintenance of ecosystem multifunctionality in the face of complex global change.


Assuntos
Ecossistema , Fabaceae , Biodiversidade , Plantas , Solo , Poluição Ambiental
5.
Diabet Med ; 41(1): e15251, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37915225

RESUMO

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most burdensome chronic diseases in the world. Health utility values are an important tool for quantifying this disease burden and conducting cost-utility analyses. This review aimed to derive a reference set of health utility values for children and adolescents with T1DM. METHODS: We searched MEDLINE and Embase from inception to March 2023 for health utility values of T1DM children and adolescents (aged ≤18 years) measured using direct and indirect preference elicitation approaches. Utility estimates were pooled by meta-analyses with subgroup analyses to evaluate differences by populations and elicitation approaches. RESULTS: Six studies involving 1276 participants were included in this study. Meta-analysis showed the overall utility value of children and adolescents with T1DM was 0.91 (95% CI 0.89-0.93). The utility value of T1DM children and adolescents with complications was 0.90 (95% CI 0.88-0.92), which was lower than those without complications (0.96, 95% CI 0.95-0.97). The utility value of children (aged <13 years) was higher than adolescents (aged 13-18 years) (0.90 vs. 0.85). The utility value measured by the EQ-5D-3L (0.91) was higher than the HUI3 (0.89), the SF-6Dv1 (0.83), and the time trade-off (0.81). The parent proxy-reported was similar to the patient self-reported (0.91 vs. 0.91). CONCLUSIONS: This study developed a reference set of pooled utility estimates for children and adolescents with T1DM, which is helpful for understanding the overall health status of T1DM and conducting economic evaluations. Further studies are needed to explore the utilities of T1DM with different types of complications.


Assuntos
Diabetes Mellitus Tipo 1 , Criança , Humanos , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Qualidade de Vida , Efeitos Psicossociais da Doença , Autorrelato , Análise Custo-Benefício
6.
Qual Life Res ; 33(3): 817-829, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38167749

RESUMO

PURPOSE: To develop the mapping functions from the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores onto the EQ-5D-5L and SF-6Dv2 utility values among the overweight and obese population in China. METHODS: A representative sample of the overweight and obese population in China stratified by age, sex, body mass index (BMI), and area of residence was collected by online survey and the sample was randomly divided into development (80%) and validation (20%) datasets. The conceptual overlap between the IWQOL-Lite and the EQ-5D-5L or SF-6Dv2 was evaluated by Spearman's correlation coefficients. Five models, including OLS, Tobit, CLAD, GLM, and PTM were explored to derive mapping functions using the development dataset. The model performance was assessed using MAE, RMSE, and the percentage of AE > 0.05 and AE > 0.1 in the validation dataset. RESULTS: A total of 1000 respondents (48% female; mean [SD] age: 51.7 [15.3]; mean [SD] BMI: 27.4 [2.8]) were included in this study. The mean IWQOL-Lite scores and the utility values of EQ-5D-5L and SF-6Dv2 were 78.5, 0.851, and 0.734, respectively. The best-performing models predicting EQ-5D-5L and SF-6Dv2 utilities both used IWQOL-Lite total score as a predictor in the CLAD model (MAE: 0.083 and 0.076 for the EQ-5D-5L and SF-6Dv2; RMSE: 0.125 and 0.103 for the EQ-5D-5L and SF-6Dv2; AE > 0.05: 20.5% and 27.5% for the EQ-5D-5L and SF-6Dv2; AE > 0.10: 9.5% and 15.0% for the EQ-5D-5L and SF-6Dv2). CONCLUSION: CLAD models with the IWQOL-Lite total score can be used to predict both the EQ-5D-5L and SF-6Dv2 utility values among overweight and obese population in China.


Assuntos
Sobrepeso , Qualidade de Vida , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Qualidade de Vida/psicologia , Inquéritos e Questionários , China , Obesidade
7.
Ecotoxicol Environ Saf ; 282: 116715, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39002378

RESUMO

Intercropping with hyperaccumulators can facilitate the safe utilization of cadmium-contaminated soil. However, the effectiveness of this approach is influenced by plant species and varieties, which necessitates research on optimal plant consortia. In this study, 8 tomato varieties (3 cherry tomatoes and 5 common large-fruit tomatoes) were intercropped with Sedum alfredii in a moderately Cd-contaminated vegetable field. The results showed that the Cd concentration in the fruits of common large-fruit tomato varieties under monoculture was 1.03-1.50 mg/kg, while that in the fruits of cherry tomato varieties was 0.67-0.71 mg/kg. After intercropping with S. alfredii, the fruit Cd concentrations of Hangza 501, Hangza 503, and Hangza 108 decreased by 16.42 %, 19.72 %, and 6.76 %, respectively, while those of the other varieties significantly increased, except for those of Hangza 8. In contrast, the shoot Cd concentration of cherry tomatoes was greater than that of large-fruit tomatoes under monoculture. Furthermore, a significant increase in the shoot Cd concentration was noted in the Hangza 501, Hangza 503 and Hangza 603 plants following intercropping. Additionally, intercropping with S. alfredii increased the concentration of soluble sugars in the fruits of Hangza 8, Hangza 501, Hangza 503 and Hangza 603 by 4.66 %, 17.91 %, 10.60 % and 17.88 %, respectively. Intercropping with tomatoes resulted in a decrease in both the biomass and Cd uptake of S. alfredii. Interestingly, the inhibitory effect on S. alfredii was less pronounced when intercropped with cherry tomatoes than when intercropped with large-fruit tomatoes. Among the intercropping treatments, S. alfredii exhibited the greatest total Cd accumulation (0.06 mg/plant) when intercropped with Hangza 503. In conclusion, the cherry tomato variety Hangza 503 was the most suitable for intercropping with S. alfredii and can be used safely for vegetable production and simultaneous phytoremediation of polluted soil. Our findings suggest that strategic selection of tomato varieties can optimize the effectiveness of "phytoextraction coupled with agro-safe production" technology for managing soil Cd concentrations.

8.
Nano Lett ; 23(2): 597-605, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36622320

RESUMO

The development of high-performance miniaturized and flexible airflow sensors is essential to meet the need of emerging applications. Graphene-based airflow sensors are hampered by the sluggish response and recovery speed and low sensitivity. Here we employ laser-induced graphene (LIG) with poststructural biomimicry for fabricating high-performance, flexible airflow sensors, including cotton-like porous LIG, caterpillar fluff-like vertical LIG fiber, and Lepidoptera scale-like suspended LIG fiber (SLIGF) structures. The structural engineering changes the deformation behavior of LIGs under stress, among which the synchronous propagation of the scale-like structure of SLIGF is the most conducive to airflow sensing. The SLIGF achieves the shortest average response time of 0.5 s, the highest sensitivity of 0.11 s/m, and a record-low detection threshold of 0.0023 m/s, benchmarked against the state-of-the-art airflow sensors. Furthermore, we showcase the SLIGF airflow sensors in weather forecasting, health, and communications applications. Our study will help develop next-generation waterflow, sound, and motion sensors.

9.
Angew Chem Int Ed Engl ; 63(15): e202400414, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38348904

RESUMO

Bipolar membranes (BPMs) have emerged as a promising solution for mitigating CO2 losses, salt precipitation and high maintenance costs associated with the commonly used anion-exchange membrane electrode assembly for CO2 reduction reaction (CO2RR). However, the industrial implementation of BPM-based zero-gap electrolyzer is hampered by the poor CO2RR performance, largely attributed to the local acidic environment. Here, we report a backbone engineering strategy to improve the CO2RR performance of molecular catalysts in BPM-based zero-gap electrolyzers by covalently grafting cobalt tetraaminophthalocyanine onto a positively charged polyfluorene backbone (PF-CoTAPc). PF-CoTAPc shows a high acid tolerance in BPM electrode assembly (BPMEA), achieving a high FE of 82.6 % for CO at 100 mA/cm2 and a high CO2 utilization efficiency of 87.8 %. Notably, the CO2RR selectivity, carbon utilization efficiency and long-term stability of PF-CoTAPc in BPMEA outperform reported BPM systems. We attribute the enhancement to the stable cationic shield in the double layer and suppression of proton migration, ultimately inhibiting the undesired hydrogen evolution and improving the CO2RR selectivity. Techno-economic analysis shows the least energy consumption (957 kJ/mol) for the PF-CoTAPc catalyst in BPMEA. Our findings provide a viable strategy for designing efficient CO2RR catalysts in acidic environments.

10.
Cancer Immunol Immunother ; 72(9): 3013-3027, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37294342

RESUMO

Currently there is a limited understanding for the optimal combination of immune checkpoint inhibitor and chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC). Here we evaluate the safety, efficacy, and immunogenicity of a phase I trial for patients with mTNBC treated with pembrolizumab plus doxorubicin. Patients without prior anthracycline use and 0-2 lines of prior systemic chemotherapies received pembrolizumab and doxorubicin every 3 weeks for 6 cycles followed by pembrolizumab maintenance until disease progression or intolerance. The primary objectives were safety and objective response rate per RECIST 1.1. Best responses included one complete response (CR), five partial responses (PR), two stable disease (SD), and one progression of disease (PD). Overall response rate was 67% (95% CI 13.7%, 78.8%) and clinical benefit rate at 6 months was 56% (95% CI 21.2%, 86.3%). Median PFS was 5.2 months (95% CI 4.7, NA); median OS was 15.6 months (95% CI 13.3, NA). Grade 3-4 AEs per CTCAE 4.0 were neutropenia n = 4/10 (40%), leukopenia n = 2/10 (20%), lymphopenia n = 2/10 (20%), fatigue n = 2/10 (20%), and oral mucositis n = 1/10 (10%). Immune correlates showed increased frequencies of circulating CD3 + T cells (p = 0.03) from pre-treatment to cycle 2 day 1 (C2D1). An expansion of a proliferative exhausted-like PD-1 + CD8 + T cell population was identified in 8/9 patients, and exhausted CD8 + T cells were significantly expanded from pre-treatment to C2D1 in the patient with CR (p = 0.01). In summary, anthracycline-naïve patients with mTNBC treated with the combination of pembrolizumab and doxorubicin showed an encouraging response rate and robust T cell response dynamics.Trial registration: NCT02648477.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Doxorrubicina/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antraciclinas/uso terapêutico , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
11.
Opt Express ; 31(12): 19604-19612, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381371

RESUMO

A Polarization Rotator-Splitter (PRS) based on thin-film lithium niobate (TFLN) is demonstrated in this work. The PRS consists of a partially etched polarization rotating taper and an adiabatic coupler, which enables the input TE0 and TM0 to be output as TE0 from two ports, respectively. The fabricated PRS using standard i-line photolithography achieved large polarization extinction ratios (PERs) of > 20 dB across the whole C-band. Excellent polarization characteristics are maintained when the width is changed by ±150 nm. The on-chip insertion losses of TE0 and TM0 are less than 1.5 dB and 1 dB, respectively.

12.
Opt Express ; 31(3): 4497-4506, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785416

RESUMO

A narrow linewidth electro-optically tuned multi-channel interference (MCI) widely tunable semiconductor laser based on carrier injection is demonstrated in this paper. The MCI laser with a common phase section and a semiconductor optical amplifier (SOA) is packaged into a 16-pin butterfly box. The laser is characterized by a strategy: shifting the longitudinal mode and then aligning the reflection peak, which obtains a quasi-continuous tuning range over 48 nm. The corresponding side mode suppression ratios (SMSRs) are higher than 40 dB and frequency deviations from ITU-grid are less than ± 1 GHz. Threshold currents are less than 28 mA. Fiber coupled output powers are higher than 20 mW and power variations with fixed gain and SOA currents are less than 0.8 dB over the whole tuning range. Lorentzian linewidths are less than 320 kHz over the entire tuning range, which is one of the lowest results for monolithic widely tunable semiconductor lasers tuned by carrier injection. These results demonstrate the potential prospects of the MCI laser with carrier injection in the field of optical sensing and optical communications.

13.
Opt Express ; 31(20): 33191-33199, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859104

RESUMO

Microresonator-based soliton crystals are a key recent advancement in the study of the rich nonlinear dynamics of soliton states. The soliton crystals are self-organized temporal pulses filling the microresonator cavity and have strong comb lines with wide spacing making them of great interest in many potential applications such as communication and meteorology. However, achieving a broad spectrum, tunable repetition rates, and high conversion efficiency are still a challenge. Here, we report the deterministic generation of versatile octave-spanning soliton crystals with various repetition rates via avoided mode crossings. In addition, we investigate the conversion efficiency of the obtained soliton crystals and achieved above ∼50% in one of the devices with a suitable coupling. Our results pave the way for accessing coherent broad and tunable on-chip soliton crystals, thus requiring a rigorous and viable microcavity design to engineer the desired mode coupling position.

14.
Opt Express ; 31(2): 3199-3211, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785317

RESUMO

Optical Phase Arrays (OPAs) are expected to be an ideal solution to achieve beam shaping, laser radar (LIDAR), free-space optical communications, and spatially resolved optical sensors, etc. We demonstrated a low-power consumption 32-channel OPA with non-uniformly spaced waveguides based on InP substrate. The phase shifters are based on a p-i-n structure which are operated with reverse bias and have a low power consumption. Besides, in order to improve the performance especially to obtain larger steering angle and narrower beam divergence without increasing the number of channels, we have optimized the spacing between the output waveguides. The fabricated OPA achieved a steering angle of 35° with the side lobe suppression ratio more than 8.2 dB across the angle range from -20° to 20° in the far field, which is the largest phase tuning steering angle reported by InP-based OPAs as far as we know. The divergence angle is about 0.46° in the phase steering dimension and the power consumption of the OPA at each steering angle is lower than 7.5 mW.

15.
J Oral Pathol Med ; 52(7): 583-592, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36829264

RESUMO

BACKGROUND: Oral tongue squamous cell carcinoma tends to metastasize to cervical lymphatic nodes early which leads to a 50% drop of survival rate. CXCL1 could be secreted by LNMTca8113 cell induced lymphatic endothelial cells and promoted LNMTca8113 cell migration. The current study aimed to further explore the effect of CXCL1 on the proliferation and migration abilities of tongue cancer cells and the prognostic value of serum CXCL1 in oral tongue squamous cell carcinoma. METHODS: Cell proliferation and migration ability were analysed by CCK8 assays and transwell migration assays. Immunofluorescence technique was used to show cytoskeleton. GST pull-down assay was applied to quantify the activation of GTPases. Blood samples of patients were collected and clinicopathological characteristics were analysed. RESULTS: CXCL1 could promote cancer cell proliferation in appropriate concentration by PI3K/AKT pathway. It also regulated the activation of Rho GTPases to mediate the rearrangements of cytoskeleton to promote tumour cell migration. Level of plasma CXCL1 could predict the possibility of early lymphatic metastasis and had a predictive value in progression-free survival and overall survival. CONCLUSIONS: CXCL1 could promote oral cancer cell proliferation, migration and invasion in vitro and contributed theoretical knowledge for the target selection in molecular targeted therapy. Level of plasma CXCL1 might serve as a biomarker for prognosis in oral tongue squamous cell carcinoma patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Neoplasias da Língua/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Prognóstico , Movimento Celular , Proliferação de Células , Quimiocina CXCL1
16.
Health Qual Life Outcomes ; 21(1): 118, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904216

RESUMO

OBJECTIVE: To evaluate and compare the measurement properties of the EQ-5D-5L and SF-6Dv2 among Chinese overweight and obesity populations. METHODS: A representative sample of Chinese overweight and obesity populations was recruited stratified by age, gender, body mass index (BMI), and area of residence. Social-demographic characteristics and self-reported EQ-5D-5L and SF-6Dv2 responses were collected through the online survey. The agreement was assessed using intraclass correlation coefficients (ICC). Convergent validity and known-group validity were examined using Spearman's rank correlation and effect sizes, respectively. The test-retest reliability was assessed using among a subgroup of the total sample. Sensitivity was compared using relative efficiency and receiver operating characteristic. RESULTS: A total of 1000 respondents (52.0% male, mean age 51.7 years, 67.7% overweight, 32.3% obesity) were included in this study. A higher ceiling effect was observed in EQ-5D-5L than in SF-6Dv2 (30.6% vs. 2.1%). The mean (SD) utility was 0.851 (0.195) for EQ-5D-5L and 0.734 (0.164) for SF-6Dv2, with the ICC of the total sample was 0.639 (p < 0.001). The Spearman's rank correlation (range: 0.186-0.739) indicated an acceptable convergent validity between the dimensions of EQ-5D-5L and SF-6Dv2. The EQ-5D-5L showed basically equivalent discriminative capacities with the SF-6Dv2 (ES: 0.517-1.885 vs. 0.383-2.329). The ICC between the two tests were 0.939 for EQ-5D-5L and 0.972 for SF-6Dv2 among the subgroup (N = 150). The SF-6Dv2 had 3.7-170.1% higher efficiency than the EQ-5D-5L at detecting differences in self-reported health status, while the EQ-5D-5L was found to be 16.4% more efficient at distinguishing between respondents with diabetes and non-diabetes. CONCLUSIONS: Both the EQ-5D-5L and SF-6Dv2 showed comparable reliability, validity, and sensitivity when used in Chinese overweight and obesity populations. The two measures may not be interchangeable given the systematic difference in utility values between the EQ-5D-5L and SF-6Dv2. More research is needed to compare the responsiveness.


Assuntos
Sobrepeso , Qualidade de Vida , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Reprodutibilidade dos Testes , Psicometria/métodos , China , Inquéritos e Questionários , Obesidade/epidemiologia
17.
J Med Genet ; 59(4): 370-376, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33563768

RESUMO

PURPOSE: Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a testing panel and whether the result would affect clinical management. METHODS: We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018. All participants received germline testing for various hereditary cancer syndromes. RESULTS: The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes was 7.8% (38/486), including 25 PVs in genes with high-risk CRC susceptibility (the minimal testing set) and 13 PVs in genes with moderate-risk CRC susceptibility or increased cancer risk other than CRC (the additional testing set). All the clinically relevant PVs were found in patients diagnosed under age 70 years. Among them, 11 patients would not have been diagnosed if testing reserved to present guidelines. Most (36/38) of the patients with PVs benefited from enhanced surveillance and tailored treatment. PVs in genes from the minimal testing set were found in all age groups, while patients carried PVs in genes from the additional testing set were older than 40 years. CONCLUSION: Universal germline testing for cancer susceptibility genes should be recommended among all patients with CRC diagnosed under age 70 years. A broad panel including genes from the additional testing set might be considered for patients with CRC older than 40 years to clarify inheritance risks. TRIAL REGISTRATION NUMBER: NCT03365986.


Assuntos
Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Adulto , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Testes Genéticos , Células Germinativas , Mutação em Linhagem Germinativa/genética , Humanos , Síndromes Neoplásicas Hereditárias/genética
18.
J Clin Pediatr Dent ; 47(1): 91-99, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36627225

RESUMO

The treatment of adolescent skeletal open-bite malocclusion with severe molar-incisor hypomineralization (MIH) remains challenging. Though conducive to open-bite treatment and endodontic management, early molar extraction may trigger a series of negative impacts on occlusion and stomatognathic development. In addition, molars' crown restoration was shown to worsen open-bite malocclusion considering the intrinsic vertical increment of hyperdivergent growth. This case report describes the successful multidisciplinary therapy combined with orthopedic and orthodontic treatment of a 10.2-year-old girl with mixed dentition, a protruding profile and skeletal open-bite malocclusion with severe MIH and crowding. During the mixed and early permanent dentition, function regulator-4 (FR-4), resin-bonding transpalatal arch (TPA) and modified spring-loaded bite blocks were implemented to correct abnormal swallowing and control the facial vertical growth. Radiographic results, including the counterclockwise rotation of the occlusion plane, decreasing mandibular angle and increasing posterior-anterior face height ratio accompanied by obvious mandibular vertical growth, indicated that the performed orthopedic treatments efficiently controlled hyperdivergent open-bite growth during puberty. After the maxillary and mandibular second molars were occluded, all first permanent molars were extracted, and fixed appliances combined with implant anchorage were used to correct malocclusion and convex profile. Ultimately, a stable Class I functional occlusion and satisfying facial improvement were achieved and maintained following a 2-year follow-up.


Assuntos
Má Oclusão Classe II de Angle , Hipomineralização Molar , Mordida Aberta , Procedimentos de Ancoragem Ortodôntica , Feminino , Humanos , Adolescente , Criança , Cefalometria/métodos , Mandíbula , Mordida Aberta/terapia , Dente Molar , Técnicas de Movimentação Dentária , Má Oclusão Classe II de Angle/terapia
19.
Small ; 18(24): e2201311, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35561067

RESUMO

Deficiencies in understanding the local environment of active sites and limited synthetic skills challenge the delivery of industrially-relevant current densities with low overpotentials and high selectivity for CO2 reduction. Here, a transient laser induction of metal salts can stimulate extreme conditions and rapid kinetics to produce defect-rich indium nanoparticles (L-In) is reported. Atomic-resolution microscopy and X-ray absorption disclose the highly defective and undercoordinated local environment in L-In. In a flow cell, L-In shows a very small onset overpotential of ≈92 mV and delivers a current density of ≈360 mA cm-2 with a formate Faradaic efficiency of 98% at a low potential of -0.62 V versus RHE. The formation rate of formate reaches up to 6364.4 µmol h-1mgIn-1$mg_{{\rm{In}}}^{--1}$ , which is nearly 39 folds higher than that of commercial In (160.7 µmol h-1mgIn-1$mg_{{\rm{In}}}^{--1}$ ), outperforming most of the previous results that have been reported under KHCO3 environments. Density function theory calculations suggest that the defects facilitate the formation of *OCHO intermediate and stabilize the *HCOOH while inhibiting hydrogen adsorption. This study suggests that transient solid-state laser induction provides a facile and cost-effective approach to form ligand-free and defect-rich materials with tailored activities.


Assuntos
Índio , Lasers de Estado Sólido , Dióxido de Carbono/química , Formiatos/química
20.
Opt Express ; 30(2): 2599-2609, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209396

RESUMO

We demonstrated a high output power distributed-Bragg-reflector (DBR) laser integrated with semiconductor optical amplifier (SOA) for the frequency-modulated continuous-wave (FMCW) light detection and ranging (LiDAR) system. In order to acquire higher output power, different from the conventional SG-DBR laser, the front mirror in this work is a section of uniform grating to get higher transmissivity. Therefore, the output power of the laser reaches 96 mW when the gain current and SOA current are 200 mA and 400 mA, respectively. Besides, we fabricated a spot size converter (SSC) at the laser output port to enhance the fiber coupling efficiency, which reached 64% coupled into the lensed fiber whose beam waist diameter is 2.5 µm. A tuning range of 2.8 nm with free spectral range (FSR) of 0.29 nm and narrow Lorentzian linewidth of 313 kHz is achieved. To realize distance and velocity measurement, we use the iterative learning pre-distortion method to linearize the frequency sweep, which is an important part of the FMCW LiDAR technology.

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