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1.
Adv Mater ; : e2409904, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254348

RESUMEN

The positive electrodes of non-aqueous aluminum ion batteries (AIBs) frequently encounter significant issues, for instance, low capacity in graphite (mechanism: anion de/intercalation and large electrode deformation induced) and poor stability in inorganic positive electrodes (mechanism: multi-electron redox reaction and dissolution of active materials induced). Here, metallo-porphyrin compounds (employed Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ as the ion centers) are introduced to effectively enhance both the cycling stability and reversible capacity due to the formation of stable conjugated metal-organic coordination and presence of axially coordinated active sites, respectively. With the regulation of electronic energy levels, the d-orbitals in the redox reactions and electron transfer pathways can be rearranged. The 5,10,15,20-tetraphenyl-21H,23H-porphine nickle(II) (NiTPP) presents the highest specific capacity (177.1 mAh g-1), with an increment of 32.1% and 77.1% in comparison with the capacities of H2TPP and graphite, respectively, which offers a new route for developing high-capacity positive electrodes for stable AIBs.

2.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 798-806, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39218607

RESUMEN

This article aims to combine deep learning with image analysis technology and propose an effective classification method for distal radius fracture types. Firstly, an extended U-Net three-layer cascaded segmentation network was used to accurately segment the most important joint surface and non joint surface areas for identifying fractures. Then, the images of the joint surface area and non joint surface area separately were classified and trained to distinguish fractures. Finally, based on the classification results of the two images, the normal or ABC fracture classification results could be comprehensively determined. The accuracy rates of normal, A-type, B-type, and C-type fracture on the test set were 0.99, 0.92, 0.91, and 0.82, respectively. For orthopedic medical experts, the average recognition accuracy rates were 0.98, 0.90, 0.87, and 0.81, respectively. The proposed automatic recognition method is generally better than experts, and can be used for preliminary auxiliary diagnosis of distal radius fractures in scenarios without expert participation.


Asunto(s)
Aprendizaje Profundo , Fracturas del Radio , Humanos , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/clasificación , Procesamiento de Imagen Asistido por Computador/métodos , Radiografía , Algoritmos , Fracturas de la Muñeca
3.
NPJ Precis Oncol ; 8(1): 200, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266619

RESUMEN

DP303c is a HER2-targeted ADC with a cleavable linker-MMAE payload. Previous in vitro studies demonstrated that DP303c showed similar or better antitumor activity than T-DM1 in xenograft models. This was a multicenter, dose escalation and dose expansion phase 1 study in China. Eligible patients were 18-75 years old with HER2-positive advanced solid tumors who were unable to benefit from standard therapy. DP303c was administered intravenously every 3 weeks, with accelerated titration at lower dose of 0.5 mg/kg and 3 + 3 design with dose levels of 1.0, 2.0, 3.0 or 4.0 mg/kg at dose escalation part, followed by the selected dose level at dose expansion part. The primary endpoints were safety and tolerability, as well as identification of recommended phase 2 dose. As of Feb 28, 2023, 94 patients were enrolled and received DP303c (dose escalation: n = 22; dose expansion: n = 72), of whom 68 patients had breast cancer. One dose limiting toxicity (Grade 3 eye pain) was observed at 4.0 mg/kg dose, and the maximum tolerated dose was not reached. The most common treatment-related adverse events at grade 3 or higher were blurred vison (16.0%), dry eye (6.4%), and peripheral neuropathy (5.3%). No treatment-related death occurred. Overall, among 91 efficacy evaluable patients, 39 patients (42.9%) achieved an objective response. Disease control was observed in 62 patients (68.1%). In 66 efficacy evaluable patients with breast cancer, 34 patients achieved an objective response (51.5%). Disease control was achieved in 51 patients (77.3%). Median PFS was 6.4 months. On a molar basis, DP303c Cmax at 3.0 mg/kg doses was 132-folder higher than that for free MMAE. DP303c demonstrated promising anti-tumor activity with acceptable safety in patients with pre-treated advanced HER2 positive solid tumors, especially in breast cancer. Based on safety and efficacy results, 3.0 mg/kg Q3W was determined as recommended phase 2 dose for DP303c. (Trial registration: ClinicalTrials.gov Identifier: NCT04146610).

4.
Cancer Cell ; 42(9): 1598-1613.e4, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39255777

RESUMEN

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , ADN Tumoral Circulante , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/sangre , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangre , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano , Mutación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
5.
Lancet ; 404(10457): 1040-1050, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39236727

RESUMEN

BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Paclitaxel , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angioplastia Coronaria con Balón/métodos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Anciano , Sirolimus/uso terapéutico , Sirolimus/administración & dosificación , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , China/epidemiología , Intervención Coronaria Percutánea/métodos
6.
BMC Cancer ; 24(1): 1082, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223545

RESUMEN

BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Irinotecán , Quinazolinas , Tiofenos , Humanos , Persona de Mediana Edad , Quinazolinas/uso terapéutico , Quinazolinas/efectos adversos , Masculino , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Anciano , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tiofenos/uso terapéutico , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Estudios Prospectivos , Adulto , Supervivencia sin Progresión , Adulto Joven
7.
Lung Cancer ; 195: 107901, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39089004

RESUMEN

BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Anciano , Adulto , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Metástasis de la Neoplasia , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/genética , Estudios de Seguimiento
8.
Oncogene ; 43(37): 2768-2780, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39138263

RESUMEN

Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin ß2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin ß2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin ß2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin ß2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin ß2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin ß2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.


Asunto(s)
Caveolina 1 , Vesículas Extracelulares , Neoplasias Peritoneales , Neoplasias Gástricas , Proteínas de Unión al GTP rab , Quinasas Asociadas a rho , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Caveolina 1/metabolismo , Caveolina 1/genética , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Animales , Quinasas Asociadas a rho/metabolismo , Vesículas Extracelulares/metabolismo , Ratones , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Línea Celular Tumoral , Transducción de Señal , Masculino , Femenino
9.
Aging (Albany NY) ; 16(15): 11577-11590, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39133141

RESUMEN

BACKGROUND: Acute ischemic stroke presents significant challenges in healthcare, notably due to the risk and poor prognosis associated with hemorrhagic transformation (HT). Currently, there is a notable gap in the early clinical stage for a valid and reliable predictive model for HT. METHODS: This single-center retrospective study analyzed data from 224 patients with acute ischemic stroke due to large vessel occlusion. We collected comprehensive clinical data, CT, and CTP parameters. A predictive model for HT was developed, incorporating clinical indicators alongside imaging data, and its efficacy was evaluated using decision curve analysis and calibration curves. In addition, we have also built a free browser-based online calculator based on this model for HT prediction. RESULTS: The study identified atrial fibrillation and hypertension as significant risk factors for HT. Patients with HT showed more extensive initial ischemic damage and a smaller ischemic penumbra. Our novel predictive model, integrating clinical indicators with CT and CTP parameters, demonstrated superior predictive value compared to models based solely on clinical indicators. CONCLUSIONS: The research highlighted the intricate interplay of clinical and imaging parameters in HT post-thrombectomy. It established a multifaceted predictive model, enhancing the understanding and management of acute ischemic stroke. Future studies should focus on validating this model in broader cohorts, further investigating the causal relationships, and exploring the nuanced effects of these parameters on patient outcomes post-stroke.


Asunto(s)
Accidente Cerebrovascular Isquémico , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Persona de Mediana Edad , Factores de Riesgo , Valor Predictivo de las Pruebas , Pronóstico , Anciano de 80 o más Años , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Trombectomía
10.
Lancet Respir Med ; 12(9): 671-680, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059398

RESUMEN

BACKGROUND: Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC. METHODS: This two-part (phase 2a and 2b), multicentre, single-arm, open-label, phase 2 study was done in 29 centres in China. Eligible participants were adults (aged ≥18 years) with histologically or cytologically confirmed ROS1-rearranged, locally advanced or metastatic stage IIIB-IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 2 or less. Patients who had previously received no or one ROS1 inhibitor were enrolled into phase 2a, and patients who were naive to ROS1 inhibitor therapy were enrolled into phase 2b cohort 1. Participants in phase 2a received 80, 120, 160, or 210 mg foritinib succinate (foritinib) orally once daily over 21-day cycles; patients in phase 2b received the recommended phase 2 dose of 160 mg. The primary endpoint was objective response rate, assessed by the independent review committee in the full analysis set (ie, all participants who received at least one dose of study treatment). The safety analysis set included all participants who received at least one dose of study treatment and had available safety assessments. This study is ongoing and is registered with ClinicalTrials.gov, NCT04237805. FINDINGS: Between March 26, 2020, and Dec 29, 2022, 104 patients were enrolled and treated. Six patients who had previously received more than one ROS1 inhibitor were enrolled in phase 2a before a protocol amendment stating that patients in this phase should have received no more than one ROS1 inhibitor; these patients were included in the safety analysis but excluded from the efficacy analysis of the ROS1-inhibitor-pretreated cohort. Therefore, the efficacy analysis set (n=98) included 42 patients from phase 2a (17 who were ROS1 inhibitor naive and 25 who had previously received ROS1 inhibitor) and 56 patients from phase 2b cohort 1. In phase 2a, the objective response rate was 94% (95% CI 71-100; 16 of 17 patients) in patients who were ROS1 inhibitor naive and 40% (21-61; ten of 25) in patients who had previously received ROS1 inhibitor. In phase 2b cohort 1, the objective response rate was 88% (95% CI 76-95; 49 of 56 patients). In a prespecified exploratory analysis in 41 patients with CNS metastases at baseline, the objective response rate was 100% (95% CI 48-100; five of five patients) in patients in phase 2a who were ROS1 inhibitor naive, 40% (16-68; six of 15) in patients in phase 2a who had previously received ROS1 inhibitor, and 90% (70-99; 19 of 21) in patients in phase 2b cohort 1. Grade 3-4 treatment-related adverse events occurred in 33 (32%) of 104 patients; the most common were hyperglycaemia (12 [12%] patients) and electrocardiogram prolonged QT interval (six [6%]). Serious treatment-related adverse events occurred in 11 (11%) patients, with hyperglycaemia (six [6%]) being most common. No treatment-related adverse events led to death. INTERPRETATION: Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases. FUNDING: Fosun Pharma, Wanbang Biopharmaceuticals, and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Anciano , China , Adulto , Reordenamiento Génico , Resultado del Tratamiento , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación
11.
Angew Chem Int Ed Engl ; : e202410110, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972839

RESUMEN

Nonaqueous organic aluminum batteries are considered as promising high-safety energy storage devices due to stable ionic liquid electrolytes and Al metals. However, the stability and capacity of organic positive electrodes are limited by their inherent high solubility and low active organic molecules. To address such issues, here porphyrin compounds with rigid molecular structures present stable and reversible capability in electrochemically storing AlCl2 +. Comparison between the porphyrin molecules with electron-donating groups (TPP-EDG) and with electron-withdrawing groups (TPP-EWG) suggests that EDG is responsible for increasing both highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels, resulting in decreased redox potentials. On the other hand, EWG is associated with decreasing both HOMO and LUMO energy levels, leading to promoted redox potentials. EDG and EWG play critical roles in regulating electron density of porphyrin π bond and electrochemical energy storage kinetics behavior. The competitive mechanism between electrochemical redox reaction and de/adsorption processes suggests that TPP-OCH3 delivers the highest specific capacity ~171.8 mAh g-1, approaching a record in the organic Al batteries.

12.
ACS Sens ; 9(8): 4216-4226, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39068608

RESUMEN

Thermoelectric (TE) hydrogels, mimicking human skin, possessing temperature and strain sensing capabilities, are well-suited for human-machine interaction interfaces and wearable devices. In this study, a TE hydrogel with high toughness and temperature responsiveness was created using the Hofmeister effect and TE current effect, achieved through the cross-linking of PVA/PAA/carboxymethyl cellulose triple networks. The Hofmeister effect, facilitated by Na+ and SO42- ions coordination, notably increased the hydrogel's tensile strength (800 kPa). Introduction of Fe2+/Fe3+ as redox pairs conferred a high Seebeck coefficient (2.3 mV K-1), thereby enhancing temperature responsiveness. Using this dual-responsive sensor, successful demonstration of a feedback mechanism combining deep learning with a robotic hand was accomplished (with a recognition accuracy of 95.30%), alongside temperature warnings at various levels. It is expected to replace manual work through the control of the manipulator in some high-temperature and high-risk scenarios, thereby improving the safety factor, underscoring the vast potential of TE hydrogel sensors in motion monitoring and human-machine interaction applications.


Asunto(s)
Aprendizaje Profundo , Hidrogeles , Temperatura , Dispositivos Electrónicos Vestibles , Humanos , Hidrogeles/química , Resinas Acrílicas/química , Carboximetilcelulosa de Sodio/química , Alcohol Polivinílico/química , Resistencia a la Tracción , Robótica
13.
Polymers (Basel) ; 16(14)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39065328

RESUMEN

In this paper, a comparative study of the mode-I fracture behaviors of two types of specimens with a V-notch defect under plane stress conditions was performed using the digital gradient sensing (DGS) method. First, two types of specimens (namely one-piece specimen and bonded specimen) with the same V-notch defect were both made of polymethyl methacrylate (PMMA), and three different V-notch angles' defect were considered for each type of specimen. Then, three-point bending tests were performed on both types of specimens. The angular deflection field of light near the V-notch region was recorded using a CCD during the experiments. Finally, by utilizing the relationship between the stress gradient and angular deflection as established by the elasto-optic effect, in conjunction with the principles of linear elastic fracture mechanics theory, the stress intensity factors (SIFs) of two types of specimens under different stress conditions were calculated using the least square method. According to the experimental results, the influence of V-notch angle on fracture load and fracture toughness of two kinds of specimens was discussed. Meanwhile, the experimental results show the significant differences in the fracture behaviors of the two types of specimens under mode-I loading conditions.

14.
Sensors (Basel) ; 24(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39065953

RESUMEN

Pavement condition monitoring is an important task in road asset management and efficient abnormal pavement condition detection is critical for timely conservation management decisions. The present work introduces a mobile pavement condition monitoring approach utilizing low-cost sensor technology and machine-learning-based methodologies. Specifically, an on-board unit (OBU) embedded with an inertial measurement unit (IMU) and global positioning system (GPS) is applied to collect vehicle posture data in real time. Through a comprehensive analysis of both time domain and frequency domain data features for both normal and abnormal pavement conditions, feature engineering is conducted to identify how the most important features affect abnormal pavement condition recognition. Six machine learning models are then developed to identify different types of pavement conditions. The performance of different algorithms and the significance of different features are then analyzed. Moreover, the influence of vehicle speed on pavement condition assessment is further examined and classification models for different speed intervals are developed. The results indicate that the random forest (RF) model that considers vehicle speed achieves the best performance in pavement condition monitoring. The outcomes of the present work would contribute to cost-effective pavement condition monitoring and provide an important reference for pavement maintenance sectors.

15.
J Cell Mol Med ; 28(14): e18521, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39021279

RESUMEN

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunohistoquímica , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Anciano , Nomogramas , Microambiente Tumoral/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transición Epitelial-Mesenquimal/genética , Estudios Retrospectivos
16.
Lancet Reg Health West Pac ; 48: 101122, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38993541

RESUMEN

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

17.
Mitochondrial DNA B Resour ; 9(6): 729-733, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859914

RESUMEN

The Sigara lateralis (Leach, 1817) is a small aquatic insect belonging to the family Corixidae. The study aims to reveal the genomic data of the mitochondrial genome of S. lateralis. The length of its circular mitochondrial genome is 15,725 bp long with an A + T bias (75.96%). The mitogenome comprises 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, and two rRNA genes. The phylogenetic analyses showed that the S. lateralis is the closest to S. septemlineata. These findings will help the conservation of Corixidae from the perspective of genetic evolution.

18.
J Imaging Inform Med ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862852

RESUMEN

Distal radius fracture (DRF) is one of the most common types of wrist fractures. We aimed to construct a model for the automatic segmentation of wrist radiographs using a deep learning approach and further perform automatic identification and classification of DRF. A total of 2240 participants with anteroposterior wrist radiographs from one hospital between January 2015 and October 2021 were included. The outcomes were automatic segmentation of wrist radiographs, identification of DRF, and classification of DRF (type A, type B, type C). The Unet model and Fast-RCNN model were used for automatic segmentation. The DenseNet121 model and ResNet50 model were applied to DRF identification of DRF. The DenseNet121 model, ResNet50 model, VGG-19 model, and InceptionV3 model were used for DRF classification. The area under the curve (AUC) with 95% confidence interval (CI), accuracy, precision, and F1-score was utilized to assess the effectiveness of the identification and classification models. Of these 2240 participants, 1440 (64.3%) had DRF, of which 701 (48.7%) were type A, 278 (19.3%) were type B, and 461 (32.0%) were type C. Both the Unet model and the Fast-RCNN model showed good segmentation of wrist radiographs. For DRF identification, the AUCs of the DenseNet121 model and the ResNet50 model in the testing set were 0.941 (95%CI: 0.926-0.965) and 0.936 (95%CI: 0.913-0.955), respectively. The AUCs of the DenseNet121 model (testing set) for classification type A, type B, and type C were 0.96, 0.96, and 0.96, respectively. The DenseNet121 model may provide clinicians with a tool for interpreting wrist radiographs.

19.
Sci Rep ; 14(1): 14604, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918493

RESUMEN

The precise delineation of urban aquatic features is of paramount importance in scrutinizing water resources, monitoring floods, and devising water management strategies. Addressing the challenge of indistinct boundaries and the erroneous classification of shadowed regions as water in high-resolution remote sensing imagery, we introduce WaterDeep, which is a novel deep learning framework inspired by the DeepLabV3 + architecture and an innovative fusion mechanism for high- and low-level features. This methodology first creates a comprehensive dataset of high-resolution remote sensing images, then progresses through the Xception baseline network for low-level feature extraction, and harnesses densely connected Atrous Spatial Pyramid Pooling (ASPP) modules to assimilate multi-scale data into sophisticated high-level features. Subsequently, the network decoder amalgamates the elemental and intricate features and applies dual-line interpolation to the amalgamated dataset to extract aqueous formations from the remote images. Experimental evidence substantiates that WaterDeep outperforms its existing deep learning counterparts, achieving a stellar overall accuracy of 99.284%, FWIoU of 95.58%, precision of 97.562%, recall of 95.486%, and F1 score of 96.513%. It also excels in the precise demarcation of edges and the discernment of shadows cast by urban infrastructure. The superior efficacy of the proposed method in differentiating water bodies in complex urban environments has significant practical applications in real-world contexts.

20.
BMC Cardiovasc Disord ; 24(1): 319, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914951

RESUMEN

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).


Asunto(s)
Angioplastia Coronaria con Balón , Catéteres Cardíacos , Fármacos Cardiovasculares , Materiales Biocompatibles Revestidos , Enfermedad de la Arteria Coronaria , Paclitaxel , Humanos , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/mortalidad , Resultado del Tratamiento , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , China , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Factores de Tiempo , Femenino , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Stents , Anciano , Stents Liberadores de Fármacos , Estudios de Equivalencia como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto
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