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Oncogenic alterations in RET have been identified in multiple tumour types, including 1–2% of non-small-cell lung cancers (NSCLCs). We aimed to assess the safety, tolerability, and antitumour activity of pralsetinib, a highly potent, oral, selective RET inhibitor, in patients with RET fusion-positive NSCLC. ARROW is a multi-cohort, open-label, phase 1/2 study done at 71 sites (community and academic cancer centres) in 13 countries (Belgium, China, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Spain, Taiwan, the UK, and the USA). Patients aged 18 years or older with locally advanced or metastatic solid tumours, including RET fusion-positive NSCLC, and an Eastern Cooperative Oncology Group performance status of 0–2 (later limited to 0–1 in a protocol amendment) were enrolled. In phase 2, patients received 400 mg once-daily oral pralsetinib, and could continue treatment until disease progression, intolerance, withdrawal of consent, or investigator decision. Phase 2 primary endpoints were overall response rate (according to Response Evaluation Criteria in Solid Tumours version 1·1 and assessed by blinded independent central review) and safety. Tumour response was assessed in patients with RET fusion-positive NSCLC and centrally adjudicated baseline measurable disease who had received platinum-based chemotherapy or were treatment-naive because they were ineligible for standard therapy. This ongoing study is registered with ClinicalTrials.gov, NCT03037385, and enrolment of patients with treatment-naive RET fusion-positive NSCLC was ongoing at the time of this interim analysis. Of 233 patients with RET fusion-positive NSCLC enrolled between March 17, 2017, and May 22, 2020 (data cutoff), 92 with previous platinum-based chemotherapy and 29 who were treatment-naive received pralsetinib before July 11, 2019 (efficacy enrolment cutoff); 87 previously treated patients and 27 treatment-naive patients had centrally adjudicated baseline measurable disease. Overall responses were recorded in 53 (61%; 95% CI 50–71) of 87 patients with previous platinum-based chemotherapy, including five (6%) patients with a complete response; and 19 (70%; 50–86) of 27 treatment-naive patients, including three (11%) with a complete response. In 233 patients with RET fusion-positive NSCLC, common grade 3 or worse treatment-related adverse events were neutropenia (43 patients [18%]), hypertension (26 [11%]), and anaemia (24 [10%]); there were no treatment-related deaths in this population. Pralsetinib is a new, well-tolerated, promising, once-daily oral treatment option for patients with RET fusion-positive NSCLC. Blueprint Medicines.

ObjectivesThe goal of the study was to determine whether endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is comparable to conventional transpapillary stenting with endoscopic retrograde cholangiopancreatography (ERCP) in palliation of malignant distal biliary obstruction. Although ERCP for the palliation of malignant biliary obstruction is the standard of care, post-procedure pancreatitis and stent dysfunctions are not uncommon. While EUS-BD has garnered interest as a viable alternative when ERCP is impossible, its role as a primary palliation of malignant distal biliary obstruction is yet to be proven.MethodsWe performed random allocation to EUS-BD or ERCP in 125 patients with unresectable malignant distal biliary obstruction at four tertiary academic referral centers in South Korea.ResultsTechnical success rates were 93.8% (60/64) for EUS-BD and 90.2% (55/61) for ERCP (difference 3.6%, 95% 1-sided confidence interval lower limit −4.4%, P = 0.003 for noninferiority margin of 10%). Clinical success rates were 90.0% (54/60) in EUS-BD and 94.5% (52/55) in ERCP (P = 0.49). Lower rates of overall adverse events (6.3% vs 19.7%, P = 0.03) including post-procedure pancreatitis (0 vs 14.8%), reintervention (15.6% vs 42.6%), and higher rate of stent patency (85.1% vs 48.9%) were observed with EUS-BD. EUS-BD was also associated with more preserved quality of life (QOL) than transpapillary stenting after 12 weeks of the procedure.ConclusionsThis study demonstrated comparable technical and clinical success rates between EUS-BD and ERCP in relief of malignant distal biliary obstruction. Substantially longer duration of patency coupled with lower rates of adverse events and reintervention, and more preserved QOL were observed with EUS-BD (cris.nih.go.kr, Identifier: KCT0001396, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=9716<ype=&rtype=).

Alectinib, a potent ALK tyrosine kinase inhibitor, was more effective and somewhat less toxic than crizotinib when used as primary therapy in patients with ALK -positive non–small-cell lung cancer. Importantly, it reduced the risk of CNS relapse.

AZD9291, an irreversible inhibitor of epidermal growth factor receptor, was associated with tumor responses in the majority of patients with advanced non–small-cell lung cancer in whom T790M-mediated drug resistance to other EGFR tyrosine kinase inhibitors had developed. Somatic mutations in the gene encoding epidermal growth factor receptor ( EGFR ) are detected in approximately 30 to 40% of non–small-cell lung cancers (NSCLCs) from Asian patients and in 10% of NSCLCs from white patients. 1 – 3 EGFR mutations lead to constitutive activation of EGFR signaling and oncogenic transformation both in vitro and in vivo. 4 , 5 Cancers with EGFR mutations ( EGFR- mutated cancers) depend on EGFR signaling for growth and survival and are often sensitive to treatment with EGFR tyrosine kinase inhibitors. 6 Among patients with advanced EGFR- mutated NSCLC, treatment with EGFR tyrosine kinase inhibitors (e.g., gefitinib, erlotinib, and . . .

Polymer electrolyte membrane water electrolysis (PEMWE) is an attractive hydrogen energy production technology that offers various advantages such as compact design, high operating pressure, high current densities, and high hydrogen gas purity. However, PEMWE still faces several critical challenges, particularly with respect to the oxygen evolution reaction (OER) at the anode. Highly active, corrosion‐resistant electrocatalytic materials are required for the acidic OER owing to its sluggish kinetics involving four‐electron transfer under harsh anodic potentials. To date, IrO2‐ or RuO2‐based noble metal electrocatalysts have been employed as commercial acidic OER electrocatalysts for PEMWE. However, they remain inadequate in terms of satisfying the industrial activity/stability‐related requirements. Above all, the two noble metals are too rare and expensive, which significantly inhibits widespread commercialization of PEMWE. Therefore, low‐cost, highly active, and highly stable OER electrocatalysts that can operate in acidic media must be urgently developed. This review paper presents various state‐of‐the‐art strategies employed to address the aforementioned issues by classifying them according to objectives such as improving activity, enhancing stability, and reducing cost. Then, finally, we summarize major tasks and strategies to overcome them and put forward a few issues in this field. In this review, we reviewed the development of oxygen evolution reaction electrocatalytic materials operating in acidic electrolytes and presented directions to be taken for commercialization of hydrogen production through polymer electrolyte membrane water electrolysis technology.

In an interim analysis of a trial involving 296 patients with ALK -positive non–small-cell lung cancer, lorlatinib, an anaplastic lymphoma kinase inhibitor, was superior to crizotinib in response (in 76% vs. 58%), 12-month progression-free survival (78% vs. 39%), and intracranial disease response (82% vs. 23%). Altered lipid levels were the major toxic effect associated with lorlatinib.

In this paper, we investigate the spectra of the prospective hidden-bottom and -charm hexaquark states with quantum numbers J PC = 0 + + , 0 - + , 1 + + and 1 - - in the framework of QCD sum rules. By constructing appropriate interpreting currents, the QCD sum rules analyses are performed up to dimension 12 of the condensates. Results indicate that there exist two possible baryonium states in b -quark sector with masses 11.84 ± 0.22 GeV and 11.72 ± 0.26 GeV for 0 + + and 1 - - , respectively. The corresponding hidden-charm partners are found lying respectively at 5.19 ± 0.24 GeV and 4.78 ± 0.23 GeV. Note that these baryonium states are all above the dibaryon thresholds, which enables their dominant decay modes could be measured at BESIII, BELLEII, and LHCb detectors.

To accomplish mass hydrogen production by electrochemical water-splitting, it is a necessary to develop robust, highly active, stable, and cost-effective hydrogen evolution reaction (HER) electrocatalysts that perform comparably to Pt in the universal pH range. In this work, cobalt phosphide hybrid nanosheets supported on carbon felt (CoP HNS/CF) are presented, which exhibit the superior electrocatalytic hydrogen production under a universal-pH. In these nanosheets, a single CoP HNS is composed of polycrystalline CoP and oxygen-enriched amorphous Co-O-P phase. Benefiting from its unique nanoarchitecture, as-fabricated CoP HNS/CF exhibits a tremendous electrocatalytic HER activity and outperforms Pt/C as well as state-of-the-art CoP electrocatalysts in universal-pH. In acidic and neutral media, the CoP HNS/CF shows superior electrocatalytic activity while maintaining its original hybrid crystalline-amorphous phase and morphology. In alkaline medium, the unexpected phase and morphological reorganization of CoP HNS/CF results in outstanding electrocatalytic operation. CoP HNS/CF not only achieves high electrocatalytic activity and kinetics, but also a stable and long operating lifetime even under a high current density of 500 mA·cm−2. Furthermore, the fabrication of CoP HNS/CF can be scaled up easily, and the large CoP HNS/CF electrode also exhibits similar electrocatalytic activity and stability.

Silicon has emerged as the most promising high-capacity material for lithium-ion batteries. Waste glass can be a potential low cost and environmentally benign silica resource enabling production of nanosized silicon at the industry level. Windshields are generally made of laminated glass comprising two separate glass bonded together with a layer of polyvinyl butyral sandwiched between them. Herein, silicon/carbon nanocomposites are fabricated from windshields for the first time via magnesiothermic reduction and facile carbonization process using both waste glass and polyvinyl butyral as silica and carbon sources, respectively. High purity reduced silicon has unique 3-dimensional nanostructure with large surface area. Furthermore, the incorporation of carbon in silicon enable to retain the composite anodes highly conductive and mechanically robust, thus providing enhanced cycle stability.

Circulating soluble programmed death-1 ligand (sPD-L1) is measurable in the serum of cancer patients. This study aimed to investigate the significance of sPD-L1 in cancer patients receiving immune checkpoint inhibitor therapy. Blood samples were obtained before and after immune checkpoint inhibitor therapy (January 2015 to January 2019). The study cohort consisted of 128 patients who were diagnosed with non-small cell lung cancer (n = 50), melanoma (n = 31), small cell lung cancer (n = 14), urothelial carcinoma (n = 13), and other cancers (n = 20). Patients with a high level (> 11.0 pg/μL) of sPD-L1 were more likely to exhibit progressive disease compared with those with a low level (41.8% versus 20.7%, p = 0.013). High sPD-L1 was also associated with worse prognosis; the median PFS was 2.9 (95% confidence interval [CI] 2.1–3.7) months versus 6.3 (95% CI 3.0–9.6) months (p = 0.023), and the median OS was 7.4 (95% CI 6.3–8.5) months versus 13.3 (95% CI 9.2–17.4) months (p = 0.005). In the multivariate analyses, high sPD-L1 was an independent prognostic factor for both decreased PFS (HR 1.928, p = 0.038) and OS (HR 1.788, p = 0.004). sPD-L1 levels did not correlate with tissue PD-L1 expression. However, sPD-L1 levels were positively correlated with neutrophil to lymphocyte ratios and negatively correlated with both the proportion and the total number of lymphocytes. We found that high pretreatment sPD-L1 levels were associated with progressive disease and were an independent prognostic factor predicting lower PFS and OS in these patients.