Gotowa bibliografia na temat „21 shi ji”

Abstract Background: Surufatinib (S, a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) plus toripalimab (T, an anti-PD-1 antibody) showed encouraging antitumor activity in solid tumors (Cao YS, 2022). Programmed death ligand 1 (PD-L1) expression is the established biomarker for 1L immune checkpoint inhibitors therapy in advanced NSCLC. We conducted an open-label, multi-cohort, single-arm phase 2 study to evaluate the safety and efficacy of S+T in patients (pts) with advanced solid tumors. Here, we reported the results of advanced NSCLC with PD-L1 positive expression cohort. Methods: Eligible pts had histologically confirmed advanced NSCLC with no prior systemic chemotherapy, PD-L1 positive (defined as PD-L1 TPS expression ≥1% [sp263]), and without EGFR, ALK or ROS1 genetic alteration if non-sq-NSCLC. Enrolled pts received 21-day cycles of S (250 mg orally QD) plus T (240 mg IV, Q3W) until disease progression or intolerable toxicity or the maximum duration of treatment with toripalimab is 24 months. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From July 2020 to September 2021, 55 pts were screened, of whom 23 pts were enrolled and received the treatment of S+T. Median age was 66 years (range: 49-73), 16 (69.6%) were male and 12 (52.2%) had squamous histology. Pts with PD-L1 TPS ≥50% and <50% were 10 and 13 respectively. At the data cutoff (Aug 31, 2022), the median follow-up duration was 13.1 mos. Among 21 pts with at least one post-baseline tumor assessment, the confirmed ORR was 57.1%, the median DOR was 8.31 mos, and DCR was 100%. Median PFS (mPFS) (95% CI) was 9.63 mos (5.49, -), median OS (mOS) (95% CI) was not reached (10.78, -), 12m-OS rate was 64%. According to PD-L1 level, the confirmed ORR were 66.7% and 50% for pts with PD-L1 TPS ≥50% and <50%, respectively; mPFS were 9.66 (0.69, -) and 6.93 mos (1.64, -), respectively; and the 12m-OS rate were 70% and 62%, respectively. mPFS did not differ with histology: 9.66 mos (5.49, -) for squamous cell carcinoma and 9.63 mos (0.69, -) for adenocarcinoma. All pts experienced ≥1 treatment emergent adverse event (TEAE). The most common Gr ≥3 TEAEs (≥5% pts) were aspartate aminotransferase increased (17.4%), malignant neoplasm progression (17.4%), hypokalemia (13.0%), hepatic function abnormal (13.0%), lymphocyte count decreased (8.7%), hypertension (8.7%) and pneumonitis (8.7%). Conclusion: Surufatinib and toripalimab combination showed a promising antitumor activity in 1L therapy for advanced PD-L1 positive NSCLC with manageable toxicity. This study might represent a potential treatment option for these pts. Clinical trial information: NCT04169672. Citation Format: Ying Cheng, Lin Shen, Zhendong Chen, Feng Ye, Xianjun Yu, Xing Zhang, Dongmei Ji, Baorui Liu, Lijie Song, Chunjiao Wu, Ming Lu, Wei Chen, Jingxun Wu, Heli Gao, Desheng Weng, Weina Shen, Rutian Li, Minjie Yang, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su. Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT225.

The presence of water inside a lithium ion (Li-ion) battery causes several interconnected chemical mechanisms that lead to material degradation including transition metal dissolution. [1-4]. As a result, cell performance is reduced, and the cell capacity rapidly fades. To mitigate transition metal dissolution caused by trace water, research groups have proposed various approaches to scavenge and neutralize the water within different components of the cell [4-6]. These methods include using a dehydratable molecular sieve within the cathode active material powder [6], direct dosing of the electrolyte with a water scavenging additive [5], and introducing a metal organic framework with water scavenging properties by mixing it with a polymer binder to create a film for use as a separator. Results from these studies show promise in improving the cycling stability of cells under abuse conditions, such as elevated temperature and high water content in the electrolyte. While these water scavenging techniques show clear benefits to cell capacity retention, they come with the trade-off of higher material cost, more complex production processes, and lower energy density, which have limited their widespread adoption in Li-ion batteries. This study focuses on the use of “cellulose”, a cheap, abundant and naturally dehydrating biopolymer, as a separator material. Cellulose-based separators have been used in Li-ion batteries and shown to be advantageous for capacity retention of the cells. The benefits of the cellulose separators have been attributed to their superior wettability, uniform pore size distribution, high porosity, and low electrical resistance [7-10]. Despite their well-known hydrophilicity, their water scavenging capabilities have not been thoroughly evaluated. In this work, we present new insights into the interaction of water with cellulose-based separator. The water scavenging properties of the cellulose separator are investigated both outside of the battery using the Karl-Fischer Coulometric Titration technique, and inside of the battery through cycling tests. As shown in Figure 1, replacing the conventional polymer-based separator with a cellulose-based nonwoven separator resulted in a significant improvement in cycle life. Furthermore, the water scavenging mechanism of cellulose-based nonwoven separator is studied using surface chemistry characterizations, suggesting water scavenging by the naturally occurring hydrogen bonding sites of cellulose. Additional discussion on drying conditions and the impact of other fiber types are also provided. References: Etacheri, V.; Marom, R.; Elazari, R.; Salitra, G.; Aurbach, D. Challenges in the development of advanced Li-ion batteries: a review. Energy & Environmental Science 2011, 4 (9), 3243-3262. Yoon, T.; Park, S.; Mun, J.; Ryu, J. H.; Choi, W.; Kang, Y.-S.; Park, J.-H.; Oh, S. M. Failure mechanisms of LiNi0. 5Mn1. 5O4 electrode at elevated temperature. Journal of power sources 2012, 215, 312-316. Lux, S.; Lucas, I.; Pollak, E.; Passerini, S.; Winter, M.; Kostecki, R. The mechanism of HF formation in LiPF6 based organic carbonate electrolytes. Electrochemistry Communications 2012, 14 (1), 47-50 Chang, Z.; Qiao, Y.; Deng, H.; Yang, H.; He, P.; Zhou, H. A stable high-voltage lithium-ion battery realized by an in-built water scavenger. Energy & Environmental Science 2020, 13 (4), 1197-1204. Sheha, E.; Refai, H. Water scavenger as effective electrolyte additive and hybrid binder‐free organic/inorganic cathode for Mg battery applications. Electrochimica Acta 2021, 372, 137883. Zhang, H.; Shi, L.; Zhao, Y.; Wang, Z.; Chen, H.; Zhu, J.; Yuan, S. A simple method to enhance the lifetime of Ni-rich cathode by using low-temperature dehydratable molecular sieve as water scavenger. Journal of Power Sources 2019, 435, 226773. Gwon, H.; Park, K.; Chung, S.-C.; Kim, R.-H.; Kang, J. K.; Ji, S. M.; Kim, N.-J.; Lee, S.; Ku, J.-H.; Do, E. C. A safe and sustainable bacterial cellulose nanofiber separator for lithium rechargeable batteries. Proceedings of the National Academy of Sciences 2019, 116 (39), 19288-19293. Jiang, F.; Yin, L.; Yu, Q.; Zhong, C.; Zhang, J. Bacterial cellulose nanofibrous membrane as thermal stable separator for lithium-ion batteries. Journal of Power Sources 2015, 279, 21-27. Wang, Y.; Liu, X.; Sheng, J.; Zhu, H.; Yang, R. Nanoporous regenerated cellulose separator for high-performance lithium ion batteries prepared by nonsolvent-induced phase separation. ACS Sustainable Chemistry & Engineering 2021, 9 (44), 14756-14765. Lv, D.; Chai, J.; Wang, P.; Zhu, L.; Liu, C.; Nie, S.; Li, B.; Cui, G. Pure cellulose lithium-ion battery separator with tunable pore size and improved working stability by cellulose nanofibrils. Carbohydrate polymers 2021, 251, 116975. Figure 1

Background:Systemic lupus erythematosus (SLE) is a chronic disease characterized by periodic flares associated with poor outcomes and subsequent organ damage (1-2). Flare prevention is important for optimal patient management and development of effective therapies.Objectives:To identify patient-level factors associated with flares among patients with moderate/severe SLE.Methods:We conducted a post-hoc analysis of 260 patients with active, autoantibody+ SLE enrolled in a phase II randomized clinical trial (Fenebrutinib) (3). The relationship between baseline demographic (age, gender, ethnicity, BMI), region (US/EU, outside US/EU), disease severity (PGA, SLEDAI-2K, BILAG domain involvement), disease duration, serologic markers (C3, C4, ANA, anti-dsDNA Ab, anti-Smith Ab), treatment arm, standard of care (SOC) and flares (BILAG and SFI) over 48 wks was assessed by survival analysis and multiple Cox Proportional Hazard models. We examined concordance between BILAG and SFI flares using Cohen’s Kappa Index.Results:The overall rate of flare was low (n=37 SFI flare, n=25 BILAG flare). Median time to first flare was 8 wks for SFI flares compared to 12 wks for BILAG flares. There was no difference in flare rate by treatment arm. Cumulative flare hazard increased over time. Concordance between SFI and BILAG flares was 0.14. Multivariable analyses identified a higher flare rate for both SFI and BILAG-defined flares in patients with severe disease at baseline (PGA >1.7, SLEDAI-2K ≥10) and <7 y disease duration.Flares were more common in patients ANA, anti-dsDNA and anti-Smith+ at baseline compared to patients with <3 + markers (p<.001). Furthermore, anti-dsDNA (p = .03) and/or anti-Smith (p = .001) positivity at baseline were better indicators of higher flare rate compared to ANA (p = 0.5). Low baseline complement level (C3 and C4) was associated with a higher flare rate (p = .03 and p = .03 respectively).Patients from non-US/EU regions had a higher flare rate compared to patients from the US/EU, despite receiving more frequent SOC therapy and higher baseline corticosteroid doses (≥10 mg/d). Overall, flare-free probability was comparable at 48 wks regardless of baseline corticosteroid dose but patients receiving <10 mg/d had a median time to flare of 4 vs 24 wks for those receiving ≥10 mg/d (p = .004).Conclusion:In this study, flares were more common among patients with more severe disease, shorter disease duration, multiple serologic markers, were from outside the US/EU, and received lower steroid doses at baseline.References:[1]Fernandez D and Kirou KA. Curr Rheumatol Rep 2016 18:14.[2]Stoll T, et al. Rheum (Oxford) 2004 43(8):1039–44.[3]Isenberg D, et al. Arth Rheum 2019 71 suppl 10.Baseline Factors (%)No Flare n=206FlareBILAG n=25SFI n=37BILAG and SFI n=8Age (mean (SD))41.8 (12)35.2 (9)40.4 (10)34.9 (8)Female199 (97)24 (96)35 (95)7 (88)PGA (mean (SD))1.7 (0.5)1.7 (0.4)1.9 (0.5)1.7 (0.6)BILAG A/B any domain197 (96)23 (92)35 (95)7 (88)SLEDAI 2K >=1087 (42)18 (72)17 (46)4 (50)Disease duration (y) (mean (SD))9.4 (7)5.3 (4)6.6 (6)2.9 (3)ANA +203 (99)24 (96)35 (95)8 (100)anti-dsDNA +102 (50)18 (72)21 (57)5 (63)anti-Smith +45 (22)13 (52)12 (32)4 (50)Low C357 (28)12 (48)13 (35)3 (38)Low C426 (13)7 (28)4 (11)1 (13)Non US/EU157 (76)21 (84)32 (87)8 (100)Corticosteroid130 (63)14 (56)21 (57)5 (63) ≥10 mg/d80 (39)9 (36)14 (38)4 (50)Immunosuppressant74 (36)12 (48)15 (41)3 (38)Antimalarial135 (66)14 (56)21 (57)5 (63)Notes: included patients 18-75 y; 1+ serologic marker of SLE; SLEDAI-2K >=8, PGA>=1; 1+ oral SOC treatmentSFI = SELENA- SLEDAI Flare IndexDisclosure of Interests:Lisa Lindsay Shareholder of: Employee of Genentech, Inc., Employee of: Employee of Genentech, Inc., Huiyan (Ashley) Mao Shareholder of: Employee of Hoffmann-La Roche Limited, Employee of: Employee of Hoffmann-La Roche Limited, Ji (Emmy) Cheng Shareholder of: Employee of Hoffmann-La Roche Limited, Employee of: Employee of Hoffmann-La Roche Limited, Ching-Yi Chuo Shareholder of: Employee of Genentech, Inc., Employee of: Employee of Genentech, Inc., Nicholas Jones Shareholder of: Employee of Genentech, Inc., Employee of: Employee of Genentech, Inc., Matthew D. Cascino Shareholder of: Employee of Genentech, Inc., Employee of: Employee of Genentech, Inc., Katie Tuckwell Shareholder of: Employee of Genentech, Inc., Employee of: Employee of Genentech, Inc.

Nanohybrid materials can exhibit the physical properties of their components and be used in various applications. Also, novel chromophores involving synthetically flexible molecules such as pyrazinacenes1 and porphyrins2 can be incorporated into these structures by different means in particular as MOFs or COFs, while other components include simple transition metal salts or oligonuclear metal-oxo clusters. In this work, we discuss nanohybrids materials containing oxoporphyrinogen (OxP), tetrapyrroles or fullerene as the organic component, with hybridization using respectively Ag(I) salt or oxo-Zr(IV) cluster. This yields nanohybrid materials having structures and properties due to their individual components. Highly-colored OxP is a tetrapyrrole macrocycle which can be stimulated to generate reactive singlet oxygen (1O2) under appropriate conditions (1O2 can be used for applications such as photodynamic therapy and environmental remediation). 1O2 generation by OxP undergoes significant enhancement over its unhybridized state when incorporated in nanohybrid structures, either MOFs or COFs, containing respectively oxo-Zr(IV) nodes or electron deficient linkers in porous coordination polymer nanoarchitectures. OxP-oxoZr(IV) nanohybrid can then be applied for oxidation of small molecule substrates to selected products.3 Also, C60 fullerene can be co-crystallized with silver(I) nitrate at the molecular level4 leading to a material that exhibits unique properties during its decomposition so that silver nitrate is released with concurrent deposition of highly nanostructured C60-only crystalline networks. The resulting nanohybrid material has been studied for application as slow-release antibacterial material.4 Other work includes porous materials for sensing applications. The utility of the nanohybrid approaches is demonstrated by using these examples. References: 1) G. J. Richards, J. P. Hill, Acc. Chem. Res., 2021, 54, 3228–3240. 2) M. K. Chahal, A. Liyanage, A. Z. Alsaleh, P. A. Karr, J. P. Hill, F. D'Souza, Chem. Sci., 2021, 12, 4925–4930. 3) J. Hynek, D.T. Payne, M.K. Chahal, F. Sciortino, Y. Matsushita, L.K. Shrestha, K. Ariga, J. Labuta, Y. Yamauchi, J.P. Hill, Mater. Today Chem., 2021, 21, 100534. 4) J. P. Hill, R. G. Shrestha, J. Song, Q. Ji, K. Ariga, L. K. Shrestha, Bull. Chem. Soc. Jpn., 2021, 94, 1347–1354.

Abstract Purpose: The primary role of sentinel lymph node biopsy (SLNB) for early breast cancer (BC) is axillary staging. In terms of clearance of axillary disease or prevention of recurrence, its role may be limited considering the low axillary recurrence rate of less than 2% even though false-negative rates are 5-10% and the 25% additional axillary lymph node (ALN) detection in the ALND arms of the ACOSOG Z0011 and AMAROS trials. The NAUTILUS trial (NCT04303715) randomized cT1-2/N0 BC patients planned for breast-conserving surgery to evaluate the non-inferiority of omitting SLNB regarding 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. We aimed to investigate the clinicopathologic characteristics and ALN status of the subjects enrolled in the NAUTILUS trial. Methods: NAUTILUS trial randomized 1,734 subjects into SLNB or no-SLNB arms from September 2020 to October 2022. Axillary ultrasonography was mandatory to determine clinical N0, defined as no suspicious ALN or no tumor on ultrasound-guided biopsy of suspicious ALN. Clinicopathologic variables and the ALN status of the SLNB arm were analyzed. Results: Among 1,734 enrolled subjects, 828 (50.3%) and 818 (49.7%) subjects in the SLNB and no-SLNB arms, respectively, were included for analysis. Clinical and pathologic T stage, hormonal receptor/HER2 status, histologic grade, age, menopausal status, and Ki-67 were evenly distributed between the two groups (p = 0.554, 0.350, 0.056, 0.369, 0.623, 0.725 and 0.214, respectively). Median age was 55.3 (range, 48.0-62.0) years, and 661 (40.2%) were premenopausal. Overall, 30 (1.8%), 1,382 (84.0%), and 229 (13.9%) subjects were pTmic, pT1, and pT2, respectively, and median tumor size was 1.3 cm (range, 0.1-5.0). In the SLNB group, 94 (11.4%) had ALN metastasis, of which 9 (1.1%), 78 (9.4%), and 5 (0.6%) were pN1mic, pN1, and pN2-3, respectively (Table 1). According to pathologic tumor size, 5.8% (16/279), 11.4% (48/421), and 23.8% (30/126) were ALN positive for ≤ 1.0 cm, &gt;1.0cm & ≤ 2.0 cm, and &gt; 2.0 & ≤ 5.0 cm, respectively. The clinical and pathologic tumor size distribution among subjects with ALN metastasis were 23 (24.5%), 43 (45.7%), 9 (9.6%) and 16 (17.0%), 48 (51.1%), 30 (31.9%), respectively, for ≤ 1.0 cm, &gt;1.0cm & ≤ 2.0 cm, and &gt; 2.0 & ≤ 5.0 cm (Table 2). Among them, 12 (12.8%) received subsequent ALND. There was no difference in ALN metastasis rate according to molecular subtype, histologic grade, age, menopausal status, and Ki-67 (p= 0.812, 0.204, 0.671, and 0.101, respectively). Conclusions: The NAUTILUS trial completed enrollment of 1,734 subjects, among which 1,646 are available to analyze basic clinicopathologic characteristics. The trial included 229 (13.9%) pT2 and 661 (40.2%) premenopausal subjects and is expected to show the impact of SLNB omission in these subgroups. Data lock is expected in October 2027. Patients characteristics SLNB, sentinel lymph node biopsy; LVI, lymphovascular invasion; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; HER2, anti-human epidermal growth factor-2; BCS, breast conserving surgery; TM, total mastectomy; ALND, axillary lymph node dissection Basic characteristics for sentinel lymph node biopsy group a revealed no lymph node metastasis by fine needle aspiration or gun biopsy ALN, axillary lymph node; LN, lymph node Citation Format: Jai Min Ryu, Han-Byoel Lee, Sei Hyun Ahn, Il-Yong Chung, Seeyoun Lee, Seho Park, Woosung Lim, Joon Jeong, Jeong Eon Lee, Eunhye Kang, Ji Hyun Chang, Jung Min Chang, Woo Kyung Moon, Wonshik Han, Eun-Kyu Kim. What to expect from the No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS] trial (KBCSG-21): Clinicopathologic characteristics and axillary lymph node status of enrolled patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-03.

Background:Systemic lupus erythematosus (SLE) is an autoimmune disorder more prevalent in the Asian population vs Caucasians. Belimumab (BEL), a monoclonal antibody targeting B-lymphocyte stimulator, is approved in patients (pts) ≥5 years with active, autoantibody-positive SLE.Objectives:Evaluate long-term safety and efficacy of intravenous (IV) BEL + standard SLE therapy (SST) in pts with SLE in Japan/Korea.Methods:In this Phase 3, multicentre, open-label (OL) study (BEL114333;NCT01597622), eligible (≥18 years of age) completers of the double-blind phase of GSK study BEL113750 in Japan and South Korea or the subcutaneous OL phase of GSK Study BEL112341 in Japan, received monthly BEL 10 mg/kg IV plus SST. Primary endpoints: safety assessments. Key secondary endpoints: SRI4 response rate at each scheduled visit (observed data), defined as a ≥4-point reduction from baseline in SELENA-SLEDAI score, no worsening in PGA (<0.3-point increase from baseline) and no new BILAG 1A/2B organ domain scores; time to first severe SFI flare over time. Endpoints were analysed relative to first BEL dose (parent or current study). No follow-up data were collected after study withdrawal.Results:Overall, 142 pts were enrolled (Japan n=72; Korea n=70), 104 (73.2%) completed the study, 1 (0.7%) died and 37 (26.1%) withdrew.Overall, 139 (97.9%) pts had ≥1 adverse event (AE) (Table). Most frequent AEs included: nasopharyngitis (60.6%); headache (28.2%); cough, herpes zoster and viral upper respiratory tract infection (18.3% each). Serious AEs (SAEs) occurred in 48 (33.8%) pts. Most common SAEs were infections and infestations, reported in 24 (16.9%) pts (Table). During this study, the annual incidence of AEs, including SAEs and AESI, remained stable or declined, with no trends of clinical concerns regarding the incidence of Grade 3 or 4 values for laboratory parameters. There was 1 transient positive immunogenicity result of no clinical concern.Table.The proportion of SRI4 responders was 47.8% at Year 1 (Week 24) and tended to increase numerically up to 84.6% at Year 7 (Week 48). The proportion of pts with a ≥4-point decrease from baseline in SELENA-SLEDAI score numerically increased from 51.5% at Year 1 (Week 24) to 84.6% at Year 7 (Week 48). Proportion of pts with no PGA worsening was 91.3-100% and the proportion with no new BILAG 1A/2B organ domain scores was 93.3-100% up to Year 7 (Week 48). A total of 21 (14.8%) pts had 24 severe SFI flares.Conclusion:BEL was well tolerated as add-on therapy to SST for ≤7 years in pts with SLE from Japan/Korea. Safety results were consistent with the known BEL safety profile.Study funding: GSK.Disclosure of Interests:Yoshiya Tanaka Grant/research support from: Received research grants from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Ono, Speakers bureau: Received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin, Sang-Cheol Bae: None declared, Damon Bass Shareholder of: GSK, Employee of: GSK, Myron Chu Shareholder of: GSK, Employee of: GSK, Paula Curtis Shareholder of: GSK, Employee of: GSK, Kathleen DeRose Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Regina Kurrasch Shareholder of: GSK, Employee of: GSK, Jenny Lowe Shareholder of: GSK, Employee of: GSK, Paige Meizlik Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

Abstract Background RMC-6291 is a potent, covalent, orally bioavailable KRASG12C(ON) inhibitor that uses a novel tri-complex mechanism to selectively target the active, GTP-bound state of the oncogenic KRASG12C. In preclinical models, RMC-6291 achieved a superior response rate, deeper regressions and longer duration of response compared to the KRASG12C(OFF) inhibitor, adagrasib. Receptor tyrosine kinase (RTK) overexpression and/or hyperactivating alterations and new synthesis of KRASG12C(ON) have been identified as potential resistance mechanisms to KRASG12C(OFF) inhibitors. Preclinical modeling shows KRASG12C(ON) inhibitors retain potency in cells with RTK activation and further are expected to rapidly extinguish newly synthesized KRASG12C(ON). Methods Patients with previously treated, advanced KRASG12C-mutated solid tumors received escalating doses of RMC-6291. Doses included 50, 100, and 200mg once daily (QD) and 100, 200, 300, and 400mg twice daily (BID). Each cycle had 21 days, with efficacy assessed every 6 weeks. Additional patients were enrolled to backfill cohorts at dose levels that cleared dose-limiting toxicity evaluation to further characterize PK, safety, and anti-tumor activity of RMC-6291. Results As of August 8, 2023, 47 patients with KRASG12C mutated solid tumors were treated, and 35 remained on treatment. The median number of prior therapies was 3 (range, 1-7). RMC-6291 exhibited dose-dependent exposure with a median Tmax of 1.0 hour and terminal half-life of 1.8 hours. Modeling projected average target occupancy of ≥~90% at 100mg BID and above. Treatment-related adverse events (TRAEs) occurring in ≥10% of patients were nausea (34%), diarrhea (30%), QTc prolongation (21%), vomiting and fatigue (15% each). The most common Gr3 TRAEs were QTc prolongation reported in 5 patients (3 at 400mg BID, 1 at 300mg, 1 at 200mg BID). Only one out of these 5 patients had an average QTc interval &gt;501ms. Most events of Gr3 QTc prolongation resolved to Gr1 or normal following dose interruption and/or reduction, and all 5 patients were asymptomatic and remained on treatment at a reduced dose. No treatment-related ≥Gr3 hepatotoxicity was observed. No patients experienced a treatment-related Gr4 or 5 AE, or a treatment-emergent AE that led to treatment discontinuation. Efficacy analysis was conducted in two dominant subgroups and included patients enrolled ≥8 weeks before data cutoff across all dose levels. The objective response rate was 57% (4/7; 3 confirmed) in NSCLC patients with recent prior KRASG12C(OFF) inhibitor treatment, and 44% (4/9; 3 confirmed) in CRC patients naive to KRASG12C(OFF) inhibitor treatment. Conclusions This preliminary data set shows promising anti-tumor activity of RMC-6291 in KRASG12C-mutated NSCLC with recent prior KRASG12C(OFF) inhibitor treatment, and in KRASG12C-mutated CRC naive to KRASG12C(OFF) inhibitor treatment. Tolerability was acceptable below 400mg BID, suggesting the potential for combination with standard therapy, including immunologic agents. Dose optimization is ongoing. Citation Format: Pasi A. Jänne, Frédéric Bigot, Kyriakos Papadopoulos, Lauriane Eberst, David Sommerhalder, Loic Lebellec, Pei Jye Voon, Bruna Pellini, Ewa Kalinka, Kathryn Arbour, Benjamin Herzberg, Valentina Boni, Stephanie Bordenave, Hyun Woo Lee, Sai I. Ou, Jonathan Wesley Riess, Joseph T. Beck, Mariano Ponz-Sarvise, Paolo Antonio Ascierto, Yoon Ji Choi, Michelle Yang, Lei Bao, Rakesh Raman, Luxi Yang, Yunming Mu, Sofia Wong, Richa Dua, Melissa Johnson. Preliminary safety and anti-tumor activity of RMC-6291, a first-in-class, tri-complex KRASG12C(ON) inhibitor, in patients with or without prior KRASG12C(OFF) inhibitor treatment [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR014.

The development of Sodium-ion battery technologies and materials is moving rapidly forward, and several companies are on the verge of commercialising their products. An important question is what knowledge and synergies that can be drawn from Lithium-ion batteries. This work has investigated whether the Doyle-Fuller-Newman model (DFN model) [1] can be used for simulating the insertion and extraction of mobile sodium ion in hard carbon. Previous work indicates that this should be the case [2]–[4]. It has been shown that the insertion process of sodium in hard carbon does not follow the same process as for lithium in hard carbon [5]. The sodium insertion in hard carbon is suggested to be a combination of capacitive adsorption, intercalation and nanopore filling [6]–[8]. Hence, the question is if capacitive adsorption and nanopore filling can be simulated as an intercalation process. In addition, the sodium-ion has a lower charge density than lithium-ion, leading to different properties for the electrolyte and the interfacial species [9], [10]. One of the issues with the DFN model is to measure, calculate or estimate the material and electrode properties needed. As a first step in investigating the above assumption, an additional assumption made is that the needed parameters can be extracted using similar methods as for Li-ion batteries. With this starting point, a parameter sensitivity analysis is made for simulating mobile sodium in hard carbon with the DFN model. References [1] M. Doyle, T. Fuller, and J. Newman, “Modeling of galvanostatic charge and discharge of the lithium/ polymer/insertion cell,” J. Electrochem. Soc., vol. 140, no. 6, pp. 1526–1533, 1993, doi: 10.1149/1.2221597. [2] K. Chayambuka, M. Jiang, G. Mulder, D. L. Danilov, and P. H. L. Notten, “Physics-based modeling of sodium-ion batteries part I: Experimental parameter determination,” Electrochim. Acta, vol. 404, p. 139726, Feb. 2022, doi: 10.1016/J.ELECTACTA.2021.139726. [3] K. Chayambuka, G. Mulder, D. L. Danilov, and P. H. L. Notten, “Physics-based modeling of sodium-ion batteries part II. Model and validation,” Electrochim. Acta, vol. 404, p. 139764, Feb. 2022, doi: 10.1016/J.ELECTACTA.2021.139764. [4] C. M. Doyle, “Peer Reviewed Title: Design and Simulation of Lithium Rechargeable Batteries,” 2010. Accessed: Feb. 01, 2021. [Online]. Available: http://www.escholarship.org/uc/item/6j87z0sp [5] H. D. Asfaw, C. W. Tai, M. Valvo, and R. Younesi, “Facile synthesis of hard carbon microspheres from polyphenols for sodium-ion batteries: insight into local structure and interfacial kinetics,” Mater. Today Energy, vol. 18, p. 100505, Dec. 2020, doi: 10.1016/j.mtener.2020.100505. [6] J. Y. Hwang, S. T. Myung, and Y. K. Sun, “Sodium-ion batteries: Present and future,” Chemical Society Reviews, vol. 46, no. 12. Royal Society of Chemistry, pp. 3529–3614, Jun. 21, 2017. doi: 10.1039/c6cs00776g. [7] D. Chen et al., “Hard carbon for sodium storage: mechanism and optimization strategies toward commercialization,” Energy Environ. Sci., vol. 14, no. 4, pp. 2244–2262, Apr. 2021, doi: 10.1039/D0EE03916K. [8] C. Bommier, T. W. Surta, M. Dolgos, and X. Ji, “New Mechanistic Insights on Na-Ion Storage in Nongraphitizable Carbon,” Nano Lett., vol. 15, no. 9, pp. 5888–5892, Sep. 2015, doi: 10.1021/ACS.NANOLETT.5B01969/ASSET/IMAGES/LARGE/NL-2015-01969W_0002.JPEG. [9] R. Mogensen, S. Colbin, and R. Younesi, “An attempt to formulate non‐carbonate electrolytes for sodium‐ion batteries,” Batter. Supercaps, p. batt.202000252, Dec. 2020, doi: 10.1002/batt.202000252. [10] L. A. Ma, A. J. Naylor, L. Nyholm, and R. Younesi, “Strategies for Mitigating Dissolution of Solid Electrolyte Interphases in Sodium-Ion Batteries,” Angew. Chemie - Int. Ed., 2020, doi: 10.1002/anie.202013803.

Heavy metals contamination is a serious threat to all life forms. Long term exposure of heavy metals can lead to different life-threatening medical conditions including cancers of different body parts. Phytoremediation and bioremediation offer a potential eco-friendly solution to such problems. Different microbes can interact with heavy metals in a variety of ways such as biotransformation, oxidation/reduction, and biosorption. Phytoremediation of the heavy metals using plants mostly involves rhizofilteration, phytoextraction, phytovolatization, and Phyto stabilization. A synergistic approach using both plants and microbes has proven much more efficient as compared to the individual applications of microbes or plants. This article aims to highlight the synergistic methods used in bioremediation, emphasizing the potent collaboration between bacteria and plants for environmental cleaning, along with the discussion of the importance of site-specific variables and potential constraints. 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Liquid crystal on silicon (LCOS) spatial light modulator (SLM) is the most widely used optical engine for digital holography. This paper aims to provide an overview of the applications of phase-only LCOS in two-dimensional (2D) holography. It begins with a brief introduction to the holography theory along with its development trajectory, followed by the fundamental operating principle of phase-only LCOS SLMs. Hardware performance of LCOS SLMs (in terms of frame rate, phase linearity and flicker) and related experimental results are presented. Finally, potential improvements and applications are discussed for futuristic holographic displays. Full Text: PDF ReferencesM. Wolfke, Physikalische Zeitschrift 21, 495 (1920). DirectLink D. Gabor, "A New Microscopic Principle", Nature 161, 777 (1948). CrossRef H. Haken, "Laser Theory", Light and Matter 5, 14 (1970). CrossRef S. Benton, "Selected Papers on Three-dimensional displays", SPIE Press (2001). DirectLink X. 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