bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patients with Locally Advanced Non–Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab
Authors: Lebow Emily S. , Shepherd Annemarie , Eichholz Jordan E. , Offin Michael , Gelblum Daphna Y. , Wu Abraham J. , Simone Charles B. , Schoenfeld Adam J. , Jones David R. , Rimner Andreas , Chaft Jamie E. , Riaz Nadeem , Gomez Daniel R. , Shaverdian Narek 
Published: January 2023

ImportanceThe addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non–small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization.ObjectivesTo evaluate whether TMB or other variants associated with radiation response are also associated with outcomes following definitive chemoradiation and adjuvant durvalumab among patients with locally advanced unresectable NSCLC.Design, Setting, and ParticipantsThis cohort study included consecutive patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab between November 2013 and March 2020 who had prospective comprehensive genomic profiling. This study was completed at a multisite tertiary cancer center. The median (IQR) follow-up time was 26 (21-36) months. Statistical analysis was conducted from April to October 2022.ExposuresPatients were grouped into TMB-high (≥10 mutations/megabase [mt/Mb]) and TMB-low (&amp;lt;10 mt/Mb) groups and were additionally evaluated by the presence of somatic alterations associated with radiation resistance (KEAP1/NFE2L2) or radiation sensitivity (DNA damage repair pathway).Main Outcomes and MeasuresThe primary outcomes were 24-month local-regional failure (LRF) and progression-free survival (PFS).ResultsIn this cohort study of 81 patients (46 [57%] male patients; median [range] age, 67 [45-85] years), 36 patients (44%) had TMB-high tumors (≥10 mt/Mb). Patients with TMB-high vs TMB-low tumors had markedly lower 24-month LRF (9% [95% CI, 0%-46%] vs 51% [95% CI, 36%-71%]; P = .001) and improved 24-month PFS (66% [95% CI, 54%-84%] vs 27% [95% CI, 13%-40%]; P = .003). The 24-month LRF was 52% (95% CI, 25%-84%) among patients with KEAP1/NFE2L2-altered tumors compared with 27% (95% CI, 17%-42%) among patients with KEAP1/NFE2L2-wildtype tumors (P = .05). On Cox analysis, only TMB status was associated with LRF (hazard ratio [HR], 0.17; 95% CI, 0.03-0.64; P = .02) and PFS (HR, 0.45; 95% CI, 0.21-0.90; P = .03). Histology, disease stage, Eastern Cooperative Oncology Group status, programmed cell death ligand 1 expression, and pathogenic KEAP1/NFE2L2, KRAS, and DNA damage repair pathway alterations were not significantly associated with LRF or PFS.Conclusions and RelevanceIn this cohort study, TMB-high status was associated with improved local-regional control and PFS after definitive chemoradiation and adjuvant durvalumab. TMB status may facilitate risk-adaptive radiation strategies in unresectable locally advanced NSCLC.
Adoption of Innovative Therapies Across Oncology Practices—Evidence From Immunotherapy
Authors: Carroll Caitlin E. , Landrum Mary Beth , Wright Alexi A. , Keating Nancy L. 
Published: January 2023

ImportanceImmunotherapies reflect an important breakthrough in cancer treatment, substantially improving outcomes for patients with a variety of cancer types, yet little is known about which practices have adopted this novel therapy or the pace of adoption.ObjectiveTo assess adoption of immunotherapies across US oncology practices and examine variation in adoption by practice type.Design, Setting, and ParticipantsThis cohort study used data from Medicare fee-for-service beneficiaries undergoing 6-month chemotherapy episodes between 2010 and 2017. Data were analyzed January 19, 2021, to September 28, 2022, for patients with cancer types for which immunotherapy was approved by the US Food and Drug Administration (FDA) during the study period: melanoma, kidney cancer, lung cancer, and head and neck cancer.ExposuresOncology practice location (rural vs urban), affiliation type (academic system, nonacademic system, independent), and size (1 to 5 physicians vs 6 or more physicians).Main Outcomes and MeasuresThe primary outcome was whether a practice adopted immunotherapy. Adoption rates for each practice type were estimated using multivariate linear models that adjusted for patient characteristics (age, sex, race and ethnicity, cancer type, Charlson Comorbidity Index, and median household income).ResultsData included 71 659 episodes at 1732 oncology practices. Of these, 264 practices (15%) were rural, 900 (52%) were independent, and 492 (28%) had 1 to 5 physicians. Most practices adopted immunotherapy within 2 years of FDA approval, but there was substantial variation in adoption rates across practice types. After FDA approval, adoption of immunotherapy was 11 (95% CI, −16 to −6) percentage points lower at rural practices than urban practices and 27 (95% CI, −32 to −22) percentage points lower at practices with 1 to 5 physicians than practices with 6 or more physicians. Adoption rates were similar at independent practices and nonacademic systems; however, both practice types had lower adoption than academic systems (independent practice difference, −6 [95% CI, −9 to −3] percentage points; nonacademic systems difference, −9 [95% CI, −11 to −6] percentage points).Conclusions and RelevanceIn this cohort study of Medicare claims, practice characteristics, especially practice size and rural location, were associated with adoption of immunotherapy. These findings suggest that there may be geographic disparities in access to important innovations for treating patients with cancer.
Thyroidectomy Outcomes in Patients Identified With RET Pathogenic Variants Through a Population Genomic Screening Program
Authors: Pichardo Priscilla F. A. , Hellums Ryan N. , Hao Jing , Savatt Juliann M. , Hassen Dina , Pellitteri Phillip K. , Alvi Madiha , Buchanan Adam H. , Purdy Nicholas C. 
Published: January 2023

ImportancePopulation-based genomic screening can facilitate early detection of medullary thyroid carcinoma (MTC) in patients with pathogenic/likely pathogenic (P/LP) RET variants.ObjectiveTo evaluate the clinical treatment and patient outcomes after identification of P/LP RET proto-oncogene variants associated with the risk of MTC via a population genomic screening program.Design, Setting, ParticipantsThis retrospective cross-sectional study was completed between June 1, 2016, and May 31, 2022, for a mean follow-up period of 22.4 months (range, 2-76 months). The study included patients who were identified as having P/LP RET variants through a population genomic screening program at a rural tertiary care center and who underwent thyroidectomy after results disclosure.Main Outcomes and MeasuresThe outcomes of interest were preoperative evaluation and treatment-related outcomes. Measures included imaging and laboratory findings, extent of surgery, pathologic diagnosis, and staging.ResultsSeventy-five patients were identified as having P/LP RET variants exclusively through genomic screening. Twenty of these patients (27%; 11 women [55%] and 9 men [45%]; median age, 48 years [range, 22-73 years]) underwent total thyroidectomy; 13 of these patients (65%) also had a central neck dissection. No patients had clinically apparent disease at the time of surgery. Pathologic findings indicated MTC for 12 patients and papillary thyroid carcinoma in 2. Of patients with MTC, 10 had stage I disease, 1 had stage II disease, 1 had stage III disease, and none had stage IV disease. Based on postoperative surveillance imaging and laboratory results, no patient had evidence of recalcitrant disease.Conclusions and RelevanceIn this cross-sectional study, all malignant neoplasms identified on surgical pathology were clinically occult, with surgical intervention based solely on the identification of the P/LP RET variant via population genomic screening. This finding suggests that genomic screening may provide opportunities for early detection and treatment of MTC, with the potential for improved patient outcomes.
Dual beam‐current transformer design for monitoring and reporting of electron ultra‐high dose rate (FLASH) beam parameters
Authors: Liu Kevin , Palmiero Allison , Chopra Nitish , Velasquez Brett , Li Ziyi , Beddar Sam , Schüler Emil 
Published: January 2023

AbstractPurposeTo investigate the usefulness and effectiveness of a dual beam‐current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real‐time, and to inform on the usefulness of this design for future eFLASH beam control.MethodsTwo BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower‐to‐upper BCT signal.ResultsA linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (R2 > 0.99). A linear relationship was also observed in the BCT signals as a function of the number of pulses delivered regardless of the PW, DPP, or PRF (R2 > 0.99). The lower‐to‐upper BCT ratio was found to correlate strongly with the energy of the eFLASH beam due to differential beam attenuation caused by the secondary scattering foil. The BCTs were also able to provide accurate information about the PW, PRF, energy, and DPP for each individual pulse delivered in real‐time.ConclusionThe dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse‐by‐pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real‐time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.
Alleviation of Hepatic Steatosis by 4‐azidophlorizin via the Degradation of Geranylgeranyl Diphosphate Synthase by the Ubiquitin‐Proteasome Pathway in Vivo and in Vitro
Authors: Ye Juan , Qi Yaling , Chen Jiao , Zhang Shihu , Liu Boyuan , Zhao Yinjuan , Yuan Xianwen , Cheng Qi , Yang Yang , Zhang Furong , Gao Hongliang , Wang Haoran , Wu Jing , Zhu Feng , Li Chaojun , Cao Peng , Xue Bin 
Published: January 2023

AbstractThere are no known approved pharmacotherapies for non‐alcoholic fatty liver disease (NAFLD) in the clinical setting. Although studies have provided substantial evidence that geranylgeranyl diphosphate synthase (GGPPS) is a potential therapeutic target for the treatment of NAFLD corresponding drug screening is rare. A GGPPS‐targeted inhibitor is identified using a structure‐based virtual small molecule screening method. The interaction of 4‐AZ and GGPPS is detected by microscale thermophoresis. 4‐AZ degradation of GGPPS by the ubiquitin‐proteasome pathway is detected by western blotting. The anti‐steatotic effect of 4‐AZ in vivo is detected by CT. Lipid‐related gene detection is detected by real‐time PCR both in primary hepatocytes and mice. The compound inhibits the accumulation of lipids in primary hepatocytes and decreases lipogenic gene expression through GGPPS. Pharmacological studies show that 4‐AZ can attenuate hepatic steatosis and improve liver injury in high‐fat diet‐induced mice. This data provides a novel application of 4‐AZ NAFLD therapy, proving that the inhibition of GGPPS is a novel strategy for the treatment of NAFLD.
“Duet‐Insurance” Eutectic Electrolytes for Zinc‐Ion Capacitor Pouch Cells
Authors: Lu Xuejun , Tao Li , Qu Keqi , Amardeep Amardeep , Liu Jian 
Published: January 2023

AbstractEutectic electrolytes are emerging to be explored to meet the high demand for aqueous zinc‐ion capacitors (AZICs) due to their high electrochemical stability and environmental‐friendly feature. Notably, a large‐scale requirement for a practical AZIC has been addressed to balance decent performance and increase package size. Thus, a “duet‐insurance” eutectic electrolyte (DIEE) is proposed by introducing successively heavy water (D2O) and dimethyl sulfoxide in an aqueous chaotropic Zn salt solution, which hindered the severe irreversibility of Zn anodes compared to that lacking this dual‐solvent protection. For example, the optimal DIEE delivered a high capacitance of 352.9 F g−1 at 0.5 A g−1 and excellent capacitance retention of ≈100% over 30,000 cycles at 2 A g−1 implementing in pouch cells and showing the ability to operate at a low temperature. Besides, experimental (e.g., nuclear magnetic resonance spectroscopy, Raman spectroscopy, electric double‐layer capacitance, etc.) and theoretical techniques (e.g., molecular dynamics simulation, density functional theory) illustrate the vital presence of contact ion pairs and aggregates ion species. Ultimately, this efficient DIEE system employing “duet‐insurance” protections provides a promising direction for designing novel eutectic electrolytes for AZICs chemistries.
Bio‐Inspired Semi‐Active Safeguarding Design with Enhanced Impact Resistance via Shape Memory Effect
Authors: Wang Wenhui , Wang Sheng , Zhou Jianyu , Deng Huaxia , Sun Shuaishuai , Xue Tian , Ma Yuqian , Gong Xinglong 
Published: January 2023

AbstractInspired by creatures reducing impact damage, a novel semi‐active protection strategy to enhance impact resistance through structural adjustment is proposed. The heat‐activated shape memory composites (PCLE) consisting of polycaprolactone (PCL) and shear stiffening elastomer are first prepared. The PCLE with 50 wt.% PCL (PCLE‐50%) presents tensile strength of 0.46 MPa, fracture strain of 148%, high shape fixity and recovery rates (97.9% and 91.1%), and stable shape‐memory repeatability. Furthermore, various PCLE‐50%‐based structures are fabricated, which show reinforced anti‐impact performance after shape‐shifting. Loading from 300 mm, the maximum drop hammer impact force of no protection, PCLE‐50%, and deformed assembled single‐branch structure are 3.98 kN, 1.75 kN, and 0.93 kN, respectively. Additionally, assembled complex structures also exhibit exceptional energy absorption properties. Ultimately, intelligent clothing is successfully manufactured. Besides good anti‐impact effect, the clothing shows excellent thermal insulation capabilities whose surface temperature is 31.7 °C after heating for 600 s at 42 °C. This study provides an innovative means to develop deformable, wearable, and intelligent protective devices.
Deciphering Electrolyte Selection for Electrochemical Reduction of Carbon Dioxide and Nitrogen to High‐Value‐Added Chemicals
Authors: Ni Jiajie , Cheng Qiyang , Liu Sisi , Wang Mengfan , He Yanzheng , Qian Tao , Yan Chenglin , Lu Jianmei 
Published: January 2023

AbstractElectrochemical reduction of CO2 (CO2RR) and nitrogen (NRR) constitute alternatives to fossil fuel‐based technologies for the production of high‐value‐added chemicals. Yet their practical application is still hampered by the low energy and Faradaic efficiencies although numerous efforts have been paid to overcome the fatal shortcomings. To date, most studies have focused on designing and developing advanced electrocatalysts, while the understanding of electrolyte, which would significantly influence the reaction microenvironment, are still not enough to provide insight to construct highly active and selective electrochemical systems. Here, a comprehensive review of the different electrolytes participating in the CO2RR and NRR is provided, including acidic, neutral, alkaline, and water‐in‐salt electrolyte as aqueous electrolytes, as well as organic electrolyte, ionic‐liquids electrolyte, and the mixture of the two as non‐aqueous electrolytes. Through the discussion of the roles of these various electrolytes, it is aimed to grasp their essential function during the electrochemical process and how these functions can be used as design parameters for improving electrocatalytic performance. Finally, priorities for future studies are suggested to support the in‐depth understanding of the electrolyte effects and thus guide efficient selection for next‐generation gas‐involving electrochemical reactions.
Personalized Bacteria Loaded with Autoantigens for the Enhancement of Tumor Immunotherapy
Authors: Wu Chenghu , He Wenjuan , Chen Yue , Cai Jie , Zeng Fanjun , Lu Zidong , Wang Jilong 
Published: January 2023

AbstractCurrently, tumor immunotherapy is becoming a new revolution in tumor treatment. Generated from tumor cell lysate (TCL) or irradiated tumor cells, the whole tumor antigen‐based vaccines have the possibility to enhance antitumor immune response without survival from immune surveillance in personalized immunotherapy. Here, polydopamine nanoparticles (PDA NPs) after self‐polymerization are covalently coated with TCL to form PDA@CL. Engineered Salmonella (EnS) wrapped with PDA@CL (EnS@PDA@CL) is targeted the localization of the tumor site by intravenous administration. EnS@PDA@CL delivered autologous antigen‐containing nanoparticles to tumor hypoxia regions through blood circulation. The PDA@CL particles promote the maturation of dendritic cells (DCs), thus eliciting the infiltration of whole tumor antigens specific cytotoxic T lymphocytes, significantly triggering antitumor immunity. The tumor regression in the Panc02 mice confirms the therapeutic potential of EnS@PDA@CL in clinical personalized immunotherapy.
Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage–Myofibroblast Transition in Bladder Remodeling
Authors: Wang Wei , Xiao Dexuan , Lin Lede , Gao Xiaoshuai , Peng Liao , Chen Jiawei , Xiao Kaiwen , Zhu Shiyu , Chen Jixiang , Zhang Fuxun , Xiong Yang , Chen Huiling , Liao Banghua , Zhou Liang , Lin Yunfeng 
Published: January 2023

AbstractBladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long‐term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO‐induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO‐induced remodeling is aimed. Four single‐strand DNAs are self‐assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF‐β1)‐induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO‐induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage–myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF‐β1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO‐induced remodeling.
Photoredox‐Promoted Co‐Production of Dihydroisoquinoline and H2O2 over Defective Zn3In2S6
Authors: Luo Juanjuan , Wei Xinfa , Qiao Yang , Wu Chenyao , Li Lanxin , Chen Lisong , Shi Jianlin 
Published: January 2023

AbstractOne of the most sustainable and promising approaches for hydrogen peroxide (H2O2) production in a low‐cost and environment‐friendly way is photosynthesis, which, however, suffers from poor carrier utilization and low H2O2 productivity. The addition of proton donors such as isopropanol or ethanol can increase H2O2 production, which, unfortunately, will inevitably elevate the entire cost while wasting the oxidizing power of holes (h+). Herein, the tetrahydroisoquinolines (THIQs) is employed as a distinctive proton donor for the thermodynamically feasible and selective semi‐dehydrogenation reaction to highly valuable dihydroisoquinolines (DHIQs), and meanwhile, to couple with and promote H2O2 generation in one photoredox reaction under the photocatalysis by dual‐functional Zn3In2S6 photocatalyst. Surprisingly, the suitably defective Zn3In2S6 offers an excellent and near‐stoichiometric co‐production performance of H2O2 and DHIQs at unprecedentedly high rates of 66.4 and 62.1 mmol h‐1 g‐1 under visible light (λ ≥ 400 nm), respectively, which outperforms all the previously available reports even though sacrificial agents were employed in those reports. Additionally, photocatalytic redox reaction mechanism demonstrates that H2O2 can be generated through multiple pathways, highlighting the synergistic effect among ROS (·O2‐ and 1O2), h+ and proton donor, which has been ignored in previous studies.
Pt‐Anchored‐Zirconium Phosphate Nanoplates as High‐Durable Carbon‐Free Oxygen Reduction Reaction Electrocatalyst for PEM Fuel Cell Applications
Authors: Kumar Sachin , Yoyakki Athira , Pandikassala Ajmal , Soni Roby , Kurungot Sreekumar 
Published: January 2023

AbstractCommercially available platinum‐supported carbon (Pt/C) catalysts are the most widely used oxygen reduction reaction (ORR) electrocatalysts in polymer electrolyte membrane fuel cells (PEMFCs). However, inadequate active triple‐phase boundary formation and carbon oxidation in Pt/C during PEMFC operation shorten its lifetime and efficiency. In this direction, a new class of carbon‐free electrocatalysts for ORR is prepared by dispersing Pt nanoparticles on ZrP (Zirconium phosphates) nanoplates. In one case (ZrP@Pt), the Pt nanoparticles are found to be closely distributed and completely covering the ZrP nanoplates, whereas in the second case (Pt/ZrP), the Pt nanoparticles selectively restrict dispersion along the edges of the support. ZrP as the support displays an intrinsic proton conductivity of ≈0.5 × 10−4 S cm−1 at 70 °C, with an activation energy (Ea) of 0.19 eV. Pt/ZrP shows better durability after 3000 start‐stop cycles. The mass activity of Pt/ZrP is increased by 4.6 times compared to Pt/C, which exhibits a loss in mass activity by 1.37 times. The single‐cell level validation of ZrP@Pt, Pt/ZrP, and Pt/C as the electrocatalysts in PEMFC at an operating potential of 0.60 V shows the achievable current densities of 0.600, 0.890, and 0.890 A cm−2.