bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan
Authors: Maeda Hideki , Shingai Riko , Takeda Kentaro , Hara Asuka , Murai Yuna , Ofuchi Momoka 
Published: April 2023

ImportanceA surrogate end point (SEP) is an end point used in clinical trials as an alternative for measuring the true clinical benefit. The use of SEPs in trials shortens their duration.ObjectivesTo investigate the use of SEPs in clinical trials to support the approval of anticancer drugs and to determine whether confirmatory studies that use overall survival (OS) as an end point are being conducted in Japan.Design, Setting, and ParticipantsIn this cross-sectional study, drug approvals and background information were obtained from publicly available information, such as the Pharmaceuticals and Medical Devices Agency website, for anticancer drugs approved in Japan from January 2001 to December 2020. Data analysis was performed from September 2021 to March 2022.Main Outcomes and MeasuresCharacteristics of approved oncology drugs in Japan, end points for pivotal clinical trials, and outcomes of confirmatory trials using OS as an end point following drug approval.ResultsThere were 299 anticancer drugs approved in Japan during the study period. Of these, 142 (47.5%) were molecular-targeted drugs, the most common of which targeted non–small cell lung cancer. There were 111 (37.1%) anticancer drugs with orphan designation. From 2001 to 2005, OS was used as an end point in 1 approval (3.6%); however, from 2006 to 2020, OS was used in 86 approvals (31.7%). Of the 212 anticancer drugs approved on the basis of SEPs, confirmatory studies with OS as the end point were conducted for only 37 approvals (17.5%); for the remaining 175 approvals, studies are under way for 35 approvals (16.5%), were waivered for 75 approvals (35.4%), and were not conducted for 65 approvals (30.7%). Furthermore, in 20 drug approvals (9.4%), the conducted confirmatory studies were not effective in determining the OS, but the drugs were approved following re-examination.Conclusions and RelevanceThe findings of this study suggest that starting from 2005, the use of OS as an end point has increased in studies supporting the approval of anticancer drugs in Japan. However, even after 2005, approximately two-thirds of these approvals were SEP based. Postmarketing surveillance studies of the true end points are necessary to validate the use of SEPs.
Cadmium: Biomolecular Interactions
Authors: Templeton Douglas M. 
Published: April 2023

AbstractCadmium has no known function in higher organisms, which evolved in an essentially cadmium‐free environment until the last several hundred years of industrial activity. Thus, cadmium's interactions with biological molecules are not selected by evolution but are determined fortuitously by its inorganic chemistry. Under physiological conditions, cadmium exists exclusively in the Cd2+ionic state, and its biomolecular interactions are dominated by two, at first sight contradictory, principles. On the one hand, Cd2+is a Group 12 “soft” ion, and as such shows preferential interaction with thiols and other soft ligands. On the other hand, its ionic radius is a close match to the “hard” ion Ca2+, and it fits by mimicry into many oxygen‐rich Ca2+‐binding sites. Both aspects of Cd2+chemistry are covered in this article. General effects of Cd2+on cellular Ca2+levels have implications for multiple signaling pathways. Interactions of Cd2+with Ca2+binding sites in specific proteins are also of consequence. Together, these aspects of Cd2+biology have consequences for cell survival and proliferation, and for mechanisms of cell death. A special class of Cd2+‐sequestering proteins, the thiol‐rich metallothioneins, buffer cytosolic levels of Cd2+, and also serve as a strong link between it and the essential Zn2+ion; displacement of Zn2+from important binding sites, not only in metallothioneins and related proteins, but also in Zn2+‐binding loops (“zinc fingers”) in various transcription factors is another important theme in the biological chemistry (and toxicology) of Cd2+. Cellular thiols are involved as both protective antioxidants against reactive oxygen species and as signaling sensors of cellular redox status. Cadmium interacts with many of these sensing and defensive pathways. The antioxidant glutathione is a crucial player in redox biology, and Cd2+exerts some of its biological effects by influencing levels of protein glutathione adducts. It also interacts with proteins involved in sensing cellular oxygen levels, such as Nrf2 and the hypoxia‐inducible factor 1. The ability of Cd2+to act both as a Ca2+mimic and a thiol group poison also allows it to interact with a wide range of other proteins. In addition to proteins involved in signaling and cell death pathways, these include interactions with cell membrane transport proteins, DNA repair enzymes, and the structural components of the cytoskeleton, all with profound biological consequences. Cadmium (as the Cd2+ion) has truly pleiotropic, and generally adverse, effects on cells that are understood by the inorganic chemistry of its interactions with biological ligands.
Four out of five buprenorphine patients drop out: Study
Authors: Knopf Alison 
Published: April 2023

Only 1 in 5 patients started on buprenorphine treatment were retained for at least 180 days from January 2016 through October 2022, a recent study has found. During that same period, the monthly initiation rate at first increased, and then flattened (prior to the COVID‐19 epidemic). The study, “Trends in Buprenorphine Initiation and Retention in the United States, 2016‐2022,” published in JAMA on April 25, is based on the IQVIA Longitudinal Prescription Database, which covers more than 90% of all prescriptions to pharmacies.
Observation of Uniaxial Strain Tuned Spin Cycloid in a Freestanding BiFeO3 Film
Authors: Ding Zhe , Sun Yumeng , Zheng Ningchong , Ma Xingyue , Wang Mengqi , Zang Yipeng , Yu Pei , Chen Zhousheng , Wang Pengfei , Wang Ya , Yang Yurong , Nie Yuefeng , Shi Fazhan , Du Jiangfeng 
Published: April 2023

AbstractBismuth ferrite (BiFeO3) possesses a non‐collinear spin order while the ferroelectric order breaks space inversion symmetry. This allows efficient electric‐field control of magnetism and makes it a promising candidate for applications in low‐power spintronic devices. Epitaxial strain effects have been intensively studied and exhibit significant modulation of the magnetic order in bismuthBiFeO3, but tuning its spin structure with continuously varied uniaxial strain is still lacking at this moment. Herein, in situ uniaxial tensile strain is applied to a freestanding BiFeO3 film by mechanically stretching an organic substrate. A scanning nitrogen‐vacancy (NV) microscopy is applied to image the nanoscale magnetic order in real space. The strain is continuously increased from 0% to 1.5% and four images under different strains are acquired during this period. The images show that the spin cycloid tilts by ≈12.6° when strain approaches 1.5%. A first principle calculation is processed to show that the tilting is energetically favorable under such strain. The in situ strain applying method in combination with scanning NV microscope real‐space imaging ability paves a new way in studying the coupling between magnetic order and strain in BiFeO3 films.
Spin Polarization of Chiral Amorphous Fe‐Ni Electrocatalysts Enabling Efficient Electrochemical Oxygen Evolution
Authors: Feng Tanglue , Chen Weihua , Xue Jie , Cao Fangfang , Chen Zhongwei , Ye Jichun , Xiao Chuanxiao , Lu Haipeng 
Published: April 2023

AbstractChiral‐induced spin selectivity is recently demonstrated in a range of spin‐dependent optoelectronics and electrochemistry. Herein, a new type of amorphous chiral tartaric acid‐FeNi coordination polymer fabricated by electrodeposition methods, achieving both high spin‐polarization and high electrocatalytic activity for oxygen evolution, is reported. Circular dichroism shows signature optical activity from the coordination polymer. Conductive atomic force microscopy measurements demonstrate a high spin polarization through the chiral electrocatalyst, which significantly suppresses the formation of hydrogen peroxide byproducts compared to the achiral ones. These chiral Fe‐Ni electrocatalysts exhibit a low overpotential of 205 and 280 mV to achieve 10 and 100 mA cm−2, respectively.
Incombustible Polymer Electrolyte Boosting Safety of Solid‐State Lithium Batteries: A Review
Authors: Han Longfei , Wang Li , Chen Zonghai , Kan Yongchun , Hu Yuan , Zhang Hao , He Xiangming 
Published: April 2023

AbstractLithium‐ion batteries with their portability, high energy density, and reusability are frequently used in today's world. Under extreme conditions, lithium‐ion batteries leak, burn, and even explode. Therefore, improving the safety of lithium‐ion batteries has become a focus of attention. Researchers believe using a solid electrolyte instead of a liquid one can solve the lithium battery safety issue. Due to the low price, good processability and high safety of the solid polymer electrolytes, increasing attention have been paid to them. However, polymer electrolytes can also decompose and burn under extreme conditions. Moreover, lithium dendrites are formed continuously due to the uneven charge distribution on the surface of the lithium metal anode. A short circuit caused by a lithium dendrite can cause the battery to thermal runaway. As a result, the safety of polymer solid‐state batteries remains a challenge. In this review, the thermal runaway mechanism of the batteries is summarized, and the batteries abuse test standard is introduced. In addition, the recent works on the high‐safety polymer electrolytes and the solution strategies of lithium anode problems in polymer batteries are reviewed. Finally, the development direction of safe polymer solid lithium batteries is prospected.
Deterministic Polymorphic Engineering of MoTe2 for Photonic and Optoelectronic Applications
Authors: Ahmed Faisal , Rodríguez‐Fernández Carlos , Fernandez Henry A. , Zhang Yi , Shafi Abde Mayeen , Uddin Md Gius , Cui Xiaoqi , Yoon Hoon Hahn , Mehmood Naveed , Liapis Andreas C. , Yao Lide , Caglayan Humeyra , Sun Zhipei , Lipsanen Harri 
Published: April 2023

AbstractDeveloping selective and coherent polymorphic crystals at the nanoscale offers a novel strategy for designing integrated architectures for photonic and optoelectronic applications such as metasurfaces, optical gratings, photodetectors, and image sensors. Here, a direct optical writing approach is demonstrated to deterministically create polymorphic 2D materials by locally inducing metallic 1T′‐MoTe2 on the semiconducting 2H‐MoTe2 host layer. In the polymorphic‐engineered MoTe2, 2H‐ and 1T′‐ crystalline phases exhibit strong optical contrast from near‐infrared to telecom‐band ranges (1–1.5 µm), due to the change in the band structure and increase in surface roughness. Sevenfold enhancement of third harmonic generation intensity is realized with conversion efficiency (susceptibility) of ≈1.7 × 10−7 (1.1 × 10−19 m2 V−2) and ≈1.7 × 10−8 (0.3 × 10−19 m2 V−2) for 1T′ and 2H‐MoTe2, respectively at telecom‐band ultrafast pump laser. Lastly, based on polymorphic engineering on MoTe2, a Schottky photodiode with a high photoresponsivity of 90 AW−1 is demonstrated. This study proposes facile polymorphic engineered structures that will greatly benefit realizing integrated photonics and optoelectronic circuits.
Albumin‐Hitchhiking Drug Delivery to Tumor‐Draining Lymph Nodes Precisely Boosts Tumor‐Specific Immunity through Autophagy Modulation of Immune Cells
Authors: Wang Xuhui , Chen Dong , Huang Kexin , Li Man , Zhan Changyou , Dong Ziyan , Deng Tao , Ren Kebai , Qiu Yue , Zhang Zhirong , He Qin 
Published: April 2023

AbstractTumor‐draining lymph nodes (TDLNs) are the first sites where tumor components reach and dendritic cells (DCs) present tumor‐associated antigens to T cells. DCs rely on autophagy to process tumor antigens into epitope peptides to form epitope‐MHC complexes. Selective delivery of autophagy‐stimulating drugs to TDLNs may be a precise strategy to boost chemotherapy‐induced antitumor immunity. Here, a multistage stimulating strategy is proposed to activate the antitumor immunity cascade by inducing immunogenic death of tumor cells and elevating antigen presentation of DCs in TDLNs. A tumor‐microenvironment‐responsive “albumin‐hitchhiking” micelle is established by self‐assembling tumor‐targeting oxaliplatin prodrug and lipophilized trehalose prodrug. This demonstrates that lipophilic modification of trehalose with a DSPE tail and the precise exposure in the tumor site enhances its binding to endogenous albumin and realizes TDLNs‐selective reflux, where it upregulates antigen processing and presentation of DCs. This study introduces an approach for targeted delivery to TDLNs and provides insights into mechanisms of autophagy in tumor‐specific immunity.
Polarization‐Driven Ultrafast Optical Switching in TiS3 Nanoribbons via Anisotropic Hot Carrier Dynamics
Authors: Suk Sang Ho , Nah Sanghee , Sajjad Muhammad , Seo Sung Bok , Song Jiacheng , Singh Nirpendra , Sim Sangwan 
Published: April 2023

AbstractLayered quasi‐1D nanomaterials exhibit strong linear dichroism and effective light‐matter interactions, promising for novel information devices driven by light‐polarization. In particular, their optical anisotropy and ultrafast photoresponse allow for polarization‐controlled nanophotonic switches and modulators. However, the technology still requires substantial further studies due to an insufficient understanding of modulation mechanisms and limited investigations of a few materials. Here, transient absorption (TA) microscopy is employed to investigate the ultrafast polarization‐based optical switching in TiS3 nanoribbons, a rising quasi‐1D material of the transition metal trichalcogenide family. Highly anisotropic sub‐picosecond near‐infrared modulation is observed, which is most pronounced when the polarization of the probe pulse is aligned with the nanoribbon axis but disappears as the polarization is rotated to the perpendicular orientation. The authors attribute this significant dependence on the probe polarization to the hot carrier‐induced broadening of an anisotropic interband resonance, as supported by analyses of transient TA line shapes and first principles calculated optical transitions. Furthermore, a strong pump polarization‐dependent modulation is obtained by tuning the pumping energy, enabling highly anisotropic all‐optical switching controlled solely by polarization. These results offer comprehensive information on both probe‐ and pump‐polarization‐based modulations and a deeper physical understanding of polarization‐dependent photoresponse through ultrafast hot carrier dynamics.
Stimuli‐Induced Subconformation Transformation of the PSI‐LHCI Protein at Single‐Molecule Resolution
Authors: Yang Zhiheng , Wang Jie , Yin Bing , Liu Wenzhe , Yin Dongbao , Shen Jianren , Wang Wenda , Li Lidong , Guo Xuefeng 
Published: April 2023

AbstractPhotosynthesis is a very important process for the current biosphere which can maintain such a subtle and stable circulatory ecosystem on earth through the transformation of energy and substance. Even though been widely studied in various aspects, the physiological activities, such as intrinsic structural vibration and self‐regulation process to stress of photosynthetic proteins, are still not in‐depth resolved in real‐time. Herein, utilizing silicon nanowire biosensors with ultrasensitive temporal and spatial resolution, real‐time responses of a single photosystem I‐light harvesting complex I (PSI‐LHCI) supercomplex of Pisum sativum to various conditions, including gradient variations in temperature, illumination, and electric field, are recorded. Under different temperatures, there is a bi‐state switch process associated with the intrinsic thermal vibration behavior. When the variations of illumination and the bias voltage are applied, two additional shoulder states, probably derived from the self‐conformational adjustment, are observed. Based on real‐time monitoring of the dynamic processes of the PSI‐LHCI supercomplex under various conditions, it is successively testified to promising nanotechnology for protein profiling and biological functional integration in photosynthesis studies.
Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
Authors: Xiong Yuxuan , Yong Zhengtao , Xu Chen , Deng Qingyuan , Wang Qiang , Li Shiyou , Wang Chong , Zhang Zhijie , Yang Xiangliang , Li Zifu 
Published: April 2023

AbstractTumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off‐target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self‐assembly of pH‐responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD‐catalyzed oxidation of glucose to H2O2 and gluconic acid by ameliorating tumor hypoxia, fueling copper‐catalyzed •OH generation and pH‐responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD‐based therapies.
Multiscale Hierarchical Structured NiCoP Enabling Ampere‐Level Water Splitting for Multi‐Scenarios Green Energy‐to‐Hydrogen Systems
Authors: Chen Ding , Bai Huawei , Zhu Jiawei , Wu Can , Zhao Hongyu , Wu Dulan , Jiao Jixiang , Ji Pengxia , Mu Shichun 
Published: April 2023

AbstractEfficient and stable low‐cost catalysts are seriously lacking for industrial water electrolysis at large‐current‐density. To meet industrial‐scale hydrogen production, fully utilized active sites by a rational structure design is an attractive route. Herein, dynamic microstructure manipulation of bimetallic phosphide NiCoP is conducted. Among different microstructures for NiCoP, as‐obtained NiCoP‐120 at hydrothermal temperature of 120 °C, shows a special multiscale hierarchical structure from 3D‐nickel foam substrates, 2D‐nanosheets to 1D‐nanoneedles, which is conducive to efficient utilization of active sites and rapid gas release, thus manifesting outstanding electrocatalytic activities and stability as required by industry. To reach a current density of 10 and 1000 mA cm−2 for the hydrogen evolution reaction (HER), NiCoP‐120 requires ultra‐low overpotentials of 56 and 247 mV, respectively. Particularly, as a bifunctional catalyst, it only needs 1.981 V to drive the 1 A cm−2 overall water splitting and can maintain stable output for 600 h, which is superior to almost all reported non‐noble metal catalysts. Moreover, its application prospect in integrated green energy‐to‐hydrogen systems, including sunlight, wind, thermal, and lithium cells, is well demonstrated. This work provides a guiding strategy for the design of industrial water electrolysis catalysts and the establishment of an externally driven water‐splitting hydrogen production system.
Do chimpanzee food calls bias listeners toward novel items?
Authors: Déaux Eloïse C. , Bonneaud Clémence , Baumeyer Adrian , Zuberbühler Klaus 
Published: April 2023

AbstractSocial learning is beneficial in almost every domain of a social animal's life, but it is particularly important in the context of predation and foraging. In both contexts, social animals tend to produce acoustically distinct vocalizations, alarms, and food calls, which have remained somewhat of an evolutionary conundrum as they appear to be costly for the signaller. Here, we investigated the hypothesis that food calls function to direct others toward novel food items, using a playback experiment on a group of chimpanzees. We showed chimpanzees novel (plausibly edible) items while simultaneously playing either conspecific food calls or acoustically similar greeting calls as a control. We found that individuals responded by staying longer near items previously associated with food calls even in the absence of these vocalizations, and peered more at these items compared with the control items, provided no conspecifics were nearby. We also found that once chimpanzees had access to both item types, they interacted more with the one previously associated with food calls than the control items. However, we found no evidence of social learning per se. Given these effects, we propose that food calls may gate and thus facilitate social learning by directing listeners' attention to new feeding opportunities, which if integrated with additional cues could ultimately lead to new food preferences within social groups.
Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome
Authors: Mgaieth Farah , Baksh R. Asaad , Startin Carla M. , Hamburg Sarah , Hithersay Rosalyn , Pape Sarah , Zetterberg Henrik , Ashton Nicholas J. , Tamayo‐Elizalde Miren , Saini Fedal , Idris Mina , Consortium The LonDownS , Strydom Andre 
Published: April 2023

AbstractIntroductionAdults with Down syndrome (DS) are at ultra‐high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers.MethodsA total of 302 adults with DS at baseline and 87 at follow‐up from the London Down Syndrome Consortium cohort completed neuropsychological assessments. Blood biomarkers were measured with the single molecule array technique in a subset of 94 participants.ResultsPoorer verbal fluency performance was observed as age increases. Number of correct words declined in those with AD compared to those without over 2 years and was negatively correlated with neurofilament light (r = –0.37, P = .001) and glial fibrillary acidic protein (r = –0.31, P = .012).DiscussionSemantic fluency may be useful as an early indicator of cognitive decline and provide additional information on AD‐related change, showing associations with biomarkers in DS.