bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principles of Dose, Schedule, and Combination Therapy
Authors: Hait William N. , Eder Joseph P. 
Published: August 2023

Overview
The discovery and development of oncology drugs are complex and associated with a high failure rate. For example, the chance of a new drug that enters clinical trial has an approximately ten percent chance of achieving regulatory approval and ultimately becoming available for patients. Determining the proper dose and schedule of a drug are arguably the two most important determinants of both safety and efficacy, the primary determinants of regulatory approval. Understanding how to best estimate the proper dose and schedule for the many types of therapeutic agents now widely available and in development is a critical skill for those in the drug discovery and development field. This area of expertise has been made more complex with the addition of biological agents such as monoclonal antibodies, alternative protein scaffolds, and vaccines to that of hormones and small molecule platforms. In this chapter, we review the basic principles that underlie the appropriate selection of dose and schedule with a major focus on cytotoxic chemotherapy. In addition, we discuss the many variables that can underlie the dose‐response relationship including characteristics of the tumor, the tumor microenvironment, the host including enzymes of drug metabolism and mechanisms of drug clearance. Finally, we review the clinical trial designs that have been successfully used to properly select dose and schedule for oncology drugs.
Alkylating Agents and Platinum Antitumor Compounds
Authors: Siddik Zahid H. 
Published: August 2023

OverviewAlkylating agents and platinum‐based compounds are highly potent antitumor drugs used in the treatment of a variety of cancers. These drugs target DNA (deoxyribonucleic acid) but require activation by spontaneous or metabolic transformation to induce formation of DNA monofunctional adducts and interstrand and intrastrand crosslinks. As a result of this damage, the DNA unwinds and/or bends, and such distortions are then recognized by specialized DNA damage recognition proteins to activate checkpoints, which arrest the cell cycle to allow cells time to repair the damage and survive. If the DNA damage is extensive and repair cannot be completed, then cells activate p53‐dependent or independent apoptosis (programmed cell death) to affect antitumor drug response. As activated species from alkylating agents and platinum compounds are not tumor‐selective, they will also interact with DNA and other endogenous macromolecules in normal cells to induce severe side effects; at times the toxicity can be irreversible and cumulative and, thereby, presents a dose‐limiting barrier. Another limitation is that genetic changes in tumors that are either intrinsic or acquired can inhibit apoptosis and induce resistance to alkylating and platinating drugs. Resistance mechanisms may be observed in the form of reduced drug accumulation, increased drug inactivation, increased DNA repair, failure of DNA damage recognition system to recognize the damage, and aberrant apoptotic signal transduction pathways. Rational strategies to circumvent resistance mechanisms are, therefore, needed desperately to enhance patient care.
Agents Targeting Microtubules and Mitotic Processes
Authors: Rowinsky Eric K. 
Published: August 2023

OverviewThe treatment of many diseases owes much to the importance of medicines derived from natural sources, and the treatment of malignant disease is no exception. Billions of years of evolutionary pressure have resulted in the natural selection of plants, fungi, and microorganisms capable of producing potent and specific toxins. After several plant‐derived compounds and other natural products, many of which targeted the mitotic processes, demonstrated prominent anticancer activity in the 1950s and 1960s, the microtubule was recognized as a subcellular target of major strategic importance.The first widely used class of antimicrotubule agents, the plant‐derived vinca alkaloids, had been the mainstay of both palliative and curative regimens for treating malignancies for several decades. The addition of the plant‐derived taxanes, which possess a unique mechanism of action and anticancer spectra, to our therapeutic arsenal several decades later resulted in renewed interest in the microtubule and mitotic processes as targets for which to develop cancer therapeutics, as well as in the identification of other natural products to treat cancers. More recently, several plant‐ and marine‐derived compounds as well as synthetic agents with yet even more distinctive disruptive actions on microtubules and other mitotic constituents have been identified. These include the analogs of the epothilones and halichondrin B, which were isolated from soil‐dwelling myxobacterium and marine sponges, respectively. They also include potent antimicrotubule agents, such as analogs of maytansine and dolastatin, which are components of antibody‐drug conjugates. This chapter focuses on the microtubule as a target for therapeutic development and antimicrotubule agents that comprise our therapeutic armamentarium.
Neoplasms of the Small Intestine, Vermiform Appendix, and Peritoneum and Carcinoma of the Colon and Rectum
Authors: Beasley Georgia M. , Sun Zhifei , Nussbaum Daniel P. , Tyler Douglas S. 
Published: August 2023

OverviewCancers of the small bowel, large bowel, and appendix compromise a multitude of distinct pathologic entities and clinical presentations. While tumors of the small bowel are uncommon with <3% of all alimentary tract tumors and 0.4% of all malignancies arise in the small bowel, colon cancer is the third most common malignant tumor and the fourth most common cause of cancer death worldwide. Although adenocarcinoma remains the common pathology, many advances have been made regarding our diagnoses and management of carcinoid tumors and even to a larger degree in gastrointestinal stromal tumors. Additional advances include our understanding of genetics, new imaging modalities, and minimally invasive surgeries. This chapter will provide a comprehensive review of the management and treatment of cancers of the small bowel, large bowel, and appendix.
Bone Tumors
Authors: Damron Timothy A. 
Published: August 2023

OverviewBone tumors are uncommon lesions that affect all ages of patients and may involve any bone in the body. Bone lesions may be benign neoplasms or reactive lesions, primary bone sarcomas, metastatic carcinomas to bone, myeloma, or lymphoma. The benign bone lesions, which predominate in children and young adults, may behave in an inactive, active, or aggressive fashion, and the latter may simulate malignancy. Primary bone sarcomas have a bimodal distribution, whereas metastatic disease, myeloma, and lymphoma of bone predominate in adults. Despite the broad spectrum of bone tumors, each individual entity has a distinct clinical and radiographic presentation, with a predilection for specific locations, which lends itself to narrowing the differential diagnosis and selecting appropriate management.Bone sarcomas account for less than 0.2% of all cancers. During 2014, approximately 3020 new cases of primary bone sarcomas were diagnosed, and approximately 1460 deaths occurred. The three most common bone sarcomas are osteosarcoma, chondrosarcoma, and Ewing sarcoma. However, the most common primary malignancy of bone is myeloma, and the most common cancer that involves bone is metastatic carcinoma.The pathologic classification of bone tumors continues to evolve. To a large extent, classification continues to be according to the cell of origin or tissue type. Primary bone tumors may derive from cartilage cells, bone cells, and vascular cells, among others, but for some tumors, the cell of origin is unknown. The most widely accepted pathologic classification system to date is that of the World Health Organization.
Plasma Cell Tumors
Authors: Raje Noopur , Hideshima Teru , Yee Andrew J. , Anderson Kenneth C. 
Published: August 2023

OverviewPlasma cell disorders have in common a proliferation of monoclonal plasma cells associated with the production of a monoclonal protein. These disorders range from the common, indolent condition of monoclonal gammopathy of undetermined significance to malignancies, such as multiple myeloma, characterized by the presence of hypercalcemia, anemia, renal dysfunction, and/or lytic lesions. Progress in the understanding of the molecular underpinnings of myeloma has led to remarkable advances in its treatment. High‐dose melphalan with autologous stem‐cell transplant was historically a mainstay of treatment. Now, highly effective and well‐tolerated drug classes such as the proteasome inhibitors (e.g., bortezomib and carfilzomib) and immunomodulatory drugs (e.g., lenalidomide and pomalidomide) have rapidly transformed the treatment of myeloma and significantly improved the overall survival. The increasing use of extended treatment strategies such as maintenance therapy and the arrival of newer drug classes such as plasma cell‐specific monoclonal antibodies are setting the stage for improving outcomes further.
Antiemetic Therapy
Authors: Forde Patrick M. , Ettinger David S. 
Published: August 2023

OverviewDramatic progress has been made in the prevention and treatment of chemotherapy‐induced emesis, especially since the introduction of the 5‐HT3 receptor antagonists in the early 1990s and the 2003 introduction of the NK‐1 receptor antagonist, aprepitant. Recent surveys indicate the need for heightened awareness of the frequency and severity of acute and, especially, delayed nausea and vomiting from chemotherapy. Fortunately, new agents have been added to the antiemetic arsenal to further enhance the efficacy of antiemetic prophylaxis. Complementary therapies such as acupuncture and mind–body interventions appear promising in controlling nausea, and are being explored further. Appropriate implementation of guidelines for prophylaxis based on the specific chemotherapy agents used will ensure that fewer patients experience these most distressing of side effects.
Association of the time of day of EVT with clinical outcomes and benefit from successful recanalization after stroke
Authors: Burbano Vanessa Granja , Wölfer Teresa A. , Vlegels Naomi , Quandt Fanny , Zimmermann Hanna , Wischmann Johannes , Kellert Lars , Liebig Thomas , Dimitriadis Konstantinos , Saver Jeffrey L. , Tiedt Steffen ,   for the GSR investigators
Published: August 2023

AbstractExperimental and neuroimaging studies suggest an influence of the time of day on acute infarct growth, but whether this could inform patient selection for acute treatments is uncertain. In a multicenter cohort of 9357 stroke patients undergoing endovascular treatment, morning treatment (05:00–10:59) was associated with lowest 90‐day mRS scores (adjusted odds ratio, 1.27 [95% CI, 1.08–1.47]; p = 0.004). The association between successful recanalization and outcome was stronger in morning compared to evening‐treated patients (pia = 0.046) with treatment benefit persisting until 24 h for morning‐treated compared to 11.5 h for evening‐treated patients suggesting that the time of day might inform patient selection for EVT.
Molecule Design of Novel Electron Acceptor with Superior Chemical Stability for Photovoltaic Applications
Authors: Wang Wenxuan , Zhang Shaoqing , Zhang Tao , Yang Yi , Cui Yong , Yu Yue , Xiao Yang , Ryu Du Hyeon , Song Chang Eun , Hou Jianhui 
Published: August 2023

AbstractThe stability of organic photovoltaic (OPV) cells is significantly affected by the decomposition of acceptor–donor–acceptor type non‐fullerene acceptors (NFAs), bringing a significant challenge for the manufacture and applications. Herein, a novel acceptor with superior chemical stability named GS‐22 is designed and synthesized and the relationship between molecular structure and chemical stability is investigated. Based on structure analysis, the exocyclic vinyl groups are proven to exhibit inferior chemical stability and can be easily destructed under an alkaline environment and illumination. Owing to the single‐bonded end groups and the completely non‐fused core, GS‐22 shows remarkably high chemical stability, contributing to obviously improved device stability. Impressively, the fitting T80 (the lifetime when power conversion efficiency retains 80% of the initial value) of the encapsulated OPV cell reaches 3770 h. This work provides an effective molecular design strategy for NFAs with superior chemical stability.
Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering
Authors: Hamilton Alex G. , Swingle Kelsey L. , Joseph Ryann A. , Mai David , Gong Ningqiang , Billingsley Margaret M. , Alameh Mohamad‐Gabriel , Weissman Drew , Sheppard Neil C. , June Carl H. , Mitchell Michael J. 
Published: August 2023

AbstractThe programmed cell death protein 1 (PD‐1) signaling pathway is a major source of dampened T cell activity in the tumor microenvironment. While clinical approaches to inhibiting the PD‐1 pathway using antibody blockade have been broadly successful, these approaches lead to widespread PD‐1 suppression, increasing the risk of autoimmune reactions. This study reports the development of an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)‐mediated transient gene knockdown in T cells. In developing this platform, interesting interactions are observed between the two RNA cargoes when co‐encapsulated, leading to improved expression and knockdown characteristics compared to delivering either cargo alone. This messenger RNA (mRNA)/small interfering RNA (siRNA) co‐delivery platform is adopted to deliver chimeric antigen receptor (CAR) mRNA and siRNA targeting PD‐1 to primary human T cells ex vivo and strong CAR expression and PD‐1 knockdown are observed without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation for a number of immunoengineering applications, including the development of improved cancer immunotherapies.
Dual Function Polymer Ligands of Perovskite Nanocrystals for Extraordinary Water Resistance and X‐Ray Imaging Scintillators
Authors: Zheng Wei , Zhang Hao , Wang Xiaojia , Zhang Xiangzhou , Long Teng , Wang Hua , Yu William W. , Zhou Chuanjian 
Published: August 2023

AbstractLead perovskite nanocrystals (PNCs) have shown great potential for optoelectronic device applications due to their excellent optoelectronic properties. However, the application of PNCs is significantly limited due to the inferior stability resulting from the highly dynamic ligands on the surface. Herein, poly(maleic anhydride‐alt‐1‐octadecene) (PMAO) with low molecular weight (Mn = 1911) is synthesized by copolymerization and used as multi‐dentate ligands to prepare CsPbBr3 PNCs via hot injection. The PNCs exhibit excellent water resistance, which maintains fluorescence for 2600 min while conventional PNCs are completely destroyed after 100 min. Density functional theory calculations demonstrate that PMAO as a multi‐dentate ligand has higher adsorption energy to the surface of PNCs. Due to the large amount of extra anhydride structure of PMAO, PMAO‐PNCs are used as a cross‐linking agent to directly prepare flexible films by an in situ one‐step polymerization reaction with 1,3‐bis(3‐aminopropyl) polydimethylsiloxane (PDMS‐NH2). The fluorescent flexible films show great potential for applications including X‐ray imaging scintillators and flexible light‐emitting diodes (LEDs). This study can provide guidance to prepare ultra‐stable PNCs and flexible perovskite films with good stability in a simple and efficient way.
Layered Gallium Monosulfide as Phase‐Change Material for Reconfigurable Nanophotonic Components On‐Chip
Authors: Gutiérrez Yael , Dicorato Stefano , Ovvyan Anna P. , Brückerhoff‐Plückelmann Frank , Resl Josef , Giangregorio Maria M , Hingerl Kurt , Cobet Christoph , Schiek Manuela , Duwe Matthias , Thiesen Peter H. , Pernice Wolfram H. P. , Losurdo Maria 
Published: August 2023

AbstractThe demand for information processing at ultrahigh speed with large data transmission capacity is continuously rising. Necessary building blocks for on‐chip photonic integrated circuits (PICs) are reconfigurable integrated low‐loss high‐speed modulators and switches. Phase change materials (PCMs) provide unique opportunities for integration into PICs. Here, the investigation of layered gallium monosulfide (GaS) as a novel low‐loss PCM from infrared to optical frequencies is pioneered, with high index contrast (Δn≈0.5) at the optical telecommunication band. The GaS bandgap switches from 1.5 ± 0.2 eV for the amorphous state to 2.1 ± 0.1 eV for the crystalline state. It is demonstrated that the reversible GaS amorphous‐to‐crystalline phase transition can be operated thermally and by picosecond green (532 nm) laser irradiation. The design of a reconfigurable integrated optical modulator on‐chip based on Mach‐Zehnder Interferometers (MZI) with the GaS PCM cell deposited on one of the arms for application is presented at the telecommunication wavelength of λ = 1310 nm, where the standard single mode optical fiber exhibits zero chromatic dispersion, and at λ = 1550 nm, where a minimum optical loss of 0.22 dB km−1is obtained. This opens the route to applications such as reconfigurable modulators, beam steering using phase modulation, and photonic neural networks.
Highly Sensitive Naked Eye Detectable Colorimetric Biosensors Made from Macroporous Framework Melamine Foams for Onsite and Simultaneous Detection of Multiple Environmental Hazards in Flowing Through Sensing Systems
Authors: Pan Bofeng , Zhao Cunyi , Norwood Makela , Wang Minyuan , Liu Gang‐Y. , Sun Gang 
Published: August 2023

AbstractPersonal‐use, naked eye‐readable, low‐cost, highly sensitive, and selective biosensors for rapid detection of environmental toxicants are relevant for many application scenarios. Here, the recent developments of highly sensitive and naked eye distinguishable colorimetric sensors by using commercially available melamine foam (MF) as basic sensing materials for instant and volume‐responsive simultaneous detection of multiple targets in fluid systems are reported. The MF possesses a unique reticulated three‐dimensional (3D) macroporous framework structure enabling rapid mass transfer of large biomolecules through the structures in all directions, ensuring easy access of numerous active binding sites of the chemically modified framework to the proteins and target molecules, and subsequently providing significantly increased sensitive and volume‐responsive detection of target molecules in flowing through sensor systems. Promising results in direct, sandwich, and competitive ELISA tests demonstrated the great application potential of the materials. Besides, an additive and simultaneous detection of two targets in one system is achieved by using different layers of the sensor materials in a flowing‐through filtering device. The novel biosensors are expected to significantly improve the sensitivity and broaden the applications of ELISA in the rapid detections of trace amounts of toxicants in liquid and aerosol systems.
Point Defects in Buckled Honeycomb PAs Monolayer: A Systematic Study of Stability, Electronic, and Magnetic Properties
Authors: Huy Huynh Anh , Nguyen‐Tat Bao‐Thien , Nguyen Duy Khanh , Guerrero‐Sanchez J. , Hoat D. M. 
Published: August 2023

AbstractIn this work, the effects of point defects on the electronic and magnetic properties of PAs monolayer are investigated. PAs monolayer is stable in a buckled hexagonal structure, exhibiting indirect gap semiconductor character and is metallized under the presence of vacancies due to the dangling bonds around defect sites. Meanwhile, the non‐magnetic semiconductor character is preserved upon creating antisite defects with a negligible variation of the band gap. Significant magnetism as well as feature‐rich electronic properties are induced by p‐ and n‐type defects. Specifically, doping with Si and Ge atoms leads to the emergence of the magnetic semiconductor nature. In these cases, the total magnetic moment of 1 is obtained, where dopant atoms are mainly responsible for the magnetization. Besides, doping with Br induce the half‐metallic nature with a total magnetic moment of 2 , where magnetic properties are produced by the dopant and its neighbor due to the strong hybridization. In contrast, weak hybridization is the main reason for the absence of magnetism in the Cl‐doped PAs monolayer. Results presented herein introduce the creation of point defects in buckled semiconductor PAs monolayer as efficient functionalization approaches for optoelectronic and spintronic applications.
A Suitable Membrane Distance Regulated by the RBD_ACE2 Interaction is Critical for SARS‐CoV‐2 Spike‐Mediated Viral Invasion
Authors: Wu Mengdan , Li Wei , Lin Sheng , Fan Jiaqi , Cui Lele , Xiang Yijuan , Li Kaiyu , Tang Linwei , Duan Yanping , Chen Zimin , Yang Fanli , Shui Weiwei , Lu Guangwen , Lai Ying 
Published: August 2023

AbstractThe receptor‐binding domain (RBD) of spike recognizing the receptor angiotensin‐converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell–vesicle content‐mixing assay, it is found that the cleavage at the S2’ site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell–vesicle and cell–cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike‐mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike‐mediated SARS‐CoV‐2 entry.
New Consideration of Degradation Accelerating of All‐Solid‐State Batteries under a Low‐Pressure Condition
Authors: Shin Hyeon‐Ji , Kim Jun Tae , Kim A‐Yeon , Noh Namgyu , Park Jungjae , Park Chang Reung , Yu Seungho , Kim Hyoungchul , Chung Kyung Yoon , Yuk Jong Min , Myung Seung‐Taek , Jung Hun‐Gi 
Published: August 2023

AbstractSulfide‐based all‐solid‐state batteries (ASSBs) are next‐generation batteries, which resolve the safety issues of energy storage systems. Elaborated intimate contact by providing constant external pressure using a customized cell is a way to overcome chemo‐mechanical deterioration associated with interfacial issues; however, it is not a practical approach. Here, ASSBs are evaluated by adopting a typical coin‐type cell at low pressure (≈0.3 MPa) and it is confirmed that cathode deterioration is a more significant factor in lowering capacity retention than contact loss. Sulfide is infused surprisingly along the grain boundary of the cathode, causing gradual lithium deficiency in the cathode active materials by capturing the active lithium, which is revealed by time‐of‐flight secondary‐ion mass spectroscopy using a lithium isotope (6Li). This study sheds light on the urgency of resolving the depletion of lithium ingredients during cycling rather than surface modification, by investigating the factors that accelerate degradation of the cathode during low‐pressure operation of ASSBs.