bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkylating Agents and Platinum Antitumor Compounds
Authors: Siddik Zahid H. 
Published: October 2022

OverviewAlkylating agents and platinum‐based compounds constitute two important classes of antitumor drugs in the war against cancer. These drugs transform spontaneously or metabolically to induce DNA monofunctional adducts and interstrand and intrastrand crosslinks. As a result, the DNA unwinds and/or bends, which are then recognized by specialized DNA damage recognition proteins to induce cell cycle arrest that allows cells time to repair the DNA and survive. If DNA damage is extensive and repair cannot be completed, then cells undergo programmed cell death to result in a positive antitumor response. Since active species in the two drug classes are not tumor‐selective, they will also interact with DNA in normal cells to induce several side effects, some of which can be irreversible and cumulative and, thereby, become life threatening. Another limitation is that tumor cells can become resistance to alkylating and platinating drugs through mechanisms that are either intrinsic or acquired. Such resistance mechanisms are manifested as 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. Therefore, identifications of rational personalized combination therapeutic strategies involving these two potent classes of DNA‐reactive drugs are desperately needed to combat resistance mechanisms and enhance curative responses.
Neoplasms of the Thyroid
Authors: Ringel Matthew D. 
Published: October 2022

Overview
Thyroid cancer is the most common malignancy of a classical endocrine organ. The most common forms of thyroid cancer derive from follicular thyroid cells, are characterized by cellular and histological patterns (e.g., papillary and follicular thyroid cancer), and are associated with outstanding overall survivorship but a high frequency of disease persistence. Less commonly, thyroid cancers can derive from thyroid neuroendocrine C‐cells (medullary thyroid cancer) that can occur as part of defined genetic syndromes (e.g., multiple endocrine neoplasia type 2). Thyroid cancers can present as or develop into poorly differentiated or dedifferentiated (anaplastic thyroid cancer) that are associated with highly aggressive courses and poor outcomes. Over the past decade, a more individualized approach has been taken for patients with early‐stage thyroid cancer, with reduced emphasis on aggressive surgical approaches, expansion of active surveillance approaches, and reduced use and/or dosing strategies for radioiodine therapy (RAI) using I‐131. RAI, TSH suppression therapy, and for selected local recurrence, reoperation, and external beam radiation therapy remain cornerstones of therapy for patients with progressive or nonremitting forms of thyroid cancer. For those who do not respond to those treatments, or those with specific gene mutations, there has been expansion of options including the use of targeted inhibitors of mutated driver oncogenes in all forms of thyroid cancer, anti‐angiogenic multikinase inhibitors in patients with progressive differentiated thyroid cancers, and immune checkpoint inhibitors.
Cancer of the Lung
Authors: Morgensztern Daniel , Boffa Daniel , Chen Alexander , Dhanasopon Andrew , Goldberg Sarah B. , Decker Roy H. , Devarakonda Siddhartha , Ko Jane P. , Solis Soto Luisa M. , Waqar Saiama N. , Wistuba Ignacio I. , Herbst Roy S. 
Published: October 2022

OverviewLung cancer is the most common cause of death from cancer both worldwide and in the United States. There has been a remarkable progress in the treatment of lung cancer with an increasing number of highly effective targeted therapies and the incorporation of immune checkpoint inhibitors into the standard therapy of non‐small‐cell lung cancer, initially in patients with metastatic disease and more recently in earlier stages. These therapeutic advances in combination with reduced incidence of lung cancer associated with the decreased tobacco smoking have led to a sharp decrease in lung cancer mortality over the past few years.
Thymomas and Thymic Tumors
Authors: Mody Mayur D. , Sica Gabriel L. , Ramalingam Suresh S. , Shin Dong M. 
Published: October 2022

OverviewMalignancies of the thymus gland comprise a group of uncommon but heterogeneous diseases with variable clinical behavior. Recent collaborative efforts have helped to create consensus histopathological and staging criteria. Furthermore, developments in molecular and gene signature technology have helped us to better understand the pathogenesis of thymic tumors. Diagnosis and treatment frequently require a multidisciplinary approach, with surgery, radiation, and systemic therapy all having a synergistically important role. While there are several chemotherapy regimens available for first‐line treatment for advanced‐stage or recurrent disease, numerous novel chemotherapeutics, immunotherapeutics, and targeted therapies are being evaluated. In this article, we provide a comprehensive overview of the histopathology, diagnosis, and management of most intriguing tumors.
Neoplasms of the Exocrine Pancreas
Authors: Wolff Robert A. , Li Donghui , Maitra Anirban , Tsai Susan , Koay Eugene , Evans Douglas B. 
Published: October 2022

Overview
Pancreatic cancer is largely preventable with healthier lifestyle choices perhaps to include a predominantly plant‐based diet. Currently, about 10% of patients have germline mutations putting them at increased risk for pancreatic cancer. Population‐wide reductions in smoking, obesity, and diabetes will probably increase the proportion of patients with genetically driven disease, expanding the options for precision medicine. Pancreatic cancer is notorious for local invasion and metastatic dissemination and treatment paradigms must account for both. Surgical resection of localized disease provides the only meaningful chance for cure, with improvements in survival seen using both adjuvant and neoadjuvant approaches. Cytotoxic therapy is the mainstay of treatment for locally advanced and metastatic disease. The role of radiation is in evolution. Small subsets of patients are benefiting from precision medicine using targeted treatments and immunotherapy.
Neoplasms of the Vulva and Vagina
Authors: Frumovitz Michael , Dewdney Summer B. 
Published: October 2022

Overview
Vulvar and vaginal carcinomas are uncommon diseases that generally affect postmenopausal women, although 19% of vulvar carcinomas occur in women <50 years old. Risk factors for vulvar carcinoma include human papilloma virus and chronic inflammation. Vulvar intraepithelial neoplasia can often be managed with wide local excision, but several other modalities have been utilized. Most vulvar malignancies are squamous cell carcinomas that are managed by surgical excision and radiotherapy. Sentinel lymph node biopsy has been used to spare the morbidity observed after regional lymph node dissection. For more advanced lesions, chemo‐radiotherapy with agents such as 5‐FU, cisplatin, and mitomycin C is utilized. Other vulvar malignancies include Bartholin gland carcinomas, basal cell carcinomas, verrucous carcinomas, and melanomas. Carcinomas of the vagina are most frequently squamous cell, but clear cell adenocarcinomas have been seen in younger women. In the past, clear cell carcinomas were associated with pre‐natal exposure to diethylstilbestrol. Vaginal melanomas can occur, as well as endodermal sinus tumors, rhabdomyosarcomas, and fibroepithelial vaginal polyps.
Neoplasms of the Cervix
Authors: Jhingran Anuja 
Published: October 2022

Overview
Cervical cancer is the third most common cancer among women worldwide and the fourth leading cause of female cancer deaths, with an estimated 529,800 new cases and 275,100 deaths in the year 2008. The incidence is declining in the United States with 13,800 new cases and 4290 deaths in 2015. Squamous cell carcinoma is the most common histology with the human papilloma virus being the most common etiology. Cervical cancer and precancer can be easily detected with pap smears and HPV testing and prevented with HPV vaccine. Early‐stage cervix cancer can be treated with surgery including now fertility‐sparing surgery and there are high cure rates. Locally advanced cervical cancer is treated with combination of chemotherapy and radiation therapy with high survival rates but there is room for improvement with advancing stage. Systemic chemotherapy can be used for treatment of both recurrent and metastatic disease, but careful attention should be paid to balancing benefit and toxicity. The key to improving overall outcomes will be translating the success seen in developed countries to areas of the world where advanced‐stage invasive cervical cancer is most common.
Malignant Melanoma
Authors: Carr Michael J. , Ko Justin M. , Swetter Susan M. , Woodman Scott E. , Sondak Vernon K. , Margolin Kim A. , Zager Jonathan S. 
Published: October 2022

OverviewMelanoma comprises a wide variety of malignant cell types arising from the skin, the mucous membranes, and the pigmented cells of the eye. While these tumors are all classified as melanoma and share a common molecular biology of pigmentation and biological resemblance to cells of neural crest origin, important distinctions in other molecular characteristics and patterns of exposure to ultraviolet light as a carcinogen determine their clinical natural history, including the response to therapeutic interventions. While the majority of melanomas are diagnosed at an early stage and curable with minimal surgery, melanoma has the potential for early and widespread dissemination via lymphatic and hematogenous routes. Surgery remains the mainstay of therapy for primary, regional, and many cases of single‐ or oligo‐metastatic disease, but systemic therapies have dramatically improved the prognosis for metastatic melanoma, particularly immunotherapies that enhance existing cellular immunity. The rapid discovery of new molecular targets, immunotherapy combinations, and understanding of the mechanisms of therapeutic resistance is likely to lead to even greater improvements in the prognosis for patients with melanoma in the near future.
Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms
Authors: Stone Richard M. , Schiffer Charles A. , DeAngelo Daniel J. 
Published: October 2022

OverviewAcute myeloid leukemia (AML) is a heterogeneous disease characterized by unbridled proliferation of myeloid stem cells resulting in bone marrow failure and death without effective therapy. The median age of AML is approximately 70; predisposing factors include inherited mutations, exposure to industrial solvents, ionizing radiation, or certain chemotherapy given for other malignancies or conditions. The disease results from the accumulation of mutations in pathways that promote cellular proliferation or impairing differentiation. Prognosis is based on a combination of host and disease factors, especially diagnostic cytogenetics and genomics. In younger fit patients, therapy consists of myelosuppressive induction chemotherapy to minimize disease burden and allow restoration of normal hematopoiesis. Postremission chemotherapy with additional myelo‐intense chemotherapy and/or allogeneic stem cell transplant is required to potentiate cure. In older and less fit patients (perhaps those with adverse prognosis) the current standard is repetitive cycles of a hypomethylating agent or low‐dose cytarabine plus the BCL‐2 inhibitor, venetoclax. The application of molecularly targeted therapies at both diagnosis and relapse may change the natural history of the disease, the management of which requires a comprehensive integration of disparate fields including social work, nutrition, pharmacy, blood bank, and medical oncology.
Chronic Lymphocytic Leukemia
Authors: Barrientos Jacqueline C. , Rai Kanti R. , Rhodes Joanna M. 
Published: October 2022

OverviewThere has been a significant progress, in the past two decades in our understanding of pathobiology ofchronic lymphocytic leukemia(CLL) and in the treatment of this disease. CLL is a monoclonal B‐cell lymphoproliferative disorder derived from antigen‐experienced B lymphocytes that differ in their level ofimmunoglobulin heavy chain variable region(IGHV) gene mutations. The understanding of CLL biology has advanced with the discovery of chromosomal abnormalities and genetic mutations that contribute to the heterogeneity of the disorder and help predict its clinical course. Equally important has been the discovery of the role of the microenvironment and of the signaling mechanisms that play a key role in CLL pathogenesis.1–4This knowledge has led to the development of agents that specifically target dysregulated pathways. A major shift in the treatment paradigm of CLL took place with the approval of several new targeted agents with unprecedented clinical activity, particularly in patients with high‐risk disease or with poor prognostic markers. Despite these rapid advances, CLL remains incurable and patients who initially achieve a remission will eventually develop disease recurrence. Current efforts are geared toward the development of novel therapeutics that target the complex biology of CLL with the goal of achieving a cure.
Urologic Complications Related to Cancer and Its Treatment
Authors: Alhalabi Omar , Abudayyeh Ala , Tannir Nizar M. 
Published: October 2022

Overview
Urologic complications of cancer itself or its treatment often require timely identification and intervention. In patients with early‐stage disease, skilled multidisciplinary management of urologic complications is critical to ensure optimal renal function and delivery of adequate doses of chemotherapy that do not compromise the likelihood of cure. Similarly, the management of urologic complications such as urinary obstruction in patients with metastatic disease can have a significant impact on the quality of life. Multiple sites of ureteric obstruction, long occlusions, or a tortuous ureter may be indications to proceed directly with percutaneous nephrostomy instead of ureteral stenting. In contrast to urinary obstruction in newly diagnosed prostate cancer that is likely sensitive to androgen deprivation, castrate‐resistant prostate cancer will likely require more permanent relief of obstruction, either by nephrostomy or suprapubic catheter.
Sexual Dysfunction
Authors: Schover Leslie R. 
Published: October 2022

Overview
Sexual problems related to cancer are usually caused by physiological damage from treatment but are exacerbated by psychosocial issues such as poor individual coping, relationship conflict, or preexisting sexual dysfunction. Sexual dysfunction affects almost two‐thirds of the estimated 17 million cancer survivors in the United States, including well over 50% of those treated for pelvic or breast cancers and at least 25% for other sites. Optimal treatment is multidisciplinary, addressing both physical damage and behavioral skills. If a committed relationship exists, it is best to include the partner in education and intervention.
Macrophages in Tumor‐Associated Adipose Microenvironment Accelerate Tumor Progression
Authors: Li Bei , Liu Siqing , Yang Qian , Li Zhiyu , Li Juanjuan , Wu Juan , Sun Shengrong , Xu Zhiliang , Sun Si , Wu Qi 
Published: October 2022

AbstractAdipose‐tissue macrophages (ATMs), a complex ensemble of diverse macrophage subtypes, are prevalent in the tumor‐adipose microenvironment (TAME) and facilitate tumor growth. However, the mechanisms in which the tumor‐adipocyte crosstalk may enable the properties and plasticity of macrophages remain unclear. The single‐cell RNA‐sequence profiling reveals that a subset of macrophages expressed CD163, CCL2, and CCL5 in TAME, exhibiting an immunosuppressive subtype. It is demonstrated that CD163+ macrophages aggregate to surround adipocytes in breast cancer tissues. The expressions of CCL2 and CCL5 are also elevated in TAME and enable the recruitment and polarize macrophages. Mechanically, the level of exosomal miRNA‐155 increased in the coculture of tumor cells and adipocytes, and then it promoted the generation and release of CCL2 and CCL5 from adipocytes by targeting the SOCS6/STAT3 pathway. Inhibition of exosomal miRNA‐155 in tumor cells reduced the CCL2 and CCL5 levels in tumor‐adipocytes coculture and further retarded tumor growth. Finally, the deletion of macrophages partially inhibited adipocyte‐induced tumor proliferation. Likewise, inhibiting chemokines and their receptors or suppressing the phosphorylation of STAT3 decreased tumor burden in preclinical models. These results demonstrate that the niche factors in TAME, such as exosomal miRNA‐155, regulate the function and polarity of macrophages to facilitate tumor progression.
Suppressing the Multiple Nucleation for the Uniform Growth of Perovskite Single‐Crystal Microplates Arrays toward High‐Performance Optoelectronic Devices
Authors: Malo Tehinke Achille , Lu Zhengjun , Deng Wei , Sun Yuye , Wang Chaoqiang , Pirzado Azhar Ali Ayaz , Jie Jiansheng , Zhang Xiujuan , Zhang Xiaohong 
Published: October 2022

AbstractThe pursuit of high‐performance and integrated perovskite optoelectronic devices drives the development of efficient methods to pattern perovskite single crystals (PSCs). However, due to stochastic and multiple nucleation, PSCs obtained from traditional patterning methods still suffer from heterogeneous morphology and low crystallinity, resulting in unwanted large variation in the device performance. Herein, an effective and universal strategy is reported for the large‐scale patterned growth of high‐quality perovskite single‐crystal microplates with uniform size and thickness. By modulating the wettability of gold nanoparticles, nucleation energetic barriers are subtly regulated and thus intractably random and multiple nucleation are fundamentally suppressed, enabling the formation of homogeneous perovskite microplates with exceptional properties in terms of ultralow surface defect density (6.1 × 107 cm−2) and high carrier mobility (176 cm2 V−1 s−1). In consequence, the photodetector array based on the patterned perovskite microplates exhibits a large photoresponsivity up to 615 A W−1, along with a low photocurrent variable coefficient <5.2%, which enables the realization of ultrasensitive and high‐contrast imaging functions. This patterning technique constitutes a major step toward the deployment of PSCs in integrated optoelectronic devices.
Photoswitchable Microgels for Dynamic Macrophage Modulation
Authors: Kim Yuri , Thangam Ramar , Yoo Jounghyun , Heo Jeongyun , Park Jung Yeon , Kang Nayeon , Lee Sungkyu , Yoon Jiwon , Mun Kwang Rok , Kang Misun , Min Sunhong , Kim Seong Yeol , Son Subin , Kim Jihwan , Hong Hyunsik , Bae Gunhyu , Kim Kanghyeon , Lee Sanghyeok , Yang Letao , Lee Ja Yeon , Kim Jinjoo , Park Steve , Kim Dong‐Hyun , Lee Ki‐Bum , Jang Woo Young , Kim Bong Hoon , Paulmurugan Ramasamy , Cho Seung‐Woo , Song Hyun‐Cheol , Kang Seok Ju , Sun Wujin , Zhu Yangzhi , Lee Junmin , Kim Han‐Jun , Jang Ho Seong , Kim Jong Seung , Khademhosseini Ali , Kim Yongju , Kim Sehoon , Kang Heemin 
Published: October 2022

AbstractDynamic manipulation of supramolecular self‐assembled structures is achieved irreversibly or under non‐physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π–cation and π–π interactions are developed that are electrostatically stabilized with Arg–Gly–Asp (RGD)‐bearing anionic polymers. Lateral swelling of RGD‐bearing microgels occurs via cis‐azobenzene formation mediated by near‐infrared‐light‐upconverted ultraviolet light, which disrupts intermolecular interactions on the visible‐light‐absorbing upconversion‐nanoparticle‐coated materials. Real‐time imaging and molecular dynamics simulations demonstrate the deswelling of RGD‐bearing microgels via visible‐light‐mediated trans‐azobenzene formation. Near‐infrared light can induce in situ swelling of RGD‐bearing microgels to increase RGD availability and trigger release of loaded interleukin‐4, which facilitates the adhesion structure assembly linked with pro‐regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD‐bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro‐inflammatory polarization. These microgels exhibit high stability and non‐toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.
Fast Transport and Transformation of Biomacromolecular Substances via Thermo‐Stimulated Active “Inhalation–Exhalation” Cycles of Hierarchically Structured Smart pNIPAM–DNA Hydrogels
Authors: Du Xiaoxue , He Ping‐Ping , Wang Chunyan , Wang Xiaowen , Mu Yali , Guo Weiwei 
Published: October 2022

AbstractAlthough smart hydrogels hold great promise in biosensing and biomedical applications, their response to external stimuli is governed by the passive diffusion‐dependent substance transport between hydrogels and environments and within the 3D hydrogel matrices, resulting in slow response to biomacromolecules and limiting their extensive applications. Herein, inspired by the respiration systems of organisms, an active strategy to achieve highly efficient biomolecular substance transport through the thermo‐stimulated “inhalation–exhalation” cycles of hydrogel matrices is demonstrated. The cryo‐structured poly(N‐isopropylacrylamide) (pNIPAM)–DNA hydrogels, composed of functional DNA‐tethered pNIPAM networks and free‐water‐containing macroporous channels, exhibit thermally triggered fast and reversible shrinking/swelling cycles with high‐volume changes, which drive the formation of dynamic water stream to accelerate the intake of external substances and expelling of endogenous substances, thus promoting the functional properties of hydrogel systems. Demonstrated by catalytic DNAzyme and CRISPR‐Cas12a‐incorporating hydrogels, significantly enhanced catalytic efficiency with up to 280% and 390% is achieved, upon the introduction of active “inhalation–exhalation” cycles, respectively. Moreover, remotely near‐infrared (NIR)‐triggering of “inhalation–exhalation” cycles is achieved after the introduction of NIR‐responsive MXene nanosheets into the hydrogel matrix. These hydrogel systems with enhanced substance transport and transformation properties hold promise in the development of more effective biosensing and therapeutic systems.
Ionic Modulation at the LaAlO3/KTaO3 Interface for Extreme High‐Mobility Two‐Dimensional Electron Gas
Authors: Yan Hong , Zeng Shengwei , Rubi Km , Omar Ganesh Ji , Zhang Zhaoting , Goiran Michel , Escoffier Walter , Ariando Ariando 
Published: October 2022

AbstractDue to the coexistence of many emergent phenomena, including 2D superconductivity and a large Rashba spin‐orbit coupling, 5d transition metal oxides‐based two‐dimensional electron systems (2DESs) have been prospected as one of the potential intrants for modern electronics. However, despite the lighter electron mass, the mobility of carriers, a key requisite for high‐performance devices, in 5d‐oxides devices remains far behind their 3d‐oxides analogs. The carriers’ mobility in these oxides is significantly hampered by the inevitable presence of defects. Here, very high mobility (≈22 650 cm2 V−1 s−1) of 5d‐2DES confined at the LaAlO3/KTaO3 interface is reported. The high mobility, which is beyond the values observed in SrTiO3 2DESs in the same carrier‐density range, is achieved using the ionic‐liquid gating at room temperature. The authors postulate that the ionic‐liquid gating affects the oxygen vacancies and efficiently reduces any disorder at the interface. Investigating density and mobility in a broad range of back‐gate voltage, the authors reveal that the mobility follows the power‐law µ ∝ n1.2, indicating the very high quality of ionic‐liquid‐gated LaAlO3/KTaO3 devices, consistent with the postulate. Furthermore, the analysis of the quantum oscillations confirms that the high‐mobility electrons occupy the electronic sub‐bands emerging from the Ta:5d orbitals of KTaO3.