bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Clinical Management of Surgical Margins in Breast-Conserving Therapy for Breast Cancer
Authors: Grobmyer Stephen R. , Cowher Michael S. , Crowe Joseph P.
Published: February 2020

There has been, and continues to be, significant controversy over the definition of an “optimal” surgical margin in breast-conserving therapy (BCT). The historic basis of this controversy stems from the original trials documenting the safety of BCT and many conflicting retrospective studies that have sought to define the association between surgical margin width and outcomes over the last 20 years. It is important to understand that margin assessment is an inexact science, and current laboratory approaches to surgical-margin assessment represent only a sampling of the surgical margin. Currently available evidence suggests that decisions regarding surgical margins in BCT should be made in the context of what is known about the biology of breast cancer, as well the interactions of tumor biology, adjuvant treatment for breast cancer, and outcomes. Achieving consensus on management of surgical margins in BCT should be a clinical priority as it offers the opportunity to reduce the burden of breast cancer treatment on patients without compromising cancer-related outcomes.
Connecting Molecular Pathways to Hereditary Cancer Risk Syndromes
Authors: Testa Joseph R. , Malkin David , Schiffman Joshua D.
Published: February 2020

An understanding of the genetic causes and molecular pathways of hereditary cancer syndromes has historically informed our knowledge and treatment of all types of cancers. For this review, we focus on three rare syndromes and their associated genetic mutations including BAP1, TP53, and SDHx (SDHA, SDHB, SDHC, SDHD, SDHAF2). BAP1 encodes an enzyme that catalyzes the removal of ubiquitin from protein substrates, and germline mutations of BAP1 cause a novel cancer syndrome characterized by high incidence of benign atypical melanocytic tumors, uveal melanomas, cutaneous melanomas, malignant mesotheliomas, and potentially other cancers. TP53 mutations cause Li-Fraumeni syndrome (LFS), a highly penetrant cancer syndrome associated with multiple tumors including but not limited to sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas. Genomic modifiers for tumor risk and genotype-phenotype correlations in LFS are beginning to be identified. SDH is a mitochondrial enzyme complex involved in the tricarboxylic acid (TCA) cycle, and germline SDHx mutations lead to increased succinate with subsequent paragangliomas, pheochromocytomas, renal cell carcinomas (RCCs), gastrointestinal stromal tumors (GISTs), and other rarer cancers. In all of these syndromes, the molecular pathways have informed our understanding of tumor risk and successful early tumor surveillance and screening programs.
Early and Late Long-Term Effects of Adjuvant Chemotherapy
Authors: Mayer Erica L.
Published: February 2020

Adjuvant chemotherapy continues to play an important role in breast cancer management. Exposure to chemotherapy can lead to a variety of early and late long-term toxicities, including ovarian failure (with resultant infertility and sexual dysfunction), bone loss, weight gain, neurotoxicity, neurocognitive changes, cardiac toxicity and secondary malignancy. Although chemotherapy effects may vary in medical severity, all effects have the potential to lead to a decrease in quality of life and a decrement on overall health status. Improved understanding of the etiology and management of chemotherapy-related toxicity may allow optimization of patient selection for treatment and ameliorate the concerns of patients who are considering embarking on a chemotherapy program. This article presents an overview of relevant early and late long-term toxicities, with a focus on recent advances and clinical management.
“Right Drug for the Right Patient”: Hurdles and the Path Forward in Colorectal Cancer
Authors: Kopetz Scott
Published: February 2020

Predictive biomarkers have been heralded as the way to develop the “right drug for the right patient.” However, despite many studies incorporating novel biomarkers with targeted therapies, there has been little progress over the 5 years since the identification of KRAS mutations' ability to predict resistance to epidermal growth factor receptor (EGFR) monoclonal antibodies. Recently approved therapeutics (regorafenib, aflibercept) or label extensions for existing therapies (bevacizumab) lack companion biomarkers. The current model of biomarker development, “target-based biomarker” design, attempts to identify individual biomarkers that are closely tied to the activity of a particular treatment. There are several limitations to prospective utilization of predictive biomarkers in novel therapy development, including technical validation of the assay and the logistics of timely biomarker determination with available material that limit the options. Tumor heterogeneity, both between different regions in the tumor and as a result of changes induced over time and under the selective pressure of chemotherapy, can reduce the precision of biomarker determination. Biomarkers present in low frequencies are increasingly common in drug development and will require efficient screening infrastructure to be feasible. Although development efforts will continue in the current target-based biomarker model for the near future, it is increasingly apparent that a new model is needed. A “taxonomy-based biomarker” model has been proposed, which is less tied to novel drug development and instead attempts to classify individual tumors based on their intrinsic biology. This requires integrating multiple characteristics of the tumors, including gene mutations, amplifications, methylation, as well as RNA and protein expression. Identification of the taxonomy of colorectal cancer will then allow more efficient development of targeted agents that can leverage the distinct molecular vulnerabilities of the resulting subsets. A transition to a taxonomy-based biomarker model would provide the classification structure and biologic insights needed to advance the ultimate goal of the right drug for the right patient.
Biologic Agents in the Treatment of Colorectal Cancer: The Last Decade; the Lost Decade?
Authors: Venook Alan P. , Saltz Leonard B.
Published: February 2020

KEY POINTS

After almost 40 years of minimal progress, the period from 1996 to 2003 saw a flurry of new drugs become available.

Progress since 2003 has been minimal.

Most new agents with activity in the metastatic setting (irinotecan, bevacizumab, cetuximab) do not have activity in the adjuvant setting and so have not increased the cure rate.

Combinations of biologics have been disappointing.

Progress to date is less than we would have expected.

Therapy individualized according to molecular characterization of each tumor appears to be the way forward.
The Economics of New Drugs: Can We Afford to Make Progress in a Common Disease?
Authors: Hirsch Bradford R. , Schulman Kevin A.
Published: February 2020

The concept of personalized medicine is beginning to come to fruition, but the cost of drug development is untenable today. To identify new initiatives that would support a more sustainable business model, the economics of drug development are analyzed, including the cost of drug development, cost of capital, target market size, returns to innovators at the product and firm levels, and, finally, product pricing. We argue that a quick fix is not available. Instead, a rethinking of the entire pharmaceutical development process is needed from the way that clinical trials are conducted, to the role of biomarkers in segmenting markets, to the use of grant support, and conditional approval to decrease the cost of capital. In aggregate, the opportunities abound.
Surgical Approaches to Invasive Adenocarcinoma of the Gastroesophageal Junction
Authors: Coit Daniel
Published: February 2020

Despite a plethora of data, the optimal surgical approach to invasive adenocarcinoma of the gastroesophageal (GE) junction remains controversial. To quote Dr. Valerie Rusch, “Strong individual preferences and some degree of surgical mystique often govern the selection of operation for resection of GE junction adenocarcinomas.” 1 The fırst of these controversies is whether the optimal open surgical approach should be via the transabdominal, transthoracic (two-incision Ivor Lewis or three-incision McKeown), or transhiatal route. Proponents of the transthoracic or transhiatal routes have voiced strong opinions on the potential advantages and disadvantages of each approach ( Table 1 ). It is clear from most large retrospective series that, in experienced hands, excellent results can be achieved by either approach. The principal advantage of the transthoracic route is the ability to perform a radical mediastinal lymphadenectomy en bloc with the primary tumor, the theory being that a more aggressive lymph node dissection would be associated with an improved long-term outcome. To date, however, this association of a more aggressive lymphadenectomy with improved outcome has remained elusive in most gastrointestinal malignancies, including esophageal cancer. Proponents of the transhiatal approach cite similar lymph node retrieval rates, the potential for lower short-term morbidity, and the potential for similar long-term outcomes. 2 With the advent of newer technology, the controversy regarding the optimal surgical approach to adenocarcinoma of the GE junction has evolved in yet another direction, with proponents of a minimally invasive approach, citing even lower perioperative morbidity and mortality, again with comparable or even superior long-term oncologic results.
Unanswered Questions in the Management of Gastroesophageal Junction Adenocarcinoma: An Overview from the Medical Oncologist's Perspective
Authors: Shah Manish A.
Published: February 2020

Patients with gastroesophageal junction (GEJ) adenocarcinoma have multiple treatment options; however, are victims of lack of consensus and wide variation in treatment, sometimes within the same hospital. While there is a consensus that surgery alone is inadequate for locally advanced disease, locoregional treatment has become the point for debate. Only in 2010 was the reclassification of GEJ cancers as esophageal cancers. Treatment options remain as varied as the classification of GEJ cancers: preoperative chemoradiotherapy, definitive chemoradiation, perioperative chemotherapy, and resection followed by postoperative chemoradiation. Several studies have examined the varying treatment paradigms; however, many fall short due to methodology or sample size. The MAGIC study determined perioperative chemotherapy to be an acceptable standard treatment option for patients with gastric cancer, althouth a significant portion of enrolled patients had distal esophageal and GEJ adenocarcinoma. The CROSS study concluded combination chemotherapy and radiation before resection beneficial. Preoperative therapy in cases of GEJ is beneficial for survival, but not as much impact is seen as in esophageal SCC, which exhibits an increased sensitivity to CRT. There is concurrence with two phase III studies from Japan and Korea on the role of adjuvant chemotherapy for gastric cancer. However, the applicability of these studies to GEJ adenocarcinoma remains a question, especially with the significantly different epidemiology of increased proximal and GEJ tumors in the West compared to Asia. To move forward with this increasingly prevalent disease, we will need to do more than understand the multiple treatment paradigms—we will need to select a strategy and examine it.
Nonhormone Therapy for Metastatic Castration-Resistant Prostate Cancer: Chemotherapy, Bone-Targeted Treatments, and Others
Authors: Fizazi Karim
Published: February 2020

There is no doubt that more therapeutic progress has been achieved during the last 3 years for patients with metastatic castration-resistant prostate cancer (mCRPC) than during the previous 30 years. During this limited time frame, not only have six compounds (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, listed in chronologic order) yielded positive results in phase III trials, we have also learned that their mechanisms of action are different, making it quite likely that part of their anticancer activity may be incremental. Most of these agents have already been approved. Further progress may well soon complete this recently enlarged armamentarium, with important trials testing new agents derived from existing families of compounds (new endocrine therapies, new immunotherapies, etc.) and exploring the activity of new families of agents (tyrosine kinase inhibitors such as cabozantinib, inhibitors of chaperone proteins like OGX-O11 and OGX-427). The availability of these agents creates a new major challenge for those who conduct clinical research in mCRPC. Will we be able to personalize therapy based on the biology of the individual's tumor, as we are already doing in other neoplasms?
Sequencing Systemic Therapies in Advanced RCC: Is There a Best Strategy?
Authors: Powles Tom , Crusz Shanthini M.
Published: February 2020

There is a strong rationale for sequencing targeted therapy in metastatic clear cell renal cancer. However the timing of the switch and the best agent to switch to remains unclear. Randomized data currently are supportive of the sequence of axitinib, followed by everolimus in those patients in which first-line vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy fails. Everolimus is also justified in the second-line setting, and the overall survival data for sorafenib in VEGF TKI resistant disease is impressive. A degree of cross-resistance appears to exist between all these current agents and has resulted in a drive toward the development of new therapies with novel modes of action.
Androgen Deprivation for Prostate Cancer: When and How, the Good and the Bad
Authors: Chi Kim N. , Nguyen Paul L. , Higano Celestia S.
Published: February 2020

Androgen deprivation therapy (ADT) is the mainstay systemic treatment of prostate cancer because of the androgen dependence of the disease. Although ADT has long been used to manage prostate cancer, its use continues to evolve as data from clinical trials mature and long-term effects are recognized. For patients with localized disease and high-risk features, short and long courses of ADT as neoadjuvant/adjuvant therapy have been shown to improve survival when used with radiation therapy, but this has not been demonstrated with radical prostatectomy. The role of ADT with salvage radiotherapy after radical prostatectomy continues to be defined. Lifelong ADT in patients with node-positive disease after surgery or with radiation is also associated with increased survival. Increasingly though, the adverse effects of ADT that go beyond those on libido and hot flashes are being acknowledged. The metabolic effects on lipids, glycemic control, and bone loss from ADT can lead to an increased risk of cardiovascular events and osteoporosis, which needs to be considered when deciding to initiate and treat patients with ADT. Large, randomized trials comparing intermittent to continuous ADT have now been reported. Although the hope for improved cancer outcomes with intermittent therapy has not come to realization, an interrupted approach to therapy may help mitigate some of the negative effects of ADT in selected patients by allowing for off-treatment intervals.
Adjuvant Chemotherapy in Older Adults with Non–Small Cell Lung Cancer
Authors: Gajra Ajeet
Published: February 2020

Platinum-based adjuvant chemotherapy is the standard of care for patients with early-stage non–small cell lung cancer (NSCLC) treated with surgery. There is a paucity of data regarding the appropriate use of adjuvant chemotherapy in the treatment of older adults. In the absence of prospective randomized controlled trials specific to this population, the available evidence is limited to post hoc analyses of prospective studies in age-unselected populations and retrospective reviews of population databases. The available evidence for treatment of older adults with adjuvant therapy using cisplatin- and carboplatin-based therapy is reviewed. Strategies for future research, as well as the role of geriatric assessment in risk stratification, will be addressed.
PI3K Pathway in Gynecologic Malignancies
Authors: Salvesen Helga B. , Werner Henrica Maria , Krakstad Camilla
Published: February 2020

Alterations in PI3K signaling are common in gynecologic malignancies. Alterations detected vary with gynecologic cancer type, histologic subtypes within these, and clinical phenotypes. The distinction into type I and type II endometrial and ovarian carcinomas is reflected in distribution of changes detected in several of the PI3K members. PIK3CA mutations and amplifications are common in endometrial, ovarian, and cervical cancers. PTEN mutations and deletions are frequent in endometrial cancers. Several immunohistochemical studies of protein expression have explored these and other potential surrogate markers for PI3K pathway activation. Biomarkers to measure level of PI3K activity in clinical samples are not established. Whether amplifications, mutations, and deletions of the PI3K pathway members, and in particular change in their expression levels, result in clinically relevant pathway activation needs to be further explored. Also, to what extent these alterations drive the tumor behavior and are critical targets for therapeutics to improve patient survival needs to be further tested to establish predictive biomarkers for response to PI3K inhibition.
Obesity and Gynecologic Cancer Etiology and Survival
Authors: Webb Penelope M.
Published: February 2020

The prevalence of overweight and obesity in the United States and elsewhere has increased dramatically in recent decades. It has long been known that obese women have an increased risk of developing endometrial cancer, but recent studies suggest this association is strongest for the most common low-grade endometrioid endometrial cancers and weaker for the other histologic subtypes. There are insufficient data to assess whether obesity affects endometrial cancer-specific survival or whether the relation with all-cause mortality is similar to that seen in the general population. Recent data suggest obesity also increases risk of ovarian cancer, although it may not influence risk of the high-grade serous cancers that account for the majority of ovarian cancer deaths, and that it is also associated with poorer outcomes. There is currently insufficient evidence to draw any clear conclusions regarding the relation between obesity and risk of/survival from other gynecologic cancers although there are suggestions that obesity may increase risk of cervical cancer, particularly adenocarcinoma, and perhaps vulvar cancer. Possible mechanisms whereby obesity might influence gynecologic cancer risk and survival include: its strong association with endogenous estrogen levels among postmenopausal women, its effects on glucose metabolism, its effects on the wide range of adipocytokines and inflammatory mediators that are produced by adipose tissue and altered in concentration among obese individuals, and its potential effects on patient management, particularly with regard to chemotherapy dosing.
Assessing and Improving Quality of Life in Patients with Head and Neck Cancer
Authors: Singer Susanne , Langendijk Johannes , Yarom Noam
Published: February 2020

Health-related quality of life (QoL) indicates the patients' perception of their health. It depends not only on disease- and treatment-related factors but also on complex inter-relationships of expectations, values and norms, psychologic distress, and comparison with other patients. This article introduces methods and challenges of QoL assessment in patients with head and neck cancer, as well as ways to overcome measurement problems and ways to improve their QoL.
National Plan for Prevention, Early Detection, and Cancer Control in Peru
Authors: Vallejos Carlos
Published: February 2020

Peru currently is executing an ambitious plan for cancer control: its first nationwide program of cancer prevention and cancer control, and the first such program launched in Latin America. The adequate strategies were identified from previous experience developing smaller initiatives and from knowledge of our epidemiology and priorities. The geographic landscape and sociocultural differences, in which inequalities play a significant role in access to quality education and specialized cancer care, are the main challenges to elaborate strategies to diminish our burden of advanced disease. Challenges were not only identified for the poorest people, but for other sectors of the population. With a growing Peruvian economy in a globalized market context, emerging sectors are being exposed to new risk factors for cancer and educational strategies were implemented. The development of the National Plan for Cancer Control was launched involving not only technical efforts by a multidisciplinary team, but also political concertation.
The Joys and Challenges of Caring for Patients
Authors: Gilewski Teresa
Published: February 2020

Optimal care of patients involves the integration of both the scientific and humanistic aspects of medicine. However, the tremendous focus on technology can easily overshadow the personal effect of patient care. The complex relationship between the physician and the patient is a reciprocal one. Not only does the physician influence the experience of the patient, but the patient may leave a significant impression on the physician. Their interactions provide a myriad of opportunities for greater insight into the human condition, but may also contribute toward the struggle of physicians to maintain their own well-being. Enhanced awareness of the significance of these human interactions is at the core of caring for patients.
Stem Cell Transplant As an Immunomodulatory Tool for Children with Hematologic Malignancies
Authors: LaBelle James L. , Cunningham John M.
Published: February 2020

Allogeneic stem cell transplantation (alloHSCT) is the most common and effective form of immunotherapy used for treatment of pediatric leukemias. A combination of graft manipulation, donor selection, fine-tuning of conditioning regimens, and use of lower and novel forms of immunosuppression following transplant has maximized the tolerability of alloHSCT in children. This outcome has facilitated new advances in disease-specific transplant regimens that seek to amplify the antitumor effects of the allograft, while reducing transplant-related mortality. However, disease relapse remains the preeminent challenge to the success of transplantation as a modality for successful treatment of high-risk disease. Separating graft versus host disease (GVHD) from graft versus leukemia (GVL) remains the most significant obstacle to enhancing disease-free survival. However, with increased clarity and discrimination in the effector mechanisms responsible for GVHD and/or GVL in patients of all ages, a new wave of clinical trials has become feasible that harnesses GVL effects to treat patients with high-risk myeloid and lymphoid malignancies. Exciting progress is being made in the use of alloHSCT with donor lymphocyte infusions (DLIs) in almost all forms of pediatric hematologic malignancies. This advance sets the stage for the use of HSCT and/or DLI in conjunction with novel disease-specific post-transplant therapies using small molecule therapeutics, tumor vaccines, and novel antibody therapies.
Photons or Protons for Non–Central Nervous System Solid Malignancies in Children: A Historical Perspective and Important Highlights
Authors: Daw Najat C. , Mahajan Anita
Published: February 2020

Over the years, major advances have occurred in radiotherapy techniques, delivery, and treatment planning. Although radiotherapy is an integral treatment component of pediatric solid tumors, it is associated with potential acute and long-term untoward effects and risk of secondary malignancy particularly in growing children. Two major advances in external beam radiotherapy are intensity-modulated radiotherapy (IMRT) and proton beam radiotherapy. Their use in the treatment of children with cancer has been steadily increasing. IMRT uses multiple modulated radiation fields that enhance the conformality of the dose distribution to the target volume and avoid high doses to normal tissues. However, IMRT may be associated with increased volume of normal tissue that receives low doses and potential risk of secondary malignancy. Contrary to IMRT, proton beam radiotherapy uses a few beams and a fast dose fall-off distal to the target volume. Although both modalities require substantial personnel time and effort, the very high cost and limited availability of proton radiotherapy have constrained its widespread use. It is anticipated that both modalities may markedly improve tumor control and quality of life for long-term cancer survivors. Clinical trials with long-term follow-up are needed to confirm the premise that proton beam therapy will decrease late effects and secondary malignancies without compromising local control in pediatric patients with cancer.
Efficient and Effective Models for Integrating Advanced Practice Professionals into Oncology Practice
Authors: Shulman Lawrence N.
Published: February 2020

Advanced practice professionals (APP), primarily nurse practitioners and physician assistants, are increasingly being integrated into oncology practices. The reasons are numerous, and models of care options are numerous as well. Models of care have developed without much forethought and are often the result of the relative interests of the physician, the APP, and the mutual “comfort” of practice style. The increasing complexity of oncology care, the pressures of the health care crisis and health care reform mean that it is necessary that we examine models of collaborative care in terms of both quality of care and productivity.
The Past, Present, and Future of Cytotoxic Chemotherapy and Pathway-Directed Targeted Agents for Soft Tissue Sarcoma
Authors: Ryan Christopher W. , Desai Jayesh
Published: February 2020

The individual rarity of the many subtypes of soft tissue sarcomas has historically mandated an empiric approach to systemic therapy. Doxorubicin, first reported to have activity in sarcomas 40 years ago, remains the generalizable first-line treatment of choice for many subtypes, with no other drug or combination having shown an overall-survival advantage. Other cytotoxic agents, such as paclitaxel for angiosarcoma or gemcitabine with docetaxel for leiomyosarcoma, are commonly used for certain histologic subtypes based on relatively small studies. Trabectedin, particularly active against leiomyosarcoma and myxoid liposarcoma, is approved in many countries worldwide but not yet in the United States or Australia. Newer cytotoxic agents, including ifosfamide derivatives, are in current phase III testing. Although advances is systemic therapy of soft-tissue sarcomas have been hampered by their biologic heterogeneity, this diversity also serves as fertile ground for discovery and validation of targetable molecular drivers. The most notable success in this regard has been the development of small molecule therapies for gastrointestinal stromal tumors. Other targets of recent interest include mouse double minute 2 homolog (MDM2) in dedifferentiated liposarcoma and anaplastic lymphoma kinase (ALK) in inflammatory myofibroblastic tumor. Molecular therapies that have shown activity in diverse sarcoma populations include mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (VEGF-R) inhibitors. Among the latter, pazopanib demonstrated a progression-free survival over placebo in prior-treated patients with advanced sarcoma, and is now approved for use in the sarcomas in many countries. Efforts to understand the key molecular aberrations in any particular tumor continue towards a goal of individualized sarcoma therapy.
Prostate Cancer Screening in BRCA and Lynch Syndrome Mutation Carriers
Authors: Castro Elena , Goh Chee L. , Eeles Rosalind A.
Published: February 2020

Prostate cancer (PrCa) remains a major public health burden worldwide. Screening programs have been established using the most efficient biomarker to date—prostate-specific antigen (PSA)—with the goal of earlier detection of this disease, which is thought to translate to a reduction in PrCa mortality. However, these screening programs have proved to be controversial following the publication of the two large, randomized, population-based studies in the United States and Europe. There is a recognized need for more refined screening strategies to address some of the deficiencies highlighted in these trials, which include the overdiagnosis and overtreatment of clinically indolent disease. One such strategy could be to include inherited genetic variants in population risk stratification to identify those at higher risk who might benefit more from screening. The genetic component for PrCa risk has been documented from case control and twin studies. The genetic variants include common variants discovered by genome-wide association studies (GWAS). However, their clinical application—including their utility in screening programs—is as yet undefined. There are, however, moderate to rare genetic variants, which confer a much higher risk of PrCa (e.g., BRCA1/2 and mismatch repair [MMR] repair genes). There is more research evidence on the clinical effect of germ-line mutations in these genes; mutation carriers are more likely to develop aggressive PrCa with worse survival. A targeted screening approach might be beneficial if earlier diagnosis, and hence treatment, was to translate into improved outcomes. Clinical trials are currently underway to investigate this further.
Mammographic Density: Intersection of Science, the Law, and Clinical Practice
Authors: Hollenbeck Scott , Keely Patricia , Seewaldt Victoria
Published: February 2020

High mammographic density is associated with a two- to sixfold increased risk of breast cancer. Mammographic density can be altered by endogenous and exogenous hormonal factors and generally declines with age. Mammographic density is affected by confounding factors such as age, parity, menopausal status, and body mass index (BMI), thus making interpretation of mammographic density challenging. None of the established means of measuring mammographic density are entirely satisfactory because they are time consuming and/or subjective. Although mammographic density has been shown to predict breast cancer risk, the role of mammographic density in precisely assessing a woman's breast cancer risk over her lifetime and evaluating response to risk-reduction strategies cannot be fully realized until we have a better understanding of the biology that links mammographic density to breast cancer risk.
Developments in the Use of Antibody-Drug Conjugates
Authors: Burris Howard A.
Published: February 2020

With the recent approvals of brentuximab for the treatment of refractory Hodgkin lymphoma and ado-trastuzumab emtansine for relapsed metastatic HER2+ breast cancer, the hope for delivering targeted chemotherapy in the form of an antibody-drug conjugate (ADC) against many cancers is rapidly growing. The strategy of delivering a potent cytotoxic via a monoclonal antibody to a tumor has been made feasible by marked advances in the technology of formulating and manufacturing these ADCs. The development of stable linkers together with the identification of relevant biomarkers has been a key to the success of this class of agent. The possibilities for deploying this technology in the treatment of a wide range of solid cancers are limited only by the discovery of suitable targets, those which are highly expressed on cancer cells and not, or minimally, on normal tissues. That said, with the improved linker engineering, the ADC affords the best opportunity at shrinking tumors while minimizing side effects. A variety of ADCs are in clinical trials studying a number of different tumor types as diverse as small cell lung and renal cell cancer. A future of potent anticancer therapy with minimal toxicity appears closer to reality for our patients.
When ‘the Use of Force’ is Prohibited? – Article 2 (4) and the ‘Threshold’ of the Use of Force
Authors: Kleczkowska Agata
Published: February 2020

This article advances the thesis that there is no threshold of the use of force. i.e. no level of the use of force which decides whether and which forcible actions undertaken by States are prohibited. The examples of actions discussed in the doctrine of law which supposedly would be ‘below’ such a threshold in fact either are regulated by other prin-ciples of international law, are not considered as regulated by ius ad bellum, or States deliberately resign from calling them a use of force for both legal and extra-legal reasons. Thus, the existence of such a threshold is not confirmed by States’ practice. This thesis will be explored using three examples: the cases of the evacuation of nationals, the extra-territorial and the Falklands/Malvinas Islands invasion of 2 April 1982. The article starts with a brief discussion of the opinions expressed in the doctrine of international law on the threshold, as well as the applicable case law.
Closing Speech - Between Theory and Practice
Authors: Kowalczyk-Ludzia Marta
Published: February 2020

The development of rhetoric in criminal procedure is reflected in every court trial. The right of the parties to present their final speech before the court (Article 406 of the Pol-ish Code of Criminal Procedure) is important for achieving the required verdict. This paper tries to answer the question about the actual extent to which the said regulation is used by the parties to achieve their objectives. The deliberations are based on an analysis of the results of research conducted by the author.
Integrating deep learning, social networks, and big data for healthcare system
Authors: Naoui Mohammed Anouar , Lejdel Brahim , Ayad Mouloud , Belkeiri Riad , Khaouazm Abd Sattar
Published: February 2020

This paper aims to propose a deep learning model based on big data for the healthcare system to predict social network data. Social network users post large amounts of healthcare information on a daily basis and at the same time hospitals and medical laboratories store very large amounts of healthcare data, such as X-rays. The authors provide an architecture that can integrate deep learning, social networks, and big data. Deep learning is one of the most challenging areas of research and is becoming increasingly popular in the health sector. It uses deep analysis to extract knowledge with optimum precision. The proposed architecture consists of three layers: the deep learning layer, the big data layer, and the social networks layer. The big data layer includes data for health care, such as X-ray images. For the deep learning layer, three Convolution Neuronal Network models are proposed for X-ray image classification. As a result, social network layer users can access the proposed system to predict their X-ray image posts.
Education Spending, Fertility Shocks and Generational Consumption Risk
Authors: Emerson Patrick M. , Knabb Shawn D.
Published: February 2020

This paper develops a model with overlapping generations to show that human capital formation can potentially attenuate factor price movements in response to fertility shocks if education spending per child is inversely related to the size of the generation subject to the fertility shock. The degree of attenuation depends on the effectiveness of education spending in producing human capital. We also find this attenuation effect concentrates generational consumption risk around the generation subject to the fertility shock. The combination of these two results suggest that there is an inverse relationship between the degree of factor price movements and lifetime consumption profiles in response to fertility shocks. Relatively larger generations will experience larger drops in lifetime consumption and relatively smaller generations will experience larger increases in lifetime consumption the less factor prices move in response to generational size. Thus, factor price smoothing does not necessarily translate into welfare smoothing across all generations.
Frequency effects in the L2 acquisition of the catenative verb construction – evidence from experimental and corpus data
Authors: Azazil Lina
Published: February 2020

This paper investigates frequency effects in the L2 acquisition of the catenative verb construction by German learners of English from a usage-based perspective by presenting findings from two experimental studies and a complementary corpus study. It was examined if and to what extent the frequency of the verb in the catenative verb construction affects the choice of the target-like complement type and if the catenative verb construction with a to-infinitive complement, which is highly frequent in English, is more accurately acquired and entrenched than the less frequent variant with an -ing complement. In all three studies, the more frequent construction with a to-infinitive yielded higher numbers of target-like complement choices. Furthermore, it was shown that the verb’s faithfulness to the construction made a significant prediction of a target-like complement preference. It is argued that a higher faithfulness promotes a target-like entrenchment of the construction and motivates a taxonomic generalisation across related exemplars. Furthermore, the results provide support for the idea that the mental representation of language is comprised of item-specific as well as more abstract schema knowledge, where frequency determines the specificity with which the construction is entrenched.
A Cognitive-Semiotic Construal of Metaphor in Discourse
Authors: Zhao Xia , Shen Rong , Zhao Xincheng
Published: February 2020

Cognitive semiotics is a new field for the study of meaning in trans-disciplines, such as semiotics, cognitive linguistics, and corpus linguistics. This paper aims at studying how cognitive semiotics is employed to construe conceptual metaphors in discourse. We conducted a corpus-based study, with Lakoff and Johnson’s Conceptual Metaphor Theory (CMT) and Fauconnier and Turner’s Blending Theory (BT), to illustrate our cognitive-semiotic model for metaphors inDragon Seed, written by Nobel Prize winner Pearl S. Buck. The major finding is that metaphors are mental constructions involving many spaces and mappings in the cognitive-semiotic network. These integration networks are related to encoders’ cognitive, cultural, and social contexts. Additionally, cognitive semiotics can be employed to construe conceptual metaphors in discourse vividly and comprehensively and thus is helpful to reveal the ideology and the theme of the discourse.
Is it possible to change the destiny of stray animals by legal means?
Authors: Anisimov Aleksey Pavlovich , Ryzhenkov Anatoliy Jakovlevich
Published: February 2020

The article deals with the theory and practice of treatment of stray animals in light of the latest changes in the Russian legislation. The research includes issues of terminology as well as the place of the function of treatment of stray animals in the system of municipal administration functions. The authors prove the unreasonableness of the strategy of returning stray animals sterilized in shelters to the habitat, argue in favor of measures for development of legal liability for violation of the legislation on treatment of stray animals, measures for registration (record) of such animals, the importance of transition to standards of circular economy in the field of waste management, measures for development of culture and education. It is proved that only a set of economic, legal and other measures can lead to success. Decrease in the number of stray animals will lead to the improvement of the sanitary situation in cities, lower the risk of bites and diseases transmitted with their help, and reduce the number of offenses related to cruelty to animals, car accidents involving stray animals, as well as cases of moral stress for children who daily observe suffering of stray cats and dogs.
Sweeping and eliminating evils: a diachronic study of mafia in China
Authors: Peng Xinlin , Gong Mingyu , Bing Jie
Published: February 2020

Mafia organizations have long been a threat to Chinese society. The development of mafia organizations in China have experienced four stages: formation, dying out, resurgence, and recurrence. The Chinese government has attached great importance to the governance of mafia organizations and has suppressed mafia forces with some notable achievements. In January 2018, the Chinese government carried out a nationwide special campaign, “sweeping and eliminating evils” [sao hei chu’ e], to crack down gangs’ crimes in China. Different from previous actions, the recent campaign has changed its focus from “fighting” [da] to “sweeping” [sao], showing the changing focus of Beijing’s strategy in the crackdown on mafia organizations. In view of this, this study investigates the past, present and future of China’s governance of mafia organization crimes in the current context from a historical, norm-analytical approach. On the basis of a systematic review on the development of mafia organizations in China, this study, drawing on the current situation, discusses the process and main strategies of the mafia organization governance, and analyses the reasons for and the problems in the special campaign “sweeping and eliminating evils” in the new era. This study also provides plans and suggestions on how to advance the campaign from the perspective of the rule of law.
Family History and the Global Politics of DNA
Authors: Abel Sarah , Tsosie Krystal S.
Published: February 2020

The global DNA ancestry industry appeals to various “markets”: diasporic groups seeking to reconstruct lost kinship links; adoptees looking for biological relatives; genealogists tracing their family trees; and those who are merely curious about what DNA can reveal about their identity. However, the language of empowerment and openness employed by DNA ancestry-testing companies in their publicity materials masks the important commercial and private interests at stake. Drawing particularly on the experiences of Native and Indigenous American communities, this article highlights some of the contradictions and dilemmas engendered by the industry, and questions to what extent its practices can empower users without infringing upon the rights of other groups.
A Competency Model for Volunteer Storytellers in Public Libraries
Authors: Peng Yu-Ping , Chuang Po-Han
Published: February 2020

In recent years, public library administrators have actively promoted children’s reading services. Storytelling activities have a significantly positive effect on enhancing children’s interest and ability in reading. Due to the shortage of human resources in some public libraries, volunteers are required to provide storytelling activities. Public libraries should enhance the competencies of volunteer storytellers and provide appropriate training for maintaining as well as improving the effectiveness of storytelling activities. The study conducted interviews in order to build a multidimensional and theoretically grounded competency model for volunteer storytellers in public libraries. Interviews were designed based on the relevant literature. The study used in-depth interviews to obtain information on the experiences, ideas, and suggestions of 15 volunteer storytellers at Taipei Public Library. The results indicate ten facets of the competency model for volunteer storytellers: knowledge about readers; knowledge about story material; assisting in planning and organizing storytelling; expressing and interpreting story skills; children resource utilization instruction skills; information technology skills; oral and writing communication; volunteer team administration and management skills; professional literacy and development; and personal attitude and characteristics. These findings can be helpful in developing competency models and practices related to competency development among volunteer storytellers for public libraries. Finally, the results can serve as a reference for administrators of public libraries and other children’s reading education institutions to implement human resources strategies and practices concerning volunteer storytellers, including planning, recruitment, education, management, and performance evaluation.
Exciton-plasmon polariton coupling and hot carrier generation in two-dimensional SiB semiconductors: a first-principles study
Authors: Ramazani Ali , Shayeganfar Farzaneh , Jalilian Jaafar , Fang Nicholas X.
Published: February 2020

Exciton (strong electron–hole interactions) and hot carriers (HCs) assisted by surface plasmon polaritons show promise to enhance the photoresponse of nanoelectronic and optoelectronic devices. In the current research, we develop a computational quantum framework to study the effect of coupled exciton and HCs on the photovoltaic energy distribution, scattering process, polarizability, and light emission of two-dimensional (2D) semiconductors. Using a stable 2D semiconductor (semihydrogenated SiB) as our example, we theoretically show that external strain and thermal effect on the SiB can lead to valley polarized plasmon quasiparticles and HC generation. Our results reveal that the electron–phonon and electron–electron (e–e) interactions characterize the correlation between the decay rate, scattering of excitons, and generation of HCs in 2D semiconductors. Moreover, phonon assisted luminescence spectra of SiB suggest that light emission can be enhanced by increasing strain and temperature. The polarized plasmon with strong coupling of electronic and photonics states in SiB makes it as a promising candidate for light harvesting, plasmonic photocurrent devices, and quantum information.
Crystal structure of poly[diaqua-(μ2-4,4′-bipyridine-κ2
N:N′)-(μ2-3,4,5,6-tetrafluorophthalato-κ2
O:O′)nickel(II)], C18H12F4NiN2O6
Authors: Li Yan-Hong , Han Min-Le
Published: February 2020

C18H12F4NiN2O6, orthorhombic, Pccn (no. 56), a = 7.4650(2) Å, b = 10.6954(2) Å, c = 22.7513(5) Å, V = 1816.49(7) Å3, Z = 4, R
gt(F) = 0.0304, wR
ref(F
2) = 0.0898, T = 293 K.
The crystal structure of 3,10-bis(4-methoxyphenyl)-6,12-dibenzyl-2,9-acetyl-6,12-diazapentacyclo[6.3.1.02,7.04,11.05,9]dodecane – acetone (1/1), C45H48N2O5
Authors: Wang Xiaoxia , Zhang Danyang , Zhuang Pengyu , Zhang Yao , Xu Jiale
Published: February 2020

C45H48N2O5, monoclinic, P21/c (no. 14), a = 21.3971(8) Å, b = 15.2249(6) Å, c = 11.2610(5) Å, β = 92.125(4)°, V = 3666.0(3) Å3, Z = 4, R
gt(F) = 0.0519, wR
ref(F
2) = 0.1308, T = 128.15 K.
Two dimensional simulation of laminar flow by three- jet in a semi-confined space
Authors: Mosaddeghi Mohammad
Published: February 2020

Equipment performance improvement in a wide range of working conditions is one of the major goals of aerodynamics. This goal can be achieved by the deformation of the object being examined or by using flow control techniques in active or inactive modes. In different researches, how to change the development ratio on the semi-confined space with input jet system is surveyed. In this study, two-dimensional simulation of the flow has been investigated in three-jet laminar flow in a semi-confined space. To determine the effective and optimal mixing in a laminar flow, critical Reynolds numbers were determined to distinguish when the flow in the channel from a steady-state symmetric flowformed downstream recirculation and ultimately transient flow. To better understand the flow characteristics, the simulations were changed at a fixed jet spacing (input jets distance to height of space ratio). Also, in this paper, for comparison, four jets were considered. Based on the results, it was observed that in all cases, mixing occurred in the space between three jets. Placing the jet along the walls of the semi-confined space allows the best combination, and increase in the distance between the first and third jets and reduction of the particle coefficient caused to reach the critical Reynolds number faster and, as a result, mixing in a laminar flow with geometric changes of the semi-confined space.