bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study
Authors: Uppal Shitanshu , Gehrig Paola A. , Peng Katherine , Bixel Kristin L. , Matsuo Koji , Vetter Monica H. , Davidson Brittany A. , Cisa M. Paige , Lees Brittany F. , Brunette Laurie L. , Tucker Katherine , Stuart Staley Allison , Gotlieb Walter H. , Holloway Robert W. , Essel Kathleen G. , Holman Laura L. , Goldfeld Ester , Olawaiye Alexander , Rose Stephen L. 
Published: February 2020

PURPOSE To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions METHODS Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017. RESULTS Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18) CONCLUSION In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.
Functional genetic analysis in a jawless vertebrate, the sea lamprey: insights into the developmental evolution of early vertebrates
Authors: York Joshua R. , McCauley David W. 
Published: February 2020

ABSTRACTLampreys and hagfishes are the only surviving relicts of an ancient but ecologically dominant group of jawless fishes that evolved in the seas of the Cambrian era over half a billion years ago. Because of their phylogenetic position as the sister group to all other vertebrates (jawed vertebrates), comparisons of embryonic development between jawless and jawed vertebrates offers researchers in the field of evolutionary developmental biology the unique opportunity to address fundamental questions related to the nature of our earliest vertebrate ancestors. Here, we describe how genetic analysis of embryogenesis in the sea lamprey (Petromyzon marinus) has provided insight into the origin and evolution of developmental-genetic programs in vertebrates. We focus on recent work involving CRISPR/Cas9-mediated genome editing to study gene regulatory mechanisms involved in the development and evolution of neural crest cells and new cell types in the vertebrate nervous system, and transient transgenic assays that have been instrumental in dissecting the evolution of cis-regulatory control of gene expression in vertebrates. Finally, we discuss the broad potential for these functional genomic tools to address previously unanswerable questions related to the evolution of genomic regulatory mechanisms as well as issues related to invasive sea lamprey population control.
Studying convergent evolution to relate genotype to behavioral phenotype
Authors: Gallant Jason R. , O'Connell Lauren A. 
Published: February 2020

ABSTRACT
Neuroscience has a long, rich history in embracing unusual animals for research. Over the past several decades, there has been a technology-driven bottleneck in the species used for neuroscience research. However, an oncoming wave of technologies applicable to many animals hold promise for enabling researchers to address challenging scientific questions that cannot be solved using traditional laboratory animals. Here, we discuss how leveraging the convergent evolution of physiological or behavioral phenotypes can empower research mapping genotype to phenotype interactions. We present two case studies using electric fish and poison frogs and discuss how comparative work can teach us about evolutionary constraint and flexibility at various levels of biological organization. We also offer advice on the potential and pitfalls of establishing novel model systems in neuroscience research. Finally, we end with a discussion on the use of charismatic animals in neuroscience research and their utility in public outreach. Overall, we argue that convergent evolution frameworks can help identify generalizable principles of neuroscience.
Symmetry and Systematic Enumeration of Twistane Derivatives. Global/Local Chirality and Global/Local RS-Stereogenicity Revisited by Fujita’s Stereoisogram Approach
Authors: Fujita Shinsaku 
Published: February 2020

Abstract
Fujita’s stereoisogram approach (S. Fujita, Mathematical Stereochemistry; De Gruyter: Berlin, 2015) has been applied to the discussion on the stereochemistry of twistane derivatives. In addition to chirality as the first kind of handedness, RS-stereogenicity is emphasized as the second kind of handedness, where an R-twistane skeleton and an S-twistane skeleton are recognized to be a pair of RS-diastereomers as a result of RS-stereogenicity. The contrast between global/local chirality and global/local RS-stereogenicity is clearly demonstrated by introducing the names, R-twistane and S-twistane, which are based on the globality of RS-stereogenicity. Among the five types of stereoisograms (type I to type V) as the full repertoire, there appear only type-I and type III stereoisograms during the discussions on twistane derivatives. Combinatorial enumeration of twistane derivatives are discussed on the basis of Fujita’s proligand method (S. Fujita, Combinatorial Enumeration of Graphs, Three-Dimensional Structures, and Chemical Compounds; University of Kragujevac, Faculty of Science: Kragujevac, 2013).
The establishment of breastfeeding in the small-for-gestational-age baby
Authors: Dooks Emma , Owens David , Stacey Tomasina 
Published: February 2020

Background Term babies born smaller than expected for a given gestation are at greater risk of short- and long-term health conditions. Breastmilk is the optimum nutrition for all babies and offers specific protection from the risks that follow from being born small for gestational age. Aim To explore breastfeeding outcomes for babies born with a birthweight below the 10th centile. Methods Data were collected on all women giving birth in one maternity unit in the north of England over a year. Method of feeding at three time points was compared between small-for-gestational-age and appropriately grown babies. Findings Small-for-gestational-age babies were significantly less likely to be breastfeeding at discharge from hospital and community services compared to larger babies. Conclusion This study suggests that small-for-gestational-age babies are disadvantaged in establishing breastfeeding.
The Appropriate Extent of Surgery for Early-Stage Breast Cancer
Authors: Morrow Monica 
Published: February 2020

Overview: Attitudes regarding the appropriate extent of surgery for breast cancer and the effect of surgery on breast cancer–specific survival have varied over time. Failure to maintain local control is associated with decreased survival, but the extent of surgery necessary for local control has decreased as other treatment modalities, such as radiotherapy and systemic therapy, have become more widely used. Both endocrine therapy and chemotherapy considerably reduce rates of local recurrence in the breast, as well as the incidence of contralateral breast cancer, and as efficacy in reducing metastatic disease increases, so does the benefit in reducing local recurrence. The excellent rates of local control in the ACOSOG Z11 trial after elimination of axillary dissection in patients with positive sentinel nodes receiving whole-breast irradiation and systemic therapy are a model for reducing surgical morbidity in the era of multimodality therapy.
Postmastectomy Radiation and Partial Breast Irradiation
Authors: Zellars Richard C. 
Published: February 2020

Overview: Between 1997 and 1999, three modern postmastectomy radiation therapy (PMXRT) trials were published. These trials showed a significant benefit with respect to local control and survival in women who received adjuvant radiation after mastectomy. Despite two decades of follow-up, reanalyses, meta-analyses and vigorous and often acrimonious debate, questions about the benefit of PMXRT in women with one to three positive lymph nodes (LNs) remain unanswered for many. This persistent debate has limited the use of PMXRT. A treatment concept certain to be as vigorously debated as that of PMXRT is that of partial breast irradiation (PBI). However, unlike PMXRT, the acceptance of PBI, by community physicians, has been nothing short of meteoric and represents the first major shift in the local therapy paradigm in more than 10 years. Herein, information will be presented that will suggest we are nearing the end of one debate—PMXRT in patients with one to three positive LNs—and beginning another—appropriateness of PBI.
Limitations of Adaptive Clinical Trials
Authors: Buyse Marc 
Published: February 2020

Overview: Adaptive designs are aimed at introducing flexibility in clinical research by allowing important characteristics of a trial to be adapted during the course of the trial based on data coming from the trial itself. Adaptive designs can be used in all phases of clinical research, from phase I to phase III. They tend to be especially useful in early development, when the paucity of prior data makes their flexibility a key benefit. The need for adaptive designs lessened as new treatments progress to later phases of development, when emphasis shifts to confirmation of hypotheses using fully prespecified, well-controlled designs.
Adjuvant Treatments for Localized Advanced Gastric Cancer: Differences among Geographic Regions
Authors: Kang Yoon-Koo , Yoo Changhoon 
Published: February 2020

Overview: After much debate, adjuvant therapy has become the standard of care worldwide for resected localized gastric cancer. However, geographic differences exist in standard adjuvant treatments: postoperative chemoradiation in North America, perioperative chemotherapy in the United Kingdom, and postoperative chemotherapy in East Asia. Now that D2 gastrectomy has been recognized as the optimal surgery for localized gastric cancer in the West as well as in Asia, the standard adjuvant treatments used in the West may need to be reconsidered. One of the most important issues in adjuvant therapy for localized gastric cancer is how to improve the clinical outcomes of current standard treatments. Recent Cancer and Leukemia Group B (CALGB) and AMC studies suggest that simply intensifying chemotherapy by adding more agents or prolonging treatment duration is insufficient. However, new strategies like early initiation of chemotherapy and/or intraperitoneal chemotherapy may further improve the current standard adjuvant therapy. In the era of targeted therapy, the role of biologic agents for gastric cancer should also be explored in the adjuvant setting. With a deeper understanding of the molecular biology of gastric cancer, adjuvant therapy for patients with localized gastric cancer can be optimized and individualized.
State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012
Authors: Sartor Oliver 
Published: February 2020

Overview: Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future, we will develop molecular “stratification systems” to better guide therapeutic choices in CRPC.
The New National Cancer Institute National Clinical Trials Network
Authors: Grubbs Stephen S. 
Published: February 2020

Overview: The National Cancer Institute (NCI) Cooperative Group Program has been reviewed by three published studies in the last 7 years evaluating the efficiency and effectiveness of this national oncology clinical trials system. The recommendations for improvement from these reports have prompted NCI to transform the Cooperative Group Program into a new NCI National Clinical Trials Network (NCTN) to improve the efficiency of large clinical trials and increase the speed of cancer translational research. The new NCTN offers community-based clinical investigators new opportunities to advance cancer research in their community setting but also presents challenges in promoting community-based research.
Opportunities and Pitfalls of Targeted Therapeutic Combinations in Solid Tumors
Authors: Mateo Joaquin , Ong Michael , Yap Timothy A. , de Bono Johann S. 
Published: February 2020

Overview: Recent advances in cancer biology have led to the discovery and development of chemical compounds and drugs that target specific cellular receptors, mediators, or effectors that are central to oncogenic survival, growth, and invasion. However, the complexity of tumor biology makes it is unrealistic to expect an antitumor therapeutic to be successful based on the inhibition of a single target or even a lone signaling pathway. Therefore, the potential success of such “targeted therapies” is likely to require the development of multiagent combinations. Combination strategies have a greater likelihood of addressing issues with genetically complex tumors, potentially avoiding drug resistance mechanisms through the inhibition of escape signaling pathways and slowing the development of newly resistant tumor cells. Combination regimes also have the potential of enhancing target inhibition through synergistic antitumor effects and minimizing drug-related toxicities to patients. However, numerous challenges to developing these combinations exist. This review will focus on the opportunities and pitfalls of developing novel targeted drug combinations, with a particular focus on early-phase drug development, where the greatest challenges exist, analyzing key points for the design and development of clinical trials for combinations of targeted agents.
Initial Management of Low-Risk Pediatric Fever and Neutropenia: Efficacy and Safety, Costs, Quality-of-Life Considerations, and Preferences
Authors: Sung Lillian 
Published: February 2020

Overview: Initial management options for pediatric low-risk fever and neutropenia (FN) include outpatient compared with inpatient management and oral compared with intravenous therapy. Single-arm and randomized trials have been conducted in children. Meta-analyses provide support for the equivalence of outpatient and inpatient approaches. Outpatient oral management may be associated with a higher risk of readmission compared with outpatient intravenous management in children with FN, although other outcomes such as treatment failure and discontinuation of the regimen because of adverse effects were similar. Importantly, there have been no reported deaths among low-risk children treated as outpatients or with oral antibiotics. Costs, whether derived directly or through cost-effectiveness analysis, are consistently reduced when an outpatient approach is used. Quality of life (QoL) and preferences should be considered in order to evaluate different strategies, plan programs, and anticipate uptake of outpatient programs. Using parent-proxy report, child QoL is consistently higher with outpatient approaches, although research evaluating child self-report is limited. Preferences incorporate estimated QoL, but, in addition, factor in issues such as costs, fear, anxiety, and logistical issues. Only approximately 50% of parents prefer outpatient management. Future research should develop tools to facilitate outpatient care and to measure caregiver burden associated with this strategy. Additional work should also focus on eliciting child preferences for outpatient management. Finally, studies of effectiveness of an ambulatory approach in the real-world setting outside of clinical trials are important.
Curative-Intent Treatment for Colorectal Liver Metastases: A Medical Oncologist's Perspective
Authors: Saltz Leonard B. 
Published: February 2020

Overview: Resection or ablation of CRC liver metastases can be offered with curative intent in some, but not all patients in whom resection is technically possible. Chemotherapy can improve the potential for cure to some degree, either in the adjuvant or neoadjuvant setting, or, in relatively rare circumstances, by converting truly unresectable disease into resectable. Careful and realistic patient selection, with an individualized and realistic assessment of curative potential, is key to providing each patient with the means to make realistic treatment choices.
Measuring and Improving Value of Care in Oncology Practices: ASCO Programs from Quality Oncology Practice Initiative to the Rapid Learning System
Authors: Jacobson Joseph O. , Neuss Michael N. , Hauser Robert 
Published: February 2020

Overview: Rising cancer care costs are no longer sustainable. Medical oncologists must focus on providing the maximum value to their patients; improving short-term, intermediate and long-term outcomes; and managing overall costs. Accurate measurement of outcomes and overall cost is essential to informing providers and institutions and in the quest for continuous improvement in value. The ASCO Quality Oncology Practice Initiative (QOPI) is an excellent tool for sampling processes of care in medical oncology practices. To achieve the larger goal of improving the value of cancer care, ASCO is investing in the development of a Rapid Learning System, which will leverage emerging information technologies to more accurately measure outcomes (including those reported by the patient) and costs, resulting in highly efficient, effective, and safe cancer care.
Ethics of Biopsy in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Authors: Foreman Nicholas K. 
Published: February 2020

Overview: To understand the ethical dilemmas that beset this issue of biopsy in children with newly diagnosed diffuse intrinsic pontine glioma, one must understand both the history behind it and the current dominant interpretation of ethics through the medium of the institutional review boards. It is also important to understand that this article represents the author's personal viewpoint. At a consensus meeting to discuss the issue of biopsies in Diffuse Intrinsic Pontine Glioma (DIPG) at the National institutes of Health held in the fall of 2011, there were a variety of opinions expressed.
Evaluation of Patients with Disseminated or Locoregionally Advanced Thyroid Cancer: A Primer for Medical Oncologists
Authors: Colevas A. Dimitrios , Shah Manisha H. 
Published: February 2020

Overview: Historically, patients with thyroid cancers are managed by endocrinologists, surgeons and radiation oncologists. Due to recent progress in this field with advances in treatment of thyroid cancer, medical oncologists are now commonly involved in care of patients with advanced thyroid cancers. In this manuscript, we describe general principles in management of patients with various types of thyroid cancers including differentiated, medullary and anaplastic thyroid cancers.
Are Oncologists Accountable Only to Patients or Also to Their Families? An International Perspective
Authors: Surbone Antonella , Baider Lea 
Published: February 2020

Overview: In most societies, health professionals traditionally carry responsibility only toward their patients. However, this is not the case in all cultures. In the contemporary practice of oncology in Western cultures, there is a shift toward assuming broader responsibility for patients with cancer' families during the illness course, the grieving stage, and in cancer prevention and genetic counseling. Traditional family, community, and religious values play a central role in determining people's perceptions and attitudes toward life and death as well as toward caregiving for a sick relative. The meaning of cancer illness within the family culture is thus influenced not only by each individual's values and beliefs but also by the family's makeup and dynamics, as well as their taboos and secrets. Global cancer care should therefore be directed at the family as a unit, while respecting patient autonomy and privacy. This reappraisal of our traditional understanding of physicians' duty as solely directed at the patient is reflected in the recent US trend toward a patient- and family-centered care approach. An additional challenge for oncology professionals is to integrate and tailor interventions toward the needs of both care recipients and caregivers and relate it to this dyad as the basic and enduring unit of care.