bluuebunny/crossref_metadata_2025 huggingface dataset:
New Treatment Options in Advanced Squamous Cell Lung Cancer
Authors: Paik Paul K. , Pillai Rathi Narayana , Lathan Christopher S. , Velasco Sylvia A. , Papadimitrakopoulou Vassiliki
Published: May 2019

The past few years have witnessed a rapid shift in the treatments for patients with squamous cell lung cancers (SQCLCs) after the U.S. Food and Drug Administration approval of a number of immune checkpoint inhibitors as second-line therapies for patients with non–small cell lung cancers. These series of approvals marked the first substantial improvement in overall survival for patients with SQCLC in over a decade. Further gains have been made more recently with the incorporation of immune checkpoint inhibition in the first-line setting, either as monotherapy or in combination with chemotherapy. These advances have, however, exposed existing deficiencies in the management of this disease. Despite a deeper understanding of the genomic alterations that characterize SQCLCs and years of trial work targeting these alterations, personalized therapies remain out of hand. Future studies will continue to focus on identifying targeted approaches to expand the treatment options for our patients.
Building Personalized Cancer Follow-up Care Pathways in the United States: Lessons Learned From Implementation in England, Northern Ireland, and Australia
Authors: Alfano Catherine M. , Jefford Michael , Maher Jane , Birken Sarah A. , Mayer Deborah K.
Published: May 2019

There is a global need to transform cancer follow-up care to address the needs of cancer survivors while efficiently using the health care system to limit the effects of provider shortages, gaps in provider knowledge, and already overburdened clinics; improve the mental health of clinicians; and limit costs to health care systems and patients. England, Northern Ireland, and Australia are implementing an approach that triages patients to personalized follow-up care pathways depending on the types and levels of resources needed for patients’ long-term care that has been shown to meet patients’ needs, more efficiently use the health care system, and reduce costs. This article discusses lessons learned from these implementation efforts, identifying the necessary components of these care models and barriers and facilitators to implementation of this care. Specifically, the United States and other countries looking to transform follow-up care should consider how to develop six key principles of this care: algorithms to triage patients to pathways; methods to assess patient issues to guide care; remote monitoring systems; methods to support patients in self-management; ways to coordinate care and information exchange between oncology, primary care, specialists, and patients; and methods to engage all stakeholders and secure their ongoing buy-in. Next steps to advance this work in the United States are discussed.
City Cancer Challenge: Changing the Future of Cancer in Urban Populations
Authors: Henshall Susan M. , Villar Hugo V. , Doria Raul , Milner Danny A.
Published: May 2019

Incidence and mortality from cancer is increasing in most countries in the world, with the highest burden in developing countries. City Cancer Challenge (C/Can), an initiative launched in 2017, aims to improve access to quality cancer care in metropolitan areas (1 million inhabitants or more) in low- and upper-middle income countries by transforming the way stakeholders at the city, regional, and national levels collectively design, plan, and implement local cancer solutions. The approach is built on the core principle that local leaders in cities define their own needs and craft solutions with the support of a network of global, regional, and local partners that reflect an understanding of the unique local context. C/Can aims to build a collective movement of cities that can together deliver quality, equitable, and sustainable cancer control solutions for all.
Induction Therapy for Newly Diagnosed Multiple Myeloma
Authors: Paul Barry , Lipe Brea , Ocio Enrique M. , Usmani Saad Z.
Published: May 2019

The frontline therapy for newly diagnosed multiple myeloma (MM) has continued to evolve over the last 10 years. There has been a growing emphasis on achieving the best depth of response in the context of minimal residual disease negativity, given its prognostic correlation with superior overall survival. Another important area of emphasis has been to improve prognostication and staging by including information on disease biology. There also a growing appreciation of global differences in drug access and patterns of care. The current review explores each of these areas and how best to incorporate the emerging induction regimens in to schema of MM therapy.
Caring for Our Trainees: Lessons From Around the World
Authors: Srivastava Ranjana , Mukherji Deborah , Bourlon Maria T.
Published: May 2019

Continuing progress in the science of oncology must be matched by an increased responsibility toward providing oncology trainees around the world with the academic guidance, emotional support, and lifelong mentoring needed to navigate an increasingly complex environment. Although the realities on the ground determine the practicalities, there are important universal lessons to be learned from heeding diverse experiences. In this paper, three faculty at different stages of their careers from countries with different resources and infrastructure share their insights into caring for trainees.
How Precision Medicine Is Changing Acute Myeloid Leukemia Therapy
Authors: Heuser Michael , Mina Alain , Stein Eytan M. , Altman Jessica K.
Published: May 2019

Pretreatment somatic mutations influence acute myeloid leukemia (AML) pathogenesis and responses to chemotherapy. Integration of cytogenetic abnormalities and molecular mutations, co-occurring and in isolation, have resulted in a more refined prognostic assessment. In addition, research performed over the last few years has led to the development of novel therapies and new drug approvals in patients with both newly diagnosed and relapsed/refractory (R/R) AML. Here we discuss the use of these newly approved therapies. Advances in AML have also occurred through development of better tools to assess response to treatment. Both multiparameter flow cytometry and polymerase chain reaction can be used to assess for the presence or absence of measurable residual disease (MRD) and increase the sensitivity of response assessment. The role of MRD assessment is gaining relevance and its integration in clinical trials and treatment decision making will be explored in the second half of this article.
Tailored Treatment Strategies for Chronic Lymphocytic Leukemia in a Rapidly Changing Era
Authors: Brander Danielle , Islam Prioty , Barrientos Jacqueline C.
Published: May 2019

The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving, with multiple agents recently approved. They include a glycoengineered monoclonal antibody (obinutuzumab), B-cell receptor signaling inhibitors (ibrutinib, idelalisib, and duvelisib), and the BCL-2 inhibitor (venetoclax). These compounds are dramatically changing the natural course of the disease. Nonetheless, despite improved survival rates, particularly in higher-risk disease (older adults, patients with unmutated IGHV, del(11q), and del(17p)/ TP53 mutated), there is still room for progress. Given the panoply of highly effective therapies commercially available, it is important to define a tailored treatment strategy for this heterogeneous condition that considers balance of treatment efficacy versus toxicity or tolerance. This article summarizes the most promising clinical advances by reviewing the data from recent clinical trials and discussing meaningful clinical endpoints, including the role of minimal residual disease assessment. The recent development of therapies targeting dysregulated pathways is revolutionary and may ultimately lead us to not only achieve prolonged remission durations but also envision the possibility of a functional cure for a larger population of patients.
All Men Are Created Equal: Addressing Disparities in Prostate Cancer Care
Authors: Borno Hala , George Daniel J. , Schnipper Lowell E. , Cavalli Franco , Cerny Thomas , Gillessen Silke
Published: May 2019

The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. By 2030, the number of cancer cases is projected to increase to 24.6 million and the number of cancer deaths, to 13 million. Global data mask the social and health disparities that influence cancer incidence and survival. Inequality in exposure to carcinogens, education, access to quality diagnostic services, and affordable treatments all affect the probability of survival. Worryingly, despite the fact that many cancers could be prevented by stronger public health actions and many others could be largely cured by better access to diagnostics and affordable treatments, the international community has yet to make a substantial move to tackle this challenge. In prostate cancer, studies show that there are geographic and racial/ethnic distribution differences as well as a number of other variables, including environmental factors, limited access to standard cancer treatments, reduced probability to be included in trials, and the financial burden of cancer treatments. Financial burden for the patients can result in poor adherence, increased debt, and poor long-term outcomes. The following article will discuss some of the important causes for disparity in prostate cancer and prostate cancer care, focused on the current situation in the United States, as well as possible remedies to address these causes.
The Future of Wearable Technologies and Remote Monitoring in Health Care
Authors: Liao Yue , Thompson Carrie , Peterson Susan , Mandrola John , Beg Muhammad Shaalan
Published: May 2019

Mobile technology has become a ubiquitous part of everyday life and is changing the way we offer clinical care and perform clinical research. We have unprecedented access to data for one’s self-care as well as for sharing with health care providers. Meeting the challenge posed by the influx of wearable device data requires a multidisciplinary team of researchers, clinicians, software developers, information technologists, and statisticians. Although the possibility of what can be achieved with the ever-evolving wearable technologies seems to be unlimited, regulatory agencies have provided a framework to establish standards for clinical applications, which will also affect research applications. Clinical programs and electronic medical records vendors should prepare to establish a framework to implement these technologies into clinicians’ workflow and to allow feedback to measure the impact on clinical outcome. In this article, we discuss how a new brand of multidisciplinary care is evolving around mobile health devices and present a vision of up-and-coming technology in this space.
Germline Genetic Testing for Breast Cancer Risk: The Past, Present, and Future
Authors: Yadav Siddhartha , Couch Fergus J.
Published: May 2019

The field of germline genetic testing for breast cancer (BC) risk has evolved substantially in the last decade. The introduction of multigene panel testing (MGPT) led to an urgent need to understand the cancer risk associated with several genes included in the panels. Although the research on understanding the cancer risk associated with mutations in several genes continues, there is also a need to understand the modifying effects of race and ethnicity, family history, and BC pathology on the prevalence of germline mutations and associated BC risk. Furthermore, polygenic risk scores (PRSs) to predict BC risk in patients with or without germline mutations in cancer-predisposition genes are now available for clinical use, although data on the clinical utility of PRSs are lacking. In patients with advanced BC associated with BRCA1/2 mutation, olaparib and talazoparib are now approved for treatment. In addition, molecular profiling studies are being used to clarify the BC tumor biology in mutation carriers to identify potential therapeutic options. In this article, we discuss these advances in the field of germline genetic testing and highlight current limitations and implications for clinical care.
Approach to the Older Adult With Multiple Myeloma
Authors: Mina Roberto , Bringhen Sara , Wildes Tanya M. , Zweegman Sonja , Rosko Ashley E.
Published: May 2019

Multiple myeloma (MM) is a disease of aging adults, and numerous therapeutic options are available for this growing demographic. MM treatment of older adults continues to evolve and includes novel combinations, new generations of targeted agents, immunotherapy, and increasing use of autologous stem cell transplantation (ASCT). Understanding age-related factors, independent of chronologic age itself, is an increasingly recognized factor in MM survivorship, especially in understudied populations, such as octogenarians. Octogenarians have inferior survival that cannot be explained by cytogenetic profiles alone. Incorporating assessments of geriatric factors can provide guidance on how to intensify or de-escalate therapeutic options. Functional status, using objective testing, is superior to traditional metrics of performance status and should be implemented to optimize the risk-benefit ratio of ASCT. ASCT is feasible and cost-effective, and chronologic age should not exclude ASCT eligibility. Upfront ASCT remains the standard of care, in the context of a sequential approach that includes pre-transplantation induction and post-transplantation maintenance. High-risk MM is classically defined by disease characteristics, yet shifting frameworks suggest that the high-risk designation could refer to any patient subgroup who is at risk for poorer outcomes—beyond disease-focused outcomes to patient-focused outcomes. Defining the optimal treatment of subgroups of older patients with high-risk disease on the basis of chromosomal abnormalities is unexplored. Here, we review tools to assess individual health status, explore vulnerability in octogenarians with MM, address ASCT decision-making, and examine high-risk MM to understand factors that contribute to survival disparities for older adults with MM.
What It Takes to Improve a First-Generation Inhibitor to a Second- or Third-Generation Small Molecule
Authors: Rodon Ahnert Jordi , Gray Nathanael , Mok Tony , Gainor Justin
Published: May 2019

Since the first generation of small molecules was included in the armamentarium of treatment of solid tumors (imatinib, erlotinib, etc.), there has been an expansion of anticancer small molecules, mostly kinase inhibitors, in development. Some of these drugs may not be a real breakthrough but may be similar in pharmacologic properties and marginal benefit over previously existing agents for the same indication (i.e., me-too drugs). Other drugs, however, have been specifically designed to solve an unmet medical need. Overcoming the problems of the blood–brain barrier and brain metastasis, emerging resistance mutations (such as gatekeeper mutations), or increasing selectivity/potency can be addressed with modern drug design. In this article, we discuss the advancements in the field of drug discovery, drug development, and clinical development that have enabled solving some of these issues. The evolution of the different generations of EGFR and anaplastic lymphoma kinase inhibitors exemplifies recent advancements in pharmacology that are driving the field of anticancer small molecules as a whole.
Patient-Centered Cancer Drug Development: Clinical Trials, Regulatory Approval, and Value Assessment
Authors: Gyawali Bishal , Hwang Thomas J. , Vokinger Kerstin Noelle , Booth Christopher M. , Amir Eitan , Tibau Ariadna
Published: May 2019

Historically, patient experience, including symptomatic toxicities, physical function, and disease-related symptoms during treatment or their perspectives on clinical trials, has played a secondary role in cancer drug development. Regulatory criteria for drug approval require that drugs are safe and effective, and almost all drug approvals have been based only on efficacy endpoints rather than on quality-of-life (QoL) assessments. In contrast to Europe, information regarding the impact of drugs on patients’ QoL is rarely included in oncology drug labeling in the United States. Until recently, patient input and preferences have not been incorporated into the design and conduct of clinical trials. In recent years, a more in-depth understanding of cancer biology, as well as regulatory changes focused on expediting cancer drug development and approval, has allowed earlier access to novel therapeutic agents. Understanding the implications of these expedited programs is important for oncologists and patients, given the rapid expansion of these programs. In this article, we provide an overview of the role of QoL in the regulatory drug–approval process, key issues regarding trial participation from the patient perspective, and the implications of key expedited approval programs that are increasingly being used by regulatory bodies for cancer care.
Evolving Treatments for Primary Central Nervous System Lymphoma
Authors: Ferreri Andrés J.M. , Holdhoff Matthias , Nayak Lakshmi , Rubenstein James L.
Published: May 2019

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis during its natural history of disease and is therefore considered stage IE disease. PCNSL is diffuse large B-cell lymphoma (DLBCL) morphology in more than 95% of patients and is designated primary diffuse large B-cell lymphoma of the CNS on the basis of the 2017 World Health Organization classification of hematopoietic and lymphoid tumors. Rapidly evolving therapeutic paradigms have been linked to evidence of progress in PCNSL, a disease long considered to be incurable. Increasing evidence supports the need for efficient diagnosis, staging, and initiation of therapy, ideally at centers with experience with this type of brain cancer. High-dose methotrexate (MTX) remains a cornerstone of induction regimens, and most data support the use of rituximab. However, clinical research challenges must address key questions, including the development of ever more effective and less toxic induction regimens and the selection of the most appropriate and effective consolidation approaches, as well as the fact that, increasingly, PCNSL affects older patients who do not tolerate strong genotoxic irradiation or high-dose chemotherapy (HDC)-based strategies. Maintenance therapy, immunotherapy, and the implementation of targeted agents on the basis of the molecular and biologic properties of the disease create opportunities for precision medicine and the potential for long-term disease-free survival and cure, with minimal treatment-related neurotoxicity, for a greater fraction of patients.
HPV Vaccination in Latin America: Global Challenges and Feasible Solutions
Authors: Nogueira-Rodrigues Angelica
Published: May 2019

HPV vaccine programs in Latin America run the risk of repeating the problems associated with Papanicolaou (Pap) test programs, an efficient, life-saving tool that is unfortunately underutilized for cancer prevention, in low- and middle-income countries. There is a great need for vigilance in the ongoing implementation of the HPV vaccine in Latin America.
Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality
Authors: Douville Nicholas J. , Jewell Elizabeth S. , Duggal Neal , Blank Ross , Kheterpal Sachin , Engoren Milo C. , Mathis Michael R.
Published: May 2019

BACKGROUND:

“Lung-protective ventilation” describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) Pao2/fractional inspired oxygen tension (Fio2), (2) postoperative pulmonary complications, and (3) 30-day mortality.

METHODS:

We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative Pao2/Fio2while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality.

RESULTS:

Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4–6), median delivered VTwas 520 mL (interquartile range = 460–580), and median driving pressure was 15 cm H2O (13–19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = −6.04; 95% CI, −8.22 to −3.87;P< .001), median Fio2(B = −0.30; 95% CI, −0.50 to −0.10;P= .003), and hours with driving pressure >16 cm H2O (B = −5.40; 95% CI, −7.2 to −4.2;P< .001) were associated with decreased postoperative Pao2/Fio2. Higher postoperative Pao2/Fio2ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331–0.740;P= .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366–0.606;P< .001, model C-statistic of 0.820). Intraoperative time with VT>500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00–1.20;P= .042).

CONCLUSIONS:

In patients requiring postoperative intubation after noncardiac surgery, increased median Fio2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative Pao2/Fio2. Intraoperative duration of VT>500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative Pao2/Fio2ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative Pao2/Fio2may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.
Influence of Remifentanil on the Control Performance of the Bispectral Index Controlled Bayesian-Based Closed-Loop System for Propofol Administration
Authors: Neckebroek Martine , Boldingh Jan-Willem H. L. , De Smet Tom , Struys Michel M. R. F.
Published: May 2019

BACKGROUND:

This study investigated the clinical performance of a model-based, patient-individualized closed-loop (CL) control system for propofol administration using the bispectral index (BIS) as a controlled variable during the induction and maintenance of anesthesia with propofol and remifentanil and studied the influence of the targeted effect-site concentration of remifentanil (CeREMI) on its clinical performance.

METHODS:

In 163 patients, propofol was administered using a CL system (BIS target [BISTARGET] between 40 and 50). Initial CeREMItargets between 2 and 7.5 ng/mL were selected as deemed clinically required. Performance parameters during induction were the time required to initially cross the target BIS, the time required to reach the maximal drug effect after induction (TPEAK, BIS) and the corresponding BIS at this moment, and the time required to regain the target BIS at the end of induction. Performance during maintenance was defined as the percentage of case time with target BIS ± 10 from target and the amount of performance error (PE) between the observed and target BIS values and its derived median PE (MDPE) as a measure of control bias, median absolute PE (MDAPE) as a measure of control inaccuracy, divergence as a measure of the time-related trend of the measured BIS values relative to the target BIS values, and wobble as a measure of intrasubject variability in prediction error. The secondary end point was the hemodynamic stability of the patient during CL control.

RESULTS:

The applied CL system induced and maintained anesthesia within clinically accepted ranges. The percentage of case time [mean (standard deviation [SD]) across all study participants] with BIS ± 10 from the target was 82% (14%). The mean (SD) population MDPE and MDAPE were −6.6% (5.5%) and 11.2% (5.5%), respectively. A negative divergence [−0.001 (0.004)] and acceptable wobble [9.7% (4.0%)] were found. The correlation between the system PE and CeREMIwas low and only influenced by a CeREMI<2.8 ng/mL. Hemodynamic stability stayed within the clinically acceptable range.

CONCLUSIONS:

The applied CL system for propofol administration has an acceptable performance in the CeREMIrange of 2.8–7.5 ng/mL during the induction and maintenance of anesthesia. There was no evidence of a strong association between CeREMand the CL performance. This study also shows that when the CeREMIis <2.8 ng/mL, it might be more challenging to prevent arousal during propofol anesthesia.
Optimal Approach to Load Progressions during Strength Training in Older Adults
Authors: BUSKARD ANDREW N. L. , JACOBS KEVIN A. , ELTOUKHY MOATAZ M. , STRAND KERI L. , VILLANUEVA LAWRENCE , DESAI PARTH P. , SIGNORILE JOSEPH F.
Published: May 2019

Progressive resistance training (RT) is one of the most effective interventions for reducing age-related deficits in muscle mass and functional capacity.

Purpose

To compare four approaches to load progressions in RT for older adults to determine if an optimal method exists.

Methods

Eighty-two healthy community-dwelling older adults (71.8 ± 6.2 yr) performed 11 wk of structured RT (2.5 d·wk−1) in treatment groups differing only by the method used to increase training loads. These included percent one repetition maximum (%1RM): standardized loads based on a percentage of the one repetition maximum (1RM); rating of perceived exertion (RPE): loads increased when perceived difficulty falls below 8/10 on the OMNI-Resistance Exercise Scale perceived exertion scale; repetition maximum (RM): loads increased when a target number of repetitions can be completed with a given load; repetitions in reserve (RiR): identical to RM except subjects must always maintain ≥1 “repetition in reserve,” thus avoiding the possibility of training to temporary muscular failure.

Results

Multiple analyses of covariance indicated no significant between-group differences on any strength (chest press 1RM; leg press 1RM) or functional performance outcome (usual walking speed, maximum walking speed, 8-ft timed up-and-go, gallon jug transfer test, 30 s sit-to-stand). The RPE group found the exercise to be significantly more tolerable and enjoyable than subjects in the RiR, RM, and %1RM groups.

Conclusion

Given the RM, RPE, %1RM, and RiR methods appear equally effective at improving muscular strength and functional performance in an older population, we conclude that the RPE method is optimal because it is likely to be perceived as the most tolerable and enjoyable, which are two important factors determining older adults’ continued participation in RT.
A piggyBac-based toolkit for inducible genome editing in mammalian cells
Authors: Schertzer Megan D. , Thulson Eliza , Braceros Keean C.A. , Lee David M. , Hinkle Emma R. , Murphy Ryan M. , Kim Susan O. , Vitucci Eva C.M. , Calabrese J. Mauro
Published: May 2019

We describe the development and application of a novel series of vectors that facilitate CRISPR-Cas9-mediated genome editing in mammalian cells, which we call CRISPR-Bac. CRISPR-Bac leverages the piggyBac transposon to randomly insert CRISPR-Cas9 components into mammalian genomes. In CRISPR-Bac, a single piggyBac cargo vector containing a doxycycline-inducible Cas9 or catalytically dead Cas9 (dCas9) variant and a gene conferring resistance to Hygromycin B is cotransfected with a plasmid expressing the piggyBac transposase. A second cargo vector, expressing a single-guide RNA (sgRNA) of interest, the reverse-tetracycline TransActivator (rtTA), and a gene conferring resistance to G418, is also cotransfected. Subsequent selection on Hygromycin B and G418 generates polyclonal cell populations that stably express Cas9, rtTA, and the sgRNA(s) of interest. We show that CRISPR-Bac can be used to knock down proteins of interest, to create targeted genetic deletions with high efficiency, and to activate or repress transcription of protein-coding genes and an imprinted long noncoding RNA. The ratio of sgRNA-to-Cas9-to-transposase can be adjusted in transfections to alter the average number of cargo insertions into the genome. sgRNAs targeting multiple genes can be inserted in a single transfection. CRISPR-Bac is a versatile platform for genome editing that simplifies the generation of mammalian cells that stably express the CRISPR-Cas9 machinery.
Diagnostic accuracy of ultrasonography versus fine-needle-aspiration cytology for predicting benign thyroid lesions
Authors: Alshoabi Sultan Abdulwadoud , Binnuhaid Abdulkhaleq Ayedh
Published: May 2019

Background and Objective: Thyroid nodules (TNs) are abnormal growths of thyroid cells that form masses within the thyroid gland. TNs are common, and the importance lies in need to exclude thyroid cancer. This study was intended to evaluate the diagnostic accuracy of ultrasonography for differentiating benign from malignant thyroid lesions in comparison with fine-needle aspiration cytology (FNA cytology).

Methods: This study involved 133 patients with thyroid lesions. All patients underwent thyroid ultrasonography and ultrasound (US)-guided-FNA cytology and results were compared.

Results: Out of 133 patients included in this study, the mean age was 41.2±15 years, and 113 (85%) were female. Thyroid lesions were benign in 126 cases (94.7%) and malignant in nine cases (5.3%). Among 124 patients with thyroid lesions diagnosed as benign with US, 122 (98.38%) were confirmed to be benign with FNA cytology, and only 2 (1.6%) were proved to be malignant. Among nine patients with thyroid lesions diagnosed as malignant by US, 5 (55.6%) were confirmed to be malignant by FNA cytology, and 4 (44.4%) were proved to be benign. The US diagnosed benign thyroid lesions with a sensitivity, specificity, positive predictive value, and negative predictive value of 98.38%, 71.42%, 98.38%, and 55.55%, respectively. The results revealed strong compatibility between diagnosis of benign thyroid lesions by the US and proved diagnosis by FNA cytology (p<0.001).

Conclusion: B-mode ultrasonography is a valuable tool in differentiating benign from malignant thyroid lesions. It can almost always predict the benign nature of thyroid lesions with excellent diagnostic accuracy.

doi: https://doi.org/10.12669/pjms.35.3.292

How to cite this:Alshoabi SA, Binnuhaid AA. Diagnostic accuracy of ultrasonography versus fine-needle-aspiration cytology for predicting benign thyroid lesions. Pak J Med Sci. 2019;35(3):630-635. doi: https://doi.org/10.12669/pjms.35.3.292

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Accessibility Mainstreaming and Beyond – Senior Citizens as Secondary Users of Audio Subtitles in Cinemas
Authors: JANKOWSKA ANNA
Published: May 2019

Audiovisual accessibility is traditionally seen as a means of providing access for people with sensory impairments, be it sight or hearing loss (Orero, 2004). Recently, a much broader perspective opened as some also see it as a way of providing linguistic accessibility (Díaz Cintas, 2005; Orero & Matamala, 2007) or even as services that cater for the specific needs of people who "cannot, or cannot properly, access the audiovisual content in its original form" (Greco, 2016: 23). This article fits squarely into this trend as it reports on a survey-based study set out to find out preferences regarding linguistic accessibility in the cinema among unimpaired senior citizens in Poland. On the whole, 40 people aged 60 or more took part in the study. Results show that senior citizens are more likely to choose voice-over and dubbing over subtitling. This could be because the majority of participants declared that they experience discomfort or difficulties when reading subtitles. As a result, they are willing to use a mobile app that would enable them to listen to audio subtitles in the cinemas.
Right place, right time: localisation and assembly of the NLRP3 inflammasome
Authors: Hamilton Claire , Anand Paras K.
Published: May 2019

The NLRP3 inflammasome is a multimeric protein complex that cleaves caspase-1 and the pro-inflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. Dysregulated NLRP3 inflammasome signalling is linked to several chronic inflammatory and autoimmune conditions; thus, understanding the activation mechanisms of the NLRP3 inflammasome is essential. Studies over the past few years have implicated vital roles for distinct intracellular organelles in both the localisation and assembly of the NLRP3 inflammasome. However, conflicting reports exist. Prior to its activation, NLRP3 has been shown to be resident in the endoplasmic reticulum (ER) and cytosol, although, upon activation, the NLRP3 inflammasome has been shown to assemble in the cytosol, mitochondria, and mitochondria-associated ER membranes by different reports. Finally, very recent work has suggested that NLRP3 may be localised on or adjacent to the Golgi apparatus and that release of mediators from this organelle may contribute to inflammasome assembly. Therefore, NLRP3 may be strategically placed on or in close proximity to these subcellular compartments to both sense danger signals originating from these organelles and use the compartment as a scaffold to assemble the complex. Understanding where and when NLRP3 inflammasome assembly occurs may help identify potential targets for treatment of NLRP3-related disorders.
EFFECTS OF WEATHER AND AGRICULTURAL TECHNIQUES ON RIPENING OF SPRING DURUM WHEAT IN THE ORENBURG PRIURALIYE
Authors: Бесалиев Ишен , Besaliev Ishen , Панфилов Александр , Panfilov Aleksandr
Published: May 2019

The aim of the study is to increase the yield of spring durum wheat in the Orenburg Urals. Spring hard wheat makes more demands on the temperature region during the formation and filling of grain. Due to the growing aridity conditions of the second half of the growing season, when the grain falls asleep, have become more unfavorable. As you know, the nature of the filling, favorable weather conditions in this period are determined by the yield and quality of grain. The studies were carried out in 2016-2018 in the Central zone of the Orenburg region on chernozems ordinary in two stages of the main tillage. Weather conditions contrasted sharply. The research method is a field experiment. Experience and research were conducted according to conventional methods. Analysis of the grain samples was performed using a laboratory balance Adam NSV 602N and furnace SESH-3M. Mathematical analysis was performed in the program Statistica 6.0. It is established that the duration of grain loading in the study area depends on the weather conditions of the year, ranging from 20-21 days to 31 days. The growth rate of dry matter accumulation in durum wheat grain is observed in the air temperature range 18.7-26.2°C, followed by an increase in temperature reduces the increase. Amid the subsurface processing plowed fields, reducing grain moisture is less intense: 10 grade Orenburg-plowing is of 0.99 – 2.46% on a day, subsurface tillage-0.80 – 2.50% daily; cultivar bezenchukskaya 210 – plowing 1.64-of 2.34%, subsurface tillage-1.03-2.32%.
THEORETICAL STUDY OF THE WORK OF THE TRACTOR DIESEL IN APPLYING DIESEL MIXTURE FUEL BASED ON RICINIC OIL
Authors: Садов Артем , Sadov Artem , Денежко Любовь , Denezhko Lyubov' , Новопашин Леонид , Novopashin Leonid
Published: May 2019

The purpose of the research is the theoretical justification for the use of diesel fuel mixture based on castor oil. The preferred type of biofuel used in agriculture and forestry is multi-component diesel fuel produced by mixing petrole-um diesel fuel (DF) and fuel oil. As raw materials to produce diesel fuel blends-entertainment oil crops that are not used in the food industry, such as safflower, camelina, canola, rape, crambe Abyssinian and castor. As diesel fuel blends investigated mixture ricinic oil (RicM) and summer diesel fuel (GOST 305-2013) three compositions. On the basis of the thermal calculation, the parameters of the engine operating cycle are determined and the dependences of the engine operating cycle indicators on the composition of the mixture are presented. The comparison of the ob-tained parameters with the indicators of traditional diesel fuel was made. Calorific value of mixing substance de-creases with increase in the proportion of the biological component (RicM), thermal characteristics of the gas mix-ture is practically unchanged, due to gain-eat proportion of oxygen in the elemental composition ricinic oil. With an increase in the concentration of ricinic oil in the mixed fuel, a decrease in the power of the D-240 engine by 1.8-1.9% compared to diesel fuel was noted, the consumption of the mixture increased by 6-8 % or by 2.3 g/kWh on average for every 5 % increase in the concentration of ricinic mass in the mixture. According to the calculations and comparisons with studies on other crops, DMF produced from ricinic oil has similar characteristics with mixtures based on rapeseed, mustard, soybean oils. These studies are aimed at diversifying fuel resources and increasing the energy independence of agricultural enterprises.
Perturbation results and the forward order law for the Moore-Penrose inverse of a product
Authors: Castro-Gonzalez Nieves , Hartwig Robert
Published: May 2019

New expressions are given for the Moore-Penrose inverse of a product $AB$ of two complex matrices. Furthermore, an expression for $(AB)\dg - B\dg A\dg$ for the case where $A$ or $B$ is of full rank is provided. Necessary and sufficient conditions for the forward order law for the Moore-Penrose inverse of a product to hold are established. The perturbation results presented in this paper are applied to characterize some mixed-typed reverse order laws for the Moore-Penrose inverse, as well as the reverse order law.
Upper Bound for the Number of Distinct Eigenvalues of a Perturbed Matrix
Authors: Moon Sunyo , Park Seungkook
Published: May 2019

In 2016, Farrell presented an upper bound for the number of distinct eigenvalues of a perturbed matrix. Xu (2017), and Wang and Wu (2016) introduced upper bounds which are sharper than Farrell's bound. In this paper, the upper bounds given by Xu, and Wang and Wu are improved.
Determinantal representations of elliptic curves via Weierstrass elliptic functions
Authors: Chien Mao-Ting , Nakazato Hiroshi
Published: May 2019

Helton and Vinnikov proved that every hyperbolic ternary form admits a symmetric derminantal representation via Riemann theta functions. In the case the algebraic curve of the hyperbolic ternary form is elliptic, the determinantal representation of the ternary form is formulated by using Weierstrass $\wp$-functions in place of Riemann theta functions. An example of this approach is given.
Explicit Block-Structures for Block-Symmetric Fiedler-like pencils
Authors: Bueno M. I. , Martin Madeline , Perez Javier , Song Alexander , Viviano Irina
Published: May 2019

In the last decade, there has been a continued effort to produce families of strong linearizations of a matrix polynomial $P(\lambda)$, regular and singular, with good properties, such as, being companion forms, allowing the recovery of eigenvectors of a regular $P(\lambda)$ in an easy way, allowing the computation of the minimal indices of a singular $P(\lambda)$ in an easy way, etc. As a consequence of this research, families such as the family of Fiedler pencils, the family of generalized Fiedler pencils (GFP), the family of Fiedler pencils with repetition, and the family of generalized Fiedler pencils with repetition (GFPR) were constructed. In particular, one of the goals was to find in these families structured linearizations of structured matrix polynomials. For example, if a matrix polynomial $P(\lambda)$ is symmetric (Hermitian), it is convenient to use linearizations of $P(\lambda)$ that are also symmetric (Hermitian). Both the family of GFP and the family of GFPR contain block-symmetric linearizations of $P(\lambda)$, which are symmetric (Hermitian) when $P(\lambda)$ is. Now the objective is to determine which of those structured linearizations have the best numerical properties. The main obstacle for this study is the fact that these pencils are defined implicitly as products of so-called elementary matrices. Recent papers in the literature had as a goal to provide an explicit block-structure for the pencils belonging to the family of Fiedler pencils and any of its further generalizations to solve this problem. In particular, it was shown that all GFP and GFPR, after permuting some block-rows and block-columns, belong to the family of extended block Kronecker pencils, which are defined explicitly in terms of their block-structure. Unfortunately, those permutations that transform a GFP or a GFPR into an extended block Kronecker pencil do not preserve the block-symmetric structure. Thus, in this paper, the family of block-minimal bases pencils, which is closely related to the family of extended block Kronecker pencils, and whose pencils are also defined in terms of their block-structure, is considered as a source of canonical forms for block-symmetric pencils. More precisely, four families of block-symmetric pencils which, under some generic nonsingularity conditions are block minimal bases pencils and strong linearizations of a matrix polynomial, are presented. It is shown that the block-symmetric GFP and GFPR, after some row and column permutations, belong to the union of these four families. Furthermore, it is shown that, when $P(\lambda)$ is a complex matrix polynomial, any block-symmetric GFP and GFPR is permutationally congruent to a pencil in some of these four families. Hence, these four families of pencils provide an alternative but explicit approach to the block-symmetric Fiedler-like pencils existing in the literature.
Spectral Bounds for the Connectivity of Regular Graphs with Given Order
Authors: Abiad Aida , Brimkov Boris , Martinez-Rivera Xavier , O Suil , Zhang Jingmei
Published: May 2019

The second-largest eigenvalue and second-smallest Laplacian eigenvalue of a graph are measures of its connectivity. These eigenvalues can be used to analyze the robustness, resilience, and synchronizability of networks, and are related to connectivity attributes such as the vertex- and edge-connectivity, isoperimetric number, and characteristic path length. In this paper, two upper bounds are presented for the second-largest eigenvalues of regular graphs and multigraphs of a given order which guarantee a desired vertex- or edge-connectivity. The given bounds are in terms of the order and degree of the graphs, and hold with equality for infinite families of graphs. These results answer a question of Mohar.
The properties of partial trace and block trace operators of partitioned matrices
Authors: Filipiak Katarzyna , Klein Daniel , Vojtková Erika
Published: May 2019

The aim of this paper is to give the properties of two linear operators defined on non-square partitioned matrix: the partial trace operator and the block trace operator. The conditions for symmetry, nonnegativity, and positive-definiteness are given, as well as the relations between partial trace and block trace operators with standard trace, vectorizing and the Kronecker product operators. Both partial trace as well as block trace operators can be widely used in statistics, for example in the estimation of unknown parameters under the multi-level multivariate models or in the theory of experiments for the determination of an optimal designs under the linear models.
Average Mixing Matrix of Trees
Authors: Godsil Chris , Guo Krystal , Sinkovic John
Published: May 2019

The rank of the average mixing matrix of trees with all eigenvalues distinct, is investigated. The rank of the average mixing matrix of a tree on n vertices with n distinct eigenvalues is bounded above by ân/2â. Computations on trees up to 20 vertices suggest that the rank attains this upper bound most of the time. An infinite family of trees whose average mixing matrices have ranks which are bounded away from this upper bound, is given. A lower bound on the rank of the average mixing matrix of a tree, is also given.
REGULARITY RADIUS: PROPERTIES, APPROXIMATION AND A NOT A PRIORI EXPONENTIAL ALGORITHM
Authors: Hartman David , Hladik Milan
Published: May 2019

The radius of regularity, sometimes spelled as the radius of nonsingularity, is a measure providing the distance of a given matrix to the nearest singular one. Despite its possible application strength this measure is still far from being handled in an efficient way also due to findings of Poljak and Rohn providing proof that checking this property is NP-hard for a general matrix. There are basically two approaches to handle this situation. Firstly, approximation algorithms are applied and secondly, tighter bounds for radius of regularity are considered. Improvements of both approaches have been recently shown by Hartman and Hlad\'{i}k (doi:10.1007/978-3-319-31769-4\_9) utilizing relaxation of the radius computation to semidefinite programming. An estimation of the regularity radius using any of the above mentioned approaches is usually applied to general matrices considering none or just weak assumptions about the original matrix. Surprisingly less explored area is represented by utilization of properties of special classes of matrices as well as utilization of classical algorithms extended to be used to compute the considered radius. This work explores a process of regularity radius analysis and identifies useful properties enabling easier estimation of the corresponding radius values. At first, checking finiteness of this characteristic is shown to be a polynomial problem along with determining a sharp upper bound on the number of nonzero elements of the matrix to obtain infinite radius. Further, relationship between maximum (Chebyshev) norm and spectral norm is used to construct new bounds for the radius of regularity. Considering situations where the known bounds are not tight enough, a new method based on Jansson-Rohn algorithm for testing regularity of an interval matrix is presented which is not a priory exponential along with numerical experiments. For a situation where an input matrix has a special form, several corresponding results are provided such as exact formulas for several special classes of matrices, e.g., for totally positive and inverse non-negative, or approximation algorithms, e.g., rank-one radius matrices. For tridiagonal matrices, an algorithm by Bar-On, Codenotti and Leoncini is utilized to design a polynomial algorithm to compute the radius of regularity.
Discontinuity Propagation in Delay Differential-Algebraic Equations
Authors: Unger Benjamin
Published: May 2019

The propagation of primary discontinuities in initial value problems for linear delay differential-algebraic equations (DDAEs) is discussed. Based on the (quasi-) Weierstra{\ss} form for regular matrix pencils, a complete characterization of the different propagation types is given and algebraic criteria in terms of the matrices are developed. The analysis, which is based on the method of steps, takes into account all possible inhomogeneities and history functions and thus serves as a worst-case scenario. Moreover, it reveals possible hidden delays in the DDAE and allows to study exponential stability of the DDAE based on the spectral abscissa. The new classification for DDAEs is compared to existing approaches in the literature and the impact of splicing conditions on the classification is studied.