bluuebunny/crossref_metadata_2025 huggingface dataset:
#MeToo, popular feminism and the news : A content analysis of UK newspaper coverage
Authors: De Benedictis Sara , Orgad Shani , Rottenberg Catherine
Published: July 2019

This article examines the first 6 months of #MeToo’s coverage in the UK press, revealing how newspapers played an important role in heightening the campaign’s visibility. Using content analysis, our study demonstrates that the press contributed to expanding and reinforcing #MeToo’s visibility in important ways. In terms of reach, the UK press has expanded the movement’s visibility beyond social media, addressing potentially new and different readerships. This attests to the pivotal role that news media continue to play in disseminating global issues and debates for a national audience. Second, in terms of content, while the news coverage developed and consolidated stories that were originally revealed on social media, it also publicized new stories. However, our study also highlights how the press’ role in enabling and expanding the visibility of #MeToo has been characterized by a number of crucial and, we argue, problematic factors. First, while #MeToo was covered positively in all newspapers, there was significant variation within newspapers, which was largely consistent with their traditional ideological alignments. Second, the #MeToo coverage seems to have followed and reinforced familiar patterns with respect to news coverage of both sexual violence and feminism, namely, support of feminism alongside a concurrent de-politicization, an individualizing tendency through a focus on celebrity and the cultural industries, and the centring of the experiences of celebrity female subjects who are predominately White and wealthy.
Cross-cultural management research: Topics, paradigms, and methods—A journal-based longitudinal analysis between 2001 and 2018
Authors: Barmeyer Christoph , Bausch Madeleine , Moncayo Daniel
Published: July 2019

Cross-cultural management (CCM) research comprises a variety of disciplines with different thematic, paradigmatic, and methodological assumptions. Since there has been no systematic analysis of the development of topics, paradigms, and methods, this article draws a landscape of these analyzing 777 articles published in two leading journals between 2001 and 2018. Results show that corporate culture, human resource management, and cultural dimensions are main topics in CCM and that positivist and quantitative papers outweigh interpretive and qualitative articles. We examine a convergence of the positivist and interpretive paradigm in 2016 and 2017, what might indicate a possible upcoming paradigmatic shift in CCM. However, positivist articles rise again since 2017. Using computer-aided tools, this study serves as a basis for future literature reviews.
Hope, Agency, and the Lived Experience of Violence: A Qualitative Systematic Review of Children’s Perspectives on Domestic Violence and Abuse
Authors: Arai Lisa , Shaw Ali , Feder Gene , Howarth Emma , MacMillan Harriet , Moore Theresa H. M. , Stanley Nicky , Gregory Alison
Published: July 2019

There is a large body of research on the impact of domestic violence and abuse (DVA) on children, mostly reporting survey data and focusing largely on psychological outcomes. Qualitative research on the views of children has the potential to enable a child-centered understanding of their experience of DVA, so their needs can be better met by professionals. This systematic review reports general findings from the ViOlence: Impact on Children Evidence Synthesis (VOICES) project that synthesized published qualitative research on the experiences of DVA from the perspective of children and young people. A thematic synthesis of 33 reports identified six themes: lived experience of DVA, children’s agency and coping, turning points and transitions, managing relationships postseparation, impact of DVA on children, and children’s expressions of hope for the future. We conclude that professionals working with children affected by DVA should be mindful of the diversity in children’s experiences and listen carefully to children’s own accounts.
Preparation and filtration performance of the circular weft-knitted seamless weft-insertion fabric materials
Authors: Tian Fei , Jiang Gaoming , Gao Zhe
Published: July 2019

Air particulate matter pollution has become a severe environment concern calling for filtration materials with great filtration performance. As the development of seamless forming technology, knitted filtration materials gradually show great potential. This study aimed to develop a novel kind of knitted seamless structure for filtration materials of filter bags with high production efficiency and excellent filtration performance. A new type of the circular weft-knitted seamless weft-insertion fabric (CKSW) filtration materials were developed on the modified circular knitting machine. This CKSW filtration materials consisting of the ground yarns, connection yarns and weft-insertion yarns, polyester full drawn yarns, and polyester draw texturing yarns with different yarn configurations were employed to realize series of CKSW samples. The polytetrafluoroethylene filaments with tourmaline particles were used to verify whether the static electric material produced an adsorption filtration effect on the CKSW filtration materials or not. After pretreatment, the filtration performance of the CKSW filtration materials was evaluated by analyzing its pore size, porosity, and filtration efficiency. Ultimately, the CKSW filtration materials with ground yarns and weft insertion yarns of draw texturing yarn and the connection yarns of full drawn yarn exhibited the most excellent filtration performance. The CKSW filtration materials show a high porosity of 87.14%, the pore size of 67.55 µm, and good filtration efficiency of 91.57% with the particles size of ≥ 5.0 µm. The successful fabrication of such knitted filtration materials may provide ideas for the development of filtration materials with new architecture mainly used as filter bags for baghouse.
Ruptured Abdominal Aortic Aneurysm and Horseshoe Kidney: Isthmus Sectioning By Endo GIA
Authors: Gabriele Pagliariccio , Emanuele Gatta , Grilli Cicilioni Carlo , Sara Schiavon , Luciano Carbonari
Published: July 2019

Introduction:

A 90-year-old patient was admitted with a hemorrhagic shock from a huge ruptured abdominal aortic aneurysm with an unfavourable infrarenal aortic neck and a horseshoe kidney (HSK).

Report:

We decided on an open surgical approach: the HSK isthmus was sectioned with an Endo GIA 45 mm, and we performed a suprarenal aortic cross-clamping and an aortic graft reconstruction. Postoperatively, no urinary leakage was detected, and renal function showed no impairment. The patient died on the 10th postoperative day from pneumonia.

Conclusion:

We believe that the sectioning of the HSK isthmus with Endo GIA is a fast and simple maneouvre.
The Role of Empathy and Compassion in Conflict Resolution
Authors: Klimecki Olga M.
Published: July 2019

Empathy and empathy-related processes, such as compassion and personal distress, are recognized to play a key role in social relations. This review examines the role of empathy in interpersonal and intergroup relations, including intractable conflicts. Despite the limitations of empathy, there is growing evidence that empathy and compassion are associated with more prosocial behavior in interpersonal relations. Furthermore, empathy and compassion have been associated with more favorable attitudes and higher readiness for reconciliation across a range of intergroup settings. This review ends by summarizing recent evidence for the beneficial effects of compassion training on interpersonal and intergroup relations and by outlining new avenues for future research on how compassion training could reduce intergroup conflicts.
Lessons on Data Collection and Curation From the NFL Injury Surveillance Program
Authors: Dreyer Nancy A. , Mack Christina D. , Anderson Robert B. , Wojtys Edward M. , Hershman Elliott B. , Sills Allen
Published: July 2019

Background:

“Research-ready” evidence platforms that link sports data with anonymized electronic health records (EHRs) or other data are important tools for evaluating injury occurrence in response to changes in games, training, rules, and other factors. While there is agreement that high-quality data are essential, there is little evidence to guide data curation.

Hypothesis:

We hypothesized that an EHR used in the course of clinical care and curated for research readiness can provide a robust evidence platform. Our purpose was to describe the data curation used for active injury surveillance by the National Football League (NFL).

Study Design:

Dynamic cohort study.

Level of Evidence:

Level 2.

Methods:

Players provide informed consent for research activities through the collective bargaining process. A league-wide EHR is used to record injuries that come to the attention of the teams’ athletic trainers and physicians, NFL medical spotters, or unaffiliated neurotrauma consultants. Information about football activities and injuries are linkable by player, setting, and event to other sports-related data, including game statistics and game-day stadium quality measures, using a unique player identification designed to protect player privacy. Ongoing data curation is used to review data completeness and accuracy and is adjusted over time in response to findings.

Results:

The core data curation activities include monthly injury summaries to team staff, queries to resolve incomplete reporting, and periodic external checks. Experiences derived from producing more than 100 reports per year on diverse topics are used to update coding training and related guidance documents in response to missing data or inconsistent coding that is observed. Roughly 20% more injuries were recorded for the same “reportable” injuries after switching from targeted reporting to an EHR.

Conclusion:

Research-ready databases need systematic curation for quality and completeness, along with related action plans. More injuries were reported through EHR than through targeted reporting.

Clinical Relevance:

Evidence-driven decision-making thrives on reliable data fine-tuned through systematic use, review, and ongoing adjustments to the curation process.
Sacral Stress Fractures: A Rare but Curable Cause of Back Pain in Athletes
Authors: Vajapey Sravya , Matic George , Hartz Clinton , Miller Timothy L.
Published: July 2019

Background:

Stress fractures of the sacrum are an uncommon cause of low back and buttock pain in athletes. They have been described in a few case reports, with the injury occurring most often in female distance runners. Given the rarity of this condition, there is a general lack of awareness of this injury, which may lead to a missed or delayed diagnosis.

Study Design:

Case series.

Level of Evidence:

Level 5.

Methods:

The 5 cases were identified by performing a medical records search within the practices of the senior authors over a 3-year period from January 2016 to December 2018.

Results:

Three of 5 patients (1 male, 2 females) returned to regular activity after diagnosis and treatment. Two (1 male, 1 female) have yet to return to regular activity. Magnetic resonance imaging was the key modality in all diagnoses. All 3 female patients had components of the female athlete triad—menstrual irregularity, disordered eating, and decreased bone mineral density.

Conclusion:

A high index of suspicion is required to make the correct diagnosis and initiate treatment for this rare condition given its association with low body mass index, vitamin D insufficiency, disordered eating, and malabsorption disorders. Appropriate treatment includes rest from the causative activity, nutritional support, and biomechanical optimization. In severe, chronic, or recurrent cases, referral for nutritional counseling, hormonal replacement therapies, and mental health support may be necessary.

Clinical Relevance:

Sacral stress fractures, though uncommon, should be included prominently in the differential diagnosis for runners with low back pain, especially if the athlete has a history of prior stress fracture or the female athlete triad.
Pharmacokinetics and safety of deltoid or gluteal injection of aripiprazole lauroxil NanoCrystal® Dispersion used for initiation of the long-acting antipsychotic aripiprazole lauroxil
Authors: Hard Marjie L. , Wehr Angela , von Moltke Lisa , Du Yangchun , Farwick Sarah , Walling David P. , Sonnenberg John
Published: July 2019

Background:

Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia in adults, can be started with either 21 days of daily oral aripiprazole supplementation or a 1-day initiation regimen consisting of a single injection of a NanoCrystal® Dispersion formulation of AL (ALNCD) and a single dose of 30 mg oral aripiprazole. This phase I study assessed the pharmacokinetics and safety of deltoid versus gluteal ALNCD injections.

Methods:

Patients with schizophrenia or schizoaffective disorder ( N = 47) were randomized 1:1 to receive a single intramuscular dose of ALNCD in the deltoid or gluteal muscle. Plasma samples were collected over 85 days to measure ALNCD concentration by injection site. Relative aripiprazole bioavailability for deltoid versus gluteal injection was assessed based on area under the curve (AUC∞ and AUClast) and maximum concentration (Cmax) values. Adverse events were monitored throughout the study.

Results:

Plasma aripiprazole concentrations after a single ALNCD injection were comparable between deltoid and gluteal administration. Mean maximum plasma aripiprazole concentrations were 196.1 ng/ml (deltoid) and 175.0 ng/ml (gluteal). Exposure to aripiprazole was similar, with mean AUC∞ values of 6591 day × ng/ml for deltoid and 6437 day × ng/ml for gluteal. Aripiprazole bioavailability was not significantly different between injection sites. ALNCD administration in the deltoid or gluteal muscle was well tolerated, with similar safety profiles at both sites.

Conclusion:

ALNCD demonstrated similar exposure and safety profiles between the two administration sites, suggesting that ALNCD can be given in either the gluteal or the deltoid muscles as a component of the 1-day initiation regimen for AL.
Reducing risk and leveraging markets: The impact of financial structure on federal contractor performance
Authors: Brunjes Benjamin M
Published: July 2019

This paper analyzes how financial controls, as established through the payment structure, are used and whether they influence federal contractor performance. These payment structures include variants on three primary types of contract: firm fixed-price, cost-reimbursement, and time-and-materials. Each of these payment structures creates different performance incentives for contractors, provides government contract managers with varying levels of information on contractor activities, and alters the dispersion of risk between the partners. The Federal Acquisition Regulation (FAR) prefers fixed-price contracts whenever possible, as they theoretically place the risk on the contractor, who is required to finish the work for the allocated price. Based on an analysis of nearly 25,000 federal definitive contracts that concluded between 2005 and 2014, findings indicate federal contracting officials tend to use payment structures in expected ways: to limit exposure to risk, leverage market forces, and reduce transaction costs when possible. Findings also show that there are important performance differences between contracts that use different financial structures, even when accounting for information asymmetries, asset specificity, and the complexity of the contracted work. Cost-reimbursement contracts are highly correlated with early contract termination.
The Iowa Gambling Task: A Review of the Historical Evolution, Scientific Basis, and Use in Functional Neuroimaging
Authors: Aram Siamak , Levy Lauren , Patel Jigar B. , Anderson Afrouz A. , Zaragoza Rachel , Dashtestani Hadis , Chowdhry Fatima A. , Gandjbakhche Amir , Tracy J. Kathleen
Published: July 2019

The Iowa Gambling Task (IGT) provides a framework to evaluate an individual decision-making process through a simulated card game where the risks and rewards vary by the decks chosen. Participants are expected to understand the logic behind the allocation of gains and losses over the course of the test and adapt their pattern of choices accordingly. This review explores the scientific work on studying problem gambling via the IGT while employing neuroimaging techniques. We first concentrate on the historical evolution of the IGT as a mechanism for studying gamblers’ behavioral patterns. Our research will also discuss the prefrontal cortex as this region of the brain is most affected by changes in behavioral patterns. In this review, we describe a number of features that may be useful in investigating decision-making patterns that lead to gambling addiction. We discuss the evidence base to date including experiments involving gambling behavior in different groups of participants (e.g., males and females, adults and minors, patients and controls) and alterations to experiment conditions that provide more thorough understanding of thought patterns in potential gamblers. We conclude that psychological testing combined with functional imaging provide powerful tools to further examine the relationships between functional impairment of the brain and a person’s ability to objectively anticipate the end results of their decisions.
Smokers Are Extraverted in Japan: Smoking Habit and The Big Five Personality Traits
Authors: Abe Shingo , Oshio Atsushi , Kawamoto Tetsuya , Ito Hiroyuki , Hirashima Taro , Tsubota Yuki , Tani Iori
Published: July 2019

Identifying psychological factors related to smoking habits is important to enact effective personalized treatment. We examined the relationship between the Big Five personality traits and smoking using a large and representative Japanese sample ( n = 4,563 [2,462 women]; Mage = 53.48 years, SD = 12.87, ranging from 23 to 79 years). The results of multinomial logistic regression analysis showed that current smokers were higher in Extraversion and lower in Conscientiousness than never smokers. Extraversion was the strongest personality trait differentiating current smokers from never smokers, especially in the younger age group. Former smokers scored significantly higher than current smokers on Conscientiousness, suggesting that Conscientiousness is associated with smoking cessation.
Impact of Capacity Building and Managerial Support on Employees’ Performance: The Moderating Role of Employees’ Retention
Authors: Wassem Muhammad , Baig Sajjad Ahmad , Abrar Muhammad , Hashim Muhammad , Zia-Ur-Rehman Muhammad , Awan Usman , Amjad Fiza , Nawab Yasir
Published: July 2019

The purpose of this study is to investigate the effects of capacity building and managers’ support on employee performance in the textile industry. Moreover, this article also investigates the moderating effect exerted by employee retention on the effects of capacity building and managers’ support on employee performance. Data were collected through a convenience sampling technique. A self-administered questionnaire survey was conducted for data collection. Two hundred copies of questionnaires were distributed, and data were collected from the lower to middle-level employees who are working in the textile sector of Pakistan. SPSS 23 and SmartPLS-3 software were used for analysis. The results indicate that capacity building has a positive and significant impact on employee performance. In contrast, managerial support has an insignificant impact on employees’ performance. However, the impact of capacity building and managerial support on employee performance is positive and significantly moderated by employee retention. The results of this study will motivate owners/policymakers to invest in capacity building to enhance their organizational performance/productivity.
Evaluation Tool for Traditional Chinese Medicine Students in China: A Competency Perspective
Authors: Zheng Boyang , Sun Guiping , Wang Hourong
Published: July 2019

Traditional Chinese medicine (TCM) is an important component of China’s medical system. How to educate TCM practitioners in China, therefore, has become a crucial issue. To contribute to this issue, the current research identified the competency model of TCM practitioners in China and developed an evaluation for TCM students. We combined Bloom’s taxonomy with our model construction to examine the current TCM practitioners’ requirements. Following the protocol of developing a measurement, we interviewed 20 TCM practitioners, conducted two rounds of surveys in China ( n = 220/ n = 489), ran exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and examined the correlation between the measurement and self-rated outcomes. The evaluation tool of TCM students consists of five factors: modern medical knowledge and skills, TCM medical knowledge and skills, professional ethics, communication and cooperation skills, and clinical practices. The reliability and validity of our evaluation tool were testified. Our work may contribute to TCM education in China.
School Administrators’ Perspectives on Teachers From Different Generations: SWOT Analysis
Authors: Polat Soner , Çelik Çaǧlar , Okçu Yıldız
Published: July 2019

The aim of this study was to examine the perspective of school administrators with regard to teachers from different generations. In this study, the strengths, weaknesses, opportunities, and threats of each generation were examined. This study was conducted as a Strength, Weakness, Opportunity, and Threat (SWOT) analysis. The study group consisted of 26 school administrators from the Dilovası district of Kocaeli province, Turkey. According to the school administrators, the Baby Boomer generation shows their strengths with discipline and experience, Generation X with determination, and Generation Y with their abilities in technology. As for the weaknesses of each generation, Baby Boomers are against innovation and disobedient of the management, Generation X claims to know everything, and Generation Y is inexperienced. What creates opportunities for schools is that Baby Boomers manage crises and transfer experience, Generation X acts as a bridge between the generations, and Generation Y applies new methods in education. For the threats of different generations to the school, the school administrators stated that Baby Boomers hinder innovation, Generation X is disloyal, and Generation Y is inexperienced and against the system.
Case report: Can a patient with an active cancer receive a kidney transplant?
Authors: Buxeda Anna , Pérez-Sáez María José , Granados Ana Marina , Redondo-Pachón Dolores , Mir Marisa , Barbosa Francesc , Rodrigo María Teresa , Sitges-Serra Antonio , Pascual Julio , Crespo Marta
Published: July 2019

Introduction:

An active cancer is an absolute contraindication for kidney transplantation and a frequent cause of wait-list patient exclusion for long periods. Waiting time for kidney transplantation after the cancer diagnosis/treatment depends on multiple factors such as type of cancer, stage, histological type, prognosis, and physicians’ opinions.

Case description:

In this study, we describe a case of a 52-year-old man with medullary thyroid carcinoma classified as T1N1bM0 stage IV-A, who received a human leukocyte antigen identical living donor kidney transplantation despite not being biochemically cured. He received maintenance immunosuppression with tacrolimus, prednisone, and mycophenolic acid, switched to everolimus plus prednisone after 8 months. After 5 years, kidney function is excellent and there is no structural recurrence of the disease on imaging tests, although serum calcitonin levels remain elevated but stable.

Conclusion:

This is the first report that exposes the case of a patient with an active thyroid neoplasm receiving kidney transplantation. The good prognosis of the active neoplasm and the fact of having an identical human leukocyte antigen optimal donor made us proceed with the transplant with an excellent 5-year outcome.
Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity
Authors: Wang Jue , Pendurthi Usha R. , Rao L. Vijaya Mohan
Published: July 2019

Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of coagulation. Typically, most TF on cell surfaces exists in a cryptic coagulant-inactive state but are transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells, and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology. As observed in cell systems, administration of adenosine triphosphate (ATP) to mice enhanced lipopolysaccharide (LPS)-induced TF procoagulant activity in monocytes. Treatment of mice with pharmacological inhibitors of acid sphingomyelinase (ASMase), desipramine and imipramine, attenuated ATP-induced TF decryption. Interestingly, ASMase inhibitors also blocked LPS-induced TF procoagulant activity without affecting the LPS-induced de novo synthesis of TF protein. Additional studies showed that LPS induced translocation of ASMase to the outer leaflet of the plasma membrane and reduced SM levels in monocytes. Studies using human monocyte-derived macrophages and endothelial cells further confirmed the role of ASMase in LPS- and cytokine-induced TF procoagulant activity. Overall, our data indicate that LPS- or cytokine-induced TF procoagulant activity requires the decryption of newly synthesized TF protein by ASMase-mediated hydrolysis of SM. The observation that ASMase inhibitors attenuate TF-induced coagulation raises the possibility of their therapeutic use in treating thrombotic disorders associated with aberrant expression of TF.
OCTANE: Oncology Clinical Trial Annotation Engine
Authors: Zeng Jia , Shufean Md Abu , Khotskaya Yekaterina , Yang Dong , Kahle Michael , Johnson Amber , Holla Vijaykumar , Sánchez Nora , Mills Shaw Kenna R. , Bernstam Elmer V. , Meric-Bernstam Funda
Published: July 2019

PURPOSE

Many targeted therapies are currently available only via clinical trials. Therefore, routine precision oncology using biomarker-based assignment to drug depends on matching patients to clinical trials. A comprehensive and up-to-date trial database is necessary for optimal patient-trial matching.

METHODS

We describe processes for establishing and maintaining a clinical trial database, focusing on genomically informed trials. Furthermore, we present OCTANE (Oncology Clinical Trial Annotation Engine), an informatics framework supporting these processes in a scalable fashion. To illustrate how the framework can be applied at an institution, we describe how we implemented an instance of OCTANE at a large cancer center. OCTANE consists of three modules. The data aggregation module automates retrieval, aggregation, and update of trial information. The annotation module establishes the database schema, implements data integration necessary for automation, and provides an annotation interface. The update module monitors trial change logs, identifies critical change events, and alerts the annotators when manual intervention may be needed.

RESULTS

Using OCTANE, we annotated 5,439 oncology clinical trials (4,438 genomically informed trials) that collectively were associated with 1,453 drugs, 779 genes, and 252 cancer types. To date, we have used the database to screen 4,220 patients for trial eligibility. We compared the update module with expert review, and the module achieved 98.5% accuracy, 0% false-negative rate, and 2.3% false-positive rate.

CONCLUSION

OCTANE is a general informatics framework that can be helpful for establishing and maintaining a comprehensive database necessary for automating patient-trial matching, which facilitates the successful delivery of personalized cancer care on a routine basis. Several OCTANE components are publically available and may be useful to other precision oncology programs.
Neuroendocrine Impairments of Polycystic Ovary Syndrome
Authors: Ruddenklau Amy , Campbell Rebecca E
Published: July 2019

Polycystic ovary syndrome (PCOS) is a prevalent and distressing disorder of largely unknown etiology. Although PCOS defined by ovarian dysfunction, accumulating evidence supports a critical role for the brain in the ontogeny and pathophysiology of PCOS. A critical pathological feature of PCOS is impaired gonadal steroid hormone negative feedback to the GnRH neuronal network in the brain that regulates fertility. This impairment is associated with androgen excess, a cardinal feature of PCOS. Impaired steroid hormone feedback to GnRH neurons is thought to drive hyperactivity of the neuroendocrine axis controlling fertility, leading to a vicious cycle of androgen excess and reproductive dysfunction. Decades of clinical research have been unable to uncover the mechanisms underlying this impairment, because of the extreme difficulty in studying the brain in humans. It is only recently, with the development of preclinical models of PCOS, that we have begun to unravel the role of the brain in the development and progression of PCOS. Here, we provide a succinct overview of what is known about alterations in the steroid hormone–sensitive GnRH neuronal network that may underlie the neuroendocrine defects in clinical PCOS, with a particular focus on those that may contribute to impaired progesterone negative feedback, and the likely role of androgens in driving this impairment.
Checkpoint Inhibitor–Associated Autoimmune Diabetes Is Distinct From Type 1 Diabetes
Authors: Tsang Venessa H M , McGrath Rachel T , Clifton-Bligh Roderick J , Scolyer Richard A , Jakrot Valerie , Guminski Alexander D , Long Georgina V , Menzies Alexander M
Published: July 2019

Context

Checkpoint inhibitor–associated autoimmune diabetes mellitus (CIADM) is a rare illness, and little is known about its incidence, clinical features, or pathogenesis.

Case Series Description

Consecutive patients from a single quaternary melanoma center who developed new-onset insulin-requiring diabetes after commencing anti–programmed cell death-1 (PD-1) immunotherapy were studied to describe CIADM characteristics. Ten (1.9%) of 538 patients with metastatic melanoma treated with anti–PD-1–based immunotherapy from March 2015 to March 2018 developed CIADM. Nine patients had no history of diabetes, and one had pre-existing type 2 diabetes mellitus. Median time from immunotherapy start to CIADM diagnosis was 25 weeks [interquartile range (IQR), 17.5 to 34.5 weeks]. All patients had normal serum C-peptide shortly before CIADM onset and an inappropriately low level when measured soon after. At CIADM diagnosis, median hemoglobin A1c was 7.6% (IQR, 7.15% to 9.75%), median glucose level was 32.5 mmol/L (IQR, 21.6 to 36.7 mmol/L), and median C-peptide concentration was 0.35 nmol/L (IQR, 0.10 to 0.49 mmol/L). Type 1 diabetes (T1D)–associated autoantibodies (DAAs) were present in two patients (both of whom had anti–glutamic acid decarboxylase antibody); all were negative for insulin-associated protein 2, insulin, and ZnT8. Three patients were heterozygous for an HLA class II T1D-risk haplotype; two additional patients also carried protective haplotypes for T1D. All patients continued immunotherapy; eight (80%) had complete or partial oncological response, and all patients required ongoing insulin therapy.

Conclusion

CIADM is characterized by sudden permanent β-cell failure occurring after immunotherapy. It is distinct from T1D, usually lacks DAA or T1D-associated HLA-risk haplotypes, and is associated with difficult glycemic control from the onset. As such, CIADM represents a new model of auto-inflammatory β-cell failure.
Levothyroxine Replacement in Obese Adults: The Role of Metabolic Variables and Aging on Thyroid Testing Abnormalities
Authors: Mele Chiara , Tagliaferri Maria Antonella , Pagano Loredana , Soranna Davide , Scacchi Massimo , Aimaretti Gianluca , Biondi Bernadette , Marzullo Paolo
Published: July 2019

Context

General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity.

Objective

We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism.

Setting

Tertiary care center.

Design

Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (<0.27 mU/L), euthyroid (0.27 to 4.2 mU/L), and high TSH (>4.2 mU/L).

Results

LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0.05). Compared with the euthyroid obese group, LT4 users showed higher adiposity, similar insulin resistance, but a healthier lipid profile. In multivariable analyses, LT4 dose was predicted by fat-free mass, hypothyroidism cause, and sex (P < 0.0001 to < 0.05). Risk of LT4 overreplacement increased with younger age (OR 0.96; 95% CI 0.94 to 0.99), higher LT4 dose (OR 2.98; 95% CI 1.44 to 6.14), and lower BMI (OR 0.93; 95% CI 0.88 to 0.99). Male sex increased the likelihood of LT4 underreplacement (OR 2.37; 95% CI 1.10 to 5.11).

Conclusions

Obesity is associated with milder rates of inadequate LT4 treatment compared with nonobese populations. LT4 adequacy increases with aging. Age, body composition, and sex are main determinants of LT4 requirements in obesity.
Comparison of Teriparatide and Denosumab in Patients Switching From Long-Term Bisphosphonate Use
Authors: Lyu Houchen , Zhao Sizheng S , Yoshida Kazuki , Tedeschi Sara K , Xu Chang , Nigwekar Sagar U , Leder Benjamin Z , Solomon Daniel H
Published: July 2019

Context

Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab.

Objective

We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years.

Design

Observational cohort study using electronic medical records from two academic medical centers in the United States.

Participants

The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab.

Outcome Measures

Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck.

Results

Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by −2.2% (95% CI −2.9 to −1.5%) and the femoral neck by −1.1% (95% CI −2.1 to −0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years.

Conclusions

Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.
Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function
Authors: Tan Lingxiao , Cho Kwang-Jin , Kattan Walaa E. , Garrido Christian M. , Zhou Yong , Neupane Pratik , Capon Robert J. , Hancock John F.
Published: July 2019

The primary site for KRAS signaling is the inner leaflet of the plasma membrane (PM). We previously reported that oxanthroquinone G01 (G01) inhibited KRAS PM localization and blocked KRAS signaling. In this study, we identified acylpeptide hydrolase (APEH) as a molecular target of G01. APEH formed a stable complex with biotinylated G01, and the enzymatic activity of APEH was inhibited by G01. APEH knockdown caused profound mislocalization of KRAS and reduced clustering of KRAS that remained PM localized. APEH knockdown also disrupted the PM localization of phosphatidylserine (PtdSer), a lipid critical for KRAS PM binding and clustering. The mislocalization of KRAS was fully rescued by ectopic expression of APEH in knockdown cells. APEH knockdown disrupted the endocytic recycling of epidermal growth factor receptor and transferrin receptor, suggesting that abrogation of recycling endosome function was mechanistically linked to the loss of KRAS and PtdSer from the PM. APEH knockdown abrogated RAS–RAF–MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic.
Evidence that dopamine is involved in neuroendocrine regulation, gill intracellular signaling pathways and ion regulation in Litopenaeus vannamei
Authors: Si Lingjun , Pan Luqing , Zhang Xin , Wang Hongdan , Wei Cun
Published: July 2019

The transport of ions and ammonia in the gills may be regulated by neuroendocrine factors, in order to explore the regulation mechanism of dopamine (DA), hemolymph neuroendocrine hormones, gill intracellular signaling pathways, ion and ammonia transporters, as well as hemolymph osmolality and ammonia concentration were investigated in Litopenaeus vannamei after 10−7 and 10−6 mol shrimp−1 DA injection. The data displayed a significant increase in crustacean hyperglycemic hormone (CHH) concentration at 1-12 h and a transient significant decrease in corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol concentrations under DA stimulation. The up-regulation of guanylyl cyclase (GC) mRNA, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) concentrations, together with down-regulation of DA receptor D4 mRNA and up-regulation of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), diacylglycerol (DAG) and protein kinase C (PKC) concentrations suggested an activation of complicated intracellular signaling pathway. The expression of cyclic AMP response element-binding protein (CREB), FXYD2 and 14-3-3 protein mRNA was significantly increased by PKA regulation. The increase in Na+/K+-ATPase (NKA) activity and the stabilization of V-type H+-ATPase (V-ATPase) activity are accompanied by an up-regulation of K+-channel, Na+/K+/2Cl− cotransporter (NKCC), Rh protein and vesicle associated membrane protein (VAMP) mRNA, resulting in an increase in hemolymph osmolality and a decrease in hemolymph ammonia concentration. These results suggest that DA stimulates the secretion of CHH and inhibits the release of cortisol, which activates intracellular signaling factors to facilitate ion and ammonia transport across the gills, and may not affect intracellular acidification.
Future of Radiotherapy in Nasopharyngeal Carcinoma
Authors: Sun Xue-Song , Li Xiao-Yun , Chen Qiu-Yan , Tang Lin-Quan , Mai Hai-Qiang
Published: July 2019

Nasopharyngeal carcinoma (NPC) is a malignancy with unique clinical biological profiles such as associated Epstein-Barr virus infection and high radiosensitivity. Radiotherapy has long been recognized as the mainstay for the treatment of NPC. However, the further efficacy brought by radical radiotherapy has reached the bottleneck in advanced patients, who are prone to develop recurrence and distant metastasis after treatment. The application of photon therapy makes it possible for radiation dose escalation in refractory cases and may provide second chance for recurrent patients with less unrecoverable tissue damage. The concept of adaptive radiotherapy is put forward in consideration of target volume shrinkage during treatment. The replanning procedure offers better protection for the organ at risk. However, the best timing and candidates for adaptive radiotherapy is still under debate. The current tendency of artificial intelligence in NPC mainly focuses on image recognition, auto-segmentation and dose prediction. Although artificial intelligence is still in developmental stage, the future of it is promising.

To further improve the efficacy of NPC, multimodality treatment is encouraged. In-depth studies on genetic and epigenetic variations help to explain the great heterogeneity among patients, and could further be applied to precise screening and prediction, personalized radiotherapy and the evolution of targeted drugs. Given the clinical benefit of immunotherapy in other cancers, the application of immunotherapy, especially immune checkpoint inhibitor, in NPC is also of great potential. Results from ongoing clinical trials combining immunotherapy with radiotherapy in NPC are expected.
Apparent diffusion coefficient (ADC) histogram analysis: differentiation of benign from malignant parotid gland tumors using readout-segmented diffusion-weighted imaging
Authors: Zhang Zanxia , Song Chengru , Zhang Yong , Wen Baohong , Zhu Jinxia , Cheng Jingliang
Published: July 2019

Objectives

To explore the utility of whole-lesion apparent diffusion coefficient (ADC) histogram analysis for differentiating parotid gland tumors following readout-segmented diffusion-weighted imaging (RESOLVE).

Methods

80 patients (40 with pleomorphic adenomas, 14 with Warthin tumors, and 26 with malignant parotid gland tumors) who underwent routine head-and-neck MRI and RESOLVE examinations, were retrospectively evaluated. RESOLVE data were acquired from a MAGNETOM Skyra 3T MR system. Eleven whole-lesion histogram parameters derived from histogram analysis (ADC_mean, ADC_minimum, ADC_maximum, ADC_1th, ADC_10th, ADC_50th, ADC_90th, ADC_99th, skewness, variance and kurtosis) were calculated for each patient using MaZda. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the ADC for distinguishing among the three groups.

Results

In total, nine parameters (ADC_minimum, ADC_maximum, ADC_mean, ADC_10th, ADC_50th, ADC_90th, ADC_99th, variance, skewness) were statistically significant (all p < 0.05) for all three groups, in the comparison of pleomorphic adenomas to Warthin tumors; the ADC_mean, ADC_50th, and skewness revealed high diagnostic efficiency with areas under the receiver operating characteristic curve of 0.976, 0.970, and 0.970, respectively. In the comparison of pleomorphic adenomas to malignant parotid gland tumors, these nine parameters were also found to be statistically different (all p < 0.05); the ADC_mean, ADC_10th and ADC_50th revealed high diagnostic efficiency with area under the curve of 0.851, 0.866, and 0.841, respectively. However, in the comparison of Warthin tumors to malignant parotid gland tumors, only three parameters (ADC_mean, ADC_50th, skewness) were statistically significant (all p < 0.05).

Conclusions

Whole-lesion ADC histograms are effective in differentiating common parotid gland tumors.
An exploratory investigation of ‘depression-like’ behaviours in a model of left-sided distal middle cerebral artery occlusion in young, male C57B6 mice
Authors: Couch Yvonne , Clausen Bettina Hjelm , Ormhøj Maria , Andersen Maria Gammelstrup , Kring Christine , Møller Maja , Lambertsen Kate Lykke
Published: July 2019

Background:Stroke is a devastating neurological injury, which can result in significant cognitive and behavioural deficits. Modelling the disease processes associated with stroke in animals is key to the development of novel therapeutic approaches. However, some aspects of stroke pathophysiology, including neuropsychiatric symptoms, do not translate well from humans to animals. Here, we aimed to investigate the development of post-stroke depression in a rodent model of stroke.

Methods:The distal middle cerebral artery (MCA) was permanently occluded by electrocoagulation in adult male C57/Bl6/J mice. Animals were allowed to survive for 6 hours, 24 hours, 2 days, 5 days or 7 days prior to behavioural testing. Brains were taken to confirm lesion volumes at the above times. Behavioural tests studied basic exploration and motivation (open field and marble burying) as well as depression-like behaviours (tail suspension and sucrose preference).

Results:Animals developed robust and reproducible lesions in the cortex but whilst stroke reduced activity in the open field, animals showed no associated behavioural deficits in any of the tests used for depression-like behaviours.

Conclusions:The distal middle cerebral artery occlusion (MCAO) model results in a small cortical lesion which produces no depression-like behaviours. These negative data are important for those wishing to investigate the more cognitive and behavioural aspects of stroke.
Strength of Association. Report 1. Graduations of Relative Risk
Authors: Котеров А. , Koterov A. , Ушенкова Л. , Ushenkova L. , Зубенкова Э. , Zubenkova E. , Вайнсон А. , Vaynson A. , Калинина М. , Kalinina M. , Бирюков А. , Biryukov A.
Published: July 2019

Purpose: To summarize data on graduation of the effect size on the base of Hill’s first causality criterion ‘Strength of association’ on relative risk parameters (RR). Material and methods: Survey of published sources: monographs, handbooks, papers, educational material on statistics in various disciplines (including on-line), etc. (128 references; of which about 30 handbooks on epidemiology, carcinogenesis and medical statistics). Results: For the RR value, the collected data summary (1980–2018) implies non-homogeneity in concepts. The most common references are to the Monson scale (two editions of the monograph on the epidemiology of occupational exposures Monson R.R., 1980; 1990). In our opinion, the optimal graduation can be developed on the basis of this scale, and it should include both the range of no effect (RR = 0.9–1.2) and the weak (RR = 1.2–1.5, or 0.7–0.9), moderate (RR = 1.5–3.0, or 0.4–0.7), strong (RR = 3.0–10.0; or 0.1–0.4) and very strong’(RR = 10.0–40.0; or 0.0–0.1) ranges. Examples of epidemiological effects with overwhelming strength of association are presented (RR > 40.0). For the effects of thalidomide, RR reached thousands, for diethylstilbestrol, conditional infinity, and when irradiated in childhood, the frequency of some cancers increased tens and even hundreds of times. The juristic aspects of compensation payment based on RR are briefly reviewed. According to the Daubert rule (Daubert ruling, Daubert standard) on the 1993 precedent in the United States, risks are recognized only at RR > 2.0, when the probability of causality is more than 50 %. Conclusions: To estimate the RR value, one should use the most common and officially established Monson scale, albeit with an expansion in the range of dramatic or overhelming risks. This study can be used as a reference guide on the graduations of effect size on RR (OR) for a wide variety of observed disciplines.