bluuebunny/crossref_metadata_2025 huggingface dataset:
Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy
Authors: Ludman Taylor , Melemedjian Ohannes K.
Published: February 2019

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN is the major cause of dose reduction or discontinuation of otherwise life-saving treatment. Unfortunately, CIPN can persist in cancer survivors, which adversely affects their quality of life. Moreover, available treatments are vastly inadequate, warranting a better understanding of the biochemical and metabolic mechanisms that occur in response to chemotherapeutics which would be critical for the development of novel therapies for CIPN. Using extracellular flux analysis, this study demonstrated that the proteasome inhibitor, bortezomib, enhanced glycolysis while suppressing oxidative phosphorylation in the sensory neurons of mice. This metabolic phenotype is known as aerobic glycolysis. Bortezomib upregulated lactate dehydrogenase A and pyruvate dehydrogenase kinase 1, which consequently enhanced the production of lactate and repressed pyruvate oxidation, respectively. Moreover, lactate dehydrogenase A- and pyruvate dehydrogenase kinase 1-driven aerobic glycolysis was associated with increased extracellular acidification, augmented calcium responses, and pain in bortezomib-induced CIPN. Remarkably, pharmacological blockade and in vivo knockdown of lactate dehydrogenase A or pyruvate dehydrogenase kinase 1 reversed the metabolic phenotype, attenuated calcium responses, and alleviated pain induced by bortezomib. Collectively, these results elucidate the mechanisms by which bortezomib induces aerobic glycolysis. Moreover, these findings establish aerobic glycolysis as a metabolic phenotype that underpins bortezomib-induced CIPN.
A cognitive assessment tool designed for data collection in the field in low- and middle-income countries
Authors: Ford Cassie B , Kim Ha Yeon , Brown Lindsay , Aber J. Lawrence , Sheridan Margaret A.
Published: February 2019

The Rapid Assessment of Cognitive and Emotional Regulation (RACER) is a tablet-based assessment tool for children that measures executive function (EF) skills. Instructions that are brief and visually presented; game-like tasks are designed to easily engage children regardless of literacy level and variable test administration settings. RACER measures inhibitory control and working memory. This study presents the theoretical rationale and empirical evidence for tablet-based assessments of EF, the process of administering the RACER assessments. The current sample consists of students in Lebanon (N=1900) and Niger (N=850). The results indicate that individual differences in EF can be assessed by the RACER tablet tasks. Specifically, we demonstrate that EF scores are associated in expected ways with age and that tasks function similarly to what has been observed in high-income countries. The feasibility and utility for researchers, practitioners, and clinicians, of this cognitive assessment tool is discussed.
Retrieval dynamics of recognition and rejection
Authors: Papesh Megan H , Hicks Jason L , Guevara Pinto Juan D
Published: February 2019

Recognition memory is often viewed as the end-product of discrete cognitive events, involving the combination of latent operations such as the assessment of memory strength, the decision time, and the memory judgement. Recently, researchers have begun using the physical dynamics of memory retrieval to provide insight into the dynamic, possibly non-discrete, processes that underlie memory decisions. In this study, the underlying distributional properties of targets and lures were manipulated by populating lists with items drawn from either homogeneous or heterogeneous word frequency and context variability ranges. In all conditions, participants’ x-, y-mouse coordinates were recorded as they processed test items, allowing estimates of response dynamics (e.g., initial deviation and area under the curve [AUC]), and eventual old/new responses. The stimulus manipulations affected the distribution shapes and, to a greater degree, the placements of subjective confidence thresholds. We observed tight correspondences between confidence and AUC for both hits and correct rejections. We interpret these results within dynamic models of recognition memory.
Breaking voice identity perception: Expressive voices are more confusable for listeners
Authors: Lavan Nadine , Burston Luke FK , Ladwa Paayal , Merriman Siobhan E , Knight Sarah , McGettigan Carolyn
Published: February 2019

The human voice is a highly flexible instrument for self-expression, yet voice identity perception is largely studied using controlled speech recordings. Using two voice-sorting tasks with naturally varying stimuli, we compared the performance of listeners who were familiar and unfamiliar with the TV show Breaking Bad. Listeners organised audio clips of speech with (1) low-expressiveness and (2) high-expressiveness into perceived identities. We predicted that increased expressiveness (e.g., shouting, strained voice) would significantly impair performance. Overall, while unfamiliar listeners were less able to generalise identity across exemplars, the two groups performed equivalently well when telling voices apart when dealing with low-expressiveness stimuli. However, high vocal expressiveness significantly impaired telling apart in both the groups: this led to increased misidentifications, where sounds from one character were assigned to the other. These misidentifications were highly consistent for familiar listeners but less consistent for unfamiliar listeners. Our data suggest that vocal flexibility has powerful effects on identity perception, where changes in the acoustic properties of vocal signals introduced by expressiveness lead to effects apparent in familiar and unfamiliar listeners alike. At the same time, expressiveness appears to have affected other aspects of voice identity processing selectively in one listener group but not the other, thus revealing complex interactions of stimulus properties and listener characteristics (i.e., familiarity) in identity processing.
Synthesis of Trifluoromethyl Heterocyclic Compounds
Authors: Zouaoui Emna , Gaïed Mohamed Moncef El
Published: February 2019

The synthesis of trifluoromethyl pyrazoles, 1,5-benzodiazepines, and 1,5-benzothiazepines is described. The regiochemistry of the pyrazole synthesis was investigated using 2D NMR methods.
An Easy Synthesis of Thermochromic Ethylenes under Microwave Irradiation
Authors: Villemin Didier , Hachémi Messaoud , Hammadi Mohamed
Published: February 2019

Thermochromic ethylenes were obtained by the reaction of anthrone with tricyclic ketones or terephthaldehyde in DMF in the presence of potassium ter-butoxide under reflux (8h) or under microwave irradiation (10 min.).
Sign in, time out, sign out checklist-changing practice through interdepartmental teamwork to improve safety at caesarean section
Authors: Lennon Roisin , Smith Alison
Published: February 2019

Three similar clinical incidences over a three-month period highlighted an issue with the readiness and availability of neonatal resuscitation personnel and equipment at the time of caesarean section (CS). This identified a potential risk to the wellbeing of the mother and baby that had to be addressed. A joint venture was undertaken with the maternity and theatre directorates. A maternity-specific checklist in use in the UK maternity services was sourced, adapted and implemented. No further incidents have been reported since with resulting overall enhanced safety of pregnant women and newborn babies in the unit.
The reflexive potential of silence: Emotions, the ‘everyday’ and ethical international relations
Authors: Beattie Amanda Russell
Published: February 2019

This article argues on behalf of an autoethnographic methodology as one, but not the only, method suited to the excavation of the emotions of everyday international relations. I suggest, drawing on my own lived experiences of writing the Life in the United Kingdom Test specifically, and being ordered deported from the United Kingdom more broadly, that a reflexive practice informed by silence allows scholars to attend to the otherwise discounted and excluded forms of emotional knowledge. As my story unfolds, and the transformative potential of trauma is rehearsed, the possibility of excavating otherwise silenced emotions, guided by an affective empathy, comes to the fore. I suggest, building on my own lived experience, that as the researcher cum agent embraces this position, discounted and discarded stories are revisited. In so doing I present a piece of evocative autoethnography in and of itself while demonstrating the role that emotions can play in the construction of everyday practices of International Relations.
The use of mindfulness in primary care
Authors: Kelly Michael
Published: February 2019

Mindfulness is a form of meditative practice in which participants are taught to bring a heightened awareness to the present moment, without judgement or reaction. Although there are a number of different intervention types, in mental health services it is often used with cognitive therapy, or stress reduction principles to help people experiencing a wide range of physical and mental health concerns. Although variations in treatment format exist, it is typically delivered in a structured group intervention comprised of eight, 2-hour sessions.
Whole-brain magnetic resonance imaging of plaque burden and lenticulostriate arteries in patients with different types of stroke
Authors: Wu Fang , Zhang Qian , Dong Kai , Duan Jiangang , Yang Xiaoxu , Wu Ye , Zhang Ling , Li Debiao , Fan Zhaoyang , Yang Qi
Published: February 2019

Background:

Large-vessel atherosclerotic disease is an important pathogenesis of deep-perforator infarction (DPI). However, altered vessel walls of intracranial large arteries and distribution of small arteries in DPI are unclear because of the limited resolution of current imaging techniques. In this study the intracranial plaque burden and lenticulostriate artery (LSA) distribution in patients with recent DPI and non-DPI using whole-brain vessel-wall imaging (WB-VWI) were investigated.

Methods:

A total of 44 patients with recent DPI (23 patients) or non-DPI (21 patients) due to intracranial atherosclerotic disease were prospectively enrolled. WB-VWI was performed in all the patients using a three-dimensional T1-weighted vessel-wall magnetic resonance technique. Hemispheres with DPI and non-DPI were considered as the DPI group and non-DPI group, respectively. Hemispheres without a history of stroke were the control group. The intracranial plaque burden was compared between the DPI and non-DPI groups. The number and length of visualized LSA branches among DPI, non-DPI, and control groups were also evaluated.

Results:

A total of 77 hemispheres were analyzed (23 in the DPI group, 21 in the non-DPI group, and 33 in the control group). Plaque burden was lower ( p = 0.047) in the DPI group (82.0 ± 45.9 mm3) compared with the non-DPI group (130.9 ± 90.3 mm3). There was a significant reduction ( p = 0.002) in length of visualized LSA branches in the DPI group (74.1 ± 21.7 mm) compared with the control group (104.6 ± 33.3 mm).

Conclusions:

WB-VWI enables the combination of vessel-wall and LSA imaging in one image setting, which can provide information about plaque burden and LSA distribution.
Tissue and Exosomal Serine Protease Inhibitors Are Significantly Overexpressed in Chronic Rhinosinusitis With Nasal Polyps
Authors: Mueller S. K. , Nocera A. L. , Dillon S. T. , Libermann T. A. , Wendler O. , Bleier B. S.
Published: February 2019

Background

The fibrinolysis pathway has been previously implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).

Objective

The purpose of this study was (1) to explore protein derangements of selected protease inhibitors of the serpin superfamily in CRSwNP and (2) to correlate the protease inhibitor derangements of the fibrinolysis pathway in tissue with exosomal samples to evaluate the potential of an exosomal noninvasive “liquid biopsy” for CRSwNP.

Methods

Institutional review board approved study in which matched tissue and mucus exosomal proteins (SerpinB2, SerpinF2, SerpinG1, and SerpinE1) were compared between control and CRSwNP patients using Western Blot analysis (n = 6/group) and immunohistochemistry (IHC). Transcriptome analysis (n = 10/group) on the same proteins was performed using whole transcriptome sequencing. Semiquantitative analysis of the Western Blots was performed using the Whitney–Mann U test.

Results

The transcriptomic data set showed multiple differentially expressed genes including SerpinB2 (fold changes [FC] 7.38), SerpinE1 (FC 1.42), SerpinF2 (FC 2.03), and SerpinG1 (FC 0.72). Western Blot and IHC analysis showed an overexpression of the Serpin protease inhibitors in tissue (SerpinB2, P < .01; SerpinE1, P < .01; SerpinF2, P < .01; and SerpinG1, P < .01) indicating a downregulation of the fibrinolysis cascade. The mucus exosomal serpin proteins exhibited similar findings.

Conclusion

Our analysis supported that protease inhibitors of the fibrinolysis pathway, especially SerpinB2, SerpinF2, and SerpinG1, are highly deranged in patients with CRSwNP. These findings suggest a downregulation of the fibrinolysis pathway via proteolytic cascade imbalance leading to excessive polyp fibrin deposition. Our data further supported our hypothesis that exosomal proteomic analyses may be used as noninvasive “liquid biopsy” for CRSwNP and a novel method to study chronic sinonasal inflammation.
Cultural educating of Palestinian youth through collaborative digital storytelling
Authors: Dahdal Sohail
Published: February 2019

Youth reliance on social media platforms as their main source of media consumption presents an opportunity to increase their cultural knowledge through engaging them in digital storytelling of their village oral history. This paper examines the results of a pilot study conducted in Palestinian villages with youth who were trained on local interviewing village elders to create digital stories. The process was designed in a collaborative game-like environment to obtain maximum engagement, thus creating a state of flow as stipulated by Csikszentmihalyi’s flow theory. The surveys conducted at the beginning and end of the project, combined with ethnographic action research, demonstrate that it is possible for the youths’ level of interest in the creation of the digital stories attains a state of flow when the process can be immersive and engaging such that a multi-phase plan that includes skilling then challenges at each phase – not unlike a game.
‘New Life Sciences: The Road Ahead’ Report on the BioVisionAlexandria 2016 Conference
Authors: Elwakil Marwa , Roman Nathalie , Rassoul Marwa Abdel , Elfayoumi Israa , Sobeih Yousra , El-Faham Mohamed
Published: February 2019

The Bibliotheca Alexandrina (BA) has organised its eighth international biennial conference, BioVisionAlexandria (BVA) 2016 on 12–14 April 2016 in Alexandria, Egypt. The theme of BVA 2016 was ‘New Life Sciences: The Road Ahead’, where cutting-edge relevant research topics at the forefront of science were presented by a variety of world-wide renowned speakers. BVA 2016 hosted around 2000 participants and speakers of diverse backgrounds, creating a multi-disciplinary arena for dialogue to explore the opportunities, benefits, and controversial threats.
Bilateral pneumothorax after general anesthesia in patient with pleomorphic sarcoma of soft tissue
Authors: Gianesello Lara , Boccaccini Alberto , Rostagno Carlo
Published: February 2019

The occurrence of a pneumothorax using supraglottic device is a rare complication during general anesthesia. Moreover, less than 2% of pneumothoraxes can be related to lung metastases, most due to soft tissue sarcoma. We present the case of a 45-year-old female diagnosed with metastatic sarcoma who developed a bilateral pneumothorax after general anesthesia with supraglottic device. Different causes of pneumothorax were discussed.
The association between handedness and clinicodemographic characteristics in people with multiple sclerosis: a brief report
Authors: Shirani Afsaneh , Cross Anne H , Naismith Robert T ,   for the Multiple Sclerosis Partners Advancing Technology and Health Solutions Investigators#
Published: February 2019

A relationship between handedness and clinicodemographic profiles of people with multiple sclerosis was sought using data from the Multiple Sclerosis Partners Advancing Technology Health Solutions network of 10 multiple sclerosis centers in the USA and Europe. Handedness data were available for 8888 multiple sclerosis patients, of which 917 (10.3%) were left-handed. Clinicodemographic profiles of right versus left-handed multiple sclerosis patients were similar except for a slightly increased proportion of men who were left-handed, and slightly reduced performance on the manual dexterity test using the non-dominant hand in left-handed patients. We found no evidence to suggest a prognostic implication of handedness in multiple sclerosis.
Detective Effort Among Complainant and Suspect Racial and Ethnic Dyads: An Exploration
Authors: Fallik Seth Wyatt , Victory Danielle , Dobrin Adam
Published: February 2019

The gap between citizen perceptions and the realities of police work is most pronounced among detective work: Little, for example, is known about how detectives use their investigative discretion. To overcome this issue within the context of race/ethnicity, detectives reported the amount of time they worked assigned cases. These data were paired with case file information containing the complainant and suspect’s racial and ethnic identity. Dyads of complainant and suspect racial/ethnic arrangements were explored to see whether there was a difference in the likelihood that a case would be worked and for how long it was worked. The results were mixed: There was no difference in the likelihood that a case would be worked or how long it was worked across differing complainant racial/ethnic identities. Cases with a minority suspect, however, were more likely to be worked and for longer periods of time. The implications for these findings are discussed.
Winning Through Deception: A Pedagogical Case Study on Using Social Deception Games to Teach Small Group Communication Theory
Authors: Tilton Shane
Published: February 2019

Social deception games are games that involve players adopting roles and teams that are not known to all players of the game. One of the components of these types of games is deceiving other players for the purpose of completing goals and tasks. The focus of this case study is to show how social deception games were used to teach aspects of small group communication (specifically the development of roles with small groups and power structures that emerge within small groups) to multiple groups of students taking a basic communication course at a large university in the United States. The framework of this case study will begin with an explanation of two social deception games (“Are You a Werewolf?” and “The Resistance”) and the previous literature related to small group communication, game-based learning, and other pedagogical frameworks. This review of literature is followed by a description of the lesson plan and course objectives that were used to frame the class time. An analysis of the reflective assignments will help describe the benefits of approaching small group communication with a ludological technique. Finally, discussion of the effectiveness of games like those in the category of social deception within the college communication curriculum is provided.
High Altitude Is an Independent Risk Factor for Developing a Pulmonary Embolism, but Not a Deep Vein Thrombosis Following a 1- to 2-Level Lumbar Fusion
Authors: Donnally Chester J. , Vakharia Ajit M. , Sheu Jonathan I. , Vakharia Rushabh M. , Damodar Dhanur , Shenoy Kartik , Gjolaj Joseph P.
Published: February 2019

Study Design:

Retrospective study.

Objective:

To identify if a 1- to 2-level posterior lumbar fusion at higher altitude is an independent risk factor for postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods:

A national Medicare database was queried for all patients undergoing 1- to 2-level lumbar fusions from 2005 to 2014. Those with a prior history of DVT, PE, coagulopathy, or peripheral vascular complications were excluded to better isolate altitude as the dependent variable. The groups were matched 1:1 based on age, gender, and comorbidities to limit potential cofounders. Using ZIP codes of the hospitals where the procedure occurred, we separated our patients into high (>4000 feet) and low (<100 feet) altitudes to investigate postoperative rates of DVTs and PEs at 90 days.

Results:

Compared with lumbar fusions performed at low-altitude centers, patients undergoing the same procedure at high altitude had significantly higher PE rates ( P = .010) at 90 days postoperatively, and similar rates of 90-day postoperative DVTs ( P = .078). There were no significant differences in age or comorbidities between these cohorts due to our strict matching process ( P = 1.00).

Conclusion:

Spinal fusions performed at altitudes >4000 feet incurred higher PE rates in the first 90 days compared with patients receiving the same surgery at <100 feet but did not incur higher rates of postoperative DVTs.
The effects of 8DSS peptide on remineralization in a rat model of enamel caries evaluated by two nondestructive techniques
Authors: Zheng Wenyue , Ding Longjiang , Wang Yufei , Han Sili , Zheng Sainan , Guo Qiang , Li Wei , Zhou Xuedong , Zhang Linglin
Published: February 2019

Nowadays, dental caries is one of the most common oral health problems, affecting most individuals. It has been found that, by remineralizing enamel at an early stage in the formation of enamel caries, teeth can be effectively protected from dental caries. In this work, a peptide with eight repetitive sequences of aspartate-serine-serine (8DSS) is applied as the bio-mineralizer in an in-vivo rat enamel caries model. Nondestructive quantitative light-induced fluorescence-digital (QLF-D) imaging and micro-computed tomography (micro-CT) are used to evaluate the remineralization of enamel carious lesions by measuring the total fluorescence radiance loss of the molar area (Δ QTotal), acquired using QLF-D imaging, and the mineral density and residual molar enamel volume, acquired using micro-CT. Correlations are explored between Δ QTotal and mineral density (strong correlation, r = 0.8000, p < 0.001) and Δ QTotal and residual molar enamel volume (moderate correlation, r = 0.6375, p < 0.001). Our results demonstrate that 8DSS is a promising in-vivo remineralization agent that exhibits comparable effects to NaF ( p < 0.05), which has been verified using the classical Keyes method. Moreover, the nondestructive QLF-D and micro-CT methods can be combined to quantify the remineralization of enamel carious lesions three-dimensionally in vivo, making them broadly applicable in quantifying hard tissues.
Macrophage immunomodulation: An indispensable tool to evaluate the performance of wound dressing biomaterials
Authors: Varela Patrícia , Sartori Susanna , Viebahn Richard , Salber Jochen , Ciardelli Gianluca
Published: February 2019

A major burden of the healthcare system resides in providing proper medical treatment for all types of chronic wounds, which are usually treated with dressings to induce a faster regeneration. Hence, to reduce healing time and improve the patient’s quality of life, it is extremely important to select the most appropriate constituent material for a specific wound dressing. A wide range of wound dressings exist but their mechanisms of action are poorly explored, especially concerning the immunomodulatory effects that occur from the interactions between immune cells and the biomaterial. Tissue-resident and monocyte-derived recruited macrophages are key regulators of wound repair. These phagocytic immune cells exert specific functions during the different stages of wound healing. The recognition of the substantial role of macrophages in the outcome of the wound healing process requires specific understanding of the immunomodulatory effects of commercially available or newly developed wound dressings. For a precise intervention, it is necessary to obtain more knowledge on macrophage polarization in different phases of wound healing in the presence of the dressings. The main purpose of this review is to collect clinical cases in which macrophage immunomodulation was taken into consideration as an indicator of the performances of novel or mainstream wound dressing materials, including those provided with antimicrobial properties.
Efficacy and Tolerability of Progen, a Nutritional Supplement Based on Innovative Plasma Proteins, in ACL Reconstruction: A Multicenter Randomized Controlled Trial
Authors: López-Vidriero Emilio , Olivé-Vilas Ramón , López-Capapé David , Varela-Sende Luisa , López-Vidriero Rosa , Til-Pérez Luís
Published: February 2019

Background:

New biologic strategies are arising to enhance healing and improve the clinical outcome of anterior cruciate ligament (ACL) reconstruction.

Purpose:

To evaluate the efficacy of a new oral nutritional supplement (Progen) that contains hydrolyzed collagen peptides and plasma proteins, a hyaluronic acid–chondroitin sulfate complex, and vitamin C.

Study Design:

Randomized controlled trial; Level of evidence, 2.

Methods:

The study included patients who underwent ACL reconstruction with hamstring autografts using the same fixation method. All patients received the same analgesia and physical therapy (PT) protocol and were randomized to receive either the nutritional supplement (supplemented group) or no additional therapy (control group). Patients were followed up at days 7, 30, 60, and 90. Pain was assessed by use of a visual analog scale (VAS) and by analgesic consumption. Clinical outcome was assessed via International Knee Documentation Committee (IKDC) score and the number of PT sessions. Perceived efficacy and tolerability were rated on a 5-point Likert scale. Graft maturation was assessed by a blinded musculoskeletal radiologist using magnetic resonance imaging. The number of adverse events (AEs) was recorded.

Results:

The intention-to-treat analysis included 72 patients, 36 allocated to the supplemented group and 36 to the control group, with no significant differences regarding demographic and preoperative characteristics. Both groups showed significant improvement in pain and function (measured by VAS and IKDC scores) during the 90-day follow-up period ( P < .001 for both), without significant differences between groups. The supplemented group had fewer patients that needed analgesics (8.5% vs 50.0%; P < .05) and attended fewer PT sessions (38.0 vs 48.4 sessions; P < .001) at 90 days and had a higher IKDC score at 60 days (62.5 vs 55.5; P = .029) compared with the control group. Patient- and physician-perceived efficacy was considered significantly higher in the supplemented group at 60 and 90 days ( P < .05). Perceived tolerability of the overall intervention was better in the supplemented group at 30, 60, and 90 days ( P < .05). Graft maturation showed more advanced degrees (grades 3 and 4) in the supplemented group at 90 days (61.8% vs 38.2%; P < .01). No intolerance or AEs associated with the nutritional supplement treatment were reported.

Conclusion:

The combination of the nutritional supplement and PT after ACL reconstruction improved pain, clinical outcome, and graft maturation. Nutritional supplementation showed higher efficacy during the second month of recovery, without causing AEs.

Registration:

NCT03355651 ( ClinicalTrials.gov identifier).
Information and Communication Technology Support for Contextualization, Polychronic Values, and Job Satisfaction: Evidence From Virtual Teams
Authors: Zhu Yaguang , Smith Stephanie A.
Published: February 2019

As companies expand geographically and information and communication technologies (ICTs) become more common, virtual teams gain popularity within corporations. As fast-paced ICT advances have created high demand for rapid response, virtual team members are often expected to have high levels of flexibility and responsiveness. Therefore, it is critical to understand how virtual team members with different polychronic values perceive the degree of ICT support for contextualization and how such a perception influences their job satisfaction. In this study, we draw on Te’eni’s cognitive-affective model of communication to examine how ICT-enabled contextualization influences job satisfaction. An online survey of virtual team workers ( N = 314) indicated that polychronic values moderate the relationship between degree of ICT support for contextualization and job satisfaction. Theoretical and practical implications are discussed.
A Rare Finding: Right-Sided Congenital Diaphragmatic Hernia With an Intrathoracic Kidney
Authors: Thompson Emma , Simmons Layla Q. , Baker Anthony L.
Published: February 2019

Congenital diaphragmatic hernia (CDH) is an opening in the diaphragm in which the abdominal viscera protrudes into the chest as the result of an embryologic defect. CDH can be an isolated anomaly or occur simultaneously with a chromosomal abnormality or genetic syndrome. Prognosis for fetuses with CDH is widely variable and depends on numerous factors including premature birth, the presence of a chromosomal abnormality or genetic disorder, location of the herniation, lung volume, and cardiac involvement. This study presents details of a case of right-sided CDH with an intrathoracic kidney detected sonographically. Fetal echocardiography and magnetic resonance imaging (MRI) were used to further characterize the herniation. Both sonography and MRI aided in accurate diagnosis and postnatal treatment planning.
Noninfectious transfusion-associated adverse events and their mitigation strategies
Authors: Goel Ruchika , Tobian Aaron A. R. , Shaz Beth H.
Published: February 2019

Blood transfusions are life-saving therapies; however, they can result in adverse events that can be infectious or, more commonly, noninfectious. The most common noninfectious reactions include febrile nonhemolytic transfusion reactions, allergic transfusion reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, and acute and delayed hemolytic transfusion reactions. These reactions can be asymptomatic, mild, or potentially fatal. There are several new methodologies to diagnose, treat, and prevent these reactions. Hemovigilance systems for monitoring transfusion events have been developed and demonstrated decreases in some adverse events, such as hemolytic transfusion reactions. Now vein-to-vein databases are being created to study the interactions of the donor, product, and patient factors in the role of adverse outcomes. This article reviews the definition, pathophysiology, management, and mitigation strategies, including the role of the donor, product, and patient, of the most common noninfectious transfusion-associated adverse events. Prevention strategies, such as leukoreduction, plasma reduction, additive solutions, and patient blood management programs, are actively being used to enhance transfusion safety. Understanding the incidence, pathophysiology, and current management strategies will help to create innovative products and continually hone in on best transfusion practices that suit individualized patient needs.
NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML
Authors: Sasca Daniel , Szybinski Jakub , Schüler Andrea , Shah Viral , Heidelberger Jan , Haehnel Patricia S. , Dolnik Anna , Kriege Oliver , Fehr Eva-Marie , Gebhardt Wolf H. , Reid George , Scholl Claudia , Theobald Matthias , Bullinger Lars , Beli Petra , Kindler Thomas
Published: February 2019

Neural cell adhesion molecule 1 (NCAM1; CD56) is expressed in up to 20% of acute myeloid leukemia (AML) patients. NCAM1 is widely used as a marker of minimal residual disease; however, the biological function of NCAM1 in AML remains elusive. In this study, we investigated the impact of NCAM1 expression on leukemogenesis, drug resistance, and its role as a biomarker to guide therapy. Beside t(8;21) leukemia, NCAM1 expression was found in most molecular AML subgroups at highly heterogeneous expression levels. Using complementary genetic strategies, we demonstrated an essential role of NCAM1 in the regulation of cell survival and stress resistance. Perturbation of NCAM1 induced cell death or differentiation and sensitized leukemic blasts toward genotoxic agents in vitro and in vivo. Furthermore, Ncam1 was highly expressed in leukemic progenitor cells in a murine leukemia model, and genetic depletion of Ncam1 prolonged disease latency and significantly reduced leukemia-initiating cells upon serial transplantation. To further analyze the mechanism of the NCAM1-associated phenotype, we performed phosphoproteomics and transcriptomics in different AML cell lines. NCAM1 expression strongly associated with constitutive activation of the MAPK-signaling pathway, regulation of apoptosis, or glycolysis. Pharmacological inhibition of MEK1/2 specifically inhibited proliferation and sensitized NCAM1+ AML cells to chemotherapy. In summary, our data demonstrate that aberrant expression of NCAM1 is involved in the maintenance of leukemic stem cells and confers stress resistance, likely due to activation of the MAPK pathway. Targeting MEK1/2 sensitizes AML blasts to genotoxic agents, indicating a role for NCAM1 as a biomarker to guide AML treatment.
Systemic inflammation induces release of cell-free DNA from hematopoietic and parenchymal cells in mice and humans
Authors: van der Meer Anne Jan , Kroeze Anna , Hoogendijk Arie J. , Soussan Aicha Ait , Ellen van der Schoot C. , Wuillemin Walter A. , Voermans Carlijn , van der Poll Tom , Zeerleder Sacha
Published: February 2019

Key Points

During a systemic inflammatory response, cell-free DNA is first released by hematopoietic cells and thereafter by nonhematopoietic cells.
Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain
Authors: Yildiz Ozge , Downes Gerald B. , Sagerström Charles G.
Published: February 2019

Background

Functioning of the adult nervous system depends on the establishment of neural circuits during embryogenesis. In vertebrates, neurons that make up motor circuits form in distinct domains along the dorsoventral axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear.

Methods

We used CRISPR/Cas9 to generate the first germline mutants for prdm12 and employed this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study prdm12b function in zebrafish. We also generated germline mutants for bhlhe22 and nkx6.1 to examine how these TFs act with prdm12b to control p1 formation.

Results

We find that prdm12b mutants lack eng1b expression in the p1 domain and also possess an abnormal touch-evoked escape response. Using luciferase reporter assays, we demonstrate that Prdm12b acts as a transcriptional repressor. We also show that the Bhlhe22 TF binds via the Prdm12b zinc finger domain to form a complex. However, bhlhe22 mutants display normal eng1b expression in the p1 domain. While prdm12 has been proposed to promote p1 fates by repressing expression of the nkx6.1 TF, we do not observe an expansion of the nkx6.1 domain upon loss of prdm12b function, nor is eng1b expression restored upon simultaneous loss of prdm12b and nkx6.1.

Conclusions

We conclude that prdm12b germline mutations produce a phenotype that is indistinguishable from that of morpholino-mediated loss of prdm12 function. In terms of prdm12b function, our results indicate that Prdm12b acts as transcriptional repressor and interacts with both EHMT2/G9a and Bhlhe22. However, bhlhe22 function is not required for eng1b expression in vivo, perhaps indicating that other bhlh genes can compensate during embryogenesis. Lastly, we do not find evidence for nkx6.1 and prdm12b acting as a repressive pair in formation of the p1 domain – suggesting that prdm12b is not solely required to repress non-p1 fates, but is specifically needed to promote p1 fates.
Short-time work in the Great Recession: firm-level evidence from 20 EU countries
Authors: Lydon Reamonn , Mathä Thomas Y. , Millard Stephen
Published: February 2019

Using firm-level data from a large-scale European survey among 20 countries, we analyse the determinants of firms using short-time work (STW). We show that firms are more likely to use STW in case of negative demand shocks. We show that STW schemes are more likely to be used by firms with high degrees of firm-specific human capital, high firing costs, and operating in countries with stringent employment protection legislation and a high degree of downward nominal wage rigidity. STW use is higher in countries with formalised schemes and in countries where these schemes were extended in response to the recent crisis. On the wider economic impact of STW, we show that firms using the schemes are significantly less likely to lay off permanent workers in response to a negative shock, with no impact for temporary workers. Relating our STW take-up measure in the micro data to aggregate data on employment and output trends, we show that sectors with a high STW take-up exhibit significantly less cyclical variation in employment.
Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS
Authors: Balleyguier Corinne , Dunant Ariane , Ceugnart Luc , Kandel Marguerite , Chauvet Marie-Pierre , Chérel Pascal , Mazouni Chafika , Henrot Philippe , Rauch Philippe , Chopier Jocelyne , Zilberman Sonia , Doutriaux-Dumoulin Isabelle , Jaffre Isabelle , Jalaguier Aurélie , Houvenaeghel Gilles , Guérin Nicole , Callonnec Françoise , Chapellier Claire , Raoust Ines , Mathieu Marie-Christine , Rimareix Françoise , Bonastre Julia , Garbay Jean-Rémi
Published: February 2019

PURPOSE

We evaluated the addition of breast magnetic resonance imaging (MRI) to standard radiologic evaluation on the re-intervention rate in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery.

PATIENTS AND METHODS

Women with biopsy-proven DCIS corresponding to a unifocal microcalcification cluster or a mass less than 30 mm were randomly assigned to undergo MRI or standard evaluation. The primary end point was the re-intervention rate for positive or close margins (< 2 mm) in the 6 months after randomization ( ClinicalTrials.gov identifier: NCT01112254).

RESULTS

A total of 360 patients from 10 hospitals in France were included in the study. Of the 352 analyzable patients, 178 were randomly assigned to the MRI arm, and 174 were assigned to the control arm. In the intent-to-treat analysis, 82 of 345 patients with the assessable end point were reoperated for positive or close margins within 6 months, resulting in a re-intervention rate of 20% (35 of 173) in the MRI arm and 27% (47 of 172) in the control arm. The absolute difference of 7% (95% CI, −2% to 16%) corresponded to a relative reduction of 26% (stratified odds ratio, 0.68; 95% CI, 0.41 to 1.1; P = .13). When considering only the per-protocol population with an assessable end point, the difference was 9% (stratified odds ratio, 0.59; 95% CI, 0.35 to 1.0; P = .05). Total mastectomy rates were 18% (31 of 176) in the MRI arm and 17% (30 of 173) in the control arm (stratified P = .93). For 100 lesions seen on MRI, nonmass-like enhancement was more predominant (82%) than mass enhancement (20%). Nevertheless, no specific morphologic and kinetic parameters for DCIS were identified.

CONCLUSION

The study did not show sufficient surgical improvement with the use of preoperative MRI to be clinically relevant in DCIS staging. However, this could be reconsidered with the improvement of new MRI sequences and new modalities in magnetic resonance techniques.
First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study
Authors: Flinn Ian W. , van der Jagt Richard , Kahl Brad , Wood Peter , Hawkins Tim , MacDonald David , Simpson David , Kolibaba Kathryn , Issa Samar , Chang Julie , Trotman Judith , Hallman Doreen , Chen Ling , Burke John M.
Published: February 2019

PURPOSE

The BRIGHT study ( ClinicalTrials.gov identifier: NCT00877006) was initiated to compare the efficacy and safety of bendamustine plus rituximab (BR) with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) for treatment-naive patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma. This publication provides long-term follow-up data.

PATIENTS AND METHODS

Patients were monitored for a minimum of 5 years after completion of study treatment for the time-to-event end points of progression-free survival (PFS), event-free survival, duration of response, and overall survival per investigator assessment. Data on the number of patients who received second-line anticancer treatment and the occurrence of other malignancies were also collected.

RESULTS

The medians were not reached for any of the time-to event end points for either the BR or R-CHOP/R-CVP study treatment groups by study completion. PFS rates at 5 years were 65.5% in the BR treatment group and 55.8% in the R-CHOP/R-CVP group. The difference in PFS was considered significant with a hazard ratio of 0.61 (95% CI, 0.45 to 0.85; P = .0025). The hazard ratio for event-free survival and duration of response ( P = .0020 and .0134, respectively) also favored the BR regimen over R-CHOP/R-CVP. However, no significant difference in overall survival was observed. The overall safety profiles of BR, R-CHOP, and R-CVP were as expected; no new safety data were collected during long-term follow-up. A higher number of secondary malignancies was noted in the BR treatment group.

CONCLUSION

Overall, BR demonstrated better long-term disease control than R-CHOP/R-CVP and should be considered as a first-line treatment option for patients with indolent and mantle-cell lymphoma.
Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone
Authors: McKay Rana R. , Ye Huihui , Xie Wanling , Lis Rosina , Calagua Carla , Zhang Zhenwei , Trinh Quoc-Dien , Chang Steven L. , Harshman Lauren C. , Ross Ashley E. , Pienta Kenneth J. , Lin Daniel W. , Ellis William J. , Montgomery Bruce , Chang Peter , Wagner Andrew A. , Bubley Glenn J. , Kibel Adam S. , Taplin Mary-Ellen
Published: February 2019

PURPOSE

Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer.

PATIENTS AND METHODS

Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored.

RESULTS

Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP.

CONCLUSION

Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.
Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline
Authors: Koyfman Shlomo A. , Ismaila Nofisat , Crook Doug , D'Cruz Anil , Rodriguez Cristina P. , Sher David J. , Silbermins Damian , Sturgis Erich M. , Tsue Terance T. , Weiss Jared , Yom Sue S. , Holsinger F. Christopher
Published: February 2019

PURPOSE

The aim of the current work is to provide evidence-based recommendations to practicing physicians and others on the management of the neck in patients with squamous cell carcinoma of the oral cavity and oropharynx.

METHODS

ASCO convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2018. Outcomes of interest included survival, regional disease control, neck recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

RESULTS

The literature search identified 124 relevant studies to inform the evidence base for this guideline. Six clinical scenarios were devised; three for oral cavity cancer and three for oropharynx cancer, and recommendations were generated for each one.

RECOMMENDATIONS

For oral cavity cancers, clinical scenarios focused on the indications for and the hallmarks of a high-quality neck dissection, indications for postoperative radiotherapy or chemoradiotherapy, and whether radiotherapy alone is sufficient elective treatment of an undissected neck compared with high-quality neck dissection. For oropharynx cancers, clinical scenarios focused on hallmarks of a high-quality neck dissection, factors that would favor operative versus nonoperative primary management, and clarifying criteria for an incomplete response to definitive chemoradiation for which salvage neck dissection would be recommended. Consensus was reached and recommendations were made for all six clinical scenarios. Additional information is available at www.asco.org/head-neck-cancer-guidelines .