bluuebunny/crossref_metadata_2025 huggingface dataset:
Quercus pyrenaica Honeydew Honey With High Phenolic Contents Cause DNA Damage, Apoptosis, and Cell Death Through Generation of Reactive Oxygen Species in Gastric Adenocarcinoma Cells
Authors: Kocyigit Abdurrahim , Aydogdu Gokhan , Balkan Ezgi , Yenigun Vildan Betül , Guler Eray Metin , Bulut Huri , Koktasoglu Fatmanur , Gören Ahmet Ceyhan , Atayoglu Ali Timucin
Published: September 2019

Many studies have shown that honey with high phenolic contents prevents cancer formation. Furthermore, recent studies have demonstrated that honey can be used for the treatment of cancer as well as cancer prevention. Antineoplastic effects of honey are often associated with their antioxidant phenolic contents. However, very few studies have dealt with the association of phenolic contents of honeys in terms of antiproliferative effects. The aim of this study was, therefore, to elucidate the cytotoxic, genotoxic, apoptotic, and reactive oxygen species (ROS) generating effects of honey samples on the basis of their phenolic and flavonoid contents. Fourteen different honey varieties were collected from various parts of Turkey, and their characteristics regarding total phenols, flavonoids, and antioxidant contents were determined to test their effects on gastric cancer cells (AGS). For convenience, 2 honey varieties were selected, namely, Ida Mountains Quercus pyrenaica honeydew honey (QPHH-IM) having the highest phenolic and antioxidant content and Canakkale multifloral honey (MFH-C) with the lowest phenolic and antioxidant content. Levels of 11 different phenolic compounds in QPHH-IM and MFH-C samples were determined by LC-MS/MS. AGS cells were incubated with different concentrations of QPHH-IM and MFH-C for 24 hours, then the cell viability, DNA damage, apoptosis, and generation of ROS were determined. We found that QPHH-IM had more cytotoxic, genotoxic, and apoptotic effects than that of MFH-C. We think that these effects are probably related to pro-oxidant activities due to the high phenolic contents present. Therefore, further research on high-phenolic honey may contribute to the future development of cancer therapeutics.
A Unique, Innovative, Easy-to-Use Program to Improve Young Children’s Attitudes About and Consumption of Fruits and Vegetables
Authors: McGlone Katalina , Banna Jinan
Published: September 2019

Getting children to eat fruits and vegetables (FV) is an important strategy for the prevention of childhood obesity. However, efforts to increase access to FV have also resulted in many of the vegetables and fruits being wasted, leaving children without the nutritional benefits and the resources not achieving their full desired impact. Multidisciplinary influences have shaped a new program for children ages 2 to 7 that can increase the desirability of and consumption of FV. The Guinea Show is easy-to-use, entertaining, and low cost and features an innovative role model. Results from field tests of The Guinea Show in preschool classrooms are included and indicate that children are more likely to try FV. Brief instructions on how to use this method are described.
The effect of using winglets to enhance the performance of swept blades of a horizontal axis wind turbine
Authors: Khalafallah Mohamed G , Ahmed Abdelnaby M , Emam Mohamed K
Published: September 2019

One of the recent methods to improve the performance of horizontal axis wind turbine is to attach a winglet at the tip of the blade of these turbines. Winglets reduce the effect of vortex flow at the blade tip and thus improve the performance of the blade. This article presents a parametric study using the computational fluid dynamics (CFD) modeling to investigate the capability of a winglet to increase the turbine power of swept blades as well as straight blades of a horizontal axis wind turbine. The effects of winglet direction, cant angle, and twist angle are studied for two winglet orientations: upstream and downstream directions. The numerical simulation was performed using ANSYS Fluent computational fluid dynamics code. A three-dimensional computational domain, cylindrical rotationally periodic, was used in the computations. The k-ω shear-stress transport turbulence model was adopted to demonstrate turbulence in the flow. Results show that horizontal axis wind turbine with winglet and sweep could enhance more power compared to their equivalent straight or swept blade. The best improvement in the coefficient of power is 4.39% at design tip speed ratio. This is achieved for downstream swept blades with winglets pointing in the upstream direction and having cant and twist angles of 40° and 10°, respectively.
On magnetized non-Newtonian rotatory fluid flow field
Authors: Khan Imad , Rehman Khalil U , Malik MY , Aly Shaban
Published: September 2019

The current pagination is devoted to offering the untapped features of non-Newtonian rotatory magnetized fluid flow over the solid disk. The said non-Newtonian fluid model is a Powell–Eyring fluid model. The flow field is further carried with suspended nanoparticles with velocity slip effects. The strength of the article is a complex mathematical modeling subject to physical effects mentioned before, and the computational results are provided through the self-coded algorithm rather than to move on with the usual built-in scheme. To make the implementation possible, the obtained flow-narrating system is converted into a system having fewer independents. The key involved parameters are Powell–Eyring fluid, magnetic field, velocity slip, thermophoresis, and Brownian motion parameters. The dependent quantities namely axial, tangential velocities, temperature, and concentration are examined against flow-controlling parameters. The obtained outcomes in this direction are offered by means of graphical trends. It is noticed that both axial and radial velocities possess direct relation with Power–Eyring parameter ( M). The Powell–Eyring fluid temperature is an increasing function of the thermophoresis parameter. Furthermore, the Powell–Eyring concentration enhances significantly toward the higher values of the Brownian motion parameter.
Affective and Semantic Representations of Valence: A Conceptual Framework
Authors: Itkes Oksana , Kron Assaf
Published: September 2019

The current article discusses the distinction between affective valence—the degree to which an affective response represents pleasure or displeasure—and semantic valence, the degree to which an object or event is considered positive or negative. To date, measures that reflect positivity and negativity are usually placed under the same conceptual umbrella (e.g., valence, affective, emotional), with minimal distinction between the modes of valence they reflect. Recent work suggests that what might seem to reflect a monolithic structure of valence has at least two different, confounding underlying sources, affective and semantic, that are fundamentally distinct, dissociable, and that obey different, recognizable rules. The current work discusses this distinction and provides implications for affective science from both the theoretical and the empirical perspective.
What Evokes Being Moved?
Authors: Cullhed Eric
Published: September 2019

Recent attempts to define being moved have difficulties agreeing on its eliciting conditions. The status quaestionis is often summarized as a question of whether the emotion is evoked by exemplifications of a wide range of positive core values or a more restricted set of values associated with attachment. This conclusion is premature. Study participants associate being moved with interactions with their loved ones not merely for what they exemplify but also for their affective bond to them. Being moved is elicited when we apprehend the value of entities to which we are connected through basic as well as extended forms of affiliative attachment. These comprise people, certain objects, and even abstract entities, including the unshakable life-guiding ideas we call “core values.”
Retinal detachment
Authors: Holliday Lois , Wilde Caroline
Published: September 2019

Around 5% of GP consultations are said to be eye-related, with loss of sight being the most feared long-term health condition. In 2013 there were 4 500 000 GP consultations related to eye health. The RCGP has stated that 50% of sight loss could be avoided through earlier diagnosis and improved eye care. It is essential that retinal detachment is recognised as an ophthalmological emergency and referred for urgent surgical repair to prevent visual loss. This article outlines the causes, presentation and management of retinal detachment, emphasising risk factors and clinical features that facilitate early diagnosis and prompt referral.
Recent advances in treatment for narcolepsy
Authors: Barateau Lucie , Dauvilliers Yves
Published: September 2019

Narcolepsy type 1 (NT1) is a chronic orphan disorder, caused by the selective and irreversible loss of hypocretin/orexin (ORX) neurons, by a probable autoimmune process. Little is known about NT2 etiology and prevalence, sharing with NT1 excessive daytime sleepiness (EDS) and dysregulation of rapid eye movement (REM) sleep, but without cataplexy and loss of ORX neurons. Despite major advances in our understanding of the neurobiological basis of NT1, management remains nowadays only symptomatic. The main and most disabling symptom, EDS, is managed with psychostimulants, as modafinil/armodafinil, methylphenidate, or amphetamines as a third-line therapy. Narcolepsy is an active area for drug development, and new wake-promoting agents have been developed over the past years. Pitolisant, a selective histamine H3 receptor inverse agonist, has been recently approved to treat patients with NT1 and NT2. Solriamfetol, a phenylalanine derivative with dopaminergic and noradrenergic activity will be soon a new therapeutic option to treat EDS in NT1 and NT2. Sodium oxybate, used for decades in adult patients with narcolepsy, was recently shown to be effective and safe in childhood narcolepsy. The discovery of ORX deficiency in NT1 opened new therapeutic options oriented towards ORX-based therapies, especially nonpeptide ORX receptor agonists that are currently under development. In addition, immune-based therapies administered as early as possible after disease onset could theoretically slow down or stop the destruction of ORX neurons in some selected patients. Further well-designed controlled trials are required to determine if they could really impact on the natural history of the disease. Given the different clinical, biological and genetic profiles, narcolepsy may provide a nice example for developing personalized medicine in orphan diseases, that could ultimately aid in similar research and clinical efforts for other conditions.
The effect of operative time on early postoperative complications in total shoulder arthroplasty: An analysis of the ACS-NSQIP database
Authors: Wilson Jacob M , Holzgrefe Russell E , Staley Christopher A , Karas Spero , Gottschalk Michael B , Wagner Eric R
Published: September 2019

Background

Total shoulder arthroplasty has been demonstrated to be an effective treatment for arthritis of the glenohumeral joint. Prior studies have identified longer operative times as a risk factor for complications after numerous types of procedures. We hypothesized that increased operative time, in 20-min intervals, would be associated with complications following total shoulder arthroplasty.

Methods

Patients undergoing total shoulder arthroplasty from 2006 to 2015 were identified from the ACS-NSQIP database. Patient demographic information, perioperative parameters, and 30-day outcomes were retrieved. Pearson's Chi-square test and multivariate Poisson regression with robust error variance were used to analyze the relationship of operative time and outcomes.

Results

A total of 10,082 patients were included. Multivariate analysis revealed that for each increase in 20 min of operative time, there were significantly increased rates of any complication (relative risk (RR) 1.24, 95% confidence interval (CI) 1.19–1.26), anemia requiring transfusion (RR 1.33, 95%CI 1.26–1.4), peripheral nerve injury (RR 1.88, 95%CI 1.53–2.31), and urinary tract infection (RR 1.24, 95%CI 1.09–1.41).

Discussion

This study indicates that increasing operative time confers increased risk for postoperative complications following total shoulder arthroplasty. We anticipate the results of this manuscript will be used for provider education, policy decision-making, and potentially to derive algorithms that can improve safety and efficiency in total shoulder arthroplasty.

Level of evidence

III.
Processing of Painful Pictures in Individuals With High and Low Rejection Sensitivity: Evidence From Event-Related Potentials
Authors: Qinqin Wu , Guangming Ran , Qi Zhang , Cao Xiaojun
Published: September 2019

An increasing number of studies have investigated the relation between the processing of painful stimuli and rejection. Little was known, however, about the impact of the rejection sensitivity (RS) on the processing of painful pictures. This study addressed this issue using high temporal resolution event-related potential techniques. Thirty high RS (20 women and 10 men who scored in the top 20th percentile of the Rejection Sensitivity Questionnaire scores) and 30 low RS (20 women and 10 men who scored in the bottom 20th percentile) volunteers participated in the experiment. All volunteers performed a discrimination task of painful pictures in which they were asked to judge whether target pictures were painful or not. Behaviorally, participants exhibited shorter reaction times for painful than nonpainful pictures. For the P100 component, low RS participants showed stronger brain activities for painful than nonpainful pictures, suggesting vigilance toward painful pictures. High RS participants, however, exhibited no P100 amplitude differences between painful and nonpainful pictures, indicating an analgesia phenomenon. Furthermore, we found that there were larger amplitudes in the late late positive complex component for painful compared with nonpainful pictures, regardless of participants’ RS. This suggested a person’s further assessment for painful pictures. In short, our findings demonstrated that the level of RS influenced the pain processing at a very early stage of processing.
Seagoing nightmares
Authors: Helmreich Stefan
Published: September 2019

This response to Peters and Steinberg’s ‘The ocean in excess’ tests the power and limits of their framings of ‘the ocean within’, ‘the ocean beyond’, and ‘the ocean imagined’ in thinking through the oceanic weave of transatlantic slave trade history and the recent long and deadly summers of migration in the Mediterranean.
Recurrent thrombosis of splanchnic and lower extremity arteries with essential thrombocythemia
Authors: Jung Sung Min , Jun Heungman
Published: September 2019

Essential thrombocythemia is a myeloproliferative neoplasm characterized by platelet aggregation and thrombosis. Clinically, essential thrombocythemia increases the risk of both thrombosis and bleeding. Essential thrombocythemia is more involved in micro- and small-sized arteries than in large arteries. Many essential thrombocythemia patients exhibit various symptoms, including microvascular thrombosis with acute coronary disease, digital ischemia, and transient ischemic attack. This study reports a rare case of recurrent thrombosis in relatively large vessels including splanchnic, lower extremity arteries, and aorta in essential thrombocythemia. A 70-year-old woman was admitted to the emergency room with abdominal pain and fever for a day. The patient underwent three operations due to recurrent arterial thrombosis of superior mesenteric, splenic, aorta, and lower extremities. She had recurrent diarrhea and acute kidney injury because of short bowel syndrome after extensive bowel resection. In conclusion, essential thrombocythemia patients aged >60 years and who have risk factors such as history of major ischemic events or severe leukocytosis must be careful of thrombosis of the medium- and large-sized arteries, including splanchnic and lower extremity arteries.
The gut virome in inflammatory bowel disease pathogenesis: From metagenomics to novel therapeutic approaches
Authors: Ungaro Federica , Massimino Luca , D’Alessio Silvia , Danese Silvio
Published: September 2019

The association of intestinal dysbiosis with the pathogenesis of inflammatory bowel disease has been well established. Besides bacteria, microbiota comprises yeasts, archaea, protists and viruses, neglected actors in inflammatory bowel disease‐associated microbiota. In the past, a great limitation in studying microbiota composition was the low sensitivity of sequencing technologies and that few computational approaches were sufficient to thoroughly analyse the whole microbiome. However, new cutting‐edge technologies in nucleic acid sequencing, ‐omics analysis and the innovative statistics and bioinformatics pipelines made possible more sensitive and accurate metagenomics, ultimately identifying novel players in intestinal inflammation, including prokaryotic and eukaryotic viruses, that together form the gut virome. The discovery of peculiar inflammatory bowel disease‐associated microbial strains will not only shed new light on inflammatory bowel disease aetiogenesis, they may also support the development of novel therapeutic strategies not merely treating symptoms, but precisely counteracting the primary cause of chronic intestinal inflammation.
Thinking Volume First: Developing a Multifaceted Systematic Approach to Volume Management in Hemodialysis
Authors: Blum Daniel , Beaubien-Souligny William , Silver Samuel A. , Wald Ron
Published: September 2019

Purpose of review:

Volume overload and hypovolemia-induced symptoms are common in the hemodialysis (HD) population and frequently result in emergency department visits and hospitalization. A structured strategy for the reporting, evaluation, and management of disordered volume status may improve clinical outcomes and the patient experience. We developed a new strategy that systematically addresses volume issues by leveraging the electronic medical record, technological adjuncts, and multidisciplinary expertise to institute new processes of care in our HD unit.

Sources of information:

This initiative was implemented in a unit located in an urban academic hospital where 250 patients receive maintenance HD. This initiative involved a multidisciplinary team of health professionals including physicians, nurse practitioners, social workers, and dieticians.

Methods:

We generated volume metrics for HD recipients based on routinely collected data from the unit’s electronic medical record. We then engaged stakeholders in a root cause analysis to identify the major causes of abnormal volume metrics locally. We subsequently developed interventions that were designed to address each of the major causes in a pragmatic and sustainable program.

Key findings:

The final product was a local volume management program with 3 components. First, we integrated volume metric reporting into the routine surveillance bloodwork reports across our unit. This enabled the clinical teams to more easily target patients at risk for volume-related adverse events and provide them with closer surveillance. Those identified with abnormal volume metrics were then evaluated with the use of technologic adjuncts such as lung ultrasound and bioimpedance spectroscopy to complement traditional assessments of volume status. Finally, those with abnormal volume metrics underwent rigorous interdisciplinary review for potential nutritional/social interventions.

Limitations:

While we report the successful initial implementation of the program within a single center, it remains unclear whether this initiative will lead to meaningful benefits for HD recipients, be readily applicable in other centers, or be sustainable in the long term.

Implications:

This volume management program will need further evaluation linked to outcome assessment and feasibility in other centers before wider adoption is advocated.
Single-Study Approvals: Quantum of Evidence Required
Authors: Sasinowski Frank J. , Butler Michelle L.
Published: September 2019

When does a single positive adequate and well-controlled study of a new drug meet the statutory requirement to demonstrate substantial evidence of effectiveness? The answer to this question, particularly with respect to new molecular entities, has been of considerable debate since 1962 when the requirement that new drugs prove their benefit to patients became law. A 1997 revision to the statute provided one pathway to a single-study approval (a single adequate and well-controlled study plus confirmatory evidence), while a 1998 guidance issued by FDA provided additional pathways, one of which is the one that is most frequently cited by FDA (a single statistically very persuasive study). This paper explains these 2 distinct pathways and provides illustrative examples of how FDA uses each of these 2 pathways. Regulators, industry, patients, and investors should each find this exegesis of these 2 independent, yet equally viable and valuable, pathways to an FDA approval both illuminating and invaluable.
Risks and Complications Associated With Intra-articular Arthroscopy of the Knee and Shoulder in an Office Setting
Authors: McMillan Sean , Chhabra Anikar , Hassebrock Jeffrey D. , Ford Elizabeth , Amin Nirav H.
Published: September 2019

Background:

Classically, arthroscopy has been considered one of the diagnostic gold standards for assessing intra-articular knee and shoulder abnormality.

Purpose:

To assess the risks associated with in-office needle arthroscopy.

Study Design:

Case series; Level of evidence, 4.

Methods:

A retrospective case series analysis was performed by evaluating consecutive diagnostic needle arthroscopies performed by 13 physicians at 13 independent institutions. The findings of both major and minor complications were reported by each of the 13 surgeons based on office documentation. The data were analyzed as a lump sum of both knee and shoulder cases and then subdivided and examined separately. The patients’ ages ranged from 14 to 78 years, and no statistical difference was noted between the numbers of men and women. A major complication was defined as infection, chondral toxicity, or the need for alternative treatment at an urgent care or emergency room secondary to the procedure. Minor complications were defined as a vasovagal event, pain that persisted after 24 hours, or the need for crutches or sling postprocedure.

Results:

Of the 1419 cases, no major complications were reported. The overall rate of vasovagal events was 1.9% for all procedures (1.6% in knees, 3% in shoulders). Persistent pain longer than 24 hours postprocedure was reported in 0.3% of cases. No patient required crutches or a sling. Postarthroscopy magnetic resonance imaging was needed in 1.4% of cases. No device failures were reported.

Conclusion:

Previous literature has evaluated the efficacy, sensitivity, and specificity of in-office diagnostic arthroscopy, and this study validates needle arthroscopy as safe in the office setting, with minimal risk of major or minor complications.
High Ankle Sprains in Professional Ice Hockey Players: Prognosis and Correlation Between Magnetic Resonance Imaging Patterns of Injury and Return to Play
Authors: Mollon Brent , Wasserstein David , Murphy Gráinne M. , White Lawrence M. , Theodoropoulos John
Published: September 2019

Background:

Hockey players sustain a greater incidence of ankle syndesmosis injuries than other athletes. These injuries have a higher morbidity and more unpredictable recovery than lateral ankle sprains. Magnetic resonance imaging (MRI) has been used to establish the diagnosis but has not been evaluated for its ability to predict return to play.

Hypothesis:

We hypothesized that patterns of injury defined on MRI could be used to predict return to play in a cohort of professional hockey players with syndesmosis sprains.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A prospectively collected National Hockey League (NHL) database was analyzed from the 2006-2007 to 2011-2012 seasons to assess return to play after an injury. A separate retrospective review of ankle MRI scans from professional hockey players with a documented high ankle sprain sustained between 2007 and 2012 was performed. Injuries were classified on MRI as complete or partial tears of the anterior-inferior tibiofibular ligament (AITFL), posterior-inferior tibiofibular ligament (PITFL), anterior talofibular ligament (ATFL), posterior talofibular ligament (PTFL), calcaneofibular ligament (CFL), and deltoid ligament. Fractures, bone contusions, and osteochondral lesions were also recorded.

Results:

A total of 105 NHL athletes sustained high ankle sprains over the 5 seasons studied. Of these athletes, 85 were unable to play and missed a median of 8 games (range, 0-65 games). A retrospective MRI evaluation of 21 scans identified complete AITFL tears in 13 (62%) and high-grade partial tears in 5 (24%) cases. In contrast, the PITFL was partially torn in 9 (43%) and normal in 12 (57%) cases. Bone contusions were seen in 71% of cases and lacked a consistent pattern. The most commonly associated ligamentous injury was of the ATFL, which was injured in 52% of cases (11/21; 3 complete and 8 partial). There was no difference in the mean number of days lost when players were stratified by patterns of injury (incomplete/complete AITFL tear ± additional ligamentous injury, bone contusion, syndesmosis width).

Conclusion:

A high ankle sprain resulted in significant variations in time of recovery among professional hockey players. A torn AITFL and bone bruising were the most common patterns of injury. Although MRI can be used to confirm the diagnosis of a syndesmosis injury, it did not predict return to play in this population.
Efficacy of Aflibercept in Bevacizumab-Resistant Macular Edema in Adult-Onset Coats Disease
Authors: Ku Cristy A. , Lema Gareth M.
Published: September 2019

Purpose:

This case is the first to our knowledge that demonstrates the efficacy of intravitreal aflibercept in bevacizumab-resistant, laser-naive macular edema (ME) in adult-onset Coats disease.

Methods:

A retrospective case report is presented.

Results:

A 74-year-old woman presented with central visual distortion in her right eye. Imaging and exam were consistent with adult-onset Coats disease with unilateral telangiectatic vessels, numerous macroaneurysms, and peripheral capillary dropout. There were also ME, lipid exudate, and localized hemorrhage. ME failed to respond to 4 intravitreal injections of bevacizumab but dramatically improved following initiation of aflibercept, with patient deferral of laser photocoagulation.

Conclusions:

To our knowledge, this is the first reported case of aflibercept as the sole treatment of bevacizumab-resistant ME in adult-onset Coats disease. Given the localized macular involvement more common to adult-onset Coats disease, antivascular endothelial growth factor (anti-VEGF) therapy may be sufficient, compared with classic childhood Coats disease, in which anti-VEGF therapy serves as an adjunct to laser photocoagulation or cryotherapy.
The whole-genome landscape of Burkitt lymphoma subtypes
Authors: Panea Razvan I. , Love Cassandra L. , Shingleton Jennifer R. , Reddy Anupama , Bailey Jeffrey A. , Moormann Ann M. , Otieno Juliana A. , Ong’echa John Michael , Oduor Cliff I. , Schroeder Kristin M. S. , Masalu Nestory , Chao Nelson J. , Agajanian Megan , Major Michael B. , Fedoriw Yuri , Richards Kristy L. , Rymkiewicz Grzegorz , Miles Rodney R. , Alobeid Bachir , Bhagat Govind , Flowers Christopher R. , Ondrejka Sarah L. , Hsi Eric D. , Choi William W. L. , Au-Yeung Rex K. H. , Hartmann Wolfgang , Lenz Georg , Meyerson Howard , Lin Yen-Yu , Zhuang Yuan , Luftig Micah A. , Waldrop Alexander , Dave Tushar , Thakkar Devang , Sahay Harshit , Li Guojie , Palus Brooke C. , Seshadri Vidya , Kim So Young , Gascoyne Randy D. , Levy Shawn , Mukhopadyay Minerva , Dunson David B. , Dave Sandeep S.
Published: September 2019

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry–based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
Inbreeding depression due to recent and ancient inbreeding in Dutch Holstein–Friesian dairy cattle
Authors: Doekes Harmen P. , Veerkamp Roel F. , Bijma Piter , de Jong Gerben , Hiemstra Sipke J. , Windig Jack J.
Published: September 2019

Background

Inbreeding decreases animal performance (inbreeding depression), but not all inbreeding is expected to be equally harmful. Recent inbreeding is expected to be more harmful than ancient inbreeding, because selection decreases the frequency of deleterious alleles over time. Selection efficiency is increased by inbreeding, a process called purging. Our objective was to investigate effects of recent and ancient inbreeding on yield, fertility and udder health traits in Dutch Holstein–Friesian cows.

Methods

In total, 38,792 first-parity cows were included. Pedigree inbreeding ($$F_{PED}$$FPED) was computed and 75 k genotype data were used to compute genomic inbreeding, among others based on regions of homozygosity (ROH) in the genome ($$F_{ROH}$$FROH).

Results

Inbreeding depression was observed, e.g. a 1% increase in$$F_{ROH}$$FROHwas associated with a 36.3 kg (SE = 2.4) decrease in 305-day milk yield, a 0.48 day (SE = 0.15) increase in calving interval and a 0.86 unit (SE = 0.28) increase in somatic cell score for day 150 through to 400. These effects equalled − 0.45, 0.12 and 0.05% of the trait means, respectively. When$$F_{PED}$$FPEDwas split into generation-based components, inbreeding on recent generations was more harmful than inbreeding on more distant generations for yield traits. When$$F_{PED}$$FPEDwas split into new and ancestral components, based on whether alleles were identical-by-descent for the first time or not, new inbreeding was more harmful than ancestral inbreeding, especially for yield traits. For example, a 1% increase in new inbreeding was associated with a 2.42 kg (SE = 0.41) decrease in 305-day fat yield, compared to a 0.03 kg (SE = 0.71) increase for ancestral inbreeding. There were no clear differences between effects of long ROH (recent inbreeding) and short ROH (ancient inbreeding).

Conclusions

Inbreeding depression was observed for yield, fertility and udder health traits. For yield traits and based on pedigree, inbreeding on recent generations was more harmful than inbreeding on distant generations and there was evidence of purging. Across all traits, long and short ROH contributed to inbreeding depression. In future work, inbreeding depression and purging should be assessed in more detail at the genomic level, using higher density information and genomic time series.
Extent of inappropriate prescription of artemisinin and anti-malarial injections to febrile outpatients, a cross-sectional analytic survey in the Greater Accra region, Ghana
Authors: Bonful Harriet Affran , Awua Adolf Kofi , Adjuik Martin , Tsekpetse Doris , Adanu Richard Mawuko Kofi , Nortey Pricillia Awo , Ankomah Augustine , Koram Kwadwo Ansah
Published: September 2019

Background

Febrile children seen in malaria hypo-endemic settings, such as the Greater Accra region (GAR) of Ghana are more likely to be suffering from a non-malarial febrile illness compared to those seen in hyper-endemic settings. The need for prescribers to rely on malaria test results to guide treatment practices in the GAR is even greater. This study was designed to investigate the factors associated with inappropriate artemisinin-based combination therapy (ACT) prescription.

Methods

A survey was conducted in six health facilities in the region in 2015. Treatment practices for febrile outpatient department (OPD) patients were obtained from their records. Prescribers were interviewed and availability of malaria commodities were assessed. The primary outcome was the proportion of patients prescribed ACT inappropriately. Independent variables included patient age and access to care, prescriber factors (professional category, work experience, access to guidelines, exposure to training). Data were analysed using Stata at 95% CI (α-value of 0.05). Frequencies and means were used to describe the characteristics of patients and prescribers. To identify the predictors of inappropriate ACT prescription, regression analyses were performed accounting for clustering.

Results

Overall, 2519 febrile OPD records were analysed; 45.6% (n = 1149) were younger than 5 years. Only 40.0% of patients were tested. The proportion of patients who were prescribed ACT inappropriately was 76.4% (n = 791 of 1036). Of these 791 patients, 141 (17.8%) were prescribed anti-malarial injections. Patients seen in facilities with rapid diagnostic tests (RDT) in stock were less likely to be prescribed ACT inappropriately, (AOR: 0.04, 95% CI 0.01–0.14, p < 0.001) compared to those seen in facilities with RDT stock-outs. Prescribers who had been trained on malaria case management within the past year were 4 times more likely to prescribe ACT inappropriately compared to those who had not been trained (AOR: 4.1; 95% CI (1.5–11.6); p < 0.01). Patients seen by prescribers who had been supervised were 8 times more likely to be  prescribed ACT inappropriately.

Conclusion

Inappropriate ACT prescription to OPD febrile cases was high. Training and supervision of health workers appears not to be yielding the desired outcomes. Further research is needed to understand this observation.
Towards modular composition of agent-based voltage control concepts
Authors: Wolgast Thomas , Nieße Astrid
Published: September 2019

In the last years, diverse agent-based concepts for voltage control in distribution grids were presented in literature. All these approaches are developed manually. Up to now, no tailoring approach has been presented to adapt these concepts to different – likewise specific – grid situations. As the effectiveness of voltage control schemes is highly dependent on the specific grid situation, this can result in multiple problems with regard to performance, applicability and expandability of the proposed agent-based control. The ideal case would be a customizable agent system that is automatically tailored to the grid it shall be applied to, considering its specific characteristics. To address that complex task, this paper proposes an approach for the modular composition of voltage control agents by recombining existing concepts from literature to new fully functional agent systems. This approach makes the first move to an optimized and scenario-specific creation of agent-based control systems that are specifically designed and automatically tailored to a given power system.
A study on the impact of data sampling rates on load signature event detection
Authors: Huchtkoetter Jana , Reinhardt Andreas
Published: September 2019

The analysis of electrical load signatures is an enabling technology for many applications, such as ambient assisted living or energy-saving recommendations. Through the digitalization of electricity metering infrastructure, meter reading intervals are gradually becoming more frequent than the traditional once-per-year reporting. In fact, across smart meter generations, samples were initially reported in 15-min intervals, more recently once per second, and even newer devices capture readings at rates on the order of several kilohertz. The advantages of using such high sampling rates have, however, not been unambiguously demonstrated in literature. We thus choose a widely considered application scenario of energy data analytics, event detection, and assess the impact of the sampling rate choice on the correct event recognition rate. More specifically, we compare the accuracy of two event detection algorithms with respect to the resolution of their input data. The results of our analysis hint at a non-linear relation between accuracy and data resolution, yet also indicate that most event occurrences can be correctly determined when using a sampling rate of approximately 1 kHz, with only minimal improvements achievable through higher rates.
On Twentieth-Century Literature’s Andrew J. Kappel Prize in Literary Criticism, 2019
Authors: Elam Michele
Published: September 2019

The winner of this year’s prize is Mark A. Tabone’s “Multidirectional Rememory: Slavery and the Holocaust in John A. Williams’s Clifford’s Blues.” The judge is Michele Elam. Elam’s scholarship and teaching in interdisciplinary humanities research spans literature and social science in order to examine changing cultural interpretations of gender and race. Her most recent scholarship is especially interested in how racial perception impacts outcomes for health, wealth, and social justice.
Neuroscience, Narrative, and Narratology
Authors: Armstrong Paul B.
Published: September 2019

Cognitive narratology needs a neuroscientifically sound understanding of language. This essay lays out a neurobiological model of narrative that explains how stories arise from and set in motion fundamental neuronal and cortical processes, and it then asks how the aims and methods of narratology should be aligned with what we know about language and the brain. The formalist goal of identifying orderly, universal structures of mind, language, and narrative does not match up well with the probabilistic, reciprocal interactions in the brain through which cognitive patterns emerge from our embodied experiences of the world. Cognitive narratology needs to break with the structuralist legacy still evident in the terminology of frames, scripts, and preference rules and to embrace the paradigm shift proposed by various pragmatically oriented, phenomenological theories of narrative that have contested the formalist program.
Can—and Should—Literary Study Develop Moral Character and Advance Social Justice? Answers from Cognitive Science
Authors: Bracher Mark
Published: September 2019

Drawing on empirical studies, the article argues that developing moral character and advancing social justice through literary study is both eminently feasible and profoundly ethical, and that claims to the contrary are based on faulty notions of the psychological bases of morality and justice. The article explains how certain literary texts together with certain pedagogical practices can achieve these ends by training students to recognize two key but routinely overlooked facts about other people—their profound sameness and interconnectedness with oneself and their ultimate blamelessness for negative life outcomes, behaviors, and character traits—as well as a key fact about themselves: that they are inherently compassionate, as manifested by their compassionate impulses and the gratification they get from helping others in need.
The Poetry and Practice of Meditation
Authors: Bradburn Elizabeth
Published: September 2019

Is reading poetry good for you? Drawing on evidence that reading poetry involves some of the same brain structures as those upon which human psychological well-being depends, this essay argues that George Herbert’s devotional lyrics, long understood as Christian meditations, center on recurring images in a manner consistent with the modern practice of mindfulness meditation. There is a significant overlap between the way meditation was understood by seventeenth-century Christians and the way it is understood by modern meditators in a secular and therapeutic context. Neurally, meditation means the reduction of activity in the brain’s default mode network; phenomenally, it means repeatedly bringing wandering attention back to a chosen meditation object. Poetry can be isomorphic with meditative practice because the image of meditation has an identifying pattern of movement—spontaneous wandering and controlled return—that can be created in several sensory modalities. Complex enough to characterize Herbert’s poetry as meditative, the pattern of wandering from and returning to a focal image potentially defines a meditative literary mode with a distinctive relationship to the imagination. The therapeutic potential of meditative poetry speaks to the value not just of poetry but of humanist education in general.
Guest Editors’ Introduction
Authors: Ross Shawna , Dowland Douglas
Published: September 2019

This introductory article argues that contemporary academic teaching contexts are filled with anxiety. Students enter the classroom with a host of uncertainties, while teachers often suffer the burden of personal and professional anxieties of their own. Although many of these are historically specific, rooted in particular political, economic, and ecological circumstances, the authors argue that they may be productively approached through the strategies outlined in this introduction and the articles of this cluster of articles. They advocate tackling the question of anxiety consciously, responsibly, and tactfully, guided both by teachers’ experiences and by their knowledge of theoretical approaches to course content. Drawing principally from affect theory, but also enfolding concepts from intersectional feminism, digital humanities, reader-response theory, and other critical methodologies, the authors share tactics for working with anxiety rather than striving to eliminate it or ignore it. They argue that, once we see our pedagogy as anxious, we begin to see opportunities to broach it as a subject that can productively engage with the core tenets of academic inquiry.
Anxiety Can Bring Us Together
Authors: Dowland Douglas
Published: September 2019

This article traces the history of the word anxiety and explores its use as a way to describe the act of literary interpretation. Returning to Stanley Fish’s idea of the interpretive community, the article argues that pedagogy often reinforces anxiety as an individual, isolating experience. This bespeaks a larger concern about the role of pedagogy in student and faculty life. The article concludes by encouraging faculty to consider anxiety as an energy that can be productively harnessed through the construction of a more emotionally aware interpretive community.
Visual Rhetoric as Performance
Authors: Farris Anelise
Published: September 2019

This article examines the use of comic adaptations of Shakespeare in the college classroom. After theorizing the class offering based upon performance pedagogy and inclusive learning practices, the author describes her experience coteaching a Shakespeare class that used three Shakespeare plays in both their traditional and graphic format. The success of the course revealed that comic adaptations of Shakespeare plays offer an accessible, rewarding means of understanding Shakespeare’s plays as both texts to be read and works to be performed.
Developmental delay in shivering limits thermogenic capacity in juvenile high-altitude deer mice (Peromyscus maniculatus)
Authors: Robertson Cayleih E. , McClelland Grant B.
Published: September 2019

Many endotherms native to cold and hypoxic high altitude (HA) environments have evolved a highly vascularized and aerobic skeletal muscle. This specialized muscle phenotype contributes via shivering to an enhanced capacity for aerobic thermogenesis (cold-induced VO2max). However, it is unclear how selection at HA for shivering thermogenesis acts early in the development of small altricial mammals, which are born with immature skeletal muscles and without the capacity for homeothermic endothermy. We have previously shown that postnatal maturation of brown adipose tissue and non-shivering thermogenesis is delayed in HA native deer mouse pups (Peromyscus maniculatus). To assess if HA adaptation has also altered the developmental program of skeletal muscle and shivering thermogenesis, we used laboratory-reared descendants of deer mice native to low (430 m a.s.l) and high (4350 m a.s.l.) altitude and a low altitude (LA) congeneric outgroup (P. leucopus). We found that LA juveniles were able to shiver robustly at 2 weeks after birth. However, HA juveniles were unable to shiver at this point, resulting in a 30% lower capacity for thermoregulation compared to lowlanders. It was only at 27 days after birth that HA juveniles had established the aerobic muscle phenotype characteristic of HA adults and a superior cold-induced VO2max compared to LA mice of the same age. The capacity for shivering may be delayed in HA mice to allow energy to be allocated to other important processes such as growth.
Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer
Authors: Ward William H. , DeMora Lyudmila , Handorf Elizabeth , Sigurdson Elin R. , Ross Eric A. , Daly John M. , Aggon Allison A. , Bleicher Richard J.
Published: September 2019

Background

Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion.

Methods

A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (≤ 30, 31–60, 61–90, 91–120, 121–365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology.

Results

Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05–1.10; P < 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9–96.1%) versus 94.9% (95% CI 94.6–95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11–1.15; P < 0.001).

Conclusions

Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised.