bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in men and women with type 2 diabetes: A systematic review and meta-analysis
Authors: Bouthoorn Selma , Valstar Gideon B , Gohar Aisha , den Ruijter Hester M , Reitsma Hans B , Hoes Arno W , Rutten Frans H
Published: July 2018

Objective:

Type 2 diabetes is a risk factor for the development of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. Our aim was to provide a summary estimate of the prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in type 2 diabetes patients and to investigate sex disparities.

Methods and results:

A systematic search of the databases Medline and Embase was conducted for studies reporting the prevalence of left ventricular diastolic dysfunction or heart failure with preserved ejection fraction among type 2 diabetes patients. Studies were only included if echocardiography was performed. Prevalence estimates were pooled using random-effects meta-analysis. A total of 28 studies were included. Data on the prevalence of left ventricular diastolic dysfunction were available in 27 studies. The pooled prevalence for left ventricular diastolic dysfunction in the hospital population (2959 type 2 diabetes participants) and in the general population (2813 type 2 diabetes participants) was 48% [95% confidence interval: 38%–59%] and 35% (95% confidence interval: 24%–46%), respectively. Heterogeneity was high in both populations, with estimates ranging from 19% to 81% in the hospital population and from 23% to 54% in the general population. For women and men, the pooled prevalence estimates of left ventricular diastolic dysfunction were 47% (95% confidence interval: 37%–58%) and 46% (95% confidence interval: 37%–55%), respectively. Only two studies presented the prevalence of heart failure with preserved ejection fraction; 8% (95% confidence interval: 5%–14%) in a hospital population and 25% (95% confidence interval: 21%–28%) in the general population [18% in men (mean age: 73.8; standard deviation: 8.6) and 28% in women (mean age: 74.9; standard deviation: 6.9)].

Conclusion:

The prevalence of left ventricular diastolic dysfunction among type 2 diabetes patients is similarly high in men and women, while heart failure with preserved ejection fraction seems to be more common in women than men, at least in community people with type 2 diabetes.
Detecting Demyelination by PET: The Lesion as Imaging Target
Authors: Brugarolas Pedro , Reich Daniel S. , Popko Brian
Published: July 2018

Noninvasive imaging of demyelination and remyelination is critical for diagnosis and clinical management of demyelinating diseases. Positron emission tomography (PET) has the potential to complement magnetic resonance imaging (MRI) by providing a quantitative measure specific to demyelination. In Brugarolas et al’s study 1 , we describe the development of the first PET tracer for voltage-gated K+ channels based on a clinically approved drug for multiple sclerosis that can be used for imaging demyelination in animal models.
A Comparison of Iron Oxide Particles and Silica Particles for Tracking Organ Recellularization
Authors: Kobes Joseph E. , Georgiev George I. , Louis Anthony V. , Calderon Isen A. , Yoshimaru Eriko S. , Klemm Louie M. , Cromey Douglas W. , Khalpey Zain , Pagel Mark D.
Published: July 2018

Reseeding of decellularized organ scaffolds with a patient’s own cells has promise for eliminating graft versus host disease. This study investigated whether ultrasound imaging or magnetic resonance imaging (MRI) can track the reseeding of murine liver scaffolds with silica-labeled or iron-labeled liver hepatocytes. Mesoporous silica particles were created using the Stöber method, loaded with Alexa Flour 647 fluorophore, and conjugated with protamine sulfate, glutamine, and glycine. Fluorescent iron oxide particles were obtained from a commercial source. Liver cells from donor mice were loaded with the silica particles or iron oxide particles. Donor livers were decellularized and reperfused with silica-labeled or iron-labeled cells. The reseeded livers were longitudinally analyzed with ultrasound imaging and MRI. Liver biopsies were imaged with confocal microscopy and scanning electron microscopy. Ultrasound imaging had a detection limit of 0.28 mg/mL, while MRI had a lower detection limit of 0.08 mg/mL based on particle weight. The silica-loaded cells proliferated at a slower rate compared to iron-loaded cells. Ultrasound imaging, MRI, and confocal microscopy underestimated cell numbers relative to scanning electron microscopy. Ultrasound imaging had the greatest underestimation due to coarse resolution compared to the other imaging modalities. Despite this underestimation, both ultrasound imaging and MRI successfully tracked the longitudinal recellularization of liver scaffolds.
Development and Validation of a Measure of Ebullient Supervision: The ES Scale
Authors: Ford Robert C. , Guzzo Renata , Abbott JeAnna L. , Bowen John T.
Published: July 2018

In an increasingly service-oriented economy, the importance of understanding supervisors’ impact on employees working in a fun work environment continues to grow. While researchers have learned much about the negative outcomes of abusive supervisors, relatively little is known about ebullient supervisors and the beneficial outcomes caused by leaders who create fun work environments for employees. The purpose of this article is to define the concept of an ebullient supervisor and develop and validate a scale to measure the construct of ebullient supervision (ES). A brief overview of the construct is presented along with its anticipated theoretical and empirical relationships with constructs that might be closely related. Construct definitions are developed and items for an ES measure are evaluated using a three-sample validation study. A combined exploratory and confirmatory factor analysis approach was used. This was followed by an analysis of the criterion-related validity. The results show that the ES has convergent validity with other supervisor support measures. One of the distinguishing factors of an ES, however, is that through the supervisor’s actions and behaviors the ebullient supervisor helps create a fun work environment for employees that may have many beneficial outcomes for organizations. Developing a measure of ES allows future researchers to add new insights to the management literature by being able to better investigate the unique benefits of this type of supervision for both organizations and employees.
Effects of the outlet position of splitter blade on the flow characteristics in low-specific-speed centrifugal pump
Authors: Zhang Jinfeng , Li Guidong , Mao Jieyun , Yuan Shouqi , Qu Yefei , Jia Jing
Published: July 2018

To elucidate the influences of the outlet position of splitter blades on the performance of a low-specific-speed centrifugal pump, two different splitter blade schemes were proposed: one located in the middle of the channel and the other having a deviation angle at the trailing edge of splitter blade toward the suction side of the main blade. Experiments on the model pump with different splitter blade schemes were conducted, and numerical simulations on internal flow characteristics in the impellers were studied by means of the shear stress transport k- ω turbulence model. The results suggest that there is a good agreement between the experimental and numerical results. The splitter blade schemes can effectively optimize the structure of the jet-wake pattern and improve the internal flow states in the impeller channel. In addition, the secondary flow and inlet circulation on the pressure surface of main blade, the flow separation on the suction side of splitter blade, the pressure coefficient distributions on blade surface can achieve an evident amelioration when the trailing edge of splitter blade toward the suction side of the main blade is mounted at an appropriate position.
Advancing Understanding of the Aesthetics of Temporal Sequences by Combining Some Principles and Practices in Music and Cuisine With Psychology
Authors: Rozin Paul , Rozin Alexander
Published: July 2018

We consider how to optimize remembered aesthetic pleasure resulting from temporal sequences of events such as music and meals. We examine what psychology and music can learn from each other and how this knowledge might be applied to tasting menus and other temporal sequences. Common practices in longer musical works suggest the importance of (a) beginnings and endings, (b) variations in affective intensity over time, (c) repetitions, (d) variations on a theme, and (e) a return to prior material at the end of a piece. Results from psychology suggest that for affective memory, the final and peak experiences are most critical. For example, because a strong positive ending may be important for affective memory, and because return is a major feature of the ending of musical works, it may be an error to end meals with desserts, which are not the favorite courses for most people and typically bear no relation to prior courses (hence no return).
Goal-Directed Allostasis: The Unique Challenge of Keeping Things as They Are and Strategies to Overcome It
Authors: Ecker Yael , Gilead Michael
Published: July 2018

We introduce the concept of goal-directed allostasis (GDA), the mental process that underlies individuals’ deliberate and proactive attempts to maintain the current state of affairs. GDA is distinct from goal-directed progress (GDP), the mental process that underlies the pursuit of change in the current state of affairs. We argue that GDA plays a crucial role in human life but that it has been largely overlooked in psychological research. We discuss the unique cognitive and motivational challenges that arise during GDA and suggest strategies to overcome these challenges. Finally, we outline how acknowledging the distinction between GDA and GDP might contribute to the study and treatment of mental illness and highlight several directions for future research.
Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study
Authors: Akinyemi Rufus O , Sarfo Fred S , Akinyemi Joshua , Singh Arti , Onoja Akpa Matthew , Akpalu Albert , Owolabi Lukman , Adeoye Abiodun M. , Obiako Reginald , Wahab Kolawole , Sanya Emmanuel , Komolafe Morenikeji , Ogbole Godwin , Fawale Michael , Adebayo Philip , Osaigbovo Godwin , Sunmonu Taofiki , Olowoyo Paul , Chukwuonye Innocent , Obiabo Yahaya , Adeniji Olaleye , Fakunle Gregory , Melikam Ezinne , Saulson Raelle , Yaria Joseph , Uwanruochi Kelechi , Ibinaiye Phillip , Amusa Ganiyu Adeniyi , Yahaya Isah Suleiman , Dambatta Abdullahi Hamisu , Faniyan Mercy , Olowoniyi Peter , Bock-Oruma Andrew , Joseph Odo Chidi , Oguntade Ayodipupo , Kolo Philip , Laryea Ruth , Lakoh Sulaiman , Uvere Ezinne , Farombi Temitope , Akpalu Josephine , Oyinloye Olalekan , Appiah Lambert , Calys-Tagoe Benedict , Shidali Vincent , Tabari Nasir Abdulkadir , Adebayo Oladimeji , Efidi Richard , Adeleye Osi , Owusu Dorcas , Ogunjimi Luqman , Aridegbe Olumayowa , Imoh Chidiebere Lucius , Sanni Taofeeq , Gebreziabher Mulugeta , Hemant Tiwari , Arulogun Oyedunni , Ogunniyi Adesola , Jenkins Carolyn , Owolabi Mayowa , Ovbiagele Bruce
Published: July 2018

Background

It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa.

Objective

To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies.

Methods

A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed.

Results

Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25–1.81) and a family history of stroke (OR 1.20, 1.03–1.39) while Islamic religion (OR=0.82, CI: 0.72–0.94), being currently unmarried (OR = 0.81, CI: 0.70–0.92), and alcohol use (OR = 0.78, CI: 0.67–0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03–1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65–0.96).

Conclusion

To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.
Explore Transplant Ontario: Adapting the Explore Transplant Education Program to Facilitate Informed Decision Making About Kidney Transplantation
Authors: Mucsi Istvan , Novak Marta , Toews Deanna , Waterman Amy
Published: July 2018

Purpose:

In this article, we describe a province-wide collaborative project in which we adapted the Explore Transplant (ET) education program for use in Ontario, Canada, to develop Explore Transplant Ontario (ETO). Kidney transplantation (KT), especially living donor kidney transplantation (LDKT), is the best treatment for many patients with end-stage kidney disease (ESKD), with the best patient survival and quality of life and also reduced health care costs. Yet KT and LDKT are underutilized both internationally and in Canada. Research has demonstrated that patients with ESKD who receive personalized transplant education are more likely to complete the transplant evaluation process and to receive LDKT compared with patients who do not receive this education.

Sources of information:

Research expertise of the lead authors and Medline search of studies assessing the impact of education interventions on access to KT and LDKT.

Methods:

The ET program, developed by Dr Amy Waterman, has been used in thousands of patients with ESKD in the United States to enhance KT and LDKT knowledge. To adapt this program for use in Ontario, we convened a working group, including patient representatives, nephrologists, transplant coordinators, dialysis nurses, and patient educators from all Ontario KT centers and selected dialysis units. In an iterative process concluding in a consensus workshop, the working group reviewed and edited the text of the original ET program and suggested changes to the videos.

Key findings:

The adapted program reflects the Ontario health care environment and responds to the specific needs of patients with chronic kidney disease (CKD) in the province. The videos feature Ontario transplant nephrologists, transplant coordinators, and patients, representative of the ethnic diversity in Ontario, sharing their transplant experience and expertise. Despite the changes, ETO is consistent with the quality and style of the original ET program. At the end of this article, we summarize subsequent steps to test and utilize ETO. Those projects, specifically the ETO pilot study and a multicomponent quality improvement initiative to increase utilization of KT and LDKT across Ontario, will be described in full in future papers.

Limitations:

This article describes a provincial initiative; therefore, our findings may not be fully generalizable without further considerations. The adapted education program has not yet been tested in large trial for effectiveness.

Implications:

As a program grounded in the theoretical model of behavior change, ETO places patients with ESKD at the center of a complex process of navigating renal replacement therapy modalities and acknowledges a broad range of patient values, priorities, and states of readiness to pursue KT.
Probable cutaneous adverse drug reaction to piroxicam in a cat
Authors: Young Amanda J , Torres Sheila M , Koch Sandra N
Published: July 2018

Case summary

A 9-year-old male neutered Devon Rex cat presented with bilaterally symmetrical ulcerative lesions with mucopurulent exudate that developed rapidly. The lesions were apparent on the axillae, ventral abdomen and inguinal areas. The cat was systemically well. Piroxicam was being administered for palliative treatment of a previously diagnosed salivary adenocarcinoma. Histopathology revealed severe extensive epidermal ulceration with focal dyskeratotic keratinocytes in the stratum granulosum without lymphocyte satellitosis. Resolution of skin lesions was observed after discontinuing piroxicam. Similar lesions developed after previous piroxicam administration, further suggesting a possible adverse reaction to this drug. In addition, the Naranjo score indicated that piroxicam was a probable cause for the ulcerative skin lesions.

Relevance and novel information

This is the first report of piroxicam, a non-steroidal anti-inflammatory drug, as a probable cause of ulcerative skin lesions in a cat.
A Commentary on Corporate Social Responsibility and Natural Disasters in India
Authors: Kumar Arvind
Published: July 2018

The purpose of this study was to evaluate the role of top 100 Indian companies in natural disasters and identify best practices of corporations in India. Results are derived from secondary data collected from websites, newsletters and annual reports of the companies. Three natural disasters were taken for the study from the year 2013–15.

It is observed that most of the companies have been engaged in disaster relief activities for social and ethical reasoning. These activities included financial help, stake holder consultation and partnerships with NGOs, non-profit organizations (NPOs) and the government. Corporations also help in disaster management simply by engaging in their regular business.

This study analyzes the role of corporations in natural disasters from a corporate social responsibility (CSR) perspective and discusses the possible way of coping with natural disasters by Indian companies.

The research findings will be very useful for Indian companies, Confederation of Indian Industries (CII), National Disaster Management Authority (NDMA), and Government, after the enactment of Companies Act 2013. It would be very helpful for normalcy of human life and business.

It analyses only top 100 Indian company’s contribution. It lacks the reflections of the other countries.
Thrombus in the Right Coronary Sinus of Valsalva Originating From the Left Atrial Appendage Causing Embolic Inferior Wall Myocardial Infarction
Authors: Abubakar Hossam , Ahmed Ahmed S. , Subahi Ahmed , Yassin Ahmed S.
Published: July 2018

Acute myocardial infarction (MI) is commonly a result of coronary atherosclerotic plaque rupture and superimposed thrombus formation. Nevertheless, uncommon causes of MI including embolism from aortic root and ascending aorta mural thrombi must be considered when coronary atherosclerotic disease is not evident. We report a case of a 84-year-old woman who presented with an inferior ST-segment elevation MI. Initial attempts to engage the right coronary artery (RCA) were unsuccessful. Aortic angiography revealed evidence of the left coronary artery ostium with absence of the right coronary ostium or RCA. Probing with a coronary wire where the RCA ostium was presumed to be located yielded resolution of the ST-segment elevation. The RCA was then easily engaged using a guide catheter, and angiographic evaluation showed a smooth vessel with no evidence of coronary artery disease except for abrupt termination of the distal PL2 branch. Contrast-enhanced computed tomography revealed an aortic root thrombus extending into the right coronary sinus of Valsalva and a thrombus in the left atrial appendage. The case reveals RCA embolism from an aortic root thrombus likely originating from the left trial appendage. A conservative approach to treatment with anticoagulation was pursued that resulted in full recovery. A review of the literature revealed that the etiology of aortic root thrombi is proposed to be multifactorial. Prospective randomized studies are needed to demonstrate the best treatment approach, although this appears to be impracticable given the rarity of the disease.
Incomplete Kawasaki Disease in an Adult South Asian Patient
Authors: Boodoosingh Neetu , Seecheran Rajeev , Varachhia Saleem , Mack Narine , Minocha Vinay , Giddings Stanley , Seecheran Naveen Anand
Published: July 2018

Kawasaki disease is an acute multisystemic vasculitis occurring predominantly in children and rarely in adults, with sequelae of potentially life-threatening coronary artery aneurysms. “Incomplete” Kawasaki disease is a novel concept and considered a diagnosis of exclusion as it alludes to patients with fever lasting ⩾5 days and 2 or 3 clinical criteria without another reasonable explanation for the illness. The multidisciplinary team should be vigilant for this oligosymptomatic clinical presentation, specifically within this subgroup despite age and ethnicity, and the syndrome should be considered as a differential diagnosis in challenging cases presenting as infectious or autoimmune disease.
Recurrent Instability Episodes and Meniscal or Cartilage Damage After Anterior Cruciate Ligament Injury: A Systematic Review
Authors: Sommerfeldt Mark , Raheem Abdul , Whittaker Jackie , Hui Catherine , Otto David
Published: July 2018

Background:

Delayed anterior cruciate ligament (ACL) reconstruction may be associated with increased risk of subsequent knee joint damage and osteoarthritis (OA). The relationship between recurrent instability episodes and meniscal or cartilage damage after first-time ACL injury is unknown.

Purpose:

To assess the association between recurrent knee instability episodes and prevalence of meniscal lesions, cartilage damage, and OA after first-time ACL injury.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

Six electronic databases were systematically searched using keywords and Medical Subject Heading terms. Studies selected were of English language, included original data, had a prospective design, and provided an outcome of recurrent instability and meniscal lesions, cartilage damage, or OA after first-time ACL injury. Adjusted odds ratios (ORs) were extracted or unadjusted ORs (95% CI) were calculated. PRISMA guidelines were followed, and 2 independent raters assessed study quality using Downs and Black criteria.

Results:

Of 905 potentially relevant studies, 7 were included. Sample sizes ranged from 43 to 541, and Downs and Black scores ranged from 2 to 12. Clinical and methodological heterogeneity precluded meta-analysis. Six studies reported a positive association between recurrent instability episodes and medial meniscal damage (OR range, 3.46 [95% CI, 1.24-9.99] to 11.56 [1.37-521.06]). The association between instability episodes and lateral meniscal or cartilage damage was inconsistent. No studies examined the association between instability episodes and OA.

Conclusion:

This systematic review provides preliminary evidence that recurrent instability episodes after first-time ACL injury may be associated with increased odds of medial meniscal damage. This highlights the importance of early diagnosis, education, and treatment for individuals with ACL injury, all of which must include a specific focus on the prevention and management of instability episodes. High-quality, prospective cohort studies are needed that assess the effects of diagnostic and treatment delay, recurrent instability episodes on secondary meniscal and cartilage damage, and OA after an initial ACL injury.
Novel PLP1 Mutations Identified With Next-Generation Sequencing Expand the Spectrum of PLP1-Associated Leukodystrophy Clinical Phenotypes
Authors: Margraf Rebecca L. , Durtschi Jacob , Krock Bryan , Newcomb Tara M. , Bonkowsky Joshua L. , Voelkerding Karl V. , Bayrak-Toydemir Pinar , Lutz Richard E. , Swoboda Kathryn J.
Published: July 2018

Next-generation sequencing was performed for 2 families with an undiagnosed neurologic disease. Analysis revealed X-linked mutations in the proteolipid protein 1 ( PLP1) gene, which is associated with X-linked Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2. In family A, the novel PLP1 missense mutation c.617T>A (p.M206K) was hemizygous in the 2 affected male children and heterozygous in the mother. In family B, the novel de novo PLP1 frameshift mutation c.359_369del (p.G120fs) was hemizygous in the affected male child. Although PLP1 mutations have been reported to cause an increasingly wide range of phenotypes inclusive of the dystonia, spastic paraparesis, motor neuronopathy, and leukodystrophy observed in our patients, atypical features included the cerebrospinal fluid deficiency of neurotransmitter and pterin metabolites and the delayed appearance of myelin abnormalities on neuroimaging studies. Next-generation sequencing studies provided a diagnosis for these families with complex leukodystrophy disease phenotypes, which expanded the spectrum of PLP1-associated leukodystrophy clinical phenotypes.
Phosphatidylinositol transfer proteins regulate megakaryocyte TGF-β1 secretion and hematopoiesis in mice
Authors: Capitano Maegan , Zhao Liang , Cooper Scott , Thorsheim Chelsea , Suzuki Aae , Huang Xinxin , Dent Alexander L. , Marks Michael S. , Abrams Charles S. , Broxmeyer Hal E.
Published: July 2018

Key Points

PITPs facilitate TGF-β1 secretion in megakaryocytes regulating hematopoiesis. Pitpα −/− /β −/− megakaryocytes have a defect in α-granule morphology and function.
Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4CRBN activity
Authors: Sievers Quinlan L. , Gasser Jessica A. , Cowley Glenn S. , Fischer Eric S. , Ebert Benjamin L.
Published: July 2018

Key Points

Genome-scale CRISPR knockout screen identifies cullin-RING ligase regulators as top mediators of lenalidomide resistance. The E2 ubiquitin-conjugating enzymes, UBE2D3 and UBE2G1, play distinct roles in lenalidomide-induced substrate ubiquitination by CRL4CRBN.
DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis
Authors: Ward-Caviness Cavin K. , Huffman Jennifer E. , Everett Karl , Germain Marine , van Dongen Jenny , Hill W. David , Jhun Min A. , Brody Jennifer A. , Ghanbari Mohsen , Du Lei , Roetker Nicholas S. , de Vries Paul S. , Waldenberger Melanie , Gieger Christian , Wolf Petra , Prokisch Holger , Koenig Wolfgang , O’Donnell Christopher J. , Levy Daniel , Liu Chunyu , Truong Vinh , Wells Philip S. , Trégouët David-Alexandre , Tang Weihong , Morrison Alanna C. , Boerwinkle Eric , Wiggins Kerri L. , McKnight Barbara , Guo Xiuqing , Psaty Bruce M. , Sotoodehnia Nona , Boomsma Dorret I. , Willemsen Gonneke , Ligthart Lannie , Deary Ian J. , Zhao Wei , Ware Erin B. , Kardia Sharon L. R. , Van Meurs Joyce B. J. , Uitterlinden Andre G. , Franco Oscar H. , Eriksson Per , Franco-Cereceda Anders , Pankow James S. , Johnson Andrew D. , Gagnon France , Morange Pierre-Emmanuel , de Geus Eco J. C. , Starr John M. , Smith Jennifer A. , Dehghan Abbas , Björck Hanna M. , Smith Nicholas L. , Peters Annette
Published: July 2018

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10−5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.
Differentiation-based model of hematopoietic stem cell functions and lineage pathways
Authors: Höfer Thomas , Rodewald Hans-Reimer
Published: July 2018

Advances in genetic labeling and barcoding of hematopoietic stem cells (HSCs) in situ now allow direct measurements of physiological HSC output, both quantitatively and qualitatively. Turning on a heritable label in HSCs and measuring the kinetics of label emergence in downstream compartments reveal rates of differentiation and self-renewal of HSCs and progenitor cells, whereas endogenous HSC barcoding probes physiological precursor-product relationships. Labels have been inserted at different stages of the hematopoietic differentiation hierarchy. Recent genetic and functional evidence suggests a phenotype (Tie2+) for tip HSCs. Fate mapping shows that many tip HSCs regularly feed into downstream stages, with individual cells contributing infrequently. Stem and progenitor cells downstream of tip HSCs serve as a major, nearly self-renewing source of day-to-day hematopoiesis, rendering the blood and immune system HSC-independent for extended periods of time. HSCs realize multilineage output, yet, fates restricted to several lineages or even a single lineage have also been observed. Single HSCs within a clone in the bone marrow that develop from a fetal HSC precursor have been observed to express clone-specific fates. Thus, the new tools probing HSC differentiation in situ are progressing beyond assays for HSC activity based on proliferation measurements and fates of transplanted stem cells, and the data challenge lineage interpretations of single-cell gene expression snapshots. Linking in vivo fate analyses to gene expression and other molecular determinants of cell fate will aid in unraveling the mechanisms of lineage commitment and the architecture of physiological hematopoiesis.
Disparities in survival by insurance status in follicular lymphoma
Authors: Goldstein Jordan S. , Nastoupil Loretta J. , Han Xuesong , Jemal Ahmedin , Ward Elizabeth , Flowers Christopher R.
Published: July 2018

Key Points

Privately insured patients have improved OS among patients of all ages with FL. Expanding access to care through insurance has the potential to improve FL outcomes.
Significant gynecological bleeding in women with low von Willebrand factor levels
Authors: Lavin Michelle , Aguila Sonia , Dalton Niall , Nolan Margaret , Byrne Mary , Ryan Kevin , White Barry , O’Connell Niamh M. , O’Sullivan Jamie M. , Di Paola Jorge , James Paula D. , O’Donnell James S.
Published: July 2018

Key Points

BATs differ significantly in sensitivity for detecting menorrhagia in women with low VWF. Despite pregnancy-related increases in plasma VWF levels, significant PPH may occur in women with low VWF.
In silico prediction of nonpermissive HLA-DPB1 mismatches in unrelated HCT by functional distance
Authors: Arrieta-Bolaños Esteban , Crivello Pietro , Shaw Bronwen E. , Ahn Kwang Woo , Wang Hai-Lin , Verneris Michael R. , Hsu Katharine C. , Pidala Joseph , Lee Stephanie J. , Fleischhauer Katharina , Spellman Stephen R.
Published: July 2018

Key Points

Nonpermissive T-cell epitope group mismatches can be predicted in silico for any HLA-DPB1 allele by functional distance scores. In silico–predicted nonpermissive DPB1 mismatches are associated with mortality and GVHD after 8/8 matched HCT.
Relationship between ambient light and glucose metabolism in healthy subjects
Authors: Hirakawa Hirofumi , Terao Takeshi , Hatano Koji , Kohno Kentaro , Ishii Nobuyoshi
Published: July 2018

Background

Given the reported inverse association between light and depressive mood, ambient light may also be associated with some of the brain regions in healthy subjects. The present study aims to investigate the effects of ambient light on glucose metabolism in the brain. We used the data of 28 healthy participants of the no intervention group from our previous randomized controlled trial and analyzed the association between ambient light and [18F]-FDG uptake in the brain.

Results

A whole brain analysis revealed a cluster of [18F]-FDG uptake that was significantly and inversely associated with log-transformed ambient light in the left culmen of the left cerebellum vermis. After adjustment for age, gender and serum melatonin levels, there remained a significant cluster of [18F]-FDG uptake with log-transformed ambient light in the left cerebellar vermis.

Conclusions

The present findings suggest that the uptake of [18F]-FDG is significantly and inversely associated with ambient light in the left cerebellar vermis in healthy subjects. The cerebellar vermis may be involved in mood suppression which may be alleviated by light exposure where glucose uptake and metabolism in this area are decreased.

Trial Registration This study is a secondary analysis of the previous randomized study which was
registered as UMIN000007537. Retrospectively registered (March 20th, 2012).
Active Learning in Flipped Life Science Courses Promotes Development of Critical Thinking Skills
Authors: Styers Melanie L. , Van Zandt Peter A. , Hayden Katherine L.
Published: July 2018

Although development of critical thinking skills has emerged as an important issue in undergraduate education, implementation of pedagogies targeting these skills across different science, technology, engineering, and mathematics disciplines has proved challenging. Our goal was to assess the impact of targeted interventions in 1) an introductory cell and molecular biology course, 2) an intermediate-level evolutionary ecology course, and 3) an upper-level biochemistry course. Each instructor used Web-based videos to flip some aspect of the course in order to implement active-learning exercises during class meetings. Activities included process-oriented guided-inquiry learning, model building, case studies, clicker-based think–pair–share strategies, and targeted critical thinking exercises. The proportion of time spent in active-learning activities relative to lecture varied among the courses, with increased active learning in intermediate/upper-level courses. Critical thinking was assessed via a pre/posttest design using the Critical Thinking Assessment Test. Students also assessed their own learning through a self-reported survey. Students in flipped courses exhibited gains in critical thinking, with the largest objective gains in intermediate and upper-level courses. Results from this study suggest that implementing active-learning strategies in the flipped classroom may benefit critical thinking and provide initial evidence suggesting that underrepresented and first-year students may experience a greater benefit.
Error-Discovery Learning Boosts Student Engagement and Performance, while Reducing Student Attrition in a Bioinformatics Course
Authors: Lee Christopher J. , Toven-Lindsey Brit , Shapiro Casey , Soh Michael , Mazrouee Sepideh , Levis-Fitzgerald Marc , Sanders Erin R.
Published: July 2018

We sought to test a hypothesis that systemic blind spots in active learning are a barrier both for instructors—who cannot see what every student is actually thinking on each concept in each class—and for students—who often cannot tell precisely whether their thinking is right or wrong, let alone exactly how to fix it. We tested a strategy for eliminating these blind spots by having students answer open-ended, conceptual problems using a Web-based platform, and measured the effects on student attrition, engagement, and performance. In 4 years of testing both in class and using an online platform, this approach revealed (and provided specific resolution lessons for) more than 200 distinct conceptual errors, dramatically increased average student engagement, and reduced student attrition by approximately fourfold compared with the original lecture course format (down from 48.3% to 11.4%), especially for women undergraduates (down from 73.1% to 7.4%). Median exam scores increased from 53% to 72–80%, and the bottom half of students boosted their scores to the range in which the top half had scored before the pedagogical switch. By contrast, in our control year with the same active-learning content (but without this “zero blind spots” approach), these gains were not observed.
Transition Experiences in MD–PhD Programs
Authors: Chakraverty Devasmita , Jeffe Donna B. , Tai Robert H.
Published: July 2018

MD–PhD training takes, on average, 8 years to complete and involves two transitions, an MD-preclinical to PhD-research phase and a PhD-research to MD-clinical phase. There is a paucity of research about MD–PhD students’ experiences during each transition. This study examined transition experiences reported by 48 MD–PhD students who had experienced at least one of these transitions during their training. We purposefully sampled medical schools across the United States to recruit participants. Semistructured interviews were audio-recorded and transcribed for analysis; items focused on academic and social experiences within and outside their programs. Using a phenomenological approach and analytic induction, we examined students’ transition experiences during their MD–PhD programs. Five broad themes emerged centering on multiple needs: mentoring, facilitating integration with students in each phase, integrating the curriculum to foster mastery of skills needed for each phase, awareness of cultural differences between MD and PhD training, and support. None of the respondents attributed their transition experiences to gender or race/ethnicity. Students emphasized the need for mentoring by MD–PhD faculty and better institutional and program supports to mitigate feelings of isolation and help students relearn knowledge for clinical clerkships and ease re-entry into the hospital culture, which differs substantially from the research culture.
Quality of Clinician-Reported Cancer History When Ordering Genetic Testing
Authors: LaDuca Holly , McFarland Rachel , Gutierrez Stephanie , Yussuf Amal , Ho Nadia , Pepper Jonathan , Reineke Patrick , Cain Taylor , Blanco Kirsten , Horton Carolyn , Dolinsky Jill S.
Published: July 2018

Purpose

Clinical history data reported on test requisition forms (TRFs) for hereditary cancer multigene panel testing (MGPT) are routinely used by genetic testing laboratories. More recently, publications have incorporated TRF-based clinical data into studies exploring yield of testing by phenotype and estimating cancer risks for mutation carriers. We aimed to assess the quality of TRF data for patients undergoing MGPT.

Patients and Methods

Ten percent of patients who underwent hereditary cancer MGPT between January and June 2015 at a clinical laboratory were randomly selected. TRF-reported cancer diagnoses were evaluated for completeness and accuracy for probands and relatives using clinical documents such as pedigrees and chart notes as the comparison standard in cases where these documents were submitted after the time of test order.

Results

TRF-reported cancer sites and ages at diagnosis were complete for > 90.0% of proband cancer diagnoses overall, and the completion rate was even higher (> 96.0%) for breast, ovarian, colorectal, and uterine cancers. When reported, these data were accurate on TRFs for > 99.5% of proband cancer sites and > 97.5% of proband ages at diagnosis. Cancer site and age at diagnosis data were also complete on the TRF for the majority of cancers among first- and second-degree relatives. Completeness decreased as relation to the proband became more distant, whereas accuracy remained high across all degrees of relation.

Conclusion

Data collected as part of cancer genetic risk assessment is completely and accurately reported on TRFs for the majority of probands and their close relatives and is comparable to information directly obtained from clinic notes, particularly for breast and other cancers commonly associated with hereditary cancer syndromes.
Rasip1 controls lymphatic vessel lumen maintenance by regulating endothelial cell junctions
Authors: Liu Xiaolei , Gu Xiaowu , Ma Wanshu , Oxendine Michael , Gil Hyea Jin , Davis George E. , Cleaver Ondine , Oliver Guillermo
Published: July 2018

Although major progress in our understanding of the genes and mechanisms that regulate lymphatic vasculature development has been made, we still do not know how lumen formation and maintenance occurs. Here, we identify the Ras-interacting protein Rasip1 as a key player in this process. We show that lymphatic endothelial cell-specific Rasip1-deficient mouse embryos exhibit enlarged and blood-filled lymphatics at embryonic day 14.5. These vessels have patent lumens with disorganized junctions. Later on, as those vessels become fragmented and lumens collapse, cell junctions become irregular. In addition, Rasip1 deletion at later stages impairs lymphatic valve formation. We determined that Rasip1 is essential for lymphatic lumen maintenance during embryonic development by regulating junction integrity, as Rasip1 loss results in reduced levels of junction molecules and defective cytoskeleton organization in vitro and in vivo. We determined that Rasip1 regulates Cdc42 activity, as deletion of Cdc42 results in similar phenotypes to those seen following the loss of Rasip1. Furthermore, ectopic Cdc42 expression rescues the phenotypes in Rasip1-deficient lymphatic endothelial cells, supporting the suggestion that Rasip1 regulates Cdc42 activity to regulate cell junctions and cytoskeleton organization, which are both activities required for lymphatic lumen maintenance.
Embryonic Tbx3+ cardiomyocytes form the mature cardiac conduction system by progressive fate restriction
Authors: Mohan Rajiv A. , Mommersteeg Mathilda T. M. , Domínguez Jorge N. , Choquet Caroline , Wakker Vincent , de Gier-de Vries Corrie , Boink Gerard J. J. , Boukens Bastiaan J. , Miquerol Lucile , Verkerk Arie O. , Christoffels Vincent M.
Published: July 2018

A small network of spontaneously active Tbx3+ cardiomyocytes forms the cardiac conduction system (CCS) in adults. Understanding the origin and mechanism of development of the CCS network are important steps towards disease modeling and the development of biological pacemakers to treat arrhythmias. We found that Tbx3 expression in the embryonic mouse heart is associated with automaticity. Genetic inducible fate mapping revealed that Tbx3+ cells in the early heart tube are fated to form the definitive CCS components, except the Purkinje fiber network. At mid-fetal stages, contribution of Tbx3+ cells was restricted to the definitive CCS. We identified a Tbx3+ population in the outflow tract of the early heart tube that formed the atrioventricular bundle. Whereas Tbx3+ cardiomyocytes also contributed to the adjacent Gja5+ atrial and ventricular chamber myocardium, embryonic Gja5+ chamber cardiomyocytes did not contribute to the Tbx3+ sinus node or to atrioventricular ring bundles. In conclusion, the CCS is established by progressive fate restriction of a Tbx3+ cell population in the early developing heart, which implicates Tbx3 as a useful tool for developing strategies to study and treat CCS diseases.
Preferences and Social Influence
Authors: Fershtman Chaim , Segal Uzi
Published: July 2018

Interaction between decision makers may affect their preferences. We consider a setup in which each individual is characterized by two sets of preferences: his unchanged core preferences and his behavioral preferences. Each individual has a social influence function that determines his behavioral preferences given his core preferences and the behavioral preferences of other individuals in his group. Decisions are made according to behavioral preferences. The paper considers different properties of these social influence functions and their effect on equilibrium behavior. (JEL D11, D83, D91, Z13)
DWI-MRI vs CT in gastric MALT lymphoma—preliminary results in 19 patients
Authors: Berzaczy Dominik , Staudenherz Anton , Raderer Markus , Weber Michael , Mayerhoefer Marius E.
Published: July 2018

Objective:

To assess the diagnostic performance of [F18] fluoro-2-desoxy-D-glucose positron emission tomography/CT [(18F) FDG-PET/CT] compared to diffusion-weighted imaging (DWI)-MRI of lesion detection in patients with non-FDG avid gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

Methods:

19 patients with histologically proven gastric MALT lymphoma were included in this prospective Institutional Review Board-approved study. Patients underwent [18F]-FDG-PET/CT and consecutive MRI/DWI. Images were evaluated for the presence of gastric lesions in two anatomically defined groups (region 1: cardia, body, fundus; region 2: antrum, pyloric region) by two senior board-certified radiologists, in an observer-blinded manner. Overall accuracy relative to the reference standard (histology obtained by biopsy) was calculated for each reader and a consensus rating.

Results:

We found a statistically significant higher accuracy of lesion detection for lesions in region 1 (p = 0.030) and 2 (p = 0.070) for DWI-MRI (100%/78.9%) than for CT (68.4%/42.1%).

Conclusion:

DWI-MRI seems to be superior accurate to CT for lesion detection in non-FDG avid gastric MALT lymphoma.

Advances in knowledge:

DWI-MRI seems to be an alternative reliable imaging method for locoregional disease evaluation of non-FDG avid gastric MALT lymphoma.
Catch Me If You Can: Effectiveness and Consequences of Online Copyright Enforcement
Authors: Aguiar Luis , Claussen Jörg , Peukert Christian
Published: July 2018

We evaluate the unexpected shutdown of kino.to, a major platform for unlicensed video streaming in the German market. Using highly disaggregated clickstream data in a difference-in-differences setting, we compare the web behavior of 20,000 consumers in Germany and three control countries. We find that this intervention was not very effective in reducing unlicensed consumption or encouraging licensed consumption, mainly because users quickly switch to alternative unlicensed sites. We highlight that the shutdown additionally had important unintended externalities. Individuals who never visited kino.to and who additionally clicked on news articles that covered the shutdown increased their visits to piracy websites substantially. We show that this effect largely comes from articles that explicitly mention alternative websites or suggest that users do not have to fear legal consequences from unlicensed streaming. Finally, we document that the unlicensed video streaming market is much more fragmented after the shutdown, potentially affecting future interventions, at least in the short run. We argue that our results can be helpful to understand why online piracy rates are still high, despite a plethora of enforcement efforts.