bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Priorities for Heart Failure With Preserved Ejection Fraction
Authors: Shah Sanjiv J. , Borlaug Barry A. , Kitzman Dalane W. , McCulloch Andrew D. , Blaxall Burns C. , Agarwal Rajiv , Chirinos Julio A. , Collins Sheila , Deo Rahul C. , Gladwin Mark T. , Granzier Henk , Hummel Scott L. , Kass David A. , Redfield Margaret M. , Sam Flora , Wang Thomas J. , Desvigne-Nickens Patrice , Adhikari Bishow B.
Published: March 2020

Heart failure with preserved ejection fraction (HFpEF), a major public health problem that is rising in prevalence, is associated with high morbidity and mortality and is considered to be the greatest unmet need in cardiovascular medicine today because of a general lack of effective treatments. To address this challenging syndrome, the National Heart, Lung, and Blood Institute convened a working group made up of experts in HFpEF and novel research methodologies to discuss research gaps and to prioritize research directions over the next decade. Here, we summarize the discussion of the working group, followed by key recommendations for future research priorities. There was uniform recognition that HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach in both humans and animal models to improve understanding of mechanisms and treatment of HFpEF. It was recognized that advances in the understanding of basic mechanisms and the roles of inflammation, macrovascular and microvascular dysfunction, fibrosis, and tissue remodeling are needed and ideally would be obtained from (1) improved animal models, including large animal models, which incorporate the effects of aging and associated comorbid conditions; (2) repositories of deeply phenotyped physiological data and human tissue, made accessible to researchers to enhance collaboration and research advances; and (3) novel research methods that take advantage of computational advances and multiscale modeling for the analysis of complex, high-density data across multiple domains. The working group emphasized the need for interactions among basic, translational, clinical, and epidemiological scientists and across organ systems and cell types, leveraging different areas or research focus, and between research centers. A network of collaborative centers to accelerate basic, translational, and clinical research of pathobiological mechanisms and treatment strategies in HFpEF was discussed as an example of a strategy to advance research progress. This resource would facilitate comprehensive, deep phenotyping of a multicenter HFpEF patient cohort with standardized protocols and a robust biorepository. The research priorities outlined in this document are meant to stimulate scientific advances in HFpEF by providing a road map for future collaborative investigations among a diverse group of scientists across multiple domains.
Are Automated Office Blood Pressure Readings More Variable Than Home Readings?
Authors: Myers Martin G. , Kaczorowski Janusz
Published: March 2020

A recent report from the American Heart Association stated that automated office blood pressure (AOBP) is preferred for evaluating office blood pressure (BP) because it is more accurate and devoid of white coat effect, which is mostly caused by higher systolic BP readings. However, AOBP has been criticized for being too variable to be used for identifying patients with possible hypertension. We, therefore, compared AOBP with home BP monitoring (HBPM) with respect to variability as determined by their relationship with the gold standard for determining BP status, awake ambulatory BP (ABP). The main focus was on systolic BP. Data on AOBP, HBPM, and awake ABP were collected on 300 patients referred from the community for 24-hour ambulatory BP monitoring. The SD of the difference between mean systolic awake ABP (136.4±11.5) and AOBP (131.2±15.7) was 13.6 mm Hg compared with 13.1 for the SD of the difference (
P
=0.52) between the systolic awake ABP and the HBPM (136.7±16.1). Coefficients of correlation were slightly lower for systolic awake ABP versus AOBP (
r
=0.54) compared with HBPM (
r
=0.60). Coefficients of variation for AOBP (12.0%) and HBPM (11.8%) and variances between AOBP and HBPM were similar. Of the 139 patients with hypertension as defined by a manual office systolic BP ≥140 mm Hg, variability in BP readings as determined by the SDs of the mean difference versus awake ABP were similar (
P
=0.56) for AOBP (14.6) and HBPM (13.9). Overall, both systolic AOBP and HBPM exhibited a similar degree of variability as assessed by the various methods.
Leveraging the Electronic Health Records for Population Health: A Case Study of Patients With Markedly Elevated Blood Pressure
Authors: Lu Yuan , Huang Chenxi , Mahajan Shiwani , Schulz Wade L. , Nasir Khurram , Spatz Erica S. , Krumholz Harlan M.
Published: March 2020

Background

The digital transformation of medical data provides opportunities to perform digital population health surveillance and identify people inadequately managed in usual care. We leveraged the electronic health records of a large health system to identify patients with markedly elevated blood pressure and characterize their follow‐up care pattern.

Methods and Results

We included 373 861 patients aged 18 to 85 years, who had at least 1 outpatient encounter in the Yale New Haven Health System between January 2013 and December 2017. We described the prevalence and follow‐up pattern of patients with at least 1 systolic blood pressure (
SBP
) ≥160 mm Hg or diastolic blood pressure (
DBP
) ≥100 mm Hg and patients with at least 1
SBP
≥180 mm Hg or
DBP
≥120 mm Hg. Of 373 861 patients included, 56 909 (15.2%) had at least 1
SBP
≥160 mm Hg or
DBP
≥100 mm Hg, and 10 476 (2.8%) had at least 1
SBP
≥180 mm Hg or
DBP
≥120 mm Hg. Among patients with
SBP
≥160 mm Hg or
DBP
≥100 mm Hg, only 28.3% had a follow visit within 1 month (time window of follow‐up recommended by the guideline) and 19.9% subsequently achieved control targets (
SBP
<130 mm Hg and
DBP
<80 mm Hg) within 6 months. Follow‐up rate at 1 month and control rate at 6 months for patients with
SBP
≥180 mm Hg or
DBP
≥120 mm Hg was 31.9% and 17.2%.

Conclusions

Digital population health surveillance with an electronic health record identified a large number of patients with markedly elevated blood pressure and inadequate follow‐up. Many of these patients subsequently failed to achieve control targets.
Subarachnoid Extension Predicts Lobar Intracerebral Hemorrhage Expansion
Authors: Morotti Andrea , Poli Loris , Leuci Eleonora , Mazzacane Federico , Costa Paolo , De Giuli Valeria , Candeloro Elisa , Busto Giorgio , Casetta Ilaria , Micieli Giuseppe , Cavallini Anna , Gamba Massimo , Magoni Mauro , Padovani Alessandro , Pezzini Alessandro , Fainardi Enrico
Published: March 2020

Background and Purpose—

We investigated whether subarachnoid extension (SAHE) of intracerebral hemorrhage (ICH) is associated with hematoma expansion (HE).

Methods—

Retrospective analysis of patients with primary spontaneous ICH admitted at 3 academic hospitals in Italy. The study population was divided into a development and a replication cohort. SAHE was rated on baseline noncontrast computed tomography by investigators blinded to clinical data. The main outcome of interest was HE, defined as ICH growth >33% mL and/or >6 mL. Predictors of HE were explored with multivariable logistic regression stratified by ICH location (lobar versus nonlobar).

Results—

A total of 360 and 192 patients were included in the development and replication cohort, respectively. SAHE was identified with good interrater reliability (
K
=0.82), and its frequency was 27.8% in the development and 24.5% in the replication cohort. In univariate analysis, HE was more common in patients with SAHE (52.0% versus 27.3%;
P
<0.001). When controlling for confounders in logistic regression, SAHE was an independent predictor of lobar HE (odds ratio, 6.00 [95% CI, 2.16–16.64];
P
=0.001) whereas there was no association with HE in nonlobar ICH (odds ratio, 0.55 [95% CI, 0.17–1.84];
P
=0.334). The increased risk of HE in lobar ICH with SAHE was confirmed in the replication cohort (odds ratio, 3.46 [95% CI, 1.07–11.20];
P
=0.038).

Conclusions—

SAHE predicts HE in lobar ICH. This may improve the stratification of HE risk in clinical practice or future trials targeting HE. Further research is needed to confirm our findings and characterize the underlying biological mechanisms.
Unsupervised Word Translation with Adversarial Autoencoder
Authors: Mohiuddin Tasnim , Joty Shafiq
Published: March 2020

Crosslingual word embeddings learned from monolingual embeddings have a crucial role in many downstream tasks, ranging from machine translation to transfer learning. Adversarial training has shown impressive success in learning crosslingual embeddings and the associated word translation task without any parallel data by mapping monolingual embeddings to a shared space. However, recent work has shown superior performance for non-adversarial methods in more challenging language pairs. In this article, we investigate adversarial autoencoder for unsupervised word translation and propose two novel extensions to it that yield more stable training and improved results. Our method includes regularization terms to enforce cycle consistency and input reconstruction, and puts the target encoders as an adversary against the corresponding discriminator. We use two types of refinement procedures sequentially after obtaining the trained encoders and mappings from the adversarial training, namely, refinement with Procrustes solution and refinement with symmetric re-weighting. Extensive experimentations with high- and low-resource languages from two different data sets show that our method achieves better performance than existing adversarial and non-adversarial approaches and is also competitive with the supervised system. Along with performing comprehensive ablation studies to understand the contribution of different components of our adversarial model, we also conduct a thorough analysis of the refinement procedures to understand their effects.
LessLex: Linking Multilingual Embeddings to SenSe Representations of LEXical Items
Authors: Colla Davide , Mensa Enrico , Radicioni Daniele P.
Published: March 2020

We present LESSLEX, a novel multilingual lexical resource. Different from the vast majority of existing approaches, we ground our embeddings on a sense inventory made available from the BabelNet semantic network. In this setting, multilingual access is governed by the mapping of terms onto their underlying sense descriptions, such that all vectors co-exist in the same semantic space. As a result, for each term we have thus the “blended” terminological vector along with those describing all senses associated to that term. LESSLEX has been tested on three tasks relevant to lexical semantics: conceptual similarity, contextual similarity, and semantic text similarity. We experimented over the principal data sets for such tasks in their multilingual and crosslingual variants, improving on or closely approaching state-of-the-art results. We conclude by arguing that LESSLEX vectors may be relevant for practical applications and for research on conceptual and lexical access and competence.
A Systematic Study of Inner-Attention-Based Sentence Representations in Multilingual Neural Machine Translation
Authors: Vázquez Raúl , Raganato Alessandro , Creutz Mathias , Tiedemann Jörg
Published: March 2020

Neural machine translation has considerably improved the quality of automatic translations by learning good representations of input sentences. In this article, we explore a multilingual translation model capable of producing fixed-size sentence representations by incorporating an intermediate crosslingual shared layer, which we refer to as attention bridge. This layer exploits the semantics from each language and develops into a language-agnostic meaning representation that can be efficiently used for transfer learning. We systematically study the impact of the size of the attention bridge and the effect of including additional languages in the model. In contrast to related previous work, we demonstrate that there is no conflict between translation performance and the use of sentence representations in downstream tasks. In particular, we show that larger intermediate layers not only improve translation quality, especially for long sentences, but also push the accuracy of trainable classification tasks. Nevertheless, shorter representations lead to increased compression that is beneficial in non-trainable similarity tasks. Similarly, we show that trainable downstream tasks benefit from multilingual models, whereas additional language signals do not improve performance in non-trainable benchmarks. This is an important insight that helps to properly design models for specific applications. Finally, we also include an in-depth analysis of the proposed attention bridge and its ability to encode linguistic properties. We carefully analyze the information that is captured by individual attention heads and identify interesting patterns that explain the performance of specific settings in linguistic probing tasks.
Who are the acknowledgees? An analysis of gender and academic status
Authors: Paul-Hus Adèle , Mongeon Philippe , Sainte-Marie Maxime , Larivière Vincent
Published: March 2020

Acknowledgements found in scholarly papers allow for credit attribution of nonauthor contributors. As such, they are associated with a different kind of recognition than authorship. While several studies have shown that social factors affect authorship and citation practices,few analyses have been performed on acknowledgements. Based on 878,250 acknowledgees mentioned in 291,167 papers published between 2015 and 2017, this study analyzes the gender and academic status of individuals named in the acknowledgements of scientific papers. Our results show that gender disparities generally found in authorship can be extended to acknowledgements, and that women are even more underrepresented in acknowledgements section than in authors’ lists. Our findings also show that women acknowledge proportionally more women than men do. Regarding academic status, our results show that acknowledgees who have already published tend to have a higher position in the academic hierarchy compared with all Web of Science (WoS) authors. Taken together, these findings suggest that acknowledgement practices might be associated with academic status and gender.
New records of Ichthyostraca Zrzavý, Hypša & Vlášková, 1997 (Pancrustacea) from Mexico with an annotated checklist of North America
Authors: LAGUNAS-CALVO OMAR , GARCÍA-PRIETO LUIS , OSORIO-SARABIA DAVID , LEÓN-RÈGAGNON VIRGINIA , OCEGUERA-FIGUEROA ALEJANDRO
Published: March 2020

In this work, we document for the first time four species of Ichthyostraca in Mexico, one Branchiura: Argulus foliaceus (fish parasite), and three Pentastomida: Porocephalus clavatus (reptile parasite), Raillietiella hebitihamata (reptile parasite) and Raillietiella orientalis (frog parasite). In addition, a total of 11 new host records and 16 new localities are presented for Ichthyostraca in Mexico. Based on the compilation of published information and on specimens deposited in scientific collections, the first checklist of Ichthyostraca from North America (Canada, United States of America and Mexico) is compiled. To March 2019, records of Ichthyostraca from North America include 64 species and 8 undetermined taxa, parasitizing 293 host species (64 of them identified only to a supra-specific level) in 77 provinces and states (8 from Canada, 47 from the USA, and 22 from Mexico). The subclass Branchiura is represented by 1 order, 1 family, 1 genus, 35 species and 1 undetermined taxa; the subclass Pentastomida includes records of 4 orders, 9 families, 14 genera, 29 species and 7 undetermined taxa. Ten species reported in this work are thought to be introduced into North America with only a few records of them parasitizing native hosts. This checklist summarizes the available records of this class of crustaceans in North America and represents a base line for future studies.
Scale insect genus names and their families in the scale insects (Hemiptera: Sternorrhyncha: Coccomorpha), a supplement
Authors: WILLIAMS DOUGLAS J. , DENNO BARBARA D.
Published: March 2020

A list of genus names in the scale insects published between 2014 and the end of 2019 is provided; it follows on from an earlier comprehensive list of the names published between 1758 and the end of 2013. Each genus name and its type species are assigned to one of the 53 scale insect families now recognised.
Genus Promalactis Meyrick, 1908 (Lepidoptera: Oecophoridae) from Malaysia, with description of three new species
Authors: LIU CHEN , WANG SHUXIA
Published: March 2020

Based on the specimens collected in Mt. Trusmadi, Sabah, Malaysia, three new species of the genus Promalactis are described: P. clavivalvata sp. nov., P. abasiloba sp. nov. and P. trusmadiensis sp. nov. In addition, females of three previously known species (P. folivalva Wang, 2018, P. sectoralis Wang et al., 2013 and P. trigonilobata Wang, 2018) are described for the first time. Two species (P. sectoralis Wang et al., 2013 and P. pileata Wang, 2019) are newly recorded for Malaysia. Images of both adults and genitalia of the new species and the genitalia of the newly described females are provided.
Hiding in plain sight: rediscovery and review of Parygrus Erichson, 1847, with description of five new species from the Neotropics (Coleoptera: Byrrhoidea: Dryopidae)
Authors: BARR CHERYL B. , SHEPARD WILLIAM D.
Published: March 2020

The history and original concept of Parygrus Erichson, 1847, is reviewed, the genus is redescribed, and the status of the type species, P. erichsoni Waterhouse, 1876, is clarified. The four original species are reviewed, with photographs provided for the type specimens of P. angustatus Grouvelle, 1896, P. elateroides Grouvelle, 1896, and P. erichsoni, and a non-type of P. parallelus (Grouvelle, 1890). The holotype of P. parallelus is apparently missing. The female holotype of P. erichsoni is redescribed. An associated male P. erichsoni specimen is compared with the holotype and the male genitalia are described and illustrated. General descriptions and provisional diagnoses are given for P. angustatus, P. elateroides and P. parallelus.  Five new species (P. guarani new species, P. lengua new species, P. maya new species, P. quechua new species, P. zamuco new species) are proposed, illustrated, and their geographic distributions mapped. For the first time, the male genitalia of Parygrus species are described and illustrated. A provisional key to the species and an updated key to the Neotropical genera of Dryopidae are provided.
Revision of Pseudastenus Bernhauer, synonym with Xenasterides Newton and six new species (Coleoptera, Staphylinidae, Paederinae)
Authors: BUSANELLO DILSON G. C. , IRMLER ULRICH , CARON EDILSON
Published: March 2020

The genus Xenasterides Newton, 2017 is considered here as a junior synonym of Pseudastenus Bernhauer, 1933, both monotypic and Neotropical genera of Paederinae (Staphylinidae). A thorough description of the genus is provided. The species Pseudastenus barretoi Bernhauer, 1933 and P. plaumanni (Bierig, 1939) are redescribed and illustrated, six new species are described, and a dichotomous key is available for species. These new species are: P. amazonicus, P. ferrugineus, P. latus, P. oculatus, P, ribeirocostae, and P. schubarti.
The taxonomic reassessment of a reportedly extinct bat, Pipistrellus sturdeei (Chiroptera: Vespertilionidae)
Authors: GÖRFÖL TAMÁS , FUKUI DAI , CSORBA GÁBOR
Published: March 2020

Insular bats are among the most vulnerable mammal species whose survival are threatened by several human-mediated factors, frequently paralleled by the paucity of information and lack of adequate management plans. Pipistrellus sturdeei is known only by the holotype collected from the remote Bonin Islands more than a hundred years ago and is declared to be extinct by the Japanese authorities. However, its taxonomic validity and collection locality is regarded ambiguous by some scholars. Here we report details about its collection circumstances and provide evidence that it morphologically differs from all other pipistrelles. We would like to raise attention on the species and the importance of a detailed study on its possible survival.
Pagastia (P.) donoliveri sp. nov.—a new Nearctic alpine stream chironomid species (Diptera: Chironomidae: Diamesinae) from the Beartooth Mountains, Wyoming, U.S.A.
Authors: MAKARCHENKO EUGENYI A. , HANSEN DEAN C.
Published: March 2020

An illustrated description of the adult male of Pagastia (P.) donoliveri sp. nov. from the Beartooth Mountains, Wyoming, of North America is provided. An updated key to the determination of all known Holarctic species of Pagastia Oliver for males is also provided.
Four Pieces on Repeal: Notes on Art, Aesthetics and the Struggle Against Ireland’s Abortion Law
Authors: Enright Máiréad
Published: March 2020

The Repeal campaign articulated new and transformative relationships between law, reproduction and the political in Ireland. During the campaign, ordinary people took ownership of and participated in mutual teaching and critique of law on a wide scale. Art, along these lines, was often used to document and archive the injustices worked by the 8th Amendment. However, art also became a means of imagining law otherwise. In this piece, I use Jacques Rancière’s work on the relationship between aesthetics and politics to analyse artistic contributions to feminist legal discourses associated with Repeal.
Broadening your horizon one day at a time: Relationship goals and exciting activities as daily antecedents of relational self-expansion
Authors: Harasymchuk Cheryl , Muise Amy , Bacev-Giles Chantal , Gere Judith , Impett Emily A.
Published: March 2020

Self-expansion in intimate relationships (i.e., broadening one’s perspective through engaging in novel, exciting activities with a partner) has been associated with relationship benefits. The goal of this study was to propose a motivational model of self-expansion to understand what prompts people to engage in self-expanding activities in their relationship on a daily basis. We hypothesized that when people report stronger daily approach relationship goals (i.e., goals focused on pursuing growth, intimacy, and rewards), they would report a greater likelihood of engaging in novel, exciting activities that enhance self-expansion and ultimately promote greater satisfaction in romantic relationships. To test our model, we recruited 122 couples for a 3-week daily diary study. In support of our hypotheses, on days when people (or their partners) reported higher than their usual approach relationship goals, they reported higher relational self-expansion, which was due, in part, to a greater likelihood of engaging in novel, exciting activities with the partner. In turn, higher relational self-expansion was associated with higher daily relationship satisfaction. Our findings have implications for understanding what promotes relationship growth on a day-to-day basis and the outcomes of daily approach-oriented relationship goals.
Systemic Amyloid A Amyloidosis in Stejneger’s Beaked Whales (Mesoplodon stejnegeri)
Authors: Nakagun Shotaro , Watanabe Kenichi , Tajima Yuko , Yamada Tadasu K. , Kobayashi Yoshiyasu
Published: March 2020

Stejneger’s beaked whales ( Mesoplodon stejnegeri) are one of the lesser known species of mammals, with little information available on their population status or incidence of diseases. Recent pathologic investigations on stranded and bycaught wild cetaceans around Hokkaido, Japan, revealed an unusually high incidence of systemic amyloidosis in this species, warranting further investigation. The objective of this study was to further characterize the systemic amyloidosis of Stejneger’s beaked whales by retrospective histopathologic analyses of tissues from animals that stranded in Japan between 1994 and 2018. Various tissues from 35 individuals were examined histologically with hematoxylin and eosin, Congo red, and immunohistochemistry for amyloid A (AA), in which 12 (34%) were diagnosed with systemic amyloidosis. The organs with the highest severity of amyloid deposition were the stomach and intestine. The type of amyloid was confirmed as AA of approximately 9 kDa by 2-dimensional gel electrophoresis with extracted amyloid from the liver and subsequent Western blotting with an antiserum against AA peptide. There were no statistically significant associations between amyloidosis and sex, body condition of the whales, or the presence of chronic inflammation. The high prevalence of this disease might be of concern for overall population numbers, and continued pathologic monitoring of stranded animals is necessary throughout its distributional range.
Augmentation of Tendon Graft–Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds
Authors: Wong Chin-Chean , Yeh Yi-Yen , Yang Tsung-Lin , Tsuang Yang-Hwei , Chen Chih-Hwa
Published: March 2020

Background:

Platelet-rich fibrin (PRF) is a bioactive biomaterial wherein cytokines are enmeshed within the interconnecting fibrin network. PRF can be fabricated into a patch to augment healing of the interface between a tendon graft and bone tunnel.

Hypothesis:

The bioactivity of a PRF scaffold is preserved after PRF is mechanically compressed into a patch. A bioactive PRF patch could promote the incorporation of a tendon graft within the bone tunnel through the formation of a tendon-bone healing zone composed of both fibrocartilaginous tissue and new bone.

Study Design:

Controlled laboratory study.

Methods:

Bioactivity of PRF was evaluated through treatment of rabbit tenocytes with PRF-conditioned medium and cultivation of cells on a PRF patch. Cellular morphologic features, viability, and differentiation were analyzed accordingly. In an animal study, a rabbit tendon-bone healing model was established through use of New Zealand White rabbits. The implanted tendon graft was enveloped circumferentially with a bioactive PRF patch before being pulled through a bone tunnel in the proximal tibia. Micro–computed tomography (micro-CT) imaging and histological and biomechanical analyses of the tendon-bone interface were performed at 12 weeks postoperatively.

Results:

PRF improved the viability of the cultured tenocytes. The effects of PRF on in vitro mineralization of tenocytes were comparable with the effects of standard culture medium. The gene expressions of type I collagen and osteopontin were upregulated upon PRF treatment. For the in vivo study, micro-CT images revealed significant new bone synthesis at the tendon-bone interface in the PRF-enveloped group. The tendon-bone healing zone was characterized by abundant fibrocartilage tissue and new bone formation as demonstrated by histological analysis. Biomechanical testing showed significantly higher ultimate loads in the PRF-enveloped group.

Conclusion:

Bioactive PRF could effectively augment healing of tendon graft to bone by inducing the formation of a transitional tendon-bone healing zone composed of fibrocartilage and bone.

Clinical Relevance:

Complete healing of the tendon graft in the bone tunnel is a prerequisite for successful ligament reconstruction, which would allow early and aggressive rehabilitation and rapid return to preinjury activity level. From a translational standpoint, the PRF-augmented healing in this rabbit animal model showed a promising biological approach to enhance tendon graft to bone healing via promotion of the functional anchorage between the 2 different materials.
A Promotor-Led Pilot Study to Increase Colorectal Cancer Screening in Latinos: The Juntos Contra El Cáncer Program
Authors: Arredondo Elva M. , Dumbauld Jill , Milla Maria , Madanat Hala , Coronado Gloria D. , Haughton Jessica , Garcia-Bigley Felipe , Ramers Christian , Nodora Jesse , Bharti Balambal , Lopez Gabriel , Diaz Mirna , Marquez Jessica , Gupta Samir
Published: March 2020

Background. Latinos have lower colorectal cancer (CRC) screening rates compared to other racial/ethnic groups in the United States, despite an overall increase in CRC screening over the past 10 years. To address this disparity, we implemented a promotor-led intervention to increase CRC screening test adherence in community-based settings, connecting community members with a partnering federally qualified health center. Purpose. To evaluate the Juntos Contra el Cáncer/Together Against Cancer (JUNTOS) intervention, by assessing pre–post changes in (1) CRC screening test adherence and (2) CRC knowledge and perceived barriers to CRC screening. We also assessed the feasibility and acceptability of program activities. Method. JUNTOS was a group-based intervention, delivered by promotores (community health workers), to promote CRC screening test adherence among Latino adults. The intervention consisted of a culturally tailored 2½-hour interactive workshop followed by an appointment scheduling assistance from a promotor. Workshop participants were Latino adults (males and females) aged 50 to 75 years who were not up-to-date with CRC screening guidelines. We conducted interviews before and 6 to 9 months after the workshop to assess program outcomes. Results. Of the 177 participants included, 118 reported completing the CRC screening test (66.7%) by 6 to 9 months postintervention. We observed baseline to 6- to 9-month increase in CRC knowledge and lower perceived barriers to obtaining CRC screening. Furthermore, the intervention was found to be feasible and acceptable. Conclusion. Results suggest that JUNTOS can be feasibly implemented in partnership with a federally qualified health center. The current study supports group-based CRC interventions in community and clinic settings.
Reanimating the Dark Knight: Superheroes, Animation and the Critical Reception ofThe Lego Batman Movie
Authors: Martin Daniel
Published: March 2020

This article explores the critical reception of The Lego Batman Movie (Chris McKay, 2017) in the context of Batman’s long history of multimedia storytelling, anchored to divergent parallel narratives across numerous platforms, and the ways the film appeals to nostalgia through metatextuality. The manner in which critics championed The Lego Batman Movie and derided the earlier live-action Batman v Superman: Dawn of Justice (Zack Snyder, 2016) gave rise to a complex discourse around the cultural value of animation and the larger blockbuster superhero cycle, and discussions of morality, merchandising and commercialism. This article therefore engages with questions of animation’s apparent suitability for particular kinds of child-centric narratives regarded by critics as a vital part of American popular culture.
Preparation of modified paints with nano-structured additives and its potential applications
Authors: Solano Ricardo , Patiño-Ruiz David , Herrera Adriana
Published: March 2020

Recently, an increase in the production of intelligent nanomaterials has been reported for the application of solid surface coating. These nanomaterials provide a wide number of functionalities such as anticorrosive, antibacterial, and self-cleaning properties. Hence, titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles were synthesized using a green chemistry approach. These nanoparticles were fully characterized by scanning electron microscopy, energy-dispersive X-ray, high-resolution transmission electron microscopy, X-ray diffraction, ultraviolet (UV)–visible spectroscopy, Brunauer–Emmett–Teller test, and nitrogen adsorption–desorption isotherm. Then, a commercial enamel-type paint was modified by using different concentrations (2, 3.5, and 5 w/v%) of nanoparticles. These nanofilled paints were then brushed onto the surface of different types of materials such as carbon steel sheets, wood sheets, and aluminum disks. Anticorrosive, self-cleaning, and antibacterial properties of the nanofilled paints were evaluated, with the aim to determine the capability for this application. According to the characterization results, TiO2 and ZnO nanoparticles exhibited similar physicochemical properties compared to those synthesized using traditional methods. The anticorrosion results revealed that nanofilled paints provide a barrier using low concentrations of nanoparticles, due to the decrease of agglomerates on the surface avoiding the presence of high porosity. In the case of self-cleaning, a proposed mechanism of degradation demonstrated that the presence of both nanoparticles in the paint provided high degradation of methylene blue due to the high surface area offered by the nanoparticles. On the other hand, antibacterial activity under UV light was observed only for ZnO nanoparticles, which may be related to the diffusion of nanoparticles into the cell membrane of the bacteria, affecting the normal function. These results showed to be promising for the modification of paints with TiO2 and ZnO nanoparticles, and the application on solid surfaces for the construction, and even in textile fields.
Clinical and biological implications of target occupancy in CLL treated with the BTK inhibitor acalabrutinib
Authors: Sun Clare , Nierman Pia , Kendall Ellen K. , Cheung Jean , Gulrajani Michael , Herman Sarah E. M. , Pleyer Christopher , Ahn Inhye E. , Stetler-Stevenson Maryalice , Yuan Constance M. , Maric Irina , Gaglione Erika M. , Harris Hailey M. , Pittaluga Stefania , Wang Min Hui , Patel Priti , Farooqui Mohammed Z. H. , Izumi Raquel , Hamdy Ahmed , Covey Todd , Wiestner Adrian
Published: March 2020

Inhibition of the B-cell receptor pathway, and specifically of Bruton tyrosine kinase (BTK), is a leading therapeutic strategy in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Target occupancy is a measure of covalent binding to BTK and has been applied as a pharmacodynamic parameter in clinical studies of BTK inhibitors. However, the kinetics of de novo BTK synthesis, which determines occupancy, and the relationship between occupancy, pathway inhibition and clinical outcomes remain undefined. This randomized phase 2 study investigated the safety, efficacy, and pharmacodynamics of a selective BTK inhibitor acalabrutinib at 100 mg twice daily (BID) or 200 mg once daily (QD) in 48 patients with relapsed/refractory or high-risk treatment-naïve CLL. Acalabrutinib was well tolerated and yielded an overall response rate (ORR) of partial response or better of 95.8% (95% confidence interval [CI], 78.9-99.9) and an estimated progression-free survival (PFS) rate at 24 months of 91.5% (95% CI, 70.0-97.8) with BID dosing and an ORR of 79.2% (95% CI, 57.9-92.9) and an estimated PFS rate at 24 months of 87.2% (95% CI, 57.2-96.7) with QD dosing. BTK resynthesis was faster in patients with CLL than in healthy volunteers. BID dosing maintained higher BTK occupancy and achieved more potent pathway inhibition compared with QD dosing. Small increments in occupancy attained by BID dosing relative to QD dosing compounded over time to augment downstream biological effects. The impact of BTK occupancy on long-term clinical outcomes remains to be determined. This trial was registered at www.clinicaltrials.gov as #NCT02337829.
Introduction to a How I Treat series on major complications after allogeneic stem cell transplantation
Authors: Zeiser Robert
Published: March 2020

In this commissioned series introduced by Associate Editor Robert Zeiser, experts contribute seminal discussions of the 3 major pitfalls following allogeneic stem cell transplantation. Through exploration of instructive real-world cases, they provide up-to-date personal recommendations for solving these common problems.
The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting
Authors: Juliusson Gunnar , Jädersten Martin , Deneberg Stefan , Lehmann Sören , Möllgård Lars , Wennström Lovisa , Antunovic Petar , Cammenga Jörg , Lorenz Fryderyk , Ölander Emma , Lazarevic Vladimir Lj , Höglund Martin
Published: March 2020

In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .0015]; NPM1mut: female, 36%; male, 27% [P = .0001]), and more males were double negative (female, 53%; male, 64%; P < .0001). Patients with FLT3ITD were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1mut (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3ITD indicated poor survival in younger patients (<60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1mut indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3ITD/NPM1mut patients, the survival was less dependent on age than in the other molecular subsets. These findings are likely to have clinical relevance for risk grouping, study design, and choice of therapy.
Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity
Authors: Abbeduto Leonard , Berry-Kravis Elizabeth , Sterling Audra , Sherman Stephanie , Edgin Jamie O. , McDuffie Andrea , Hoffmann Anne , Hamilton Debra , Nelson Michael , Aschkenasy Jeannie , Thurman Angela John
Published: March 2020

Background

The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status.

Methods

Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ< 70). ELS procedures for collecting samples in conversation and narration were followed and analyzed separately. Five measures were derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers): number of C-units per minute (talkativeness), number of different word roots (vocabulary), C-unit length in morphemes (syntax), percentage of C-units containing dysfluency (utterance planning), and percentage of C-units that were fully or partly unintelligible (articulatory quality). ELS procedures were administered twice at 4-week intervals for each participant. Standardized tests and informant reports were administered and provided measures for evaluating construct validity of ELS measures.

Results

We found low rates of noncompliance, suggesting the task can be completed meaningfully by most individuals with FXS, although noncompliance was higher for younger, lower IQ, and more autistic participants. Minimal practice effects and strong test-retest reliability over the 4-week interval were observed for the full sample and across the range of ages, IQs, and autism symptom severity. Evidence of convergent construct validity was observed for the measures of vocabulary, syntax, and unintelligibility for the full sample and across the range of IQ and autism symptom severity, but not for participants under age 12. Conversation and narration yielded largely similar results in all analyses.

Conclusions

The findings suggest that the ELS procedures are feasible and yield measures with adequate psychometric properties for a majority of 6 to 23 years with FXS who have ID. The procedures work equally well regardless of level of ID or degree of ASD severity. The procedures, however, are more challenging and have somewhat less adequate psychometric properties for individuals with FXS under age 12.
Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in congenital dyserythropoietic anemia type I disease
Authors: Swickley Grace , Bloch Yehoshua , Malka Lidor , Meiri Adi , Noy-Lotan Sharon , Yanai Amiel , Tamary Hannah , Motro Benny
Published: March 2020

Background

Congenital dyserythropoietic anemia type I (CDA I), is an autosomal recessive disease with macrocytic anemia in which erythroid precursors in the bone marrow exhibit pathognomonic abnormalities including spongy heterochromatin and chromatin bridges. We have shown previously that the gene mutated in CDA I encodes Codanin-1, a ubiquitously expressed and evolutionarily conserved large protein. Recently, an additional etiologic factor for CDA I was reported, C15Orf41, a predicted nuclease. Mutations in both CDAN1 and C15Orf41 genes results in very similar erythroid phenotype. However, the possible relationships between these two etiologic factors is not clear.

Results

We demonstrate here that Codanin-1 and C15Orf41 bind to each other, and that Codanin-1 stabilizes C15Orf41. C15Orf41 protein is mainly nuclear and Codanin-1 overexpression shifts it to the cytoplasm. Phylogenetic analyses demonstrated that even though Codanin-1 is an essential protein in mammals, it was lost from several diverse and unrelated animal taxa. Interestingly, C15Orf41 was eliminated in the exact same animal taxa. This is an extreme case of the Phylogenetic Profiling phenomenon, which strongly suggests common pathways for these two proteins. Lastly, as the 3D structure is more conserved through evolution than the protein sequence, we have used the Phyre2 alignment program to find structurally homologous proteins. We found that Codanin-1 is highly similar to CNOT1, a conserved protein which serves as a scaffold for proteins involved in mRNA stability and transcriptional control.

Conclusions

The physical interaction and the stabilization of C15Orf41 by Codanin-1, combined with the phylogenetic co-existence and co-loss of these two proteins during evolution, suggest that the major function of the presumptive scaffold protein, Codanin-1, is to regulate C15Orf41 activities. The similarity between Codanin-1 and CNOT1 suggest that Codanin-1 is involved in RNA metabolism and activity, and opens up a new avenue for the study of the molecular pathways affected in CDAI.
Stress-mediated convergence of splicing landscapes in male and female rock doves
Authors: Lang Andrew S. , Austin Suzanne H. , Harris Rayna M. , Calisi Rebecca M. , MacManes Matthew D.
Published: March 2020

Background

The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.

Results

This study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, after subjecting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3’UTR (untranslated region) end of transcripts than the 5’UTR or coding regions.

Conclusions

Our results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.
Identification of microRNAs and their Endonucleolytic Cleavaged target mRNAs in colorectal cancer
Authors: Zhou Fangbin , Tang Donge , Xu Yong , He Huiyan , Wu Yan , Lin Liewen , Dong Jun , Tan Wenyong , Dai Yong
Published: March 2020

Background

Colorectal cancer (CRC) ranks the third among the most common malignancies globally. It is well known that microRNAs (miRNAs) play vital roles in destabilizing mRNAs and repressing their translations in this disease. However, the mechanism of miRNA-induced mRNA cleavage remains to be investigated.

Method

In this study, high-throughput small RNA (sRNA) sequencing was utilized to identify and profile miRNAs from six pairs of colorectal cancer tissues (CTs) and adjacent tissues (CNs). Degradome sequencing (DS) was employed to detect the cleaved target genes. The Database for Annotation, Visualization and Integrated Discovery (DAVID) software was used for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis.

Results

In total, 1278 known miRNAs (clustered into 337 families) and 131 novel miRNAs were characterized in the CT and CN libraries, respectively. Of those, 420 known and eight novel miRNAs were defined as differentially expressed miRNAs (DEmiRNAs) by comparing the expression levels observed in the CT and CN libraries. Furthermore, through DS, 9685 and 202 potential target transcripts were characterized as target genes for 268 known and 33 novel miRNAs, respectively. It was further predicted that a total of 264 targeted genes for the 85 DEmiRNAs are involved in proteoglycans in cancer and the AMP-activated protein kinase signaling pathway. After systemic analysis of prognosis-related miRNA targets in those cancer-related signal pathways, we found that two targets ezrin (EZR) and hematopoietic cell-specific Lyn substrate 1 (HCLS1) had the potential prognostic characteristics with CRC regarding over survival (OS) or recurrence.

Conclusion

In total, we found that endonucleolytic miRNA-directed mRNA cleavage occurs in CRC. A number of potential genes targeted by CRC-related miRNAs were identified and some may have the potential as prognosis markers of CRC. The present findings may lead to an improved better appreciation of the novel interaction mode between miRNAs and target genes in CRC.