bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Nervous System Lymphoma
Authors: Correia Carlos Eduardo , Schaff Lauren R. , Grommes Christian 
Published: June 2020

Abstract
Central nervous system lymphoma (CNSL) is a rare form of extranodal non-Hodgkin lymphoma. Central nervous system lymphoma can be primary (isolated to the central nervous space) or secondary in the setting of systemic disease. Treatment of CNSL has improved since the introduction of high-dose methotrexate and aggressive consolidation regimens. However, results after treatment are durable in only half of patients, and long-term survivors may experience late neurotoxicity, impacting quality of life. Given the rarity of this disease, few randomized prospective trials exist. This leaves many questions unanswered regarding optimal first-line and salvage treatments. Recent advances in the knowledge of pathophysiology of CNSL will hopefully help the development of future treatments. This review gives an overview of the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of immunocompetent patients with CNSL.
Molecular Classification and Treatment of Diffuse Large B-Cell Lymphoma and Primary Mediastinal B-Cell Lymphoma
Authors: Roschewski Mark , Phelan James D. , Wilson Wyndham H. 
Published: June 2020

Abstract
Diffuse large B-cell lymphoma (DLBCL) encompasses a group of aggressive B-cell non-Hodgkin lymphomas with striking genetic heterogeneity and variable clinical presentations. Among these is primary mediastinal B-cell lymphoma (PMBL), which has unique clinical and molecular features resembling Hodgkin lymphoma. Treatment of DLBCL is usually curative, but identifiable subsets at highest risk for treatment failure may benefit from intensified chemotherapy regimens and/or targeted agents added to frontline therapy. Recent comprehensive genomic analyses have identified distinct genetic subtypes of DLBCL with characteristic genetic drivers and signaling pathways that are targetable. Immune therapy with chimeric antigen receptor T cells and checkpoint inhibitors has revolutionized the treatment of relapsed or refractory disease, and antibody drug conjugates have weaponized otherwise intolerable cytotoxic agents. Ongoing clinical trials are further refining the specificity of these approaches in different genetic subtypes and moving them from the setting of recurrent disease to frontline treatment in high-risk patient populations.
Diagnosis, Risk Stratification, and Treatment of Peripheral T-Cell Lymphomas
Authors: Pearse William B. , Pro Barbara 
Published: June 2020

Abstract
Peripheral T-cell lymphomas represent an evolving class of aggressive T-cell malignancies that are generally refractory to conventional treatments and historically carry a poor prognosis. Recent advances in gene expression profiling have begun to unravel the specific molecular mechanisms of tumorigenesis in these disease processes, allowing for discrete classification schemes that help guide discussions regarding prognosis and therapy options. We outline here a review of the histopathology, epidemiology, clinical features, and treatment strategies currently used in the management of these diseases.
Individual-Level and Clinic-Level Factors Associated With Achieving Glycemic Control in a Large Cohort of People With HIV in Care-Washington, DC
Authors: Happ Lindsey Powers , Monroe Anne K. , Young Heather A. , Ma Yan , Greenberg Alan E. , Horberg Michael A. , Castel Amanda D. ,   on behalf of the DC Cohort Executive Committee
Published: June 2020

Background:
Optimal management of noncommunicable diseases, including diabetes mellitus (DM), is crucially important as people with HIV (PWH) live longer with antiretroviral therapy. Our objective was to assess patient-level and clinic-level factors associated with achieving hemoglobin A1c (HbA1c) ≤7.0% among PWH and DM.

Setting:
The DC Cohort, an observational clinical cohort of PWH, followed from 2011 to 2019 at 12 sites in Washington, DC.

Methods:
Among PWH with diagnosed DM and elevated HbA1c (>7.0%), we examined the association between achieving HbA1c ≤7.0% and demographic and clinical factors, including time-updated medication data, and clinic-level factors related to services and structure. A multilevel marginal extended Cox regression model was generated to identify factors associated with time to HbA1c ≤7.0%.

Results:
Over half (52.3%) of 419 participants achieved HbA1c ≤7.0%. Individual-level factors associated with HbA1c ≤7.0% included a diagnosis of DM after enrollment and a longer time since HIV diagnosis [hazard ratio (HR) = 2.65 and 1.13, P < 0.05 for both]. Attending a clinic with an endocrinologist was associated with the outcome [adjusted HR (aHR) = 1.41 95% confidence interval (CI): (1.01 to 1.97)]. In addition, comparing clinics that treat everyone, refer everyone or have a mix of treating and referring, showed an association between attending a clinic that treats everyone [aHR = 1.52 95% CI: (1.21 to 1.90)] or a clinic that refers everyone [aHR = 2.24 95% CI: (1.63 to 3.07)] compared with clinics with a mix in achieving glycemic control.

Conclusion:
Multiple factors are associated with achieving glycemic control in an urban cohort of PWH. Determining if specific services or structures improve DM outcomes may improve health outcomes for PWH and DM.
Periodontitis and Cytomegalovirus Associate With Atherosclerosis Among HIV Patients After 5 Years on ART
Authors: Wulandari Endah A. T. , Wijaya Ika Prasetya , Karim Birry , Ariyanto Ibnu , Tanudjaja Selita Agnes , Lee Silvia , Price Patricia 
Published: June 2020

Objectives:
Atherosclerosis has been linked with periodontitis in the general population and with persistent immune activation and a high burden of cytomegalovirus (CMV) in HIV patients responding to antiretroviral therapy (ART). Here, we assess risk factors for cardiovascular changes in younger HIV patients representative of patient populations in Asia.

Study Design:
HIV-infected adults (n = 82) with <200 CD4 T-cells/μl were examined as they began ART at Cipto Mangunkusumo Hospital, Jakarta, and after 3 months. 32 patients were re-assessed after 5 years, alongside 32 age-matched healthy controls.

Methods:
We assessed the community periodontal index of treatment needs, carotid -thickness (cIMT), plasma markers of immune activation (using commercial enzyme-linked immunosorbent assay) and CMV antibodies by in-house enzyme-linked immunosorbent assay.

Results:
Periodontitis persisted in 16/32 patients after 5 years and was potentiated by greater age (P = 0.03) and poor oral hygiene (P = 0.05), with no effect of smoking, pulmonary tuberculosis, oral candidiasis, or low CD4+ T-cell counts (P > 0.05). After 5 years on ART, right and left cIMT were greater in HIV patients with periodontitis (P = 0.02, 0.006, respectively). Moreover, cIMT values were higher in patients with periodontitis (P = 0.05–0.01) than in equivalent controls. Simple linear regressions showed that patients with periodontitis had greater right (P = 0.01) and left (P = 0.004) cIMT than those without periodontitis. Multiple linear regressions showed that periodontitis and CMV antibody levels optimally predicted poor right and left cIMT (Adjusted R2 = 0.36, P = 0.0013; Adjusted R2 = 0.40, P = 0.001, respectively).

Conclusions:
Our data identify periodontitis and CMV as independent predictors of atherosclerosis in young adult HIV patients.
Brief Report: Vascular Dysfunction and Monocyte Activation Among Women With HIV
Authors: Toribio Mabel , Awadalla Magid , Cetlin Madeline , Fulda Evelynne S. , Stanley Takara L. , Drobni Zsofia D. , Szczepaniak Lidia S. , Nelson Michael D. , Jerosch-Herold Michael , Burdo Tricia H. , Neilan Tomas G. , Zanni Markella V. 
Published: June 2020

Objective:
Women with HIV (WHIV) on antiretroviral therapy (ART) face an increased risk of cardiovascular disease (CVD) in the context of heightened systemic immune activation. Aortic stiffness, a measure of vascular dysfunction and a robust predictor of CVD outcomes, is highly influenced by immune activation. We compared aortic stiffness among women with and without HIV and examined interrelationships between aortic stiffness and key indices of systemic immune activation.

Methods:
Twenty WHIV on ART and 14 women without HIV group-matched on age and body mass index (BMI) were prospectively recruited and underwent cardiovascular magnetic resonance imaging, as well as metabolic and immune phenotyping.

Results:
Age and BMI did not differ significantly across groups (age: 52 ± 4 vs. 53 ± 6 years; BMI: 32 ± 7 vs. 32 ± 7 kg/m2). Aortic pulse wave velocity (aPWV) was higher among WHIV (8.6 ± 1.3 vs. 6.5 ± 1.3 m/s, P < 0.0001), reflecting increased aortic stiffness. Among the whole group and among WHIV, aPWV related to sCD163 levels (whole group: R = 0.65, P < 0.0001; WHIV: R = 0.73, P = 0.0003) and to myocardial fibrosis (extracellular volume; whole group: R = 0.54, P = 0.001; WHIV: R = 0.47, P = 0.04). Both HIV status and sCD163 levels independently predicted aPWV, controlling for age, BMI, cigarette smoking status, and systolic blood pressure (HIV status: β-estimate = 0.69, 95% CI [0.1 to 1.3], P = 0.02; sCD163: β-estimate = 0.002, 95% CI [0.0006 to 0.004], P = 0.01). Among WHIV, sCD163 levels independently predicted aPWV, controlling for duration of HIV, CD4 count, and HIV viral load (sCD163: β-estimate = 0.004, 95% CI [0.002 to 0.005], P = 0.0005).

Conclusions:
Asymptomatic WHIV on ART have increased aortic stiffness as compared to matched control subjects. Among WHIV, aPWV related to heightened monocyte activation (sCD163) and to downstream CVD pathology (myocardial fibrosis).

ClinicalTrials.gov Registration:
NCT02874703.
Comparison of the Accuracy of Short Cognitive Screens Among Adults With Cognitive Complaints in Turkey
Authors: Varan Hacer D. , Kizilarslanoglu Muhammet C. , Balci Cafer , Deniz Olgun , Coteli Suheyla , Dogrul Rana T. , Aycicek Gozde S. , Kilic Mustafa K. , O’Caoimh Rónán , Molloy David William , Svendrovski Anton , Halil Meltem , Cankurtaran Mustafa , Goker Berna , Yavuz Burcu B. 
Published: June 2020

Background:
Cutoff values of cognitive screen tests vary according to age and educational levels.

Objective:
The objective of this study was to compare the accuracy and determine cutoffs for 3 short cognitive screening instruments: the Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), and Quick Mild Cognitive Impairment Screen-Turkish version (Qmci-TR), in older adults with low literacy in Turkey.

Methods:
In all 321 patients, 133 with subjective cognitive complaints (SCC), 88 amnestic-type mild cognitive impairment (aMCI), and 100 with probable Alzheimer disease (AD) with a median of 5 years education were included. Education and age-specific cutoffs were determined.

Results:
For the overall population, the Qmci-TR was more accurate than the MoCA in distinguishing between aMCI and AD (area under the curve=0.83 vs. 0.76, P=0.004) and the Qmci-TR and Mini-Mental State Examination were superior to the MoCA in discriminating SCC from aMCI and AD. All instruments had similar accuracy among those with low literacy (primary school and lower educational level or illiterate).

Conclusions:
To distinguish between SCC, aMCI, and AD in a sample of older Turkish adults, the Qmci-TR may be preferable. In very low literacy, the choice of the instrument appears less important.
Identification and characterization of a new soybean promoter induced byPhakopsora pachyrhizi, the causal agent of Asian soybean rust
Authors: Cabre Lisa , Peyrard Stephane , Sirven Catherine , Gilles Laurine , Pelissier Bernard , Ducerf Sophie , Poussereau Nathalie 
Published: June 2020

ABSTRACTBackgroundPhakopsora pachyrhiziis a biotrophic fungal pathogen responsible for the Asian soybean rust disease causing important yield losses in tropical and subtropical soybean-producing countries.P. pachyrhizitriggers important transcriptional changes in soybean plants during infection, with several hundreds of genes being either up- or downregulated.ResultsBased on published transcriptomic data, we identified a predicted chitinase gene, referred to asGmCHIT1, that was upregulated in the first hours of infection. We first confirmed this early induction and showed that this gene was expressed as early as 8 hours afterP. pachyrhizi inoculation. To investigate the promoter ofGmCHIT1, transgenic soybean plants expressing the green fluorescence protein (GFP) under the control of theGmCHIT1promoter were generated. Following inoculation of these transgenic plants withP. pachyrhizi, GFP fluorescence was detected in a limited area located around appressoria, the fungal penetration structures. Fluorescence was also observed after mechanical wounding whereas no variation in fluorescence of pGmCHIT1:GFP transgenic plants was detected after a treatment with an ethylene precursor or a methyl jasmonate analogue.ConclusionWe identified a soybean chitinase promoter exhibiting an early induction byP. pachyrhizilocated in the first infected soybean leaf cells. Our results on the induction ofGmCHIT1promoter byP. pachyrhizicontribute to the identification of a new pathogen inducible promoter in soybean and beyond to the development of a strategy for the Asian soybean rust disease control using biotechnological approaches.
The ontology of the anatomy and development of the solitary ascidianCiona
Authors: Hotta Kohji , Dauga Delphine , Manni Lucia 
Published: June 2020

AbstractCiona robusta(Ciona intestinalistype A), a model organism for biological studies, belongs to ascidians, the main class of tunicates, which are the closest relatives of vertebrates. InCiona, a project on the ontology of both development and anatomy is ongoing for several years. Its goal is to standardize a resource relating each anatomical structure to developmental stages. Today, the ontology is codified until the hatching larva stage. Here, we present its extension throughout the swimming larva stages, the metamorphosis, until the juvenile stages. For standardizing the developmental ontology, we acquired different time-lapse movies, confocal microscope images and histological serial section images for each developmental event from the hatching larva stage (17.5 hour post fertilization) to the juvenile stage (7 days post fertilization). Combining these data, we defined 12 new distinct developmental stages (from Stage 26 to Stage 37), in addition to the previously defined 26 stages, referred to embryonic development. The new stages were grouped into four Periods named: Adhesion, Tail Absorption, Body Axis Rotation, and Juvenile. To build the anatomical ontology, 203 anatomical entities were identified, defined according to the literature, and annotated, taking advantage from the high resolution and the complementary information obtained from confocal microscopy and histology. The ontology describes the anatomical entities in hierarchical levels, from the cell level (cell lineage) to the tissue/organ level. Comparing the number of entities during development, we found two rounds on entity increase: in addition to the one occurring after fertilization, there is a second one during the Body Axis Rotation Period, when juvenile structures appear. Vice versa, one-third of anatomical entities associated with the embryo/larval life were significantly reduced at the beginning of metamorphosis. Data was finally integrated within the web-based resource “TunicAnatO”, which includes a number of anatomical images and a dictionary with synonyms. This ontology will allow the standardization of data underpinning an accurate annotation of gene expression and the comprehension of mechanisms of differentiation. It will help in understanding the emergence of elaborated structures during both embryogenesis and metamorphosis, shedding light on tissue degeneration and differentiation occurring at metamorphosis.
Mucin-derivedO-glycans supplemented to diet mitigate diverse microbiota perturbations
Authors: Pruss K. M. , Marcobal A. , Southwick A.M. , Dahan D. , Smits S.A. , Ferreyra J.A. , Higginbottom S.K. , Sonnenburg E.D. , Kashyap P.C. , Choudhury B. , Bode L. , Sonnenburg J. L. 
Published: June 2020

AbstractMicrobiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins may serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally-administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purifiedO-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppressC. difficileabundance, delay the onset of diet-induced obesity, and increase relative abundance of residentAkkermansia muciniphila. In silicoanalysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout evolution of the host-microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.
A comparative study of supervised machine learning algorithms for the prediction of long-range chromatin interactions
Authors: Vanhaeren Thomas , Divina Federico , García-Torres Miguel , Gómez-Vela Francisco , Vanhoof Wim , Martínez García Pedro Manuel 
Published: June 2020

AbstractThe role of three-dimensional genome organization as a critical regulator of gene expression has become increasingly clear over the last decade. Most of our understanding of this association comes from the study of long range chromatin interaction maps provided by Chromatin Conformation Capture-based techniques, which have greatly improved in recent years. Since these procedures are experimentally laborious and expensive,in silicoprediction has emerged as an alternative strategy to generate virtual maps in cell types and conditions for which experimental data of chromatin interactions is not available. Several methods have been based on predictive models trained on one-dimensional (1D) sequencing features, yielding promising results. However, different approaches vary both in the way they model chromatin interactions and in the machine learning-based strategy they rely on, making it challenging to carry out performance comparison of existing methods. In this study, we use publicly available 1D sequencing signals to model chromatin interactions in two human cell lines and evaluate the prediction performance of 5 popular machine learning algorithms: decision trees, random forests, gradient boosting, support vector machines and multi-layer perceptron. Our approach accurately predicts long-range interactions and reveals that gradient boosting significantly outperforms the other four algorithms, yielding accuracies of ~ 95%. We show that chromatin features in close genomic proximity to the anchors cover most of the predictive information. Moreover, we demonstrate that gradient boosting models trained with different subsets of chromatin features, unlike the other methods tested, are able to produce accurate predictions. In this regard, and besides architectural proteins, transcription factors are shown to be highly informative. Our study provides a framework for the systematic prediction of long-range chromatin interactions, identifies gradient boosting as the best suited algorithm for this task and highlights cell-type specific binding of transcription factors at the anchors as important determinants of chromatin wiring.
Cytoplasmic accumulation of FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and defects in inhibitory synapses
Authors: Scekic-Zahirovic Jelena , Sanjuan-Ruiz Inmaculada , Kan Vanessa , Megat Salim , De Rossi Pierre , Dieterlé Stéphane , Cassel Raphaelle , Kessler Pascal , Wiesner Diana , Tzeplaeff Laura , Demais Valérie , Muller Hans-Peter , Picchiarelli Gina , Mishra Nibha , Dirrig-Grosch Sylvie , Kassubek Jan , Rasche Volker , Ludolph Albert , Boutillier Anne-Laurence , Polymenidou Magdalini , Lagier-Tourenne Clotilde , Liebscher Sabine , Dupuis Luc 
Published: June 2020

AbstractGene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS, lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, including locomotor hyperactivity and alterations in social interactions, in the absence of widespread neuronal loss. Mechanistically, we identified a profound increase in neuronal activity in the frontal cortex ofFusknock-in micein vivo. Importantly, RNAseq analysis suggested involvement of defects in inhibitory neurons, that was confirmed by ultrastructural and morphological defects of inhibitory synapses and increased synaptosomal levels of mRNAs involved in inhibitory neurotransmission. Thus, cytoplasmic FUS triggers inhibitory synaptic deficits, leading to increased neuronal activity and behavioral phenotypes. FUS mislocalization may trigger deleterious phenotypes beyond motor neuron impairment in ALS, but also in other neurodegenerative diseases with FUS mislocalization.
Taking Fright: The Decline of Australian Pied OystercatchersHaematopus longirostrisat South Ballina Beach, New South Wales
Authors: Totterman Stephen 
Published: June 2020

SUMMARYThis study reviewed data from the Richmond River Area Pied Oystercatcher Protection Program 1997–2013 and Richmond River Area Shorebird Protection Program 2014–2018, on the far north coast of the State of New South Wales (NSW), Australia. The Australian Pied OystercatcherHaematopus longirostrisbreeding population size for South Ballina Beach has decreased from 15–16 pairs in 1994–1996 to 7–9 pairs in 2016–2018. This is despite control of the European Red FoxVulpes vulpessuccessfully reducing depredation of eggs and chicks and > 207 oystercatchers fledging from beaches in the Richmond River area in 1997–2018. The negative trend for South Ballina is contrasted with the positive trend for Bombing Range Beach, where the population size has increased from 4–5 pairs in 2002–2004 to 8–9 pairs in 2016–2018. Vehicle-based recreation has increased at South Ballina in the past two decades versus Bombing Range has remained closed to the public. It is proposed that human recreation disturbance is preventing recruitment into the South Ballina oystercatcher breeding population. Without strong protection of habitat from such disturbance, the NSW oystercatcher breeding population size is predicted to continue to decrease.