bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection
Authors: Jiang Guochun , Santos Rocha Clarissa , Hirao Lauren A. , Mendes Erica A. , Tang Yuyang , Thompson George R. , Wong Joseph K. , Dandekar Satya 
Published: May 2017

ABSTRACT

Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4
+
T cell cultures
in vitro
and a simian immunodeficiency virus (SIV) model of AIDS
in vivo
. Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4
+
T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV
in vitro
as well as
ex vivo
in the primary CD4
+
T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.

IMPORTANCE
Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and treatment strategies. Most investigations focused on the viral pathogenic mechanisms leading to immune dysfunction following robust viral infection and dissemination. Less is known about mechanisms that enable HIV to establish its presence despite rapid onset of host antiviral innate response. Our novel findings provide insights into the viral strategy that hijacks the host innate response of the suppression of protein biosynthesis to restrict the virus production. The virus leverages transcription factor ATF4 expression during the GCN2-ATF4 signaling response and utilizes it to activate viral transcription through the LTR to support viral transcription and production in both HIV and SIV infections. This unique viral strategy is exploiting the innate response and is distinct from the mechanisms of immune dysfunction after the critical mass of viral loads is generated.
Chlamydia
Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning
Authors: Wesolowski Jordan , Weber Mary M. , Nawrotek Agata , Dooley Cheryl A. , Calderon Mike , St. Croix Claudette M. , Hackstadt Ted , Cherfils Jacqueline , Paumet Fabienne 
Published: May 2017

ABSTRACT

The intracellular bacterium
Chlamydia trachomatis
develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which
Chlamydia
coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified
Chlamydia
strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that
Chlamydia
uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion.

IMPORTANCE
Chlamydia trachomatis
is an important cause of morbidity and a significant economic burden in the world. However, how
Chlamydia
develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered
Chlamydia
mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that
Chlamydia trachomatis
hijacks this novel function of ARF to reposition the Golgi complex.
Invasive meningococcal disease in the Veneto region of Italy: a capture-recapture analysis for assessing the effectiveness of an integrated surveillance system
Authors: Baldovin Tatjana , Lazzari Roberta , Cocchio Silvia , Furlan Patrizia , Bertoncello Chiara , Saia Mario , Russo Francesca , Baldo Vincenzo 
Published: May 2017

BackgroundEpidemiology ofNeisseria meningitidishas been changing since the introduction of universal vaccination programmes against meningococcal serogroup C (MenC) and meningococcal serogroup B (MenB) has now become dominant. This study aimed to analyse the cases reported in institutional data recording systems to estimate the burden of invasive meningococcal diseases (IMDs) and assess the effectiveness of surveillance in Veneto region (Italy).MethodsAnalysis was performed from 2007 to 2014 on data recorded in different systems: Mandatory Notification System, National Surveillance of Invasive Bacterial Diseases System and Laboratories Surveillance System (LSS), which were pooled into a combined surveillance system (CSS) and hospital discharge records (HDRs). A capture-recapture method was used and completeness of each source estimated. Number of cases with IMD by source of information and year, incidence of IMD by age group, case fatality rate (CFR) and distribution of meningococcal serogroups by year were also analysed.ResultsCombining the four data systems enabled the identification of 179 confirmed cases with IMD, achieving an overall sensitivity of 94.7% (95% CI: 90.8% to 98.8%), while it was 76.7% (95% CI: 73.6% to 80.1%) for CSS and 77.2% (95% CI: 74.1% to 80.6%) for HDRs. Typing of isolates was done in 80% of cases, and 95.2% of the typed cases were provided by LSS. Serogroup B was confirmed in 50.3% of cases. The estimated IMD notification rate (cases with IMD diagnosed and reported to the surveillance systems) was 0.48/100 000 population, and incidence peaked at 6.2/100 000 in children aged <1 year old (60.9% due to MenB), and increased slightly in the age group between 15 and 19 years (1.1/100 000). A CFR of 14% was recorded (8.7% in paediatric age).ConclusionsQuality of surveillance systems relies on case ascertainment based on serological characterisation of the circulating strains by microbiology laboratories. All available sources should be routinely combined to improve the epidemiology of IMD and the information used by public health departments to conduct timely preventive measures.
Characteristics associated with requests by pathologists for second opinions on breast biopsies
Authors: Geller Berta M , Nelson Heidi D , Weaver Donald L , Frederick Paul D , Allison Kimberly H , Onega Tracy , Carney Patricia A , Tosteson Anna N A , Elmore Joann G 
Published: May 2017

AimsSecond opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests.MethodsCollected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations.Results115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses.ConclusionsPathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions.
Coronary Artery Calcium and Risk of Dementia in MESA (Multi-Ethnic Study of Atherosclerosis)
Authors: Fujiyoshi Akira , Jacobs David R. , Fitzpatrick Annette L. , Alonso Alvaro , Duprez Daniel A. , Sharrett A. Richey , Seeman Teresa , Blaha Michael J. , Luchsinger José A. , Rapp Stephen R. 
Published: May 2017

Background—
Studies suggest a link between vascular injuries and dementia. Only a few studies, however, examined a longitudinal relation of subclinical vascular disease with dementia. We tested whether baseline coronary artery calcium (CAC), a biomarker of subclinical vascular disease, is associated with incident dementia independent of vascular risk factors and APOE-ε4 genotype in a community-based sample.

Methods and Results—

We analyzed 6293 participants of MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years at baseline (2000–2002), initially free of cardiovascular disease and noticeable cognitive deficit. Dementia cases were identified using hospital and death certificate International Statistical Classification of Diseases and Related Health Problems codes. Cox models were used to obtain hazard ratios according to CAC category, or per 1 SD log2[CAC+1], adjusted for vascular risk factor, APOE-ε4, with or without exclusion of interim stroke or cardiovascular disease. We observed 271 dementia cases in a median follow-up of 12.2 years. Baseline CAC had a graded positive association with dementia risk. Compared with no CAC, CAC score of 1 to 400, 401 to 1000, and ≥1001 had increased risk of dementia by 23%, 35%, and 71%, respectively, (
P
trend
=0.026) after adjustment. 1 SD higher log2[CAC+1] was associated with 24% (95% confidence interval, 8%–41%;
P
=0.002) increase in dementia risk. Although the association was partially explained by interim stroke/cardiovascular disease, it remained significant even after excluding the interim events, or regardless of baseline age.

Conclusions—
Higher baseline CAC was significantly associated with increased risk of dementia independent of vascular risk factor, APOE-ε4, and incident stroke. This is consistent with a hypothesis that vascular injuries play a role in the development of dementia.
Thirty-Day Readmissions After Endovascular or Surgical Therapy for Critical Limb Ischemia
Authors: Kolte Dhaval , Kennedy Kevin F. , Shishehbor Mehdi H. , Abbott J. Dawn , Khera Sahil , Soukas Peter , Mamdani Shafiq T. , Hyder Omar N. , Drachman Douglas E. , Aronow Herbert D. 
Published: May 2017

Background:
Thirty-day readmission rates have gained increasing importance as a key quality metric. A significant number of patients are hospitalized for the management of critical limb ischemia (CLI), but limited data are available on the incidence, predictors, and causes of 30-day readmission after hospitalization for CLI.

Methods:
Hospitalizations for a primary diagnosis of CLI during which patients underwent endovascular or surgical therapy (revascularization and/or amputation) and were discharged alive were identified in the 2013 to 2014 Nationwide Readmissions Databases. Incidence, reasons, and costs of 30-day unplanned readmissions were determined. Hierarchical logistic regression models were used to identify independent predictors of 30-day readmissions.

Results:
We included 60 998 (national estimate, 135 110) index CLI hospitalizations (mean age, 68.9±11.9 years; 40.8% women; 24.6% for rest pain, 37.2% for ulcer, and 38.2% for gangrene). The 30-day readmission rate was 20.4%. Presentation with ulcer or gangrene, age ≥65 years, female sex, large hospital size, teaching hospital status, known coronary artery disease, heart failure, diabetes mellitus, chronic kidney disease, anemia, coagulopathy, obesity, major bleeding, acute myocardial infarction, vascular complications, and sepsis were identified as independent predictors of 30-day readmission. Mode of revascularization was not independently associated with readmissions. Infections (23.5%), persistent or recurrent manifestations of peripheral artery disease (22.2%), cardiac conditions (11.4%), procedural complications (11.0%), and endocrine issues (5.7%) were the most common reasons for readmission. The inflation-adjusted aggregate costs of 30-day readmissions for CLI during the study period were $624 million.

Conclusions:
Approximately 1 in 5 patients hospitalized for CLI and undergoing revascularization is readmitted within 30 days. Risk of readmission is influenced by CLI presentation, patient demographics, comorbidities, and in-hospital complications, but not by the mode of revascularization.
Million Hearts: Description of the National Surveillance and Modeling Methodology Used to Monitor the Number of Cardiovascular Events Prevented During 2012–2016
Authors: Ritchey Matthew D. , Loustalot Fleetwood , Wall Hilary K. , Steiner Claudia A. , Gillespie Cathleen , George Mary G. , Wright Janet S. 
Published: May 2017

Background
This study describes the national surveillance and modeling methodology developed to monitor achievement of the Million Hearts initiative's aim of preventing 1 million acute myocardial infarctions, strokes, and other related cardiovascular events during 2012–2016.

Methods and Results

We calculate sex‐ and age‐specific cardiovascular event rates (combination of emergency department, hospitalization, and death events) among
US
adults aged ≥18 from 2006 to 2011 and, based on log‐linear models fitted to the rates, calculate their annual percent change. We describe 2 baseline strategies to be used to compare observed versus expected event totals during 2012–2016: (1)
stable baselines
assume no rate changes, with modeled 2011 rates held constant through 2016; and (2)
trend baselines
assume 2006–2011 rate trends will continue, with the annual percent changes applied to the modeled 2011 rates to calculate expected 2012–2016 rates. Events prevented estimates during 2012–2013 were calculated using available data: 115 210 (95%
CI
, 60 858, 169 562) events were prevented using stable baselines and an excess of 43 934 (95%
CI
, −14 264, 102 132) events occurred using trend baselines. Women aged ≥75 had the most events prevented (stable, 76 242 [42 067, 110 417]; trend, 39 049 [1901, 76 197]). Men aged 45 to 64 had the greatest number of excess events (stable, 22 912 [95%
CI
, 855, 44 969]; trend, 38 810 [95%
CI
, 15 567, 62 053]).

Conclusions
Around 115 000 events were prevented during the initiative's first 2 years compared with what would have occurred had 2011 rates remained stable. Recent flattening or reversals in some event rate trends were observed supporting intensifying national action to prevent cardiovascular events.
A View of Tropical Cyclones from Above: The Tropical Cyclone Intensity Experiment
Authors: Doyle James D. , Moskaitis Jonathan R. , Feldmeier Joel W. , Ferek Ronald J. , Beaubien Mark , Bell Michael M. , Cecil Daniel L. , Creasey Robert L. , Duran Patrick , Elsberry Russell L. , Komaromi William A. , Molinari John , Ryglicki David R. , Stern Daniel P. , Velden Christopher S. , Wang Xuguang , Allen Todd , Barrett Bradford S. , Black Peter G. , Dunion Jason P. , Emanuel Kerry A. , Harr Patrick A. , Harrison Lee , Hendricks Eric A. , Herndon Derrick , Jeffries William Q. , Majumdar Sharanya J. , Moore James A. , Pu Zhaoxia , Rogers Robert F. , Sanabia Elizabeth R. , Tripoli Gregory J. , Zhang Da-Lin 
Published: May 2017

AbstractTropical cyclone (TC) outflow and its relationship to TC intensity change and structure were investigated in the Office of Naval Research Tropical Cyclone Intensity (TCI) field program during 2015 using dropsondes deployed from the innovative new High-Definition Sounding System (HDSS) and remotely sensed observations from the Hurricane Imaging Radiometer (HIRAD), both on board the NASA WB-57 that flew in the lower stratosphere. Three noteworthy hurricanes were intensively observed with unprecedented horizontal resolution: Joaquin in the Atlantic and Marty and Patricia in the eastern North Pacific. Nearly 800 dropsondes were deployed from the WB-57 flight level of ∼60,000 ft (∼18 km), recording atmospheric conditions from the lower stratosphere to the surface, while HIRAD measured the surface winds in a 50-km-wide swath with a horizontal resolution of 2 km. Dropsonde transects with 4–10-km spacing through the inner cores of Hurricanes Patricia, Joaquin, and Marty depict the large horizontal and vertical gradients in winds and thermodynamic properties. An innovative technique utilizing GPS positions of the HDSS reveals the vortex tilt in detail not possible before. In four TCI flights over Joaquin, systematic measurements of a major hurricane’s outflow layer were made at high spatial resolution for the first time. Dropsondes deployed at 4-km intervals as the WB-57 flew over the center of Hurricane Patricia reveal in unprecedented detail the inner-core structure and upper-tropospheric outflow associated with this historic hurricane. Analyses and numerical modeling studies are in progress to understand and predict the complex factors that influenced Joaquin’s and Patricia’s unusual intensity changes.
Large-Eddy Simulation of a Katabatic Jet along a Convexly Curved Slope. Part I: Statistical Results
Authors: Brun Christophe , Blein Sébastien , Chollet Jean-Pierre 
Published: May 2017

Abstract
Large-eddy simulation is performed to study a katabatic jet along a convexly curved slope with a maximum angle of about 35.5°. The design of this numerical simulation of turbulent shear flow is discussed, and a qualitative assessment of the method is proposed. The katabatic flow is artificially generated by ground surface cooling, and a stable atmospheric boundary layer with constant stratification is considered as a reference state. A quantitative statistical analysis is used to describe the present turbulent flow, with a focus on the outer-layer shear of the katabatic jet, which extends about 50 m above the jet maximum. The Prandtl model for a katabatic jet is applied to the present results, and revisited versions of the model found in the literature are discussed, with an emphasis on specific momentum and turbulent heat diffusion. The vertical and downslope variability of the turbulent kinetic energy budget is also discussed, and it is shown that advection and production contributions in the downslope direction are far from negligible in katabatic flows along curved slopes. A specific effect that the convex curvature has on the katabatic jet is one of centrifugal deceleration and an increase of the flow’s turbulent production and turbulent intensity in the outer-layer shear. A strong thickening of the outer layer is also observed.
Supporting scholarly identity and practice: Narratives of occupational therapy academics
Authors: Carra Kylie A , Fortune Tracy , Ennals Priscilla , D’Cruz Kate , Kohn Hilarie 
Published: May 2017

Introduction Internationally, an increasing number of occupational therapists are making the transition from clinical practice to academia. Many make this transition with strong practitioner identities, limited academic skills, and inadequate preparation for a competitive academic environment. A group of 13 Australian occupational therapy academics participated in blogs as part of a 12-month action research project, with the aim of being and becoming more scholarly academics. Method Throughout an action research project titled Growing Scholarship, co-participants/researchers participated in a closed blog for sharing experiences of being and becoming more scholarly academics. In the present study, qualitative data from the blogs were analysed through an iterative and inductive process and themes generated by the research team. Findings Constructing and reconstructing identity emerged as a key theme during analysis of the blogs, with the sub-themes striving to reach one’s potential and growing through collaboration and support emphasising the significance of individual and macro factors in shaping academic identity formation. Conclusion This study demonstrated how the occupation of blogging can be used to support the scholarly identity and practice of occupational therapy academics. Other professionals facing change and uncertainty in the workplace could consider a similar approach to support the process of identity reconstruction.
Clinical Observations with Frenquel in Chronic Schizophrenia
Authors: Lindan O. , Cahn C. H. , Lehmann H. E. 
Published: May 2017

Twenty-four hallucinated patients who had been hospitalized for schizophrenia for over 5 years were treated with Frenquel for 1 to 2 months; none of these showed any distinct improvement neither with regard to hallucinations nor any other symptoms. Our results are compared and contrasted with those reported in 3 other publications on Frenquel.