bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection
Authors: Eller Michael A. , Goonetilleke Nilu , Tassaneetrithep Boonrat , Eller Leigh Anne , Costanzo Margaret C. , Johnson Susan , Betts Michael R. , Krebs Shelly J. , Slike Bonnie M. , Nitayaphan Sorachai , Rono Kathleen , Tovanabutra Sodsai , Maganga Lucas , Kibuuka Hannah , Jagodzinski Linda , Peel Sheila , Rolland Morgane , Marovich Mary A. , Kim Jerome H. , Michael Nelson L. , Robb Merlin L. , Streeck Hendrik 
Published: February 2016

ABSTRACT

Attrition within the CD4
+
T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8
+
T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8
+
T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38
+
CD27
−
CD8
+
T cells characterized by the low expression of the CD8 receptor (CD8
dim
). Interestingly, while high frequencies of HIV-specific CD8
+
T cell responses occur within the CD38
+
CD27
−
CD8
dim
T cell population, the minority populations of CD8
bright
T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8
dim
T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8
dim
T cells, and the size of this population inversely correlates with the acute loss of CD4
+
T cells. These data indicate, for the first time, that early CD4
+
T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8
dim
T cell population less efficient in controlling HIV viremia.

IMPORTANCE
A distinct population of activated CD8
+
T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8
+
T cell dysfunction during acute infection.
Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIV
SF162P3N
-Infected Macaques
Authors: Jia Manxue , Lu Hong , Markowitz Martin , Cheng-Mayer Cecilia , Wu Xueling 
Published: February 2016

ABSTRACT

To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIV
SF162P3N
and 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120-directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs.

IMPORTANCE
HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIV
SF162P3N
-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare, but their development might have been faster in some of the studied macaques. Plasma mapping with monomeric gp120 indicated that most bnAbs bind to the envelope trimer rather than the gp120 monomer. In support of this, none of the isolated gp120-reactive monoclonal antibodies (MAbs) displayed the neutralization breadth observed in the corresponding plasma. However, the MAb sequences revealed similarity between human and macaque genes used to encode some V3-directed MAbs. Our study sheds light on the timing and development of bnAbs in SHIV-infected macaques in comparison to HIV-1-infected humans and highlights the use of envelope trimer probes for efficient recovery of bnAbs.
Nuclear Translocation Sequence and Region in Autographa californica Multiple Nucleopolyhedrovirus ME53 That Are Important for Optimal Baculovirus Production
Authors: Liu Yang , de Jong Jondavid , Nagy Éva , Theilmann David A. , Krell Peter J. 
Published: February 2016

ABSTRACT

Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) is in the family
Baculoviridae
, genus
Alphabaculovirus
. AcMNPV
me53
is a highly conserved immediate early gene in all lepidopteran baculoviruses that have been sequenced and is transcribed up to late times postinfection. Although
me53
is not essential for viral DNA synthesis, infectious budded virus (BV) production is greatly attenuated when it is deleted. ME53 associates with the nucleocapsid on both budded virus and occlusion-derived virus, but not with the virus envelope. ME53 colocalizes in plasma membrane foci with the envelope glycoprotein GP64 in a GP64-dependent manner. ME53 localizes in the cytoplasm early postinfection, and despite the lack of a reported nuclear localization signal (NLS), ME53 translocates to the nucleus at late times postinfection. To map determinants of ME53 that facilitate its nuclear translocation, recombinant AcMNPV bacmids containing a series of ME53 truncations, internal deletions, and peptides fused with hemagglutinin (HA) or green fluorescent protein (GFP) tags were constructed. Intracellular-localization studies identified residues within amino acids 109 to 137 at the N terminus of ME53 that acted as the nuclear translocation sequence (NTS), facilitating its nuclear transport at late times postinfection. The first 100 N-terminal amino acids and the last 50 C-terminal amino acids of ME53 are dispensable for high levels of budded virus production. The region within amino acids 101 to 398, which also contains the NTS, is critical for optimal levels of budded virus production.

IMPORTANCE
Baculovirus
me53
is a conserved immediate early gene found in all sequenced lepidopteran alpha- and betabaculoviruses. We first identified residues within amino acids 109 to 137 at the N terminus that act as the ME53 nuclear translocation sequence (NTS) to facilitate its nuclear translocation and defined an internal region within amino acids 101 to 398, which includes the NTS, as being necessary for optimal budded virus production. Altogether, these results indicate a previously unidentified nuclear role that ME53 plays in virus replication.
Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection
Authors: Mäntylä Elina , Salokas Kari , Oittinen Mikko , Aho Vesa , Mäntysaari Pekka , Palmujoki Lassi , Kalliolinna Olli , Ihalainen Teemu O. , Niskanen Einari A. , Timonen Jussi , Viiri Keijo , Vihinen-Ranta Maija 
Published: February 2016

ABSTRACT

The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and
in situ
proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, the two viral promoters in particular were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitors efficiently interfered with the expression of viral proteins and infection progress. Altogether, our data suggest that the acetylation of histones on parvoviral DNA is essential for viral gene expression and the completion of the viral life cycle.

IMPORTANCE
Viral DNA introduced into cell nuclei is exposed to cellular responses to foreign DNA, including chromatinization and epigenetic silencing, both of which determine the outcome of infection. How the incoming parvovirus resists cellular epigenetic downregulation of its genes is not understood. Here, the critical role of epigenetic modifications in the regulation of parvovirus infection was demonstrated. We showed for the first time that a successful parvovirus infection is characterized by the deposition of nucleosomes with active histone acetylation on the viral promoter areas. The results provide new insights into the regulation of parvoviral gene expression, which is an important aspect of the development of parvovirus-based virotherapy.
Effects of aerobic and muscle strengthening exercise in adults with rheumatoid arthritis: a narrative review summarising a chapter inPhysical activity in the prevention and treatment of disease(FYSS 2016)
Authors: Swärdh E , Brodin N 
Published: February 2016

BackgroundBesides pharmacological treatment, regular exercise is one of the cornerstones of care in rheumatoid arthritis (RA). In many of the earlier studies of exercise in RA, the intensity of the exercise did not reach the current recommendations or is not described in satisfactory detail. This narrative review is based on randomised controlled trials with a detailed description of the exercise type, frequency, duration and intensity.ResultsThere is moderate-quality evidence that short-term land-based aerobic exercise of moderate to high intensity augments oxygen uptake but does not improve muscle strength. Short-term water-based aerobic exercise of moderate to high intensity augments oxygen uptake; short term land-based aerobic and muscle strengthening exercise of moderate to high intensity augments oxygen uptake and muscle strength. Long-term land-based aerobic and muscle strengthening exercise of moderate to high intensity reduces activity limitations and improves both oxygen uptake and muscle strength.ConclusionsClinicians should recommend that patients with RA participate in various types of exercise.
The alcohol tracker application: an initial evaluation of user preferences
Authors: Zhang Melvyn W B , Ward John , Ying John J B , Pan Fang , Ho Roger C M 
Published: February 2016

BackgroundThe prevalence of at-risk drinking and alcohol use disorders is increasing. Advances in technology have resulted in numerous smartphone applications for this disorder. However, there are still concerns about the evidence base of previously developed alcohol applications.ObjectiveThe following study aims to illustrate how the authors have made use of innovative methodologies to overcome the issues relating to the accuracy of tracking the amount of alcohol one has consumed; it also aims to determine user perceptions about the innovative tracker and various other features of an alcohol self-management application among a group of individuals from the general population of a developed country (Canada).MethodologyA native alcohol self-management application was developed. In order to determine user perspectives towards this new innovative application, the authors took advantage and made use of crowdsourcing to acquire user perspectives.ResultsOur results showed that smartphone ownership is highest among the age group of 35–44 years (91%) and lowest for those aged between 55 and 64 (58%). Our analysis also showed that 25–34-year-olds and 35–44-year-olds drink more frequently than the other groups. Results suggest that notification and information were the two most useful functions, with psychotherapy expected to be the least useful. Females indicated that notification service was the most useful function, while males preferred the information component.ConclusionsThis study has demonstrated how the authors have made use of innovative technologies to overcome the existing concerns pertaining to the utilisation of the blood alcohol concentration levels as a tracker. In addition, the authors have managed to highlight user preferences with regard to an alcohol application.
Effect of telehealth on hospital utilisation and mortality in routine clinical practice: a matched control cohort study in an early adopter site
Authors: Steventon Adam , Ariti Cono , Fisher Elizabeth , Bardsley Martin 
Published: February 2016

ObjectivesTo assess the effects of a home-based telehealth intervention on the use of secondary healthcare and mortality.DesignObservational study of a mainstream telehealth service, using person-level administrative data. Time to event analysis (Cox regression) was performed comparing telehealth patients with controls who were matched using a machine-learning algorithm.SettingA predominantly rural region of England (North Yorkshire).Participants716 telehealth patients were recruited from community, general practice and specialist acute care, between June 2010 and March 2013. Patients had chronic obstructive pulmonary disease, congestive heart failure or diabetes, and a history of associated inpatient admission. Patients were matched 1:1 to control patients, also selected from North Yorkshire, with respect to demographics, diagnoses of health conditions, previous hospital use and predictive risk score.InterventionsTelehealth involved the remote exchange of medical data between patients and healthcare professionals as part of the ongoing management of the patient's health condition. Monitoring centre staff alerted healthcare professionals if the telemonitored data exceeded preset thresholds. Control patients received usual care, without telehealth.Primary and secondary outcome measuresTime to the first emergency (unplanned) hospital admission or death. Secondary metrics included time to death and time to first admission, outpatient attendance and emergency department visit.ResultsMatched controls and telehealth patients were similar at baseline. Following enrolment, telehealth patients were more likely than matched controls to experience emergency admission or death (adjusted HR 1.34, 95% CI 1.16 to 1.56, p<0.001). They were also more likely to have outpatient attendances (adjusted HR=1.25, 1.11 to 1.40, p<0.001), but mortality rates were similar between groups. Sensitivity analyses showed that we were unlikely to have missed reductions in the likelihood of an emergency admission or death because of unobserved baseline differences between patient groups.ConclusionsTelehealth was not associated with a reduction in secondary care utilisation.
Genetics of Glucose regulation in Gestation and Growth (Gen3G): a prospective prebirth cohort of mother–child pairs in Sherbrooke, Canada
Authors: Guillemette Laetitia , Allard Catherine , Lacroix Marilyn , Patenaude Julie , Battista Marie-Claude , Doyon Myriam , Moreau Julie , Ménard Julie , Bouchard Luigi , Ardilouze Jean-Luc , Perron Patrice , Hivert Marie-France 
Published: February 2016

PurposeWe initiated the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort to increase our understanding of biological, environmental and genetic determinants of glucose regulation during pregnancy and their impact on fetal development.ParticipantsBetween January 2010 and June 2013, we invited pregnant women aged ≥18 years old who visited the blood sampling in pregnancy clinic in Sherbrooke for their first trimester clinical blood samples: 1034 women accepted to participate in our cohort study.Findings to dateAt first and second trimester, we collected demographics and lifestyle questionnaires, anthropometry measures (including fat and lean mass estimated using bioimpedance), blood pressure, and blood samples. At second trimester, women completed a full 75 g oral glucose tolerance test and we collected additional blood samples. At delivery, we collected cord blood and placenta samples; obstetrical and neonatal clinical data were abstracted from electronic medical records. We also collected buffy coats and extracted DNA from maternal and/or offspring samples (placenta and blood cells) to pursue genetic and epigenetic hypotheses. So far, we have found that low adiponectin and low vitamin D maternal levels in first trimester predict higher risk of developing gestational diabetes.Future plansWe are now in the phase of prospective follow-up of mothers and offspring 3 and 5 years postdelivery to investigate the consequences of maternal dysglycaemia during pregnancy on offspring adiposity and metabolic profile.Trial registration numberNCT01623934.
Role of gender, family, lifestyle and psychological factors in self-rated health among urban adolescents in Peru: a school-based cross-sectional survey
Authors: Sharma Bimala , Nam Eun Woo , Kim Dohyeong , Yoon Young Min , Kim Yeunju , Kim Ha Yun 
Published: February 2016

ObjectiveWe examined the role of gender, family, lifestyle and psychological factors in self-rated health.DesignCross-sectional study.SettingA total of 970 randomly selected students from 11 secondary schools in Lima and Callao, Peru, participated in 2014.Main outcome measureSelf-rated health was measured with a single item: ‘In general, how would you rate your health?’ Responses were arranged along a five-point Likert-type scale: ‘excellent’, ‘very good’, ‘good’, ‘fair’ and ‘poor’. The outcome variable was dichotomised as ‘good’ (excellent, very good or good) or ‘poor/fair’ (poor or fair).MethodsWe calculated adjusted ORs (AORs) and 95% CIs for poor/fair self-rated health using multivariate logistic regression analyses at 3-graded levels.Results32.5% of the respondents had fair/poor self-rated health, 23.7% of the total males and 40.0% of the total female samples. Males were less likely to have poor/fair self-rated health (AOR 0.61; CI 0.41 to 0.91). Poor family support strongly increased the likelihood of having poor/fair self-rated health (no support, (AOR 3.15; CI 1.63 to 6.09); low support, (AOR 2.50; CI 1.29 to 4.85)). The other associated variables were missed meals due to a shortage of food (AOR 1.97; CI 1.15 to 3.36), television watching during leisure time (AOR 1.70; CI 1.09 to 2.67), low physical activity (AOR 1.49; CI 1.03 to 2.15), school absenteeism (AOR 1.54; CI 1.03 to 2.31) and perceived life satisfaction (AOR 0.28; CI 0.15 to 0.25).ConclusionsGender, missing meals due to a shortage of food, family support, physical activity and life satisfaction influenced self-rated health among adolescents in Peru. Interventions that focus on promoting physical activity for at least 1 h each day for 3 or more days per week, food security and strengthening supportive family roles may improve self-rated health during adolescence.
The usefulness of cardiopulmonary exercise testing in assessment of patients with suspected coronary artery disease
Authors: Mazaheri Reza , Shakerian Farshad , Vasheghani-Farahani Ali , Halabchi Farzin , Mirshahi Maryam , Mansournia Mohammad Ali 
Published: February 2016

AbstractObjectiveThe aim of this study is to assess different parameters of cardiopulmonary exercise testing that can predict the development of myocardial ischaemia in patients with suspected coronary artery disease (CAD) and to identify the parameters which have more correlation with myocardial ischaemia.Study designCross-sectional study.MethodsIn this study, a total of 31 men (mean age 57.23±11.09 years) with suggestive symptoms of CAD underwent an exercise stress test with breath-by-breath gas exchange analysis, followed by coronary angiography as the gold standard for diagnosing CAD.ResultsThe ventilation versus CO2 output (VE/VCO2) peak was significantly different between patients with negative and positive angiography results. Receiver operator characteristic analysis showed an area under the curve of 0.73 for VE/VCO2 peak with diagnostic threshold equal to 35 (95% CI 0.54 to 0.9; p=0.05). Exercise stress testing had sensitivity and specificity of 75% and 40%, respectively.ConclusionsA change in ventilatory efficiency assessed using the VE/VCO2 peak has the predictive ability to identify exercise-induced myocardial ischaemia. The present study has provided additional evidence of the potential clinical value of cardiopulmonary exercise testing in the diagnosis of CAD.
Evaluation of abnormal liver function tests
Authors: Agrawal Swastik , Dhiman Radha K , Limdi Jimmy K 
Published: February 2016

AbstractIncidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests.