bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4
+
and CD8
+
T-Cell Responses
Authors: Sauermann Ulrike , Radaelli Antonia , Stolte-Leeb Nicole , Raue Katharina , Bissa Massimiliano , Zanotto Carlo , Krawczak Michael , Tenbusch Matthias , Überla Klaus , Keele Brandon F. , De Giuli Morghen Carlo , Sopper Sieghart , Stahl-Hennig Christiane 
Published: September 2017

ABSTRACT

An effective AIDS vaccine should elicit strong humoral and cellular immune responses while maintaining low levels of CD4
+
T-cell activation to avoid the generation of target cells for viral infection. The present study investigated two prime-boost regimens, both starting vaccination with single-cycle immunodeficiency virus, followed by two mucosal boosts with either recombinant adenovirus (rAd) or fowlpox virus (rFWPV) expressing SIVmac239 or SIVmac251
gag/pol
and
env
genes, respectively. Finally, vectors were switched and systemically administered to the reciprocal group of animals. Only mucosal rFWPV immunizations followed by systemic rAd boost significantly protected animals against a repeated low-dose intrarectal challenge with pathogenic SIVmac251, resulting in a vaccine efficacy (i.e., risk reduction per exposure) of 68%. Delayed viral acquisition was associated with higher levels of activated CD8
+
T cells and Gag-specific gamma interferon (IFN-γ)-secreting CD8
+
cells, low virus-specific CD4
+
T-cell responses, and low Env antibody titers. In contrast, the systemic rFWPV boost induced strong virus-specific CD4
+
T-cell activity. rAd and rFWPV also induced differential patterns of the innate immune responses, thereby possibly shaping the specific immunity. Plasma
CXCL10
levels after final immunization correlated directly with virus-specific CD4
+
T-cell responses and inversely with the number of exposures to infection. Also, the percentage of activated CD69
+
CD8
+
T cells correlated with the number of exposures to infection. Differential stimulation of the immune response likely provided the basis for the diverging levels of protection afforded by the vaccine regimen.

IMPORTANCE
A failed phase II AIDS vaccine trial led to the hypothesis that CD4
+
T-cell activation can abrogate any potentially protective effects delivered by vaccination or promote acquisition of the virus because CD4
+
T helper cells, required for an effective immune response, also represent the target cells for viral infection. We compared two vaccination protocols that elicited similar levels of Gag-specific immune responses in rhesus macaques. Only the animal group that had a low level of virus-specific CD4
+
T cells in combination with high levels of activated CD8
+
T cells was significantly protected from infection. Notably, protection was achieved despite the lack of appreciable Env antibody titers. Moreover, we show that both the vector and the route of immunization affected the level of CD4
+
T-cell responses. Thus, mucosal immunization with FWPV-based vaccines should be considered a potent prime in prime-boost vaccination protocols.
New distributional records of Mecoptera (Insecta) from Colombia
Authors: Ardila-Camacho Adrian , Vargas Juan Felipe , Arango Carlos Julio , García-García Alexander , Machado Renato Jose Pires 
Published: September 2017

We present new distributional records for two Colombian species of Bittacidae. Pazius convolutus García-García & Cadena-Castañeda, 2015 and Bittacus panamensis Byers, 1958 previously known from Cundinamarca department are herein newly recorded from Santander and Magdalena, respectively. In addition, we recorded Bittacus pignatelli Navás, 1932 in Colombia for the first time, increasing the number of species of Mecoptera in the country. Comments about mating behavior of P. convolutus, as well as a distribution map and a check-list of Colombian species of Mecoptera are included.
Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker
Authors: Zadora Julianna , Singh Manvendra , Herse Florian , Przybyl Lukasz , Haase Nadine , Golic Michaela , Yung Hong Wa , Huppertz Berthold , Cartwright Judith E. , Whitley Guy , Johnsen Guro M. , Levi Giovanni , Isbruch Annette , Schulz Herbert , Luft Friedrich C. , Müller Dominik N. , Staff Anne Cathrine , Hurst Laurence D. , Dechend Ralf , Izsvák Zsuzsanna 
Published: September 2017

Background:
Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia.

Methods:
We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis.

Results:

We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including
GATA3
and
DLX5
, with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting,
DLX5
was upregulated in 69% of preeclamptic placentas. Levels of
DLX5
correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5
high
phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in trophoblasts in vitro. The transcriptional profile of such cells mimics the transcriptome of preeclamptic placentas. Pan-mammalian comparative analysis identified
DLX5
as part of the human-specific regulatory network of trophoblast differentiation.

Conclusions:

Our analysis provides evidence of a true association among disturbed imprinting, gene expression, and preeclampsia. As a result of disturbed imprinting, the upregulated
DLX5
affects trophoblast proliferation. Our in vitro model might fill a vital niche in preeclampsia research. Human-specific regulatory circuitry of
DLX5
might help explain certain aspects of preeclampsia.
Increased Hazard of Myocardial Infarction With Insulin‐Provision Therapy in Actively Smoking Patients With Diabetes Mellitus and Stable Ischemic Heart Disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial
Authors: Khan Asrar A. , Chung Matthew J. , Novak Eric , Brown David L. 
Published: September 2017

Background

In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (
IP
) therapy, as opposed to insulin sensitization (
IS
) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of
IP
therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (
MI
).

Methods and Results

We analyzed
BARI
2D patients who were active smokers randomized to
IP
or
IS
therapy. The primary end point was fatal or nonfatal
MI
.
PAI
‐1 (plasminogen activator inhibitor 1) activity was analyzed at 1, 3, and 5 years. Of 295 active smokers,
MI
occurred in 15.4% randomized to
IP
and in 6.8% randomized to
IS
over the 5.3 years (
P
=0.023).
IP
therapy was associated with a 3.2‐fold increase in the hazard of
MI
compared with
IS
therapy (hazard ratio: 3.23; 95% confidence interval, 1.43–7.28;
P
=0.005). Baseline
PAI
‐1 activity (19.0 versus 17.5 Au/mL,
P
=0.70) was similar in actively smoking patients randomized to
IP
or
IS
therapy. However,
IP
therapy resulted in significantly increased
PAI
‐1 activity at 1 year (23.0 versus 16.0 Au/mL,
P
=0.001), 3 years (24.0 versus 18.0 Au/mL,
P
=0.049), and 5 years (29.0 versus 15.0 Au/mL,
P
=0.004) compared with
IS
therapy.

Conclusions

Among diabetic patients with stable ischemic heart disease who were actively smoking,
IP
therapy was independently associated with a significantly increased hazard of
MI
. This finding may be explained by higher
PAI
‐1 activity in active smokers treated with
IP
therapy.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00006305.
Imaging of rare appendicular non-acral soft-tissue chondromas in adults with histopathologic correlation
Authors: Nouh Mohamed Ragab , Amr Hanan Abd El-Aziz , Ali Rola H 
Published: September 2017

Background Soft-tissue chondroma (STC) is a rare benign soft tissue tumor that arises primarily in acral extra-skeletal locations. Occasionally, STCs may arise in more proximal non-acral locations, accompanied by non-classic features that label them as indeterminate lesions and pose diagnostic challenge for both radiologists and pathologists alike. Purpose To explicate the potential of diagnostic imaging in the identification and characterization of appendicular non-acral STCs with emphasis on their morphologic magnetic resonance imaging (MRI) enhancement. Material and Methods Our clinical database records were searched for patients with histologically proven primary soft-tissue chondroid lesions over a five-year period. Two musculoskeletal (MSK) trained radiologists evaluated the imaging studies and an MSK pathologist revised the pathological findings. Results The study included six cases of appendicular non-acral STCs (mean age = 40.5 years). The mean size of the tumors was 5.6 cm, with four localized to the knee region, one in the thigh, and one in the sternoclavicular region. All cases showed high signal intensity matrix with low-signal intensity septa on T2-weighted MRI and post-contrast marginal/septal enhancement. The lesions were lobulated and lacked host tissue reaction except for one showing subjacent mild soft-tissue edema. Histologically, the cases lacked overt features of malignancy although one was originally misdiagnosed as chondrosarcoma. Conclusion Non-acral STCs are benign cartilaginous tumors that may pose a diagnostic challenge, both radiologically and pathologically. Collaborative imaging and pathologic workup is needed for better characterization of non-aggression of these lesions, and to avoid diagnostic pitfalls and unnecessary radical resections.
Cluster headache – clinical pattern and a new severity scale in a Swedish cohort
Authors: Steinberg Anna , Fourier Carmen , Ran Caroline , Waldenlind Elisabet , Sjöstrand Christina , Belin Andrea Carmine 
Published: September 2017

Background The aim of this study was to investigate clinical features of a cluster headache cohort in Sweden and to construct and test a new scale for grading severity. Methods Subjects were identified by screening medical records for the ICD 10 code G44.0, that is, cluster headache. Five hundred participating research subjects filled in a questionnaire including personal, demographic and medical aspects. We constructed a novel scale for grading cluster headache in this cohort: The Cluster Headache Severity Scale, which included number of attacks per day, attack and period duration. The lowest total score was three and the highest 12, and we used the Cluster Headache Severity Scale to grade subjects suffering from cluster headache. We further implemented the scale by defining a cluster headache maximum severity subgroup with a high Cluster Headache Severity Scale score ≥ 9. Results A majority (66.7%) of the patients reported that attacks appear at certain time intervals. In addition, cluster headache patients who were current tobacco users or had a history of tobacco consumption had a later age of disease onset (31.7 years) compared to non-tobacco users (28.5 years). The Cluster Headache Severity Scale score was higher in the patient group reporting sporadic or no alcohol intake than in the groups reporting an alcohol consumption of three to four standard units per week or more. Maximum severity cluster headache patients were characterised by higher age at disease onset, greater use of prophylactic medication, reduced hours of sleep, and lower alcohol consumption compared to the non-cluster headache maximum severity group. Conclusion There was a wide variation of severity grade among cluster headache patients, with a very marked impact on daily living for the most profoundly affected.
Mental Health Services Use Trends in Canadian Veterans: A Population-Based Retrospective Cohort Study in Ontario
Authors: Mahar Alyson L. , Aiken Alice B. , Cramm Heidi , Whitehead Marlo , Groome Patti , Kurdyak Paul 
Published: September 2017

Objective: A substantial evidence base in the peer-reviewed literature exists investigating mental illness in the military, but relatively less is documented about mental illness in veterans. This study uses provincial, administrative data to study the use of mental health services by Canadian veterans in Ontario. Method: This was a retrospective cohort study of Canadian Armed Forces and Royal Canadian Mounted Police veterans who were released between 1990 and 2013 and resided in Ontario. Mental health–related primary care physician, psychiatrist, emergency department (ED) visits, and psychiatric hospitalisations were counted. Repeated measures were presented in 5-year intervals, stratified by age at release. Results: The cohort included 23,818 veterans. In the first 5 years following entry into the health care system, 28.9% of veterans had ≥1 mental health–related primary care physician visit, 5.8% visited a psychiatrist at least once, and 2.4% received acute mental health services at an ED. The use of mental health services was consistent over time. Almost 8% of veterans aged 30 to 39 years saw a psychiatrist in the first 5 years after release, compared to 3.5% of veterans aged ≥50 years at release. The youngest veterans at release (<30 years) were the most frequent users of ED services for a mental health–related reason (5.1% had at least 1 ED visit). Conclusion: Understanding how veterans use the health care system for mental health problems is an important step to ensuring needs are met during the transition to civilian life.
Anatomical characteristics of the styloid process in internal carotid artery dissection: Case–control study
Authors: Amorim José M , Pereira Daniela , Rodrigues Marta G , Beato-Coelho José , Lopes Margarida , Cunha André , Figueiredo Sofia , Mendes-Pinto Mafalda , Ferreira Carla , Sargento-Freitas João , Castro Sérgio , Pinho João 
Published: September 2017

Introduction Pathophysiology of cervical artery dissection is complex and poorly understood. In addition to well-known causative and predisposing factors, including major trauma and monogenic connective tissue disorders, morphological characteristics of the styloid process have been recently recognized as a possible risk factor for cervical internal carotid artery dissection. Aims To study the association of the anatomical characteristics of styloid process with internal carotid artery dissection. Methods Retrospective, multicenter, case–control study of patients with internal carotid artery dissection and age- and sex-matched controls. Consecutive patients with internal carotid artery dissection and controls with ischemic stroke or transient ischemic attack of any etiology excluding internal carotid artery dissection, who had performed computed tomography angiography, diagnosed between January 2010 and September 2016. Two independent observers measured styloid process length and styloid process distance to internal carotid artery. Results Sixty-two patients with internal carotid artery dissection and 70 controls were included. Interobserver agreement was good for styloid process length and styloid process–internal carotid artery distance (interclass correlation coefficient = 0.89 and 0.76, respectively). Styloid process ipsilateral to dissection was longer than left and right styloid process in controls (35.8 ± 14.4 mm versus 30.4 ± 8.9 mm and 30.3 ± 8.2 mm, p = 0.011 and p = 0.008, respectively). Styloid process–internal carotid artery distance ipsilateral to dissection was shorter than left and right distance in controls (6.3 ± 1.9 mm versus 7.2 ± 2.1 mm and 7.0 ± 2.3 mm, p = 0.003 and p = 0.026, respectively). Internal carotid artery dissection was associated with styloid process length (odds ratio = 1.04 mm−1, 95% confidence interval = 1.01–1.08, p = 0.015) and styloid process–internal carotid artery distance (OR = 0.77 mm−1, 95% confidence interval = 0.64–0.92, p = 0.004). Conclusion Longer styloid process and shorter distance between styloid process and cervical internal carotid artery are associated with cervical internal carotid artery dissection.
Selecting a Risk-Based SQC Procedure for a HbA1c Total QC Plan
Authors: Westgard Sten A. , Bayat Hassan , Westgard James O. 
Published: September 2017

Background: Recent US practice guidelines and laboratory regulations for quality control (QC) emphasize the development of QC plans and the application of risk management principles. The US Clinical Laboratory Improvement Amendments (CLIA) now includes an option to comply with QC regulations by developing an individualized QC plan (IQCP) based on a risk assessment of the total testing process. The Clinical and Laboratory Standards Institute (CLSI) has provided new practice guidelines for application of risk management to QC plans and statistical QC (SQC). Methods: We describe an alternative approach for developing a total QC plan (TQCP) that includes a risk-based SQC procedure. CLIA compliance is maintained by analyzing at least 2 levels of controls per day. A Sigma-Metric SQC Run Size nomogram provides a graphical tool to simplify the selection of risk-based SQC procedures. Applications: Current HbA1c method performance, as demonstrated by published method validation studies, is estimated to be 4-Sigma quality at best. Optimal SQC strategies require more QC than the CLIA minimum requirement of 2 levels per day. More complex control algorithms, more control measurements, and a bracketed mode of operation are needed to assure the intended quality of results. Conclusions: A total QC plan with a risk-based SQC procedure provides a simpler alternative to an individualized QC plan. A Sigma-Metric SQC Run Size nomogram provides a practical tool for selecting appropriate control rules, numbers of control measurements, and run size (or frequency of SQC). Applications demonstrate the need for continued improvement of analytical performance of HbA1c laboratory methods.
Anconeus Muscle-Pedicle Bone Graft With Periosteal Coverage for Osteochondritis Dissecans of the Humeral Capitellum
Authors: Shimada Kozo , Temporin Ko , Oura Keiichiro , Tanaka Hiroyuki , Noguchi Ryosuke 
Published: September 2017

Background: Treatment of advanced osteochondritis dissecans (OCD) of the capitellum is controversial, especially in moderate-sized lesions. Purpose: To establish a treatment algorithm for capitellum OCD, we tried to determine the utility of and problems associated with anconeus muscle-pedicle bone graft with periosteal coverage (ABGP) for the treatment of moderate-sized articular OCD defects of the capitellum. Study Design: Case series; Level of evidence, 4. Methods: According to our protocol for elbow OCD, 16 patients (15 males, 1 female; age range, 12-17 years; mean age, 14.4 years) with a moderate-sized OCD lesion of the humeral capitellum were treated with ABGP. All patients had a full-thickness, unstable OCD lesion that was 10 to 15 mm in diameter. Clinical results and postoperative images, including radiographs and magnetic resonance imaging (MRI), were evaluated at a mean follow-up of 31 months (range, 24-66 months). Results: All but 1 patient had functional improvement after the procedure and returned to previous sporting activities within 6 months. One female patient needed 1 year for functional recovery due to development of postoperative chronic regional pain syndrome (CRPS). Two patients required additional surgery, including shaving of the protruding cartilage, and they returned to their previous level of activity. Mean arc of range of flexion-extension motion was 117° preoperatively and 129° at follow-up ( P = .031). Mean elbow function as assessed with the clinical rating system of Timmerman and Andrews was 136 preoperatively and 186 at follow-up ( P = .00012). Bony union of the graft as demonstrated by trabecular bone bridging on radiography was obtained within 3 months in all patients. Postoperative MRI was examined for 14 patients at 6 to 12 months after the procedure; the MRIs showed near-normal articular surface integrity in 9 of the 14 patients (64%) and underlying bony structure in 10 of the 14 patients (71%). Conclusion: Improvement after ABGP was obtained within 6 months in all except 1 patient, who developed CRPS. Postoperative radiography and MRI revealed near-normal articular surface integrity or underlying bony structure. This procedure is useful as a surgical option for a moderate-sized articular OCD lesion in the elbow.
Significance of the Bucegi Conglomerate olistoliths in the Albian source-to-sink system from the Carpathian Bend basin in Romania
Authors: Jipa Dan C. , Olariu Cornel 
Published: September 2017

The presence of exotic blocks (or olistoliths) in sedimentary deposits is usually regarded as an indication of a deepwater slope environment. We evaluate olistoliths accumulated in shallow water at the upper edge of a slope setting using outcrop data. The study area is in the Bucegi Mountains in the southeast “bend” of the Carpathian Mountains in Romania. The studied deposits belong to the Bucegi Formation, a dominantly conglomerate succession of Albian age. The Lower Bucegi member has been accumulated as a large conglomerate submarine fan. The Upper Member forms a shelf-to-trench sedimentary system with deposits dominated by sandstones and conglomerates. The olistoliths are embedded in debris flow conglomerates, most of them from the Bucegi Upper Member, and a lower number from the Bucegi Lower Member. The olistoliths are all located in a small ([Formula: see text]) zone, close to the Dambovicioara source area. The olistoliths have been transported into the basin for up to 10 km on relative gentle gradients. The blocks’ deposition is restricted to the shallow-water environment on a narrow low-gradient shelf and in some instances on the upper continental slope. Within the Albian source-to-sink system, the olistoliths occurrence marks the entry zone of the land-derived detrital material into the basin and points to the main sediment transport fairways into deeper parts of the basin.