bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Neisseria gonorrhoeae and Chlamydia trachomatis from pooled rectal, pharyngeal and urine specimens in men who have sex with men
Authors: Speers David John , Chua I-Ly Joanna , Manuel Justin , Marshall Lewis 
Published: October 2017

ObjectivesScreening of men who have sex with men (MSM) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) requires sampling from anorectal and pharyngeal sites in addition to urogenital sampling. Due to the cost of testing multiple anatomical sites individually testing of pooled specimens has potential merit. The Cepheid GeneXpert CT/NG assay (GeneXpert), which also has potential for point-of-care nucleic acid testing in the sexual health clinic, has not been assessed for pooled specimen testing.MethodsWe prospectively compared GeneXpert testing of pooled pharyngeal and rectal swabs with urine samples to standard of care testing of individual specimens from 107 participants using the Roche cobas 4800 CT/NG assay (cobas) for CT and NG in high-risk MSM attending an inner city sexual health clinic.ResultsWe found testing of pooled pharyngeal, rectal and urine samples by the GeneXpert to have 100% agreement for NG and 94% overall agreement for CT when compared with individual specimen testing by cobas. For CT testing, 14 cases were detected for both tests, 4for cobas only, 2 for GeneXpert only and 89 participants were negative for both tests.ConclusionsPooled specimen CT and NG testing by the GeneXpert was accurate when compared with single specimen testing and has potential for screening MSM for CT and NG. The role of pooled specimen testing with the GeneXpert as a point-of-care nucleic acid test in MSM requires further investigation.
Effects of long‐term use of the preferential COX‐2 inhibitor meloxicam on growing pigs
Authors: Gorissen Ben M C , Uilenreef Joost J , Bergmann Wilhelmina , Meijer Ellen , van Rietbergen Bert , van der Staay Franz Josef , van Weeren P René , Wolschrijn Claudia F 
Published: October 2017

Meloxicam, a preferential COX‐2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long‐term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long‐term use of meloxicam in young, growing piglets.
The Kölliker-Fuse nucleus orchestrates the timing of expiratory abdominal nerve bursting
Authors: Barnett William H. , Jenkin Sarah E. M. , Milsom William K. , Paton Julian F. R. , Abdala Ana P. , Molkov Yaroslav I. , Zoccal Daniel B. 
Published: October 2017

Coordination of respiratory pump and valve muscle activity is essential for normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is the emergence of active exhalation, characterized by abdominal muscle pumping during the late one-third of expiration (late-E phase). Late-E abdominal activity during hypercapnia has been attributed to the activation of expiratory neurons located within the parafacial respiratory group (pFRG). However, the mechanisms that control emergence of active exhalation, and its silencing in restful breathing, are not completely understood. We hypothesized that inputs from the Kölliker-Fuse nucleus (KF) control the emergence of late-E activity during hypercapnia. Previously, we reported that reversible inhibition of the KF reduced postinspiratory (post-I) motor output to laryngeal adductor muscles and brought forward the onset of hypercapnia-induced late-E abdominal activity. Here we explored the contribution of the KF for late-E abdominal recruitment during hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate arterially perfused rat preparations. These data were combined with previous results and incorporated into a computational model of the respiratory central pattern generator. Disinhibition of the KF through local parenchymal microinjections of gabazine (GABAA receptor antagonist) prolonged vagal post-I activity and inhibited late-E abdominal output during hypercapnia. In silico, we reproduced this behavior and predicted a mechanism in which the KF provides excitatory drive to post-I inhibitory neurons, which in turn inhibit late-E neurons of the pFRG. Although the exact mechanism proposed by the model requires testing, our data confirm that the KF modulates the formation of late-E abdominal activity during hypercapnia. NEW & NOTEWORTHY The pons is essential for the formation of the three-phase respiratory pattern, controlling the inspiratory-expiratory phase transition. We provide functional evidence of a novel role for the Kölliker-Fuse nucleus (KF) controlling the emergence of abdominal expiratory bursts during active expiration. A computational model of the respiratory central pattern generator predicts a possible mechanism by which the KF interacts indirectly with the parafacial respiratory group and exerts an inhibitory effect on the expiratory conditional oscillator.
Central pattern generators in the turtle spinal cord: selection among the forms of motor behaviors
Authors: Stein Paul S. G. 
Published: October 2017

Neuronal networks in the turtle spinal cord have considerable computational complexity even in the absence of connections with supraspinal structures. These networks contain central pattern generators (CPGs) for each of several behaviors, including three forms of scratch, two forms of swim, and one form of flexion reflex. Each behavior is activated by a specific set of cutaneous or electrical stimuli. The process of selection among behaviors within the spinal cord has multisecond memories of specific motor patterns. Some spinal cord interneurons are partially shared among several CPGs, whereas other interneurons are active during only one type of behavior. Partial sharing is a proposed mechanism that contributes to the ability of the spinal cord to generate motor pattern blends with characteristics of multiple behaviors. Variations of motor patterns, termed deletions, assist in characterization of the organization of the pattern-generating components of CPGs. Single-neuron recordings during both normal and deletion motor patterns provide support for a CPG organizational structure with unit burst generators (UBGs) whose members serve a direction of a specific degree of freedom of the hindlimb, e.g., the hip-flexor UBG, the hip-extensor UBG, the knee-flexor UBG, the knee-extensor UBG, etc. The classic half-center hypothesis that includes all the hindlimb flexors in a single flexor half-center and all the hindlimb extensors in a single extensor half-center lacks the organizational complexity to account for the motor patterns produced by turtle spinal CPGs. Thus the turtle spinal cord is a valuable model system for studies of mechanisms responsible for selection and generation of motor behaviors. NEW & NOTEWORTHY The concept of the central pattern generator (CPG) is a major tenet in motor neuroethology that has influenced the design and interpretations of experiments for over a half century. This review concentrates on the turtle spinal cord and describes studies from the 1970s to the present responsible for key developments in understanding the CPG mechanisms responsible for the selection and production of coordinated motor patterns during turtle hindlimb motor behaviors.
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
Authors: Canale Fernando P. , Ramello María C. , Núñez Nicolás , Furlan Cintia L. Araujo , Bossio Sabrina N. , Serrán Melisa Gorosito , Boari Jimena Tosello , del Castillo Andrés , Ledesma Marta , Sedlik Christine , Piaggio Eliane , Gruppi Adriana , Rodríguez Eva V. Acosta , Montes Carolina L. 
Published: October 2017

Abstract
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNγ production by responder CD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.
Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1); 115–28. ©2017 AACR.
Evidence for Kaposi Sarcoma Originating from Mesenchymal Stem Cell through KSHV-induced Mesenchymal-to-Endothelial Transition
Authors: Li Yuqing , Zhong Canrong , Liu Dawei , Yu Wenjing , Chen Weikang , Wang Yan , Shi Songtao , Yuan Yan 
Published: October 2017

Abstract
The major transmission route for Kaposi sarcoma–associated herpesvirus (KSHV) infection is the oral cavity through saliva. Kaposi sarcoma (KS) frequently occurs in the oral cavity in HIV-positive individuals and is often the first presenting sign of AIDS. However, the oral target cells for KSHV infection and the cellular origin of Kaposi sarcoma remain unknown. Here we present clinical and experimental evidences that Kaposi sarcoma spindle cells may originate from virally modified oral mesenchymal stem cells (MSC). AIDS-KS spindle cells expressed neuroectodermal stem cell marker (Nestin) and oral MSC marker CD29, suggesting an oral/craniofacial MSC lineage of AIDS-associated Kaposi sarcoma. Furthermore, oral MSCs were highly susceptible to KSHV infection, and infection promoted multilineage differentiation and mesenchymal-to-endothelial transition (MEndT). KSHV infection of oral MSCs resulted in expression of a large number of cytokines, a characteristic of Kaposi sarcoma, and upregulation of Kaposi sarcoma signature and MEndT-associated genes. These results suggest that Kaposi sarcoma may originate from pluripotent MSC and KSHV infection transforms MSC to Kaposi sarcoma–like cells through MEndT.
Significance: These findings indicate that Kaposi sarcomas, which arise frequently in AIDS patients, originate from neural crest-derived mesenchymal stem cells, with possible implications for improving the clnical treatment of this malignancy. Cancer Res; 78(1); 230–45. ©2017 AACR.
T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma
Authors: Stromnes Ingunn M. , Hulbert Ayaka , Pierce Robert H. , Greenberg Philip D. , Hingorani Sunil R. 
Published: October 2017

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to most therapies, including immune checkpoint blockade. To elucidate mechanisms of immunotherapy resistance, we assessed immune parameters in resected human PDA. We demonstrate significant interpatient variability in T-cell number, localization, and phenotype. CD8+ T cells, Foxp3+ regulatory T cells, and PD-1+ and PD-L1+ cells were preferentially enriched in tertiary lymphoid structures that were found in most tumors compared with stroma and tumor cell nests. Tumors containing more CD8+ T cells also had increased granulocytes, CD163+ (M2 immunosuppressive phenotype) macrophages, and FOXP3+ regulatory T cells. PD-L1 was rare on tumor cells, but was expressed by CD163+ macrophages and an additional stromal cell subset commonly found clustered together adjacent to tumor epithelium. The majority of tumoral CD8+ T cells did not express molecules suggestive of recent T-cell receptor (TCR) signaling. However, 41BB+PD-1+ T cells were still significantly enriched in tumors compared with circulation. Tumoral CD8+PD-1+ T cells commonly expressed additional inhibitory receptors, yet were mostly T-BEThi and EOMESlo, consistent with a less terminally exhausted state. Analysis of gene expression and rearranged TCR genes by deep sequencing suggested most patients have a limited tumor-reactive T-cell response. Multiplex immunohistochemistry revealed variable T-cell infiltration based on abundance and location, which may result in different mechanisms of immunotherapy resistance. Overall, the data support the need for therapies that either induce endogenous, or provide engineered, tumor-specific T-cell responses, and concurrently relieve suppressive mechanisms operative at the tumor site. Cancer Immunol Res; 5(11); 978–91. ©2017 AACR.
Interleukin‐6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52) Trial
Authors: Fanola Christina L. , Morrow David A. , Cannon Christopher P. , Jarolim Petr , Lukas Mary Ann , Bode Christoph , Hochman Judith S. , Goodrich Erica L. , Braunwald Eugene , O'Donoghue Michelle L. 
Published: October 2017

Background

Interleukin‐6 (
IL
‐6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (
ACS
). We aimed to evaluate the prognostic implications of
IL
‐6 post‐
ACS
.

Methods and Results

IL
‐6 concentration was assessed at baseline in 4939 subjects in
SOLID
‐
TIMI
52 (Stabilization of Plaque Using Darapladib—Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from
ACS
. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index
ACS
,
ACS
type, and randomized treatment arm. For every
SD
increase in
IL
‐6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj
HR
] 1.10, 95% confidence interval [
CI
] 1.01‐1.19) and a 22% higher risk of cardiovascular death or heart failure (adj
HR
1.22, 95%
CI
1.11‐1.34). Patients in the highest
IL
‐6 quartile had a higher risk of major adverse cardiovascular events (adj
HR
Q4:Q1 1.57, 95%
CI
1.22‐2.03) and cardiovascular death or heart failure (adj
HR
2.29, 95%
CI
1.6‐3.29). After further adjustment for biomarkers (high‐sensitivity C‐reactive protein, lipoprotein‐associated phospholipase A
2
activity, high‐sensitivity troponin I, and B‐type natriuretic peptide),
IL
‐6 remained significantly associated with the risk of major adverse cardiovascular events (adj
HR
Q4:Q1 1.43, 95%
CI
1.09‐1.88) and cardiovascular death or heart failure (adj
HR
1.79, 95%
CI
1.22‐2.63).

Conclusions

In patients after
ACS
,
IL
‐6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of
IL
‐6 as a potential therapeutic target in patients with unstable ischemic heart disease.
Effect of Monthly, High‐Dose, Long‐Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy
Authors: Sluyter John D. , Camargo Carlos A. , Stewart Alistair W. , Waayer Debbie , Lawes Carlene M. M. , Toop Les , Khaw Kay‐Tee , Thom Simon A. McG. , Hametner Bernhard , Wassertheurer Siegfried , Parker Kim H. , Hughes Alun D. , Scragg Robert 
Published: October 2017

Background

The effects of monthly, high‐dose, long‐term (≥1‐year) vitamin D supplementation on central blood pressure (
BP
) parameters are unknown.

Methods and Results

A total of 517 adults (58% male, aged 50–84 years) were recruited into a double‐blinded, placebo‐controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9–1.5 years), either (1) vitamin D
3
200 000 IU (initial dose) followed 1 month later by monthly 100 000‐IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow‐up (n=380), suprasystolic oscillometry was undertaken, yielding aortic
BP
waveforms and hemodynamic parameters. Mean deseasonalized 25‐hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow‐up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were −5.3 mm Hg (95% confidence interval [CI], −11.8 to 1.3) for brachial systolic
BP
(
P
=0.11), −2.8 mm Hg (95% CI, −6.2 to 0.7) for brachial diastolic
BP
(
P
=0.12), −7.5 mm Hg (95% CI, −14.4 to −0.6) for aortic systolic
BP
(
P
=0.03), −5.7 mm Hg (95% CI, −10.8 to −0.6) for augmentation index (
P
=0.03), −0.3 m/s (95% CI, −0.6 to −0.1) for pulse wave velocity (
P
=0.02), −8.6 mm Hg (95% CI, −15.4 to −1.9) for peak reservoir pressure (
P
=0.01), and −3.6 mm Hg (95% CI, −6.3 to −0.8) for backward pressure amplitude (
P
=0.01).

Conclusions

Monthly, high‐dose, 1‐year vitamin D supplementation lowered central
BP
parameters among adults with vitamin D deficiency but not in the total sample.

Clinical Trial Registration

URL
:
http://www.anzctr.org.au
. Unique identifier:
ACTRN
12611000402943.
Benefit of Vasodilating β‐Blockers in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention: Nationwide Multicenter Cohort Study
Authors: Chung Jaehoon , Han Jung‐Kyu , Kim Young Jo , Kim Chong Jin , Ahn Youngkeun , Chan Cho Myeong , Chae Shung Chull , Chae In‐Ho , Chae Jei Keon , Seong In‐Whan , Yang Han‐Mo , Park Kyung‐Woo , Kang Hyun‐Jae , Koo Bon‐Kwon , Jeong Myung Ho , Kim Hyo‐Soo , Ahn Tae Hoon , Cha Kwang Soo , Gwon Hyeon‐Cheol , Hwang Jin‐Yong , Joo Seung Jae , Kim Doo‐il , Kim Kwon‐Bae , Oh Dong Joo , Oh Seok Kyu , Seung Ki‐Bae , Yoon Jung‐Han 
Published: October 2017

Background

Although current guidelines recommend β‐blocker after acute myocardial infarction (
MI
), the role of β‐blocker has not been well investigated in the modern reperfusion era. In particular, the benefit of vasodilating β‐blocker over conventional β‐blocker is still unexplored.

Methods and Results

Using nation‐wide multicenter Korean Acute Myocardial Infarction Registry data, we analyzed clinical outcomes of 7127 patients with acute MI who underwent successful percutaneous coronary intervention with stents and took β‐blockers: vasodilating β‐blocker (n=3482), and conventional β‐blocker (n=3645). In the whole population, incidence of cardiac death at 1 year was significantly lower in the vasodilating β‐blocker group (vasodilating β‐blockers versus conventional β‐blockers, 1.0% versus 1.9%;
P=
0.003). In 2882 pairs of propensity score–matched population, the incidence of cardiac death was significantly lower in the vasodilating β‐blocker group (1.1% versus 1.8%;
P=
0.028). Although incidences of
MI
(1.1% versus 1.5%;
P=
0.277), any revascularization (2.8% versus 3.0%;
P=
0.791), and hospitalization for heart failure (1.4% versus 1.9%;
P=
0.210) were not different between the 2 groups, incidences of cardiac death or
MI
(2.0% versus 3.1%;
P=
0.010), cardiac death,
MI
, or hospitalization for heart failure (3.0% versus 4.5%;
P=
0.003), cardiac death,
MI
, or any revascularization (3.9% versus 5.3%;
P=
0.026), and cardiac death,
MI
, any revascularization, or hospitalization for heart failure (4.8% versus 6.5%;
P=
0.011) were significantly lower in the vasodilating β‐blocker group.

Conclusions
Vasodilating β‐blocker therapy resulted in better clinical outcomes than conventional β‐blocker therapy did in patients with acute MI in the modern reperfusion era. Vasodilating β‐blockers could be recommended preferentially to conventional ones for acute MI patients.
Eddy Diffusivity Estimates from Lagrangian Trajectories Simulated with Ocean Models and Surface Drifter Data—A Case Study for the Greater Agulhas System
Authors: Rühs Siren , Zhurbas Victor , Koszalka Inga M. , Durgadoo Jonathan V. , Biastoch Arne 
Published: October 2017

AbstractThe Lagrangian analysis of sets of particles advected with the flow fields of ocean models is used to study connectivity, that is, exchange pathways, time scales, and volume transports, between distinct oceanic regions. One important factor influencing the dispersion of fluid particles and, hence, connectivity is the Lagrangian eddy diffusivity, which quantifies the influence of turbulent processes on the rate of particle dispersal. Because of spatial and temporal discretization, turbulence is not fully resolved in modeled velocities, and the concept of eddy diffusivity is used to parameterize the impact of unresolved processes. However, the relations between observation- and model-based Lagrangian eddy diffusivity estimates, as well as eddy parameterizations, are not clear. This study presents an analysis of the spatially variable near-surface lateral eddy diffusivity estimates obtained from Lagrangian trajectories simulated with 5-day mean velocities from an eddy-resolving ocean model (INALT01) for the Agulhas system. INALT01 features diffusive regimes for dynamically different regions, some of which exhibit strong suppression of eddy mixing by mean flow, and it is consistent with the pattern and magnitude of drifter-based eddy diffusivity estimates. Using monthly mean velocities decreases the estimated diffusivities less than eddy kinetic energy, supporting the idea that large and persistent eddy features dominate eddy diffusivities. For a noneddying ocean model (ORCA05), Lagrangian eddy diffusivities are greatly reduced, particularly when the Gent and McWilliams parameterization of mesoscale eddies is employed.