bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for service use and trends in coverage of different HIV testing and counselling models in northwest Tanzania between 2003 and 2010
Authors: Cawley Caoimhe , Wringe Alison , Todd Jim , Gourlay Annabelle , Clark Benjamin , Masesa Clemens , Machemba Richard , Reniers Georges , Urassa Mark , Zaba Basia 
Published: July 2015

AbstractObjectivesTo investigate the relative effectiveness of different HIV testing and counselling (HTC) services in improving HIV diagnosis rates and increasing HTC coverage in African settings.MethodsPatient records from three HTC services [community outreach HTC during cohort study rounds (CO‐HTC), walk‐in HTC at the local health centre (WI‐HTC) and antenatal HIV testing (ANC‐HTC)] were linked to records from a community cohort study using a probabilistic record linkage algorithm. Characteristics of linked users of each HTC service were compared to those of cohort participants who did not use the HTC service using logistic regression. Data from three cohort study rounds between 2003 and 2010 were used to assess trends in the proportion of persons testing at different service types.ResultsThe adjusted odds ratios for HTC use among men with increasing numbers of sexual partners in the past year, and among HIV‐positive men and women compared to HIV‐negative men and women, were higher at WI‐HTC than at CO‐HTC and ANC‐HTC. Among sero‐survey participants, the largest numbers of HIV‐positive men and women learned their status via CO‐HTC. However, we are likely to have underestimated the numbers diagnosed at WI‐HTC and ANC‐HTC, due to low sensitivity of the probabilistic record linkage algorithm.ConclusionsCompared to CO‐HTC or ANC‐HTC, WI‐HTC was most likely to attract HIV‐positive men and women, and to attract men with greater numbers of sexual partners. Further research should aim to optimise probabilistic record linkage techniques, and to investigate which types of HTC services most effectively link HIV‐positive people to treatment services relative to the total cost per diagnosis made.
Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy products and biologic profile in treated patients
Authors: Tournois Claire , Pignon Bernard , Sevestre Marie‐Antoinette , Djerada Zoubir , Capiod Jean‐Claude , Poitevin Gaël , Delloup Anne‐Marie , Nguyen Philippe 
Published: July 2015

BACKGROUNDCell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). Autologous cell therapy products (CTP) are obtained from patients with advanced peripheral arterial disease to be injected at the site of ischemia. Thrombogenicity of CTPs has not yet been assessed. The objectives were: 1) to assess thrombotic risk in candidates for cell therapy, 2) to evaluate two different CTPs in terms of thrombogenic potential, and 3) to evaluate clinical thrombotic events.STUDY DESIGN AND METHODSIn this ancillary study of a Phase I and II clinical trial, bone marrow (BM)‐CTPs (n = 20) and CTPs obtained by cytapheresis (peripheral blood [PB]‐CTPs; n = 20) were compared. Inflammatory and coagulation markers were measured at baseline and 24 hours after CTP implantation. CTP cell content and tissue factor (TF) expression (mRNA and protein) were analyzed. Thrombin generation assessed CTP‐related thrombogenicity.RESULTSAll patients presented cardiovascular risk factors. At baseline, the patients’ biologic profile was characterized by high levels of fibrinogen, C‐reactive protein (CRP), D‐dimer, interleukin (IL)‐6, and plasmatic TF, whereas IL‐10 was low. Although different in terms of cell composition, both BM‐ and PB‐CTPs support low thrombin generation. Twenty‐four hours after implantation, biologic markers remained stable in the PB‐CTP group, except for IL‐6. In the BM‐CTP group, a significant increase of IL‐6 but also of CRP and D‐dimer was observed. Clinically, one single patient developed deep vein thrombosis 24 hours after the implantation of autologous PB‐CTP.CONCLUSIONCTPs supported low thrombin generation and were well tolerated after calf implantation.
Atmospheric circulation patterns influencing variations in organic carbon fluxes in the River Oulujoki, Finland
Authors: Marttila Hannu , Irannezhad Masoud , Saukkoriipi Jaakko , Kløve Bjørn 
Published: July 2015

AbstractAtmospheric circulation generally influences regional climate variability and thereby controls catchment hydrology and consequently transport of elements in natural riverine systems. This study examined dependencies between total organic carbon (TOC) variability in the River Oulujoki (Finland) during 1963–2011 and prominent atmospheric circulation patterns (ACPs), which manifest natural climatic conditions over Finland and control hydrological processes in the river catchment. North Atlantic Oscillation, Scandinavia, East Atlantic and East Atlantic/West Russia patterns were statistically significant ACPs affecting variations in TOC export at River Oulujoki lower basin area. In the River Oulujoki, TOC export was largely controlled by changes in TOC fluxes generated from tributaries of river and near areas to its main channel. Besides, runoff from Lake Oulujärvi slightly influenced TOC export variability in the River Oulujoki. Understanding such responses of TOC fluxes to ACPs is a useful tool for sustainable water resources planning and management on regional and local scales.
Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-σ Factor
Authors: Herrou Julien , Willett Jonathan W. , Crosson Sean 
Published: July 2015

ABSTRACT

The anti-σ factor NepR plays a central role in regulation of the general stress response (GSR) in alphaproteobacteria. This small protein has two known interaction partners: its cognate extracytoplasmic function (ECF) σ factor and the anti-anti-σ factor, PhyR. Stress-dependent phosphorylation of PhyR initiates a protein partner switch that promotes phospho-PhyR binding to NepR, which frees ECF σ to activate transcription of genes required for cell survival under adverse or fluctuating conditions. We have defined key functional roles for structured and intrinsically disordered domains of
Caulobacter crescentus
NepR in partner binding and activation of GSR transcription. We further demonstrate that NepR strongly stimulates the rate of PhyR phosphorylation
in vitro
and that this effect requires the structured and disordered domains of NepR. This result provides evidence for an additional layer of GSR regulation in which NepR directly influences activation of its binding partner, PhyR, as an anti-anti-σ factor. We conclude that structured and intrinsically disordered domains of NepR coordinately control multiple functions in the GSR signaling pathway, including core protein partner switch interactions and pathway activation by phosphorylation.

IMPORTANCE
Anti-σ factors are key molecular participants in a range of adaptive responses in bacteria. The anti-σ factor NepR plays a vital role in a multiprotein partner switch that governs general stress response (GSR) transcription in alphaproteobacteria. We have defined conserved and unconserved features of NepR structure that determine its function as an anti-σ factor and uncovered a functional role for intrinsically disordered regions of NepR in partner binding events required for GSR activation. We further demonstrate a novel function for NepR as an enhancer of PhyR phosphorylation; this activity also requires the disordered domains of NepR. Our results provide evidence for a new layer of GSR regulatory control in which NepR directly modulates PhyR phosphorylation and, hence, activation of the GSR.
Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance
Authors: Ene Iuliana V. , Walker Louise A. , Schiavone Marion , Lee Keunsook K. , Martin-Yken Hélène , Dague Etienne , Gow Neil A. R. , Munro Carol A. , Brown Alistair J. P. 
Published: July 2015

ABSTRACT

The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown
Candida albicans
cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock.

IMPORTANCE
The
C. albicans
cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by a network of cell wall polysaccharides, which are remodeled in response to growth conditions and environmental stress. However, little is known about how cell wall elasticity is regulated and how it affects adaptation to stresses such as sudden changes in osmolarity. We show that elasticity is critical for survival under conditions of osmotic shock, before stress signaling pathways have time to induce gene expression and drive glycerol accumulation. Critical cell wall remodeling enzymes control cell wall flexibility, and its regulation is strongly dependent on host nutritional inputs. We also demonstrate an entirely new level of cell wall dynamism, where significant architectural changes and structural realignment occur within seconds of an osmotic shock.
Biot number constraints on the thermal regime of acidic magmas in the subvolcanic crust: an integrated approach using numerical modelling and petrology
Authors: Pla F. , Álvarez-Valero A. M. 
Published: July 2015

Abstract
Crustal xenoliths are key subvolcanic material for studying processes that operate in a magma dyke during intrusion into its surrounding country rock. The Biot number is the appropriate parameter to advance knowledge of the rock–magma thermal interaction. We present an interactive approach that combines the petrological study of natural subvolcanic samples, through crustal xenoliths, which represents an essential pilot to explore and constrain the input parameters and boundary conditions in numerical simulations of fluid dynamics under a volcano. Our results – as a function of different dyke depths, aspect ratios and temperature gradients at the host and dyke – allow an accurate interpretation of the thermal history of magma flow in the dyke, revealing significant differences in heat transfer and thermal resistance between the crust and ascending magma. Conclusively, melt flow within rigid-walled channels depends directly on the depth (pressure gradient) and width of the dyke according to a balance between the rate of magma input and heat loss that determines how fast the magma may ascend. In addition, and with implications for crustal assimilation, there is evidence of a strong relationship between the preconditioning temperature and the integrity of the host rock over the time that xenoliths are immersed in the magma dyke.
Vitamin D and Cancer: Diversity, Complexity, and Still a Ways to Go
Authors: Albanes Demetrius 
Published: July 2015

AbstractVitamin D has taken a center-stage role in our basic and population research quest for the panacea for all human maladies, including cancer, yet sufficient evidence for a beneficial role has existed only for bone health. This Commentary discusses and places into a broader context the report of Chandler and colleagues that found a protective association for higher vitamin D status in colorectal cancer in women, consistent with most other cohort studies but not with limited supplementation trial data. Little human evidence exists for the preventive potential in other malignancies, including breast cancer, with the exception of possible benefit in bladder cancer and an adverse serologic association with prostate cancer (pancreatic cancer risk may be similarly influenced) that is supported by vitamin D genetic data. Current vitamin D trials are examining high-dose supplementation (i.e., 1,600–3,333 IU daily) for effects on multiple outcomes, but they may not have sufficient power to test efficacy in colorectal or other specific malignancies and are unlikely to inform any benefit for higher physiologic levels. A more complete understanding of vitamin D and human carcinogenesis will come from multifaceted lines of research, including elucidation of organ site–specific biologic mechanisms, prospective serologic analyses, testing of vitamin D–related genetic variation, and short-term clinical–metabolic biomarker studies of multidose vitamin D supplementation, including metabolomic profiling of controlled supplementation in these and past or ongoing trials. Cancer Prev Res; 8(8); 657–61. ©2015 AACR.See related article by Chandler et al., p. 675
Association of 6‐Minute Walk Performance and Physical Activity With Incident Ischemic Heart Disease Events and Stroke in Peripheral Artery Disease
Authors: McDermott Mary M. , Greenland Philip , Tian Lu , Kibbe Melina R. , Green David , Zhao Lihui , Criqui Michael H. , Guralnik Jack M. , Ferrucci Luigi , Liu Kiang , Wilkins John T. , Huffman Mark D. , Shah Sanjiv J. , Liao Yihua , Lloyd‐Jones Donald M. 
Published: July 2015

Background

We determined whether poorer 6‐minute walk performance and lower physical activity levels are associated with higher rates of ischemic heart disease (
IHD
) events in people with lower extremity peripheral artery disease (
PAD
).

Methods and Results

Five hundred ten
PAD
participants were identified from Chicago‐area medical centers and followed prospectively for 19.0±9.5 months. At baseline, participants completed the 6‐minute walk and reported number of blocks walked during the past week (physical activity).
IHD
events were systematically adjudicated and consisted of new myocardial infarction, unstable angina, and cardiac death. For 6‐minute walk, IHD event rates were 25/170 (14.7%) for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169 (3.5%) for the first (best) tertile (
P
=0.003). For physical activity, IHD event rates were 21/154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the second tertile, and 5/182 (2.7%) for the first (best) tertile (
P
=0.001). Adjusting for age, sex, race, smoking, body mass index, comorbidities, and physical activity, participants in the poorest 6‐minute walk tertile had a 3.28‐fold (95%
CI
1.17 to 9.17,
P
=0.024) higher hazard for
IHD
events, compared with those in the best tertile. Adjusting for confounders including 6‐minute walk, participants in the poorest physical activity tertile had a 3.72‐fold (95%
CI
1.24 to 11.19,
P
=0.019) higher hazard for
IHD
events, compared with the highest tertile.

Conclusions

Six‐minute walk and physical activity predict
IHD
event rates in
PAD
. Further study is needed to determine whether interventions that improve 6‐minute walk, physical activity, or both can reduce
IHD
events in
PAD
.
Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke
Authors: Andersson Charlotte , Preis Sarah R. , Beiser Alexa , DeCarli Charles , Wollert Kai C. , Wang Thomas J. , Januzzi James L. , Vasan Ramachandran S. , Seshadri Sudha 
Published: July 2015

Background and Purpose—
Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort.

Methods—
We followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination.

Results—

After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (
β
coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: −0.71% for GDF-15;
P
=0.002 and 0.47% for sST2;
P
=0.02) and worse performance on the visual reproduction test (
β
coefficients for Q4 versus Q1: −0.62 for GDF-15;
P
=0.009 and −0.40 for sST2;
P
=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (
β
for Q4 versus Q1=0.19;
P
=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and
P
=0.03.

Conclusions—
Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury.
Role of Neurexin-1β and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats
Authors: Shen Haitao , Chen Zhouqing , Wang Yang , Gao Anju , Li Haiying , Cui Yonghua , Zhang Li , Xu Xiang , Wang Zhong , Chen Gang 
Published: July 2015

Background and Purpose—
Neurexin-1β and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1β and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.

Methods—
In vivo, 228 Sprague–Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1β and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1β and neuroligin-1, as well as neurological outcome.

Results—
Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1β and neuroligin-1 and the interaction between neurexin-1β and neuroligin-1 in neurons. In addition, the interaction between neurexin-1β and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1β and neuroligin-1 and aggravated by the knockdown of neurexin-1β and neuroligin-1. More importantly, neurexin-1β and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1β and neuroligin-1 knockdown induced an opposite effect.

Conclusions—
Enhancing the expressions of neurexin-1β and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1β and neuroligin-1 might be good targets for improving cognitive function after SAH.
Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke
Authors: Acosta Sandra A. , Tajiri Naoki , Hoover Jaclyn , Kaneko Yuji , Borlongan Cesar V. 
Published: July 2015

Background and Purpose—
Adult stem cell therapy is an experimental stroke treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) in chronic stroke.

Methods—

At 60 days post stroke, adult Sprague–Dawley rats received intravenous hBMSCs (4×10
6
labeled or nonlabeled cells) or vehicle (saline). A sham surgery group served as additional control. In vivo imaging was conducted between 1 hour and 11 days post transplantation, followed by histological examination.

Results—

Labeled hBMSCs migrated to spleen which emitted significantly higher fluorescent signal across all time points, especially during the first hour, and were modestly detected in the head region at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused stroke animals, or sham (
P
<0.05). At 11 days post transplantation, ex vivo imaging confirmed preferential hBMSC migration to the spleen over the brain. Hematoxylin and eosin staining revealed significant 15% and 30% reductions in striatal infarct and peri-infarct area, and a trend of rescue against neuronal loss in the hippocampus. Unbiased stereology showed significant 75% and 60% decrements in major histocompatibility complex II–activated inflammatory cells in gray and white matter, and a 43% diminution in tumor necrosis factor-α cell density in the spleen of transplanted stroke animals compared with vehicle-infused stroke animals (
P
<0.05). Human antigen immunostaining revealed 0.03% hBMSCs survived in spleen and only 0.0007% in brain. MSC migration to spleen, but not brain, inversely correlated with reduced infarct, peri-infarct, and inflammation.

Conclusions—
hBMSC transplantation is therapeutic in chronic stroke possibly by abrogating the inflammation-plagued secondary cell death.