bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection
Authors: Hochman Sarah E. , Madaline Theresa F. , Wassmer Samuel C. , Mbale Emmie , Choi Namjong , Seydel Karl B. , Whitten Richard O. , Varughese Julie , Grau Georges E. R. , Kamiza Steve , Molyneux Malcolm E. , Taylor Terrie E. , Lee Sunhee , Milner Danny A. , Kim Kami 
Published: September 2015

ABSTRACT

Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%,
P
< 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%,
P
= 0.0178, chi-square test). HIV-infected (HIV
+
) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months,
P
= 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV
+
and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV
+
children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV
+
children exacerbates the pathological features associated with CM.

IMPORTANCE
There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing coma and death are uncertain. Sub-Saharan Africa has a high HIV prevalence, with 3 million HIV-infected (HIV
+
) children, but the effects of HIV on CM pathogenesis and mortality are unknown. In a study of pediatric CM in Malawi, HIV prevalence was high and CM-attributed mortality was higher in HIV
+
than in HIV-uninfected children. Brain pathology in children with fatal CM was notable not only for sequestered malaria parasites but also for intravascular accumulations of monocytes and platelets that were more severe in HIV
+
children. Our findings raise the possibility that HIV
+
children at risk for malaria may benefit from targeted malaria prophylaxis and that adjunctive treatments targeting inflammation and/or coagulation may improve CM outcomes.
The Widespread Multidrug-Resistant Serotype O12 Pseudomonas aeruginosa Clone Emerged through Concomitant Horizontal Transfer of Serotype Antigen and Antibiotic Resistance Gene Clusters
Authors: Thrane Sandra Wingaard , Taylor Véronique L. , Freschi Luca , Kukavica-Ibrulj Irena , Boyle Brian , Laroche Jérôme , Pirnay Jean-Paul , Lévesque Roger C. , Lam Joseph S. , Jelsbak Lars 
Published: September 2015

ABSTRACT

The O-specific antigen (OSA) in
Pseudomonas aeruginosa
lipopolysaccharide is highly varied by sugar identity, side chains, and bond between O-repeats. These differences classified
P. aeruginosa
into 20 distinct serotypes. In the past few decades, O12 has emerged as the predominant serotype in clinical settings and outbreaks. These serotype O12 isolates exhibit high levels of resistance to various classes of antibiotics. Here, we explore how the
P. aeruginosa
OSA biosynthesis gene clusters evolve in the population by investigating the association between the phylogenetic relationships among 83
P. aeruginosa
strains and their serotypes. While most serotypes were closely linked to the core genome phylogeny, we observed horizontal exchange of OSA biosynthesis genes among phylogenetically distinct
P. aeruginosa
strains. Specifically, we identified a “serotype island” ranging from 62 kb to 185 kb containing the
P. aeruginosa
O12 OSA gene cluster, an antibiotic resistance determinant (

gyrA
C248T

), and other genes that have been transferred between
P. aeruginosa
strains with distinct core genome architectures. We showed that these genes were likely acquired from an O12 serotype strain that is closely related to
P. aeruginosa
PA7. Acquisition and recombination of the “serotype island” resulted in displacement of the native OSA gene cluster and expression of the O12 serotype in the recipients. Serotype switching by recombination has apparently occurred multiple times involving bacteria of various genomic backgrounds. In conclusion, serotype switching in combination with acquisition of an antibiotic resistance determinant most likely contributed to the dissemination of the O12 serotype in clinical settings.

IMPORTANCE
Infection rates in hospital settings by multidrug-resistant (MDR)
Pseudomonas aeruginosa
clones have increased during the past decades, and serotype O12 is predominant among these epidemic strains. It is not known why the MDR phenotype is associated with serotype O12 and how this clone type has emerged. This study shows that evolution of MDR O12 strains involved a switch from an ancestral O4 serotype to O12. Serotype switching was the result of horizontal transfer and genetic recombination of lipopolysaccharide (LPS) biosynthesis genes originating from an MDR taxonomic outlier
P. aeruginosa
strain. Moreover, the recombination event also resulted in acquisition of antibiotic resistance genes. These results impact on our understanding of MDR outbreak strain and serotype evolution and can potentially assist in better monitoring and prevention.
Blastomyces
Virulence Adhesin-1 Protein Binding to Glycosaminoglycans Is Enhanced by Protein Disulfide Isomerase
Authors: Beaussart Audrey , Brandhorst Tristan , Dufrêne Yves F. , Klein Bruce S. 
Published: September 2015

ABSTRACT

Blastomyces
adhesin-1 (BAD-1) protein mediates the virulence of the yeast
Blastomyces dermatitidis
, in part by binding host lung tissue, the extracellular matrix, and cellular receptors via glycosaminoglycans (GAGs), such as heparan sulfate. The tandem repeats that make up over 90% of BAD-1 appear in their native state to be tightly folded into an inactive conformation, but recent work has shown that they become activated and adhesive upon reduction of a disulfide linkage. Here, atomic force microscopy (AFM) of a single BAD-1 molecule interacting with immobilized heparin revealed that binding is enhanced upon treatment with protein disulfide isomerase and dithiothreitol (PDI/DTT). PDI/DTT treatment of BAD-1 induced a plateau effect in atomic force signatures that was consistent with sequential rupture of tandem binding domains. Inhibition of PDI in murine macrophages blunted BAD-1 binding to heparin
in vitro
. Based on AFM, we found that a short Cardin-Weintraub sequence paired with a WxxWxxW sequence in the first, degenerate repeat at the N terminus of BAD-1 was sufficient to initiate heparin binding. Removal of half of the 41 BAD-1 tandem repeats led to weaker adhesion, illustrating their role in enhanced binding. Mass spectroscopy of the tandem repeat revealed that the PDI-induced interaction with heparin is characterized by ruptured disulfide bonds and that cysteine thiols remain reduced. Further binding studies showed direct involvement of thiols in heparin ligation. Thus, we propose that the N-terminal domain of BAD-1 governs the initial association with host GAGs and that proximity to GAG-associated host PDI catalyzes activation of additional binding motifs conserved within the tandem repeats, leading to enhanced avidity and availability of reduced thiols.

IMPORTANCE
Pathogenic fungi and other microbes must adhere to host tissue to initiate infection. Surface adhesins promote this event and may be required for disease pathogenesis. We studied a fungal adhesin essential for virulence (BAD-1;
Blastomyces
adhesin-1) and found that host products induce its structural reconfiguration and foster its optimal binding to tissue structures.
Enhancement of thermoelectric power factor in CrSi2 film via Si:B addition
Authors: Hou Q. R. , Gu B. F. , Chen Y. B. 
Published: September 2015

In this paper, we report a large enhancement in the thermoelectric power factor in CrSi2 film via Si:B (1 at.% B content) addition. The Si:B-enriched CrSi2 films are prepared by co-sputtering CrSi2 and heavily B-doped Si targets. Both X-ray diffraction patterns and Raman spectra confirm the formation of the crystalline phase CrSi2. Raman spectra also indicate the crystallization of the added Si:B. With the addition of Si:B, the electrical resistivity [Formula: see text] decreases especially at low temperatures while the Seebeck coefficient [Formula: see text] increases above 533 K. As a result, the thermoelectric power factor, [Formula: see text], is greatly enhanced and can reach [Formula: see text] at 583 K, which is much larger than that of the pure CrSi2 film.
Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies
Authors: van Harten-Gerritsen A. Suzanne , Balvers Michiel G.J. , Witkamp Renger F. , Kampman Ellen , van Duijnhoven Fränzel J.B. 
Published: September 2015

Abstract
Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a valuable next step. This review starts with an overview of inflammatory processes suggested to be involved in colorectal cancer progression and regulated by vitamin D. Next, we provide recommendations on how to study inflammatory markers in future epidemiologic studies on vitamin D and colorectal cancer survival. Mechanistic studies have shown that calcitriol—active form of vitamin D—influences inflammatory processes involved in cancer progression, including the enzyme cyclooxygenase 2, the NF-κB pathway, and the expression of the cytokines TNFα, IL1β, IL6, IL8, IL17, and TGFβ1. Based on this and taking into account methodologic issues, we recommend to include analysis of specific soluble peptides and proteins, such as cytokines, in future epidemiologic studies on this issue. Vitamin D and the markers should preferably be measured at multiple time points during disease progression or recovery and analyzed using mediation analysis. Including these markers in epidemiologic studies may help answer whether inflammation mediates a causal relationship between vitamin D and colorectal cancer survival. Cancer Epidemiol Biomarkers Prev; 24(12); 1820–8. ©2015 AACR.
Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research
Authors: Michaud Dominique S. , Houseman E. Andres , Marsit Carmen J. , Nelson Heather H. , Wiencke John K. , Kelsey Karl T. 
Published: September 2015

AbstractUnderstanding the precise role of the immune system in cancer has been hindered by the complexity of the immune response and challenges in measuring immune cell types in health and disease in the context of large epidemiologic studies. In this review, we present the rationale to study immunity in cancer and highlight newly available tools to further elucidate the epidemiologic factors driving individual variation in the immune response in cancer. Here, we summarize key studies that have evaluated the role of immunologic status on risk of cancer, discuss tools that have been used in epidemiologic studies to measure immune status, as well as new evolving methodologies where application to epidemiology is becoming more feasible. We also encourage further development of novel emerging technologies that will continue to enable prospective assessment of the dynamic and complex role played by the immune system in cancer susceptibility. Finally, we summarize characteristics and environmental factors that affect the immune response, as these will need to be considered in epidemiologic settings. Overall, we consider the application of a systems biologic approach and highlight new opportunities to understand the immune response in cancer risk. Cancer Epidemiol Biomarkers Prev; 24(12); 1811–9. ©2015 AACR.
Perihematomal Edema and Functional Outcomes in Intracerebral Hemorrhage
Authors: Murthy Santosh B. , Moradiya Yogesh , Dawson Jesse , Lees Kennedy R. , Hanley Daniel F. , Ziai Wendy C. ,   VISTA-ICH Steering Committee Collborators are:, Butcher K. , Davis S. , Gregson B. , Lyden P. , Mayer S. , Muir K. , Steiner T. 
Published: September 2015

Background and Purpose—
Perihematomal edema (PHE) is associated with poor outcomes after intracerebral hemorrhage (ICH). PHE evolves in the early period after ICH, providing a therapeutic target and window for intervention. We studied the effect of PHE volume expansion in the first 72 hours (iPHE) and its relationship with functional outcomes.

Methods—
We used data contained in the Virtual International Stroke Trials Archive. We included patients who presented within 6 hours of symptom onset, had baseline clinical, radiological, and laboratory data, and further computed tomographic scan data at 72 hours and 90-day functional outcomes. We calculated iPHE and used logistic regression analysis to assess relationships with outcome. We adjusted for confounding variables and the primary outcome measure poor day-90 outcome (defined as modified Rankin Scale score of ≥3. We performed subgroup analyses by location and by volume of ICH.

Results—
We included 596 patients with ICH. Median baseline hematoma volume was 15.0 mL (IQR, 7.9–29.2) and median baseline PHE volume was 8.7 mL (IQR, 4.5–15.5). Hematoma expansion occurred in 122 (34.9%) patients. Median iPHE was 14.7 mL (IQR, 6.6–30.3). The odds of a poor outcome were greater with increasing iPHE (OR, 1.78; CI, 1.12–2.64 per mL increase). Subgroup analyses showed that iPHE was only related to poor functional outcomes in basal ganglia and small (<30 mL) ICH.

Conclusions—
Absolute increase in PHE during 72 hours was associated with worse functional outcomes after ICH, particularly with basal ganglia ICH and hematomas <30 mL.
Fibroblast Growth Factor 23 and Incidence of Subarachnoid Hemorrhage
Authors: Söderholm Martin , Engström Gunnar 
Published: September 2015

Background and Purpose—
Fibroblast growth factor 23 (FGF23) is a hormone with regulatory effects on mineral metabolism and arterial calcification. We aimed to study the association between FGF23 and risk of incident subarachnoid hemorrhage (SAH) in a nested case-control study.

Methods—
FGF23 was analyzed in stored blood samples from incident SAH cases (n=79) and control subjects (n=232), participating in the prospective, population-based Malmö Diet and Cancer Study. The association between FGF23 and SAH was studied using conditional logistic regression.

Results—

High FGF23 was associated with incident SAH. In the highest compared with the lowest quartile of FGF23, the odds ratio for SAH was 3.28 (95% confidence interval, 1.34–8.00),
P
for trend=0.006, after adjustment for SAH risk factors.

Conclusions—
High FGF23 was associated with increased risk of incident SAH in subjects from the general population. Further studies should elucidate whether FGF23 is a causal risk factor for SAH, or could be used in risk prediction.
Sedum album subsp. rupi-melitense (Crassulaceae), a new vegetatively reproducing subspecies from Malta (Maltese Islands, Central Mediterranean)
Authors: Mifsud Stephen Martin , Stephenson Ray , Thiede Joachim 
Published: September 2015

Plants of Sedum album (Sedum ser. Alba; Crassulaceae) from Malta (Maltese Islands) differ from previously known S. album plants in having very rarely formed inflorescences mostly without peduncular leaves and floral bracts, flowers in which (3–)5 stamens of one whorl, mostly of the antepetalous one, have dysfunctional and often abortive anthers and only the stamens of the other whorl having 5, dark maroon to blackish-brown, mostly indehiscent anthers at anthesis, pollen which is partly deformed and shrivelled, carpels without nectary scales, and fruits and seeds which remain undeveloped and sterile. The Maltese plants have apparently switched from generative to almost exclusively vegetative reproduction and are described as a new endemic subspecies Sedum album subsp. rupi-melitense. The local history, distribution, habitat, phenology, and conservation status of this new taxon (which is categorized as Critically Endangered according to IUCN Red List Criteria) are discussed.
Integration of Scientific Echo Sounders with an Adaptable Autonomous Vehicle to Extend Our Understanding of Animals from the Surface to the Bathypelagic
Authors: Moline Mark A. , Benoit-Bird Kelly , O’Gorman David , Robbins Ian C. 
Published: September 2015

AbstractAcoustic echo sounders designed to map and discriminate organisms in the water column have primarily been deployed on ships. Because of acoustic attenuation of higher frequencies used to detect and discriminate micronekton and nekton, this has effectively restricted the range of this information to the upper water column. In an effort to overcome these range limitations by reducing the distance between the transducer and the targets of interest, dual-frequency (38 and 120 kHz) split-beam echo sounders were integrated into a Remote Environmental Monitoring Units (REMUS) 600 autonomous underwater vehicle (AUV), effectively doubling the range of quantitative acoustic data into the mesopelagic zone (600–1200 m). Data from the first set of missions in a range of conditions revealed that the AUV provided a stable platform for the echo sounders and improved vertical and horizontal positional accuracy over echo sounders towed by ships. In comparison to hull-mounted echo sounders, elimination of ship noise and surface bubbles provided a 17- and 19-dBW decrease in the noise floor for the 38- and 120-kHz echo sounders, respectively, effectively increasing the sampling range by 30%–40%. The extended depth range also increased the resolution of the acoustic horizontal footprint from 37–40 to 0.6–3.7 m, enabling discrimination of individual targets at depth. Also developed here is novel onboard echo sounder data processing and autonomy to allow sampling not feasible in a surface ship or towed configuration. Taken together, these data demonstrate an effective new tool for examining the biology of animals in the mesopelagic zone (600–1200 m) in ways previously only possible in the upper ocean.
Long-term effects of a progressive and specific balance-training programme with multi-task exercises for older adults with osteoporosis: a randomized controlled study
Authors: Halvarsson Alexandra , Oddsson Lars , Franzén Erika , Ståhle Agneta 
Published: September 2015

Objective: To evaluate long-term effects of balance-training on concerns about falling, gait, balance performance, and physical function in older adults with osteoporosis and increased risk of falling. Design: Randomized controlled trial, including three groups (training, training+physical activity, and control group), with follow-ups at three, nine, and 15 months. Short-term, three-month follow-up, benefits for those who fulfilled the first follow-up ( n = 69) have previously been reported. Setting: Stockholm, Sweden. Participants: A total of 96 elderly, age 66–87, with verified osteoporosis. Interventions: Balance-training programme including dual- and multitasks, with or without supplementary physical activity, three times/week over 12 weeks. Measurements: Concerns about falling Falls Efficacy Scale -International (FES-I), walking at preferred speed with and without a cognitive dual-task and at fast speed, balance tests (one-leg stance and modified figure-of-eight), and physical function Late-Life Function and Disability Instrument (LLFDI). Results: Participants in the training group maintained positive effects throughout the study period for concerns about falling (baseline vs. 15 months, median 27.5 vs. 23 points, p < 0.001) and walking performance (baseline vs. 15 months, p ⩽ 0.05 with an improvement of 0.9–1.4 m/s). The Training+physical activity group declined to baseline values at the nine-month follow-up, and were even lower at the 15-month follow-up for concerns about falling (median 26 vs. 26 points), walking performance (changes of −0.02 to 0.04 m/s), and physical function (mean 44.0 vs. 42.9 points). The control group remained unchanged throughout the study period. Conclusions: This balance-training programme reduced concerns about falling, and also improved gait in older adults with osteoporosis and increased risk of falling in a long-term perspective – important issues for fall prevention.
Creative art therapy to enhance rehabilitation for stroke patients: a randomized controlled trial
Authors: Kongkasuwan Ratcharin , Voraakhom Kotchakorn , Pisolayabutra Prim , Maneechai Pichai , Boonin Jiraporn , Kuptniratsaikul Vilai 
Published: September 2015

Objective: To examine the efficacy of creative art therapy plus conventional physical therapy, compared with physical therapy only, in increasing cognitive ability, physical functions, psychological status and quality of life of stroke patients. Design: Randomized controlled trial with blinded assessor. Setting: An in-patient setting Participants: One hundred and eighteen stroke patients aged ⩾50 years who could communicate verbally. Interventions: All participants received conventional physical therapy five days per week. An intervention group received additional creative art therapy, twice a week for four weeks, in a rehabilitation ward. Main outcomes: Cognitive function, anxiety and depression, physical performance and quality of life were measured with the Abbreviated Mental Test, the Hospital Anxiety and Depression Scale, the modified Barthel Index scale and the pictorial Thai Quality of Life questionnaire, respectively. Results: Mean differences for the intervention group were significantly greater than the control group for depression (−4.5, 95% CI −6.5, −2.5, p< 0.001), physical functions (1.2, 95% CI 0.1, 2.3, p= 0.043) and quality of life (8.9, 95% CI 3.8, 13.8, p< 0.001).Compared with baseline measures, both groups experienced improved cognition, physical functions and quality of life and reduced anxiety and depression. Eighty-five percent of patients were satisfied with the creative art therapy and most reported improved concentration (68.5%), emotion (79.6%), self-confidence (72.2%) and motivation (74.1%). Conclusion: Creative art therapy combined with conventional physical therapy can significantly decrease depression, improve physical functions and increase quality of life compared with physical therapy alone.