bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood group A and D negativity are associated with symptomatic West Nile virus infection
Authors: Kaidarova Zhanna , Bravo Marjorie D. , Kamel Hany T. , Custer Brian S. , Busch Michael P. , Lanteri Marion C. 
Published: May 2016

BACKGROUNDWest Nile virus (WNV) infection is mostly asymptomatic (AS) but 20% of subjects report WNV fever and 1% of patients experience neurologic diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic (S) infections, it is essential to understand prognostic factors influencing S disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. This study investigates the association between the ABO and D blood group status and WNV disease outcome.STUDY DESIGN AND METHODSThe distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 AS and 130 S WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O, and D blood groups and WNV clinical disease outcome.RESULTSS WNV+ donors exhibited increased frequencies of blood group A (S 47.6%, AS 36.8%, p = 0.04; odds ratio [OR], 1.56; 95% confidence interval [CI], 1.01‐2.40) and D– individuals (S 21.5%, AS 13.1%, p = 0.03; OR, 1.82; 95% CI, 1.04‐3.18).CONCLUSIONThe findings suggest a genetic susceptibility placing blood group A and D– individuals at risk for the development of S disease outcome after WNV infection.
The Effect of Variation of Plyometric Push-Ups on Force-Application Kinetics and Perception of Intensity
Authors: Dhahbi Wissem , Chaouachi Anis , Dhahbi Anis Ben , Cochrane Jodie , Chèze Laurence , Burnett Angus , Chamari Karim 
Published: May 2016

Purpose:To examine differences between ground-reaction-force (GRF)-based parameters collected from 5 types of plyometric push-ups. Between-trials reliability and the relationships between parameters were also assessed.Methods:Thirty-seven highly active commando soldiers performed 3 trials of 5 variations of the plyometric push-up in a counterbalanced order: standard countermovement push-up (SCPu), standard squat push-up (SSPu), kneeling countermovement push-up (KCPu), kneeling squat push-up (KSPu), and drop-fall push-up (DFPu). Vertical GRF was measured during these exercises using a portable Kistler force plate. The GRF applied by the hands in the starting position (initial force supported), peak GRF and rate of force development during takeoff, flight time, impact force, and rate of force development impact on landing were determined.Results:During standard-position exercises (SCPu and SSPu) the initial force supported and impact force were higher (P < .001) than with kneeling exercises (KCPu, KSPu, and DFPu). The peak GRF and rate of force development during takeoff were higher (P < .001) in the countermovement push-up exercises ([CMP] SCPu, KCPu, and DFPu) than squat push-up exercises ([SP] SSPu and KSPu). Furthermore, the flight time was greater (P < .001) during kneeling exercises than during standard-position exercises. A significant relationship (P < .01) between impact force and the rate of force development impact was observed for CMP and SP exercises (r = .83 and r = .62, respectively). The initial force supported was also negatively related (P < .01) to the flight time for both CMP and SP (r = –.74 and r = –.80, respectively). It was revealed that the initial force supported and the peak GRF during takeoff had excellent reliability; however, other parameters had poor absolute reliability.Conclusions:It is possible to adjust the intensity of plyometric push-up exercises and train athletes’ muscle power by correctly interpreting GRF-based parameters. However, caution is required as some parameters had marginal absolute reliability.
Type I Interferons in Newborns—Neurotoxicity versus Antiviral Defense
Authors: Bogunovic Dusan 
Published: May 2016

ABSTRACT

In most children and adults, primary infection with herpes simplex virus 1 (HSV-1) is asymptomatic. However, very rarely (incidence of 1 in 1,000,000), it can cause herpes simplex encephalitis (HSE). HSE also occurs in infants but with a much starker incidence of one in three. This age difference in susceptibility to HSV-1-caused HSE is not well understood. In a recent article in
mBio
, authors have identified the choroid plexus as the anatomical site of robust HSV-1 replication in the brain. They point to low levels of type I interferon (IFN) receptor as causal of the lack of HSV-1 replication control in neonates, in contrast to adults. Here, I discuss these findings in the context of human genetic evidence. I point to the balancing act of type I IFN acting as a neurotoxin and an antiviral agent, an evolutionary choice of a lesser evil.
Evolution of Myeloid Cells
Authors: Barreda Daniel R. , Neely Harold R. , Flajnik Martin F. 
Published: May 2016

ABSTRACTIn 1882, Elie Metchnikoff identified myeloid-like cells from starfish larvae responding to the invasion by a foreign body (rose thorn). This marked the origins for the study of innate immunity, and an appreciation that cellular immunity was well established even in these “primitive” organisms. This chapter focuses on these myeloid cells as well as the newest members of this family, the dendritic cells, and explores their evolutionary origins. Our goal is to provide evolutionary context for the development of the multilayered immune system of mammals, where myeloid cells now serve as central effectors of innate immunity and regulators of adaptive immunity. Overall, we find that core contributions of myeloid cells to the regulation of inflammation are based on mechanisms that have been honed over hundreds of millions of years of evolution. Using phagocytosis as a platform, we show how fairly simple beginnings have offered a robust foundation onto which additional control features have been integrated, resulting in central regulatory nodes that now manage multifactorial aspects of homeostasis and immunity.
Strategies Used by Bacteria to Grow in Macrophages
Authors: Mitchell* Gabriel , Chen* Chen , Portnoy Daniel A. 
Published: May 2016

ABSTRACTIntracellular bacteria are often clinically relevant pathogens that infect virtually every cell type found in host organisms. However, myeloid cells, especially macrophages, constitute the primary cells targeted by most species of intracellular bacteria. Paradoxically, macrophages possess an extensive antimicrobial arsenal and are efficient at killing microbes. In addition to their ability to detect and signal the presence of pathogens, macrophages sequester and digest microorganisms using the phagolysosomal and autophagy pathways or, ultimately, eliminate themselves through the induction of programmed cell death. Consequently, intracellular bacteria influence numerous host processes and deploy sophisticated strategies to replicate within these host cells. Although most intracellular bacteria have a unique intracellular life cycle, these pathogens are broadly categorized into intravacuolar and cytosolic bacteria. Following phagocytosis, intravacuolar bacteria reside in the host endomembrane system and, to some extent, are protected from the host cytosolic innate immune defenses. However, the intravacuolar lifestyle requires the generation and maintenance of unique specialized bacteria-containing vacuoles and involves a complex network of host-pathogen interactions. Conversely, cytosolic bacteria escape the phagolysosomal pathway and thrive in the nutrient-rich cytosol despite the presence of host cell-autonomous defenses. The understanding of host-pathogen interactions involved in the pathogenesis of intracellular bacteria will continue to provide mechanistic insights into basic cellular processes and may lead to the discovery of novel therapeutics targeting infectious and inflammatory diseases.
Candida–Bacteria Interactions: Their Impact on Human Disease
Authors: Allison Devon L. , Willems Hubertine M. E. , Jayatilake J.A.M.S. , Bruno Vincent M. , Peters Brian M. , Shirtliff Mark E. 
Published: May 2016

ABSTRACTCandidaspecies are the most common infectious fungal species in humans; out of the approximately 150 known species,Candida albicansis the leading pathogenic species, largely affecting immunocompromised individuals. Apart from its role as the primary etiology for various types of candidiasis,C. albicansis known to contribute to polymicrobial infections. Polymicrobial interactions, particularly betweenC. albicansand bacterial species, have gained recent interest in which polymicrobial biofilm virulence mechanisms have been studied including adhesion, invasion, quorum sensing, and development of antimicrobial resistance. These trans-kingdom interactions, either synergistic or antagonistic, may help modulate the virulence and pathogenicity of bothCandidaand bacteria while uniquely impacting the pathogen–host immune response. As antibiotic and antifungal resistance increases, there is a great need to explore the intermicrobial cross-talk with a focus on the treatment ofCandida-associated polymicrobial infections. This article explores the current literature on the interactions betweenCandidaand clinically important bacteria and evaluates these interactions in the context of pathogenesis, diagnosis, and disease management.
Symptoms of depression and all-cause mortality in farmers, a cohort study: the HUNT study, Norway
Authors: Letnes Jon Magne , Torske Magnhild Oust , Hilt Bjørn , Bjørngaard Johan Håkon , Krokstad Steinar 
Published: May 2016

ObjectivesTo explore all-cause mortality and the association between symptoms of depression and all-cause mortality in farmers compared with other occupational groups, using a prospective cohort design.MethodsWe included adult participants with a known occupation from the second wave of the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag 2 (HUNT2) 1995–1997), Norway. Complete information on emigration and death from all causes was obtained from the National Registries. We used the depression subscale of the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of depression. We compared farmers to 4 other occupational groups. Our baseline study population comprised 32 618 participants. Statistical analyses were performed using the Cox proportional hazards models.ResultsThe estimated mortality risk in farmers was lower than in all other occupations combined, with a sex and age-adjusted HR (0.91, 95% CI 0.82 to 1.00). However, farmers had an 11% increased age-adjusted and sex-adjusted mortality risk compared with the highest ranked socioeconomic group (HR 1.11, 95% CI 0.98 to 1.25). In farmers, symptoms of depression were associated with a 13% increase in sex-adjusted and age-adjusted mortality risk (HR 1.13, 95% CI 0.88 to 1.45). Compared with other occupations this was the lowest HR, also after adjusting for education, marital status, long-lasting limiting somatic illness and lifestyle factors (HR 1.08, 95% CI 0.84 to 1.39).ConclusionsFarmers had lower all-cause mortality compared with the other occupational groups combined. Symptoms of depression were associated with an increased mortality risk in farmers, but the risk increase was smaller compared with the other occupational groups.
Service factors causing delay in specialist assessment for TIA and minor stroke: a qualitative study of GP and patient perspectives
Authors: Wilson Andrew , Coleby Dawn , Regen Emma , Phelps Kay , Windridge Kate , Willars Janet , Robinson Tom 
Published: May 2016

ObjectiveTo understand how service factors contribute to delays to specialist assessment following transient ischaemic attack (TIA) or minor stroke.DesignQualitative study using semistructured interviews, analysis by constant comparison.SettingLeicester, UK.ParticipantsPatients diagnosed with TIA or minor stroke, at hospital admission or in a rapid-access TIA clinic (n=42), general practitioners (GPs) of participating patients if they had been involved in the patients’ care (n=18).DataAccounts from patients and GPs of factors contributing to delay following action to seek help from a healthcare professional (HCP).ResultsThe following categories of delay were identified. First, delay in assessment in general practice following contact with the service; this related to availability of same day appointments, and the role of the receptionist in identifying urgent cases. Second, delays in diagnosis by the HCP first consulted, including GPs, optometrists, out-of-hours services, walk-in centres and the emergency department. Third, delays in referral after a suspected diagnosis; these included variable use of the ABCD2(Age, Blood pressure, Clinical features, Duration, Diabetes) risk stratification score and referral templates in general practice, and referral back to the patients’ GP in cases where he/she was not the first HCP consulted.ConclusionsPrimary and emergency care providers need to review how they can best handle patients presenting with symptoms that could be due to stroke or TIA. In general practice, this may include receptionist training and/or triage by a nurse or doctor. Mechanisms need to be established to enable direct referral to the TIA clinic when patients whose symptoms have resolved present to other agencies. Further work is needed to improve diagnostic accuracy by non-specialists.
The costs of inequality: whole-population modelling study of lifetime inpatient hospital costs in the English National Health Service by level of neighbourhood deprivation
Authors: Asaria Miqdad , Doran Tim , Cookson Richard 
Published: May 2016

BackgroundThere are substantial socioeconomic inequalities in both life expectancy and healthcare use in England. In this study, we describe how these two sets of inequalities interact by estimating the social gradient in hospital costs across the life course.MethodsHospital episode statistics, population and index of multiple deprivation data were combined at lower-layer super output area level to estimate inpatient hospital costs for 2011/2012 by age, sex and deprivation quintile. Survival curves were estimated for each of the deprivation groups and used to estimate expected annual costs and cumulative lifetime costs.ResultsA steep social gradient was observed in overall inpatient hospital admissions, with rates ranging from 31 298/100 000 population in the most affluent fifth of areas to 43 385 in the most deprived fifth. This gradient was steeper for emergency than for elective admissions. The total cost associated with this inequality in 2011/2012 was £4.8 billion. A social gradient was also observed in the modelled lifetime costs where the lower life expectancy was not sufficient to outweigh the higher average costs in the more deprived populations. Lifetime costs for women were 14% greater than for men, due to higher costs in the reproductive years and greater life expectancy.ConclusionsSocioeconomic inequalities result in increased morbidity and decreased life expectancy. Interventions to reduce inequality and improve health in more deprived neighbourhoods have the potential to save money for health systems not only within years but across peoples’ entire lifetimes, despite increased costs due to longer life expectancies.
α‐Chloralose poisoning in a cat
Authors: Grau‐Roma Llorenç , Stephens Adam , Wessmann Annette , Carmichael Nick , de Brot Simone 
Published: May 2016

A five‐year‐old domestic cat with acute unexplainable neurological signs was presented for postmortem examination. Clinically, the cat showed an acute onset of ataxia, depressed mentation and continuous twitching/seizure activity in the morning after having been outside overnight. Despite immediate treatment, the cat progressed within 24 hours to a comatose state, opisthotonus and severe miosis unresponsive to light. Given a poor prognosis, euthanasia was elected. Gross findings were disappointing and consisted of a non‐specific lung oedema and congested lungs and spleen. Surprisingly, within the stomach and intestines, fragments of cockshafers were found. Histological examination confirmed the gross findings and additionally showed evidence of mild brain oedema, but failed to identify a cause for the severe clinical signs. In a final attempt to solve the case, a urine sample was tested for toxic substances and it was found to contain a significant amount of α‐chloralose. This finding was unexpected.
My Text in Your Handwriting
Authors: Haines Tom S. F. , Mac Aodha Oisin , Brostow Gabriel J. 
Published: May 2016

There are many scenarios where we wish to imitate a specific author’s pen-on-paper handwriting style. Rendering new text in someone’s handwriting is difficult because natural handwriting is highly variable, yet follows both intentional and involuntary structure that makes a person’s style self-consistent. The variability means that naive example-based texture synthesis can be conspicuously repetitive.
We propose an algorithm that renders a desired input string in an author’s handwriting. An annotated sample of the author’s handwriting is required; the system is flexible enough that historical documents can usually be used with only a little extra effort. Experiments show that our glyph-centric approach, with learned parameters for spacing, line thickness, and pressure, produces novel images of handwriting that look hand-made to casual observers, even when printed on paper.
Downregulation of the TGFβ Pseudoreceptor BAMBI in Non–Small Cell Lung Cancer Enhances TGFβ Signaling and Invasion
Authors: Marwitz Sebastian , Depner Sofia , Dvornikov Dmytro , Merkle Ruth , Szczygieł Magdalena , Müller-Decker Karin , Lucarelli Philippe , Wäsch Marvin , Mairbäurl Heimo , Rabe Klaus F. , Kugler Christian , Vollmer Ekkehard , Reck Martin , Scheufele Swetlana , Kröger Maren , Ammerpohl Ole , Siebert Reiner , Goldmann Torsten , Klingmüller Ursula 
Published: May 2016

Abstract
Non–small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in this disease. Substantial activation of this pathway was detected in human lung cancer tissues with concomitant downregulation of BAMBI, a negative regulator of the TGFβ signaling pathway. Alterations of epithelial-to-mesenchymal transition (EMT) marker expression were observed in lung cancer samples compared with tumor-free tissues. Distinct alterations in the DNA methylation of the gene regions encoding TGFβ pathway components were detected in NSCLC samples compared with tumor-free lung tissues. In particular, epigenetic silencing of BAMBI was identified as a hallmark of NSCLC. Reconstitution of BAMBI expression in NSCLC cells resulted in a marked reduction of TGFβ-induced EMT, migration, and invasion in vitro, along with reduced tumor burden and tumor growth in vivo. In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFβ signaling as a candidate therapeutic target in this setting. Cancer Res; 76(13); 3785–801. ©2016 AACR.
mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress
Authors: Li Jing , Shin Sejeong , Sun Yang , Yoon Sang-Oh , Li Chenggang , Zhang Erik , Yu Jane , Zhang Jianming , Blenis John 
Published: May 2016

Abstract
mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. Cancer Res; 76(16); 4816–27. ©2016 AACR.
Circulating Cancer-Associated Macrophage-Like Cells Differentiate Malignant Breast Cancer and Benign Breast Conditions
Authors: Adams Daniel L. , Adams Diane K. , Alpaugh R. Katherine , Cristofanilli Massimo , Martin Stuart S. , Chumsri Saranya , Tang Cha-Mei , Marks Jeffrey R. 
Published: May 2016

Abstract
Background: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation.
Methods: We report on two related but separate studies: 1) CellSieve microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n = 41). Prevalence and specificity was compared against healthy volunteers (n = 16). 2) A follow-up double-blind pilot study was conducted on women (n = 41) undergoing core-needle biopsy to diagnose suspicious breast masses.
Results: CAMLs were found in 93% of known malignant patients (n = 38/41), averaging 19.4 cells per sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n = 15/17) and 26% with benign breast conditions (n = 5/19).
Conclusion: These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals.
Impact: We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage. Cancer Epidemiol Biomarkers Prev; 25(7); 1037–42. ©2016 AACR.