bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T cells: a potential target in cancer immunotherapy
Authors: Shitara Kohei , Nishikawa Hiroyoshi 
Published: March 2018

AbstractCancer immunotherapy involving blockade of immune checkpoint molecules, such as CTLA‐4 and PD‐1, has shown remarkable clinical success across several types of malignancies. However, a fraction of patients experience disease progression after treatment; thus, exploring resistant mechanisms for immune checkpoint inhibitors and improving their treatment outcome with additional modalities are of great importance. CD4+ regulatory T (Treg) cells characterized by expression of the master regulatory transcription factor FOXP3 are a highly immune‐suppressive subset of CD4+ T cells that maintain immune homeostasis. Several preclinical and clinical studies suggest that Treg cells hamper immune surveillance against cancer in healthy individuals, prevent the development of effective antitumor immunity in tumor‐bearing patients, and promote tumor progression. Therefore, targeting Treg cells should be crucial to improving the treatment outcomes of cancer immunotherapy. Several clinical studies directly or indirectly targeting Treg cells in combination with immune checkpoint inhibitors are ongoing or being planned. Understanding the characteristics and roles of Treg cells in cancer settings could make disease‐specific Treg‐targeted therapy more efficacious and reduce the incidence of immune‐related adverse effects mediated by Treg cell inhibition.
Is there a common experience? Somali new mothers’ childbirth experiences in Norway and the United States
Authors: Clark Connie Lynn , Glavin Kari , Missal Bernita Eileen , Sæteren Berit 
Published: March 2018

AbstractBackgroundDue to civil war, Somalis immigrants have settled in Norway and the United States. Large families are valued among Somalis and Somali women continue to give birth in their new countries. Research studies have been conducted with Somali immigrant new mothers in Norway and Minnesota, United States to understand perceptions of their childbirth experience.PurposeThe purpose of this qualitative study was to compare the childbirth experiences of Somali immigrant mothers in the United States and Norway to make recommendations to improve health care practice.DesignThis paper presents a comparison of two research studies in order to identify and explain similarities and differences between cross‐cultural immigrant populations.ResultsBoth studies identified themes related to the importance of family support in the postpartum period, fear of Cesarean delivery, and relationships with nurses. These studies give recommendations for nurses on how to provide culturally sensitive care for Somali new mothers.ConclusionsImplications for practice are that nurses should develop trusting relationships with Somali mothers and facilitate cultural and religious practices. Information regarding support resources in the community should be provided to Somali mothers throughout the perinatal period.
Profiling of
PDR1
and
MSH2
in Candida glabrata Bloodstream Isolates from a Multicenter Study in China
Authors: Hou Xin , Xiao Meng , Wang He , Yu Shu-Ying , Zhang Ge , Zhao Yanan , Xu Ying-Chun 
Published: March 2018

ABSTRACT

Among 158
Candida glabrata
bloodstream isolates collected from numerous centers in China, a resistance to fluconazole was seen in 8.9%. Three isolates (1.9%) were resistant to all echinocandins. Multilocus sequence typing (MLST) revealed that sequence type 7 ([ST7] 65.8%) was the most common type, followed by ST3 (7.6%).
PDR1
polymorphisms were associated with the acquisition of fluconazole resistance in
C. glabrata
isolates, while
MSH2
polymorphisms were associated with the STs and microsatellite genotypes, irrespective of fluconazole resistance.
Induction of Genes Encoding Plant Cell Wall-Degrading Carbohydrate-Active Enzymes by Lignocellulose-Derived Monosaccharides and Cellobiose in the White-Rot Fungus Dichomitus squalens
Authors: Casado López Sara , Peng Mao , Issak Tedros Yonatan , Daly Paul , de Vries Ronald P. , Mäkelä Miia R. 
Published: March 2018

ABSTRACT

Fungi can decompose plant biomass into small oligo- and monosaccharides to be used as carbon sources. Some of these small molecules may induce metabolic pathways and the production of extracellular enzymes targeted for degradation of plant cell wall polymers. Despite extensive studies in ascomycete fungi, little is known about the nature of inducers for the lignocellulolytic systems of basidiomycetes. In this study, we analyzed six sugars known to induce the expression of lignocellulolytic genes in ascomycetes for their role as inducers in the basidiomycete white-rot fungus
Dichomitus squalens
using a transcriptomic approach. This identified cellobiose and
l
-rhamnose as the main inducers of cellulolytic and pectinolytic genes, respectively, of
D. squalens
. Our results also identified differences in gene expression patterns between dikaryotic and monokaryotic strains of
D. squalens
cultivated on plant biomass-derived monosaccharides and the disaccharide cellobiose. This suggests that despite conservation of the induction between these two genetic forms of
D. squalens
, the fine-tuning in the gene regulation of lignocellulose conversion is differently organized in these strains.

IMPORTANCE
Wood-decomposing basidiomycete fungi have a major role in the global carbon cycle and are promising candidates for lignocellulosic biorefinery applications. However, information on which components trigger enzyme production is currently lacking, which is crucial for the efficient use of these fungi in biotechnology. In this study, transcriptomes of the white-rot fungus
Dichomitus squalens
from plant biomass-derived monosaccharide and cellobiose cultures were studied to identify compounds that induce the expression of genes involved in plant biomass degradation.
Candida albicans White-Opaque Switching Influences Virulence but Not Mating during Oropharyngeal Candidiasis
Authors: Solis Norma V. , Park Yang-Nim , Swidergall Marc , Daniels Karla J. , Filler Scott G. , Soll David R. 
Published: March 2018

ABSTRACT

The capacity of
Candida albicans
to switch reversibly between the white phenotype and the opaque phenotype is required for the fungus to mate. It also influences virulence during hematogenously disseminated candidiasis. We investigated the roles of the mating type loci (
MTL
) and white-opaque switching in the capacity of
C. albicans
to mate in the oropharynx and cause oropharyngeal candidiasis (OPC). When immunosuppressed mice were orally infected with mating-competent opaque
a/a
and α/α cells either alone or mixed with white cells, no detectable mating occurred, indicating that the mating frequency was less than 1.6 × 10
−6
. Opaque cells were also highly attenuated in virulence; they either were cleared from the oropharynx or switched to the white phenotype during OPC. Although there were strain-to-strain differences in the virulence of white cells, they were consistently more virulent than opaque cells.
In vitro
studies indicated that relative to white cells, opaque cells had decreased capacity to invade and damage oral epithelial cells. The reduced invasion of at least one opaque strain was due to reduced surface expression of the Als3 invasin and inability to activate the epidermal growth factor receptor, which is required to stimulate the epithelial cell endocytic machinery. These results suggest that mating is a rare event during OPC because opaque cells have reduced capacity to invade and damage the epithelial cells of the oral mucosa.
Staphylococcus aureus Utilizes Host-Derived Lipoprotein Particles as Sources of Fatty Acids
Authors: Delekta Phillip C. , Shook John C. , Lydic Todd A. , Mulks Martha H. , Hammer Neal D. 
Published: March 2018

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects of
S. aureus
physiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis (FASII) pathway. FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL), represent a potentially rich source of exogenous fatty acids for
S. aureus
during infection. We sought to test the ability of LDLs to serve as a fatty acid source for
S. aureus
and show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth of
S. aureus
fatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids for
S. aureus
during infection.

IMPORTANCE
Inhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused by
S. aureus
and other human pathogens. However,
S. aureus
incorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the clinical utility of targeting bacterial fatty acid synthesis is debated. Moreover, the fatty acid reservoir(s) exploited by
S. aureus
is not well understood. Human low-density lipoprotein particles represent a particularly abundant
in vivo
source of fatty acids and are present in tissues that
S. aureus
colonizes. Herein, we establish that
S. aureus
is capable of utilizing the fatty acids present in low-density lipoproteins to bypass both chemical and genetic inhibition of fatty acid synthesis. These findings imply that
S. aureus
targets LDLs as a source of fatty acids during pathogenesis.
High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia
Authors: Riley Thomas V. , Collins Deirdre A. , Karunakaran Rina , Kahar Maria Abdul , Adnan Ariza , Hassan Siti Asma , Zainul Nadiah Hanim , Rustam F. R. Mohammed , Wahab Z. Abd , Ramli Ramliza , Lee Yeong Yeh , Hassan Hamimah 
Published: March 2018

ABSTRACT

Accumulating evidence shows a high prevalence of
Clostridium difficile
in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated
C. difficile
infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of
C. difficile
characterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.
H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells
Authors: Mazel-Sanchez B. , Boal-Carvalho I. , Silva F. , Dijkman R. , Schmolke M. 
Published: March 2018

ABSTRACTHighly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans.IMPORTANCEAquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction factor of the viral polymerase complex HAX-1. Interestingly, we found that human influenza A virus polymerase complexes are already adapted to HAX-1 and do not require this function of PB1-F2. We thus propose that a functional full-length PB1-F2 supports direct transmission of bird viruses into humans.
Acceptability of a parental early warning tool for parents of infants with complex congenital heart disease: a qualitative feasibility study
Authors: Gaskin Kerry Louise , Wray Jo , Barron David J 
Published: March 2018

AimTo explore the acceptability and feasibility of a parental early warning tool, called the Congenital Heart Assessment Tool (CHAT), for parents going home with their infant between first and second stage of surgery for complex congenital heart disease.BackgroundHome monitoring programmes were developed to aid early recognition of deterioration in fragile infants between first and second surgical stage. However, this necessitates good discharge preparation to enable parents to develop appropriate knowledge and understanding of signs of deterioration to look for and who to contact.DesignThis was a longitudinal qualitative feasibility study, within a constructivist paradigm. Parents were taught how to use the CHAT before taking their infant home and asked to participate in semistructured interviews at four time points: before discharge (T0), 2 weeks after discharge (T1), 8 weeks after discharge (T2) and after stage 2 surgery (T3). Interviews were transcribed verbatim and thematically analysed.SettingOne tertiary children’s cardiac centre in the UK.SubjectsTwelve parents of eight infants who were discharged following first stage cardiac surgery for complex congenital heart disease, between August 2013 and February 2015.ResultsFour main themes emerged: (1) parental preparation and vigilance, (2) usability, (3) mastery, and (4) reassurance and support.ConclusionsThe study highlighted the benefit of appropriately preparing parents before discharge, using the CHAT, to enable identification of normal infant behaviour and to detect signs of clinical deterioration. The study also demonstrated the importance of providing parents with information about when and who to call for management advice and support.
Motivation and main flavour of use, use with nicotine and dual use of electronic cigarettes in Barcelona, Spain: a cross-sectional study
Authors: Bunch Kailey , Fu Marcela , Ballbè Montse , Matilla-Santader Nuria , Lidón-Moyano Cristina , Martin-Sanchez Juan Carlos , Fernandez Esteve , Martínez-Sánchez Jose M 
Published: March 2018

ObjectiveThis study seeks to describe current e-cigarette users’ patterns of use including primary motivation for use, dual use, use with nicotine and principal flavour used, according to individuals’ sociodemographic characteristics and conventional tobacco consumption in Barcelona, Spain.Design, setting and participantsThis is a cross-sectional study of adult (≥18) current e-cigarette users of Barcelona (n=600), recruited in 2015. Researchers calculated percentages and ORs with their 95% CIs of users’ e-cigarette use with nicotine, primary motivation for use and preferred flavour. The analyses were stratified by sociodemographic variables including sex, age and level of education and by patterns of e-cigarette use and past and current conventional tobacco use.ResultsThe most prevalent motivation for using e-cigarettes was to reduce tobacco smoking (48%, n=288), followed by quitting smoking (39.2%, n=235), and to use e-cigarettes in places where tobacco smoking was prohibited (10.2%, n=61). The most prevalent primary flavour used was tobacco (49%, n=294), followed by fruit (19.5%, n=117). People younger than 25 years old (OR=4.36, 95% CI 1.99 to 9.57) were more likely than older people to use them where smoking cigarettes was prohibited. A greater proportion of those in the youngest age group preferred fruit flavour compared with older individuals (29.3%, n=41).ConclusionsYounger users of e-cigarettes and non-smokers are more likely to use flavours other than tobacco and to use e-cigarettes mainly for recreational purposes.
A novel inpatient complex pain team: protocol for a mixed-methods evaluation of a single-centre pilot study
Authors: Mordecai Luke , Vindrola-Padros Cecilia , Wood Victoria J , Swart Nicholas , Morris Stephen , Williams Amanda , Curran Natasha , Moonesinghe Ramani 
Published: March 2018

IntroductionComplex pain is a debilitating condition that is responsible for low quality of life and significant economic impacts. Although best practice in the treatment of complex pain employs a multidisciplinary team, many patients do not have access to this care, leading to poor outcomes.Methods and analysisThis study evaluates a novel inpatient complex pain team at a large London teaching hospital. A multidisciplinary pain team comprising specialist doctors, nurses, psychologists and physiotherapists was instituted for inpatients with complex pain who will undergo an intense and bespoke evidence-based programme which will then be integrated into the community. A mixed-methods evaluation will take place and patients will be recruited over the course of 1 year. A qualitative arm will interview 15 staff and 15 patients on recruitment and again 6 months later looking to compare and contrast the new pain team with past experiences of pain management. A quantitative arm will assess clinical outcomes using validated scoring tools. An economic evaluation will seek to evaluate the relative cost of the service by comparing healthcare costs before and after the intervention.Ethics and disseminationThe study was categorised as a service evaluation, so formal ethical approval was not considered necessary. Participant recruitment began in January 2016 and the 1-year follow-up will end in November 2017. The results of this study will be published in 2018.
Reliability of coded data to identify earliest indications of cognitive decline, cognitive evaluation and Alzheimer’s disease diagnosis: a pilot study in England
Authors: Dell’Agnello Grazia , Desai Urvi , Kirson Noam Y , Wen Jody , Meiselbach Mark K , Reed Catherine C , Belger Mark , Lenox-Smith Alan , Martinez Carlos , Rasmussen Jill 
Published: March 2018

ObjectivesEvaluate the reliability of using diagnosis codes and prescription data to identify the timing of symptomatic onset, cognitive assessment and diagnosis of Alzheimer’s disease (AD) among patients diagnosed with AD.MethodsThis was a retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD). The study cohort consisted of a random sample of 50 patients with first AD diagnosis in 2010–2013. Additionally, patients were required to have a valid text-field code and a hospital episode or a referral in the 3 years before the first AD diagnosis. The earliest indications of cognitive impairment, cognitive assessment and AD diagnosis were identified using two approaches: (1) using an algorithm based on diagnostic codes and prescription drug information and (2) using information compiled from manual review of both text-based and coded data. The reliability of the code-based algorithm for identifying the earliest dates of the three measures described earlier was evaluated relative to the comprehensive second approach. Additionally, common cognitive assessments (with and without results) were described for both approaches.ResultsThe two approaches identified the same first dates of cognitive symptoms in 33 (66%) of the 50 patients, first cognitive assessment in 29 (58%) patients and first AD diagnosis in 43 (86%) patients. Allowing for the dates from the two approaches to be within 30 days, the code-based algorithm’s success rates increased to 74%, 70% and 94%, respectively. Mini-Mental State Examination was the most commonly observed cognitive assessment in both approaches; however, of the 53 tests performed, only 19 results were observed in the coded data.ConclusionsThe code-based algorithm shows promise for identifying the first AD diagnosis. However, the reliability of using coded data to identify earliest indications of cognitive impairment and cognitive assessments is questionable. Additionally, CPRD is not a recommended data source to identify results of cognitive assessments.