bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of B Cells in Host Defense against Primary Coxiella burnetii Infection
Authors: Schoenlaub Laura , Elliott Alexandra , Freches Danielle , Mitchell William J. , Zhang Guoquan 
Published: October 2015

ABSTRACTDespiteCoxiella burnetiibeing an obligate intracellular bacterial pathogen, our recent study demonstrated that B cells play a critical role in vaccine-induced immunity toC. burnetiiinfection by producing protective antibodies. However, the role of B cells in host defense against primaryC. burnetiiinfection remains unclear. In this study, we investigated whether B cells play an important role in host defense against primaryC. burnetiiinfection. The results showed that peritoneal B cells were able to phagocytose virulentC. burnetiibacteria and formCoxiella-containing vacuoles (CCVs) and thatC. burnetiican infect and replicate in peritoneal B1a subset B cellsin vitro, demonstrating a potential role for peritoneal B cells in host defense againstC. burnetiiinfectionin vivo. In addition, the results showing that B1a cells secreted a high level of interleukin-10 (IL-10) in response toC. burnetiiinfectionin vitrosuggest that B1a cells may play an important role in inhibiting theC. burnetiiinfection-induced inflammatory response. The observation that adoptive transfer of peritoneal B cells did not significantly affect the severity ofC. burnetiiinfection-induced diseases in both severe combined immunity-deficient (SCID) and μMT mice indicates that peritoneal B cells alone may not be able to controlC. burnetiiinfection. In contrast, our finding thatC. burnetiiinfection induced more-severe splenomegaly and a higher bacterial burden in the spleens of B1a cell-deficient Bruton's tyrosine kinase x-linked immunity-deficient (BTKxid) mice than in their wild-type counterparts further suggests that B1a cells play an important role in host defense against primaryC. burnetiiinfection.
A systematic review protocol for reporting deficiencies within surgical case series
Authors: Agha Riaz , Fowler Alexander J , Lee Seon-Young , Gundogan Buket , Whitehurst Katharine , Sagoo Hakiran , Jeong Kyung Jin Lee , Altman Douglas G , Orgill Dennis P 
Published: October 2015

IntroductionCase series are an important and common study type in surgical literature. There is evidence that key data are excluded from published case series, and currently no reporting guideline exists for case series. There is, therefore, the potential to change practices and improve the reporting of case series. Reporting guidelines have been shown to be efficacious in raising the bar for reporting quality. We present our protocol for the first stage of guideline development—a systematic review of previously identified deficiencies in how surgical case series are reported.Methods and analysisElectronic searches will be conducted on MEDLINE, EMBASE, Cochrane Methods Register, Science Citation Index and Conference Proceedings Citation Index, from the start of indexing until 5 November 2014. The electronic search strategy was developed with an information specialist. Two independent researchers will identify articles for inclusion, specifically those that describe reporting deficiencies within surgical case series. Data will be extracted to specifically focus on the deficiencies of reporting. These will be categorised according to their type, and other identified issues will also be presented. Data will be presented with descriptive statistics to determine frequently missing types of data, and the commonest reporting issues tabulated.Ethics and disseminationThe authors hope to disseminate the findings as widely as possible, irrespective of results, as these will add to the wider corpora of information on this subject. The systematic review will be published in a peer-reviewed journal and will be presented at a wide range of national and international conferences. Ultimately, this will inform a Delphi process for the development of a surgical case series reporting guideline.Protocol registrationCRD42015016145.
Willingness to pay per quality-adjusted life year for life-saving treatments in Thailand
Authors: Nimdet Khachapon , Ngorsuraches Surachat 
Published: October 2015

ObjectiveTo estimate the willingness to pay (WTP) per quality-adjusted life year (QALY) value for life-saving treatments and to determine factors affecting the WTP per QALY value.DesignA cross-sectional survey with multistage sampling and face-to-face interviews.SettingGeneral population in the southern part of Thailand.ParticipantsA total of 600 individuals were included in the study. Only 554 (92.3%) responses were usable for data analyses.Outcome measureParticipants were asked for the maximum amount of WTP value for life-saving treatments by an open-ended question. EQ-5D-3L and visual analogue scale (VAS) were used to estimate additional QALY.ResultsThe amount of WTP values varied from 0 to 720 000 Baht/year (approximately 32 Baht=US$1). The averages of additional QALY obtained from VAS and EQ-5D-3L were only slightly different (0.872 and 0.853, respectively). The averages of WTP per QALY obtained from VAS and EQ-5D-3L were 244720 and 243120 Baht/QALY, respectively. As compared to male participants, female participants were more likely to pay less for an additional QALY (p=0.007). In addition, participants with higher household incomes tended to have higher WTP per QALY values (p<0.001).ConclusionsOur study added another WTP per QALY value specifically for life-saving treatments, which would complement the current cost-effectiveness threshold used in Thailand and optimise patient access to innovative treatments or technologies.
Association between COX-2 gene polymorphisms and risk of hepatocellular carcinoma development: a meta-analysis
Authors: Lu Si-Cong , Zhong Jian-Hong , Tan Jun-Tao , Tang Hua-Lin , Liu Xiao-Guang , Xiang Bang-De , Li Le-Qun , Peng Tao 
Published: October 2015

ObjectiveTo investigate the association between cyclo-oxygenase-2 (COX-2) polymorphism and the risk of hepatocellular carcinoma (HCC) development.DesignSystematic review and meta-analysis of COX-2 polymorphism and risk of HCC development among people with or without HCC.Data sourcesEMBASE, PubMed, Public Library of Science, SCOPUS, Web of Knowledge and Chinese National Knowledge Infrastructure were searched for all clinical and experimental case–control studies of COX-2 polymorphism and HCC risk. Studies published up to March 2015 were included.Review methodTen studies were included for data extraction, which were mainly from Asian countries.Results2538 people with HCC and 3714 without HCC were found to satisfy the inclusion criteria and included in the review. The associations of specific genotypes in the eight polymorphic variants of COX-2 and the risk of HCC development were analysed. GG genotype at the A-1195G polymorphism may be associated with a reduced risk of HCC development: the OR across all studies was 0.87 (95% CI 0.75 to 1.02) for the G allele versus the A allele, 0.72 (0.53 to 0.97) for GG versus AA, 0.72 (0.57 to 0.92) for GG versus GA+AA and 1.05 (0.77 to 1.44) for AA versus GA+GG. Similar results were found when the meta-analysis was repeated separately for the Chinese subgroup. However, more reliable data are needed to demonstrate associations between variants in G-765C, T+8473C, A-1290G, G-899C and introns 1, 5 and 6 polymorphisms and the risk of HCC development.ConclusionsOnly the COX-2 A-1195G gene polymorphism may be associated with a decreased risk of HCC development. These conclusions should be verified in further studies.
Reconstruction of inverted sedimentary basins from syn-tectonic remagnetizations. A methodological proposal
Authors: Villalaín Juan J. , Casas-Sainz Antonio M. , Soto Ruth 
Published: October 2015

Abstract
Syn-tectonic remagnetizations related to burial processes that occurred during their extensional stage are frequently recognized in inverted sedimentary basins. The incremental fold test is the main analytical tool used to detect these syn-tectonic remagnetizations. However this test gives spurious results when asymmetrical folding occurs (i.e. both limbs were not tilted simultaneously at the same rate). Asymmetrical folding is very common in sedimentary basins, especially at their margins, during the basinal stage and subsequent tectonic inversion. To correctly analyse syn-tectonic remagnetizations in these scenarios, we propose a method to restore palaeomagnetic vectors, which allows determining the tilting of beds at the remagnetization stage and therefore gives some hints on the geometry of sedimentary basins and/or folds at the overprint acquisition time. In this paper we consider the analysis of syn-tectonic remagnetization directions for basin reconstruction in two end-member basin models (i.e. syncline vs roll-over geometry). Finally, we compare the results obtained with several northern Iberian examples (Cameros basin in the Iberian Chain, Cabuérniga and Polientes Basin in the Pyrenées), formed during the Mesozoic as extensional basins and subsequently inverted during the Cenozoic compression. From these examples we propose generalizations for the application of syn-tectonic remagnetizations to constrain the geometry of sedimentary basins.
Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression
Authors: Anz David , Rapp Moritz , Eiber Stephan , Koelzer Viktor H. , Thaler Raffael , Haubner Sascha , Knott Max , Nagel Sarah , Golic Michaela , Wiedemann Gabriela M. , Bauernfeind Franz , Wurzenberger Cornelia , Hornung Veit , Scholz Christoph , Mayr Doris , Rothenfusser Simon , Endres Stefan , Bourquin Carole 
Published: October 2015

Abstract
The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I–like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration. Mechanistic investigations indicated that Treg blockade was a consequence of reduced intratumoral CCL22 levels caused by type I IFN. Notably, stable expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR ligands. Taken together, our findings argue that type I IFN blocks the Treg-attracting chemokine CCL22 and thus helps limit the recruitment of Treg to tumors, a finding with implications for cancer immunotherapy. Cancer Res; 75(21); 4483–93. ©2015 AACR.
Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models
Authors: Sameni Mansoureh , Tovar Elizabeth A. , Essenburg Curt J. , Chalasani Anita , Linklater Erik S. , Borgman Andrew , Cherba David M. , Anbalagan Arulselvi , Winn Mary E. , Graveel Carrie R. , Sloane Bonnie F. 
Published: October 2015

Abstract
Purpose: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is associated with poor clinical outcome. There is a vital need for effective targeted therapeutics for TNBC patients, yet treatment strategies are challenged by the significant intertumoral heterogeneity within the TNBC subtype and its surrounding microenvironment. Receptor tyrosine kinases (RTK) are highly expressed in several TNBC subtypes and are promising therapeutic targets. In this study, we targeted the MET receptor, which is highly expressed across several TNBC subtypes.
Experimental Design: Using the small-molecule inhibitor cabozantinib (XL184), we examined the efficacy of MET inhibition in preclinical models that recapitulate human TNBC and its microenvironment. To analyze the dynamic interactions between TNBC cells and fibroblasts over time, we utilized a 3D model referred to as MAME (Mammary Architecture and Microenvironment Engineering) with quantitative image analysis. To investigate cabozantinib inhibition in vivo, we used a novel xenograft model that expresses human HGF and supports paracrine MET signaling.
Results: XL184 treatment of MAME cultures of MDA-MB-231 and HCC70 cells (± HGF-expressing fibroblasts) was cytotoxic and significantly reduced multicellular invasive outgrowths, even in cultures with HGF-expressing fibroblasts. Treatment with XL184 had no significant effects on METneg breast cancer cell growth. In vivo assays demonstrated that cabozantinib treatment significantly inhibited TNBC growth and metastasis.
Conclusions: Using preclinical TNBC models that recapitulate the breast tumor microenvironment, we demonstrate that cabozantinib inhibition is an effective therapeutic strategy in several TNBC subtypes. Clin Cancer Res; 22(4); 923–34. ©2015 AACR.
Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women
Authors: Hodson Leanne , Banerjee Rajarshi , Rial Belén , Arlt Wiebke , Adiels Martin , Boren Jan , Marinou Kyriakoula , Fisher Ciaran , Mostad Ingrid L. , Stratton Irene M. , Barrett P. Hugh R. , Chan Dick C. , Watts Gerald F. , Harnden Karin , Karpe Fredrik , Fielding Barbara A. 
Published: October 2015

Background

Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low‐density lipoprotein (
VLDL
) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre‐ and postmenopausal women.

Methods and Results

We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404±30 versus 268±26 mg/kg lean mass,
P
<0.001) but not small
VLDL
(160±11 versus 142±13). However, postmenopausal status had a pronounced effect on the characteristics of small
VLDL
particles, which were considerably triglyceride‐enriched (production ratio of
VLDL
2
‐ triglyceride:apolipoprotein B 30±5.3 versus 19±1.6,
P
<0.05). In contrast to postmenopausal women, there was a tight control of hepatic fatty acid metabolism and triglyceride production in premenopausal women, whereby oxidation (
r
s
=−0.49,
P
=0.006), de novo lipogenesis (
r
s
=0.55,
P
=0.003), and desaturation (
r
s
=0.48,
P
=0.012) were closely correlated with abdominal obesity‐driven large
VLDL
‐triglyceride secretion rate.

Conclusions

In women, abdominal obesity is a major driver of hepatic large
VLDL
particle secretion, whereas postmenopausal status was characterized by increased small
VLDL
particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
Factors influencing junior doctors’ choices of future specialty: trends over time and demographics based on results from UK national surveys
Authors: Smith Fay , Lambert Trevor W , Goldacre Michael J 
Published: October 2015

Objective To study trends in factors influencing junior doctors’ choice of future specialty. Design Respondents were asked whether each of 15 factors had a great deal of influence on their career choice, a little influence or no influence on it. Percentages are reported of those who specified that a factor had a great deal of influence on their career choice. Setting UK. Participants A total of 15,765 UK-trained doctors who graduated between 1999 and 2012. Main outcome measures Questions about career choices and factors which may have influenced those choices, in particular comparing doctors who qualified in 2008–2012 with those who qualified in 1999–2002. Results Enthusiasm for and commitment to the specialty was a greater influence on career choice in the 2008–2012 qualifiers (81%) than those of 1999–2002 (64%), as was consideration of their domestic circumstances (43% compared with 20%). Prospects for promotion were less important to recent cohorts (16%) than older cohorts (21%), as were financial prospects (respectively, 10% and 14%). Domestic circumstances and working hours were considered more important, and financial prospects less important, by women than men. Inclination before medical school was rated as important by 41% of doctors who were over 30 years old, compared with 13% of doctors who were under 21, at the time of starting medical school. Conclusions The increasing importance of both domestic circumstances and enthusiasm for their specialty choice in recent cohorts suggest that today’s young doctors prize both work-life balance and personal fulfilment at work more highly than did their predecessors. The differences in motivations of older and younger generations of doctors, men and women, and doctors who start medical school relatively late are worthy of note.
Climate change, conflict and health
Authors: Bowles Devin C , Butler Colin D , Morisetti Neil 
Published: October 2015

Summary Future climate change is predicted to diminish essential natural resource availability in many regions and perhaps globally. The resulting scarcity of water, food and livelihoods could lead to increasingly desperate populations that challenge governments, enhancing the risk of intra- and interstate conflict. Defence establishments and some political scientists view climate change as a potential threat to peace. While the medical literature increasingly recognises climate change as a fundamental health risk, the dimension of climate change-associated conflict has so far received little attention, despite its profound health implications. Many analysts link climate change with a heightened risk of conflict via causal pathways which involve diminishing or changing resource availability. Plausible consequences include: increased frequency of civil conflict in developing countries; terrorism, asymmetric warfare, state failure; and major regional conflicts. The medical understanding of these threats is inadequate, given the scale of health implications. The medical and public health communities have often been reluctant to interpret conflict as a health issue. However, at times, medical workers have proven powerful and effective peace advocates, most notably with regard to nuclear disarmament. The public is more motivated to mitigate climate change when it is framed as a health issue. Improved medical understanding of the association between climate change and conflict could strengthen mitigation efforts and increase cooperation to cope with the climate change that is now inevitable.
Patient perceptions and recall of consent for regional anaesthesia compared with consent for surgery
Authors: Zarnegar Roxaneh , Brown Matthew RD , Henley Matthew , Tidman Victoria , Pathmanathan Ahilan 
Published: October 2015

Objective In Britain, consent for surgery is documented using a Department of Health form signed by the surgeon and the patient. In contrast, anaesthetic procedures have no formalised consent process. Evidence on the process of consent for regional anaesthesia, and patient perceptions of this, is scarce outside obstetric practice. We aimed to determine patient recall and perceptions of consent for interscalene brachial plexus block and compared this to surgical consent for shoulder arthroplasty. Design Prospective observational survey. Setting A specialist musculoskeletal centre, UK. Participants Forty-six patients (female:male 30:16, mean age 61 years) undergoing shoulder arthroplasty with interscalene brachial plexus block. Main outcome measures Recall and understanding of consent for regional anaesthesia and surgery was examined using a semi-structured questionnaire 1–2 days after arthroplasty. Surgical consent forms and discussions recorded by the anaesthetist were examined in participants’ medical notes to compare against the level of recall. Analysis to determine statistical significance was conducted using McNemar’s test. Results Recall of surgical risks was overall significantly better than recall of brachial plexus block risks. Compared to their recollections of surgical risk, patients remembered fewer specific risks for brachial plexus block ( p < 0.001). There were more patients unable to recall any risks when questioned about brachial plexus block than about their surgery ( p < 0.05). One-third of patients did not regard the consent discussion about regional anaesthesia as important as consent for surgery and over one-quarter had not recognised the preoperative discussion about the brachial plexus block as a consent process similar to that conducted for surgery. Conclusions Fundamental misunderstandings about the consent process are prevalent. Future work in this area should seek to investigate how documentation of the consent process and patients’ understanding of consent for regional anaesthesia can be improved.
Grey matter involvement by focal cervical spinal cord lesions is associated with progressive multiple sclerosis
Authors: Kearney Hugh , Miszkiel Katherine A , Yiannakas Marios C , Altmann Daniel R , Ciccarelli Olga , Miller David H 
Published: October 2015

Background: The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. Objective: The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. Methods: We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing–remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). Results: The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS ( p = 0.03) and PPMS ( p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 ( p = 0.002) and 5.7 ( p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability ( p < 0.001). Conclusions: More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.