bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Herpesvirus 8 Induces Polyfunctional B Lymphocytes That Drive Kaposi’s Sarcoma
Authors: Knowlton Emilee R. , Rappocciolo Giovanna , Piazza Paolo , Lepone Lauren M. , Nadgir Sagar V. , Bullotta Arlene , Berendam Stella J. , Li Jun , Reinhart Todd A. , Jenkins Frank J. , Rinaldo Charles R. 
Published: September 2014

ABSTRACTKaposi’s sarcoma (KS) is an unusual neoplasia wherein the tumor consists primarily of endothelial cells infected with human herpesvirus 8 (HHV-8; Kaposi’s sarcoma-associated herpesvirus) that are not fully transformed but are instead driven to excess proliferation by inflammatory and angiogenic factors. This oncogenic process has been postulated but unproven to depend on a paracrine effect of an abnormal excess of host cytokines and chemokines produced by HHV-8-infected B lymphocytes. Using newly developed measures for intracellular detection of lytic cycle proteins and expression of cytokines and chemokines, we show that HHV-8 targets a range of naive B cell, IgM memory B cell, and plasma cell-like populations for infection and induction of interleukin-6, tumor necrosis factor alpha, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, and interleukin-8in vitroand in the blood of HHV-8/HIV-1-coinfected subjects with KS. These B cell lineage subsets that support HHV-8 infection are highly polyfunctional, producing combinations of 2 to 5 of these cytokines and chemokines, with greater numbers in the blood of subjects with KS than in those without KS. Our study provides a new paradigm of B cell polyfunctionality and supports a key role for B cell-derived cytokines and chemokines produced during HHV-8 infection in the development of KS.IMPORTANCEKaposi’s sarcoma (KS) is the most common cancer in HIV-1-infected persons and is caused by one of only 7 human cancer viruses, i.e., human herpesvirus 8 (HHV-8). It is unclear how this virus causes neoplastic transformation. Development and outgrowth of endothelial cell lesions characteristic of KS are hypothesized to be dependent on virus replication and multiple immune mediators produced by the KS cells and inflammatory cells, yet the roles of these viral and cell factors have not been defined. The present study advances our understanding of KS in that it supports a central role for HHV-8 infection of B cells inducing multiple cytokines and chemokines that can drive development of the cancer. Notably, HIV-1-infected individuals who developed KS had greater numbers of such HHV-8-infected, polyfunctional B cells across a range of B cell phenotypic lineages than did HHV-8-infected persons without KS. This intriguing production of polyfunctional immune mediators by B cells serves as a new paradigm for B cell function and classification.
Ancient-Pathogen Genomics: Coming of Age?
Authors: Whatmore Adrian M. 
Published: September 2014

ABSTRACT

The potentially debilitating zoonotic disease brucellosis is thought to have been a scourge of mankind throughout history. New work by Kay et al. [mBio 5(4):e01337-14, 2014] adds to evidence for this by exploiting the huge advances in next-generation sequencing technology and applying shotgun metagenomics to a calcified nodule obtained from a 14th-century skeleton from Sardinia. While not the first DNA-based confirmation of
Brucella
in medieval DNA samples, Kay et al.’s study goes much further than previous reports based on single gene fragments in that it allows a full-genome reconstruction and thus facilitates meaningful comparative analysis of relationships with extant
Brucella
strains. These analyses confirm the close relationship of the genome to contemporary isolates from the western Mediterranean, illustrating the continuity of this lineage in the region over centuries. The study, along with recent studies characterizing other ancient-pathogen genomes, confirms that shotgun metagenomics offers us a powerful tool to fully characterize pathogens from ancient samples. Such studies promise to revolutionize our understanding of the nature of infectious disease in these materials and of the wider picture of the emergence, evolution, and spread of bacterial pathogens over history.
The long-term course of patients undergoing alternative and integrative therapy for lumbar disc herniation: 3-year results of a prospective observational study
Authors: Shin Joon-Shik , Lee Jinho , Kim Me-riong , Shin Byung-Cheul , Lee Myeong Soo , Ha In-Hyuk 
Published: September 2014

ObjectivesThis study aimed to assess the efficacy and safety of an integrative complementary and alternative medicine (CAM) approach in the management of lumbar herniated disc (LHD) with sciatic pain and investigate pain relapse, use of medical care and surgery rates in patients who actively chose non-surgical CAM treatment for LHD.Study design/SettingThis prospective observational study was undertaken at a Korean medicine hospital outpatient setting in Korea.ParticipantsA total of 128 consecutive patients with LHD with a numeric rating scale for leg pain of ≥5 completed 6 months of CAM treatment after recruitment from November 2006, and 73/128 participants (57%) attended follow-up 3 years later.Interventions6 months of CAM treatment (herbal medicine, acupuncture, bee venom pharmacopuncture, and Chuna manipulation).Primary outcome measuresVisual analogue scale (VAS) for low back and leg pain, Oswestry Disability Index (ODI), and Short Form (SF)-36 Health Survey.Secondary outcome measuresNeurological impairment (muscular weakness, sensory loss, Straight Leg Raise test), MRIs, recurrence of low back pain and/or radiating pain, and use of medical care.Results92 patients could be assessed for surgical state, of whom 4 replied that they had received surgery. 73 patients attended the 3-year follow-up. The baseline VAS of back pain (4.37±2.70) decreased after treatment (0.90±1.01; p<0.001) and was maintained at 3 years (1.12±1.64; p=0.19). The baseline VAS of leg pain (7.57±1.40) also decreased on treatment (0.82±1.18; p<0.001) and was sustained at 3 years (0.99±1.58; p=0.34). ODI scores declined from 40.74±16.15 to 9.84±9.67 (p<0.001), then decreased further to 6.30±7.19 (p<0.01). SF-36 scores increased from 34.96±13.30 to 69.20±14.96 (p<0.001), reaching 76.19±14.45 (p<0.001) at 3 years. 37 patients reported recurrence of pain and most chose CAM treatment for management of relapse symptoms.ConclusionsAlthough the absence of a control group prevents validation of effectiveness, many patients showed favourable long-term outcomes.Trial registration numberClinicalTrials.gov Identifier:NCT01989403.
Improving care for patients whose recovery is uncertain. The AMBER care bundle: design and implementation
Authors: Carey Irene , Shouls Susanna , Bristowe Katherine , Morris Michelle , Briant Linda , Robinson Carole , Caulkin Ruth , Griffiths Mathew , Clark Kieron , Koffman Jonathan , Hopper Adrian 
Published: September 2014

IntroductionDespite preferences to the contrary, 53% of deaths in England occur in hospital. Difficulties in managing clinical uncertainty can result in delayed recognition that a person may be approaching the end of life, and a failure to address his/her preferences. Planning and shared decision-making for hospital patients need to improve where an underlying condition responds poorly to acute medical treatment and there is a risk of dying in the next 1–2 months. This paper suggests an approach to improve this care.InterventionA care bundle (the AMBER care bundle) was designed by a multiprofessional development team, which included service users, utilising the model for improvement following an initial scoping exercise. The care bundle includes two identification questions, four subsequent time restricted actions and systematic daily follow-up.Clinical impactThis paper describes the development and implementation of a care bundle. From August 2011 to July 2012, 638 patients received care supported by the AMBER care bundle. In total 42.8% died in hospital and a further 14.5% were readmitted as emergencies within 30 days of discharge. Clinical outcome measures are in development.ConclusionsIt has been possible to develop a care bundle addressing a complex area of care which can be a lever for cultural change. The implementation of the AMBER care bundle has the potential to improve care of clinically uncertain hospital patients who may be approaching the end of life by supporting their recognition and prompting discussion of their preferences. Outcomes associated with its use are currently being formally evaluated.
Social media and palliative medicine: a retrospective 2-year analysis of global Twitter data to evaluate the use of technology to communicate about issues at the end of life
Authors: Nwosu Amara Callistus , Debattista Maria , Rooney Claire , Mason Stephen 
Published: September 2014

BackgroundSocial media describes technological applications which are used to exchange information in a virtual environment. The use of social media is increasing, in professional and social contexts, on a variety of platforms such as Twitter; however, the scope and breadth of its use to discuss end-of-life care has not previously been reported.AimsTo determine the frequency, sentiment and trend of Twitter ‘tweets’ containing palliative care-related identifiers (hashtags) and/or phrases sent by users over a 2-year period.MethodsA 2-year retrospective analysis of Twitter posts (tweets), between the 1 August 2011 to 31 July 2013, using a social media analytics tool: TopsyPro. Thirteen search terms were identified and analysed for tweet volume, frequency, sentiment and acceleration.ResultsA total of 683.5K tweets containing a combination of 13 palliative care terms were analysed. The tweet volume for all terms increased by 62.3% between 2011–2012 (262.5K) and 2012–2013 (421K). The most popular terms include ‘end-of-life’ (210K), #hpm (114K) and ‘palliative care’ (93.8K). Sentiment was high with 89% of tweets rated more positive than all other tweets sent on Twitter during this period. The term ‘Liverpool Care Pathway’ experienced the highest percentage increase in tweets (55% increase) reaching a peak in July 2013.ConclusionsA lot of discussion about palliative care is taking place on Twitter, and the majority of this is positive. Social media presents a novel opportunity for engagement and ongoing dialogue with public and professional groups.
Grading of breast cancer on needle core biopsy: does a reduction in mitotic count threshold improve agreement with grade on excised specimens?
Authors: Dhaliwal Catharine Ann , Graham Catriona , Loane Joseph 
Published: September 2014

BackgroundAccurate assessment of invasive breast cancer grade on needle core biopsy (NCB) is important as it guides treatment.AimTo assess the agreement between grade of invasive cancer on NCB and excision and determine whether altering the mitotic count score threshold on NCB improves it.MethodsPathology slides from patients with an NCB diagnosis of invasive breast cancer who underwent subsequent breast conservation surgery in 2012 were reviewed. Mitotic counts were assessed and tumour grade agreement between NCB and excision evaluated. The mitotic count thresholds were altered and grade agreement was reassessed.ResultsIn 283/359 (79%) cases, there was concurrence on histological grade between NCB and excision. Reduction in mitotic count thresholds did not improve either overall tumour grade agreement or agreement within any subgroup of patients.ConclusionsIn our experience, the current mitotic count score thresholds are appropriate and should be maintained.
A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of ‘penicillin allergy’ in a UK teaching hospital
Authors: Li M , Krishna M T , Razaq S , Pillay D 
Published: September 2014

AimsTo perform a pharmaco-economic analysis of prescribing alternative antibiotics in patients with a diagnostic label of ‘penicillin allergy’ and assess whether collation of information from a structured history and liaison with the family physician could reduce costs.MethodsA prospective pro-forma-based interview of randomly selected in-patients and their family physician was used to assess the validity of the diagnostic label of ‘penicillin allergy’. Cost analysis of prescription of alternative antibiotics was performed and compared with first-line agents.Results102 patients were assessed and only 40% (n=41) were found to have a history consistent with penicillin hypersensitivity, 40% (n=41) were likely ‘not allergic’ and 20% (n=20) had ‘indeterminate’ reactions. Total cost of antibiotics prescribed for patients with penicillin allergy was 1.82–2.58-fold higher than for first-line antibiotics.ConclusionsObtaining a structured history from the patient and family physician alone can enable an accurate identification of penicillin allergy status. Total acquisition cost of second-line antibiotics is higher than if these patients were prescribed first-line antibiotics.
Women's experiences of endometriosis: a systematic review and synthesis of qualitative research
Authors: Young Kate , Fisher Jane , Kirkman Maggie 
Published: September 2014

BackgroundEndometriosis is experienced by approximately 10% of women worldwide; it is associated with significant burden on the woman, her family, and society.AimThe aim of this systematic review was to synthesise the available qualitative literature to increase our understanding of the effects of endometriosis on women's lives.MethodsSeven social science and medical databases (PubMed, Medline, CINAHL, Web of Science, ScienceDirect, PsycInfo and Embase) and Google Scholar were searched for peer-reviewed papers published in English of research using qualitative methods.Results and conclusionsEighteen papers reporting 11 studies met the inclusion criteria. Participant numbers ranged from 15 to 61 women, all recruited from support groups and specialised clinics. Studies were conducted in high-income, Anglophone countries. The review identified four prominent themes: Life, Symptoms, Medical Experience, and Self. Women's reported experiences demonstrated opportunities for enhancing current clinical practice, including improved education about endometriosis for health professionals, the need to take a comprehensive approach to pain treatment, and initiating appropriate discussion of the impact on sex life. Significant evidence gaps were identified: there was inadequate investigation of women's experiences of endometriosis-associated infertility and of the impact of reduced social participation on perceived support and emotional well-being, and limited or no inclusion of the experiences of adolescent and post-menopausal women, women from low socioeconomic backgrounds, women who do not identify as Caucasian, and non-heterosexual women.
On the Fekete and Szegö Problem for the Class of Starlike Mappings in Several Complex Variables
Authors: Xu Qing-Hua , Liu Tai-Shun 
Published: September 2014

LetSbe the familiar class of normalized univalent functions in the unit disk. Fekete and Szegö proved the well-known resultmaxf∈S⁡a3-λa22=1+2e-2λ/(1-λ)forλ∈0, 1. We investigate the corresponding problem for the class of starlike mappings defined on the unit ball in a complex Banach space or on the unit polydisk inCn, which satisfies a certain condition.
A Quantitative Sensory Analysis of Peripheral Neuropathy in Colorectal Cancer and Its Exacerbation by Oxaliplatin Chemotherapy
Authors: de Carvalho Barbosa Mariana , Kosturakis Alyssa K. , Eng Cathy , Wendelschafer-Crabb Gwen , Kennedy William R. , Simone Donald A. , Wang Xin S. , Cleeland Charles S. , Dougherty Patrick M. 
Published: September 2014

Abstract
Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. Cancer Res; 74(21); 5955–62. ©2014 AACR.
l-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer
Authors: Shim Eun-Hee , Livi Carolina B. , Rakheja Dinesh , Tan Jubilee , Benson Daniel , Parekh Vishwas , Kho Eun-Young , Ghosh Arindam P. , Kirkman Richard , Velu Sadanan , Dutta Shilpa , Chenna Balachandra , Rea Shane L. , Mishur Robert J. , Li Qiuhua , Johnson-Pais Teresa L. , Guo Lining , Bae Sejong , Wei Shi , Block Karen , Sudarshan Sunil 
Published: September 2014

Abstract
Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG)–dependent dioxygenases that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of-function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the l enantiomer of 2HG (l-2HG). High-2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC), consistent with 2HG-mediated inhibition of ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5hmC. l-2HG elevation is mediated in part by reduced expression of l-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers l-2HG and promotes 5hmC accumulation. In addition, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies l-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer.
Significance: Here, we report elevations of the putative oncometabolite l-2HG in the most common subtype of kidney cancer and describe a novel mechanism for the regulation of DNA 5hmC levels. Our findings provide new insight into the metabolic basis for the epigenetic landscape of renal cancer. Cancer Discov; 4(11); 1290–8. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 1243
Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity
Authors: Park Yongwhi , Tantry Udaya , Ahn Jong-Hwa , Kim Kye Hwan , Koh Jin-Sin , Park Jeong-Rang , Hwang Seok-Jae , Kwak Choong Hwan , Hwang Jin-Yong , Gurbel Paul , Jeong Young-Hoon 
Published: September 2014

SummaryAdjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: –2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.
Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome
Authors: Brandt Johanna , Herwald Heiko , Teupser Daniel , Küchenhoff Helmut , Karshovska Ela , Mause Sebastian , Siess Wolfgang , Wasmuth Hermann , Soehnlein Oliver , Koenen Rory , Weber Christian , Blanchet Xavier , Cesarek Katja , Hundelshausen Philipp von 
Published: September 2014

SummaryActivated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.Note: The review process for this paper was fully handled by Gregory Y. H. Lip, Editor in Chief.