bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen Reversal Identifies Targets of Opsonizing IgGs against Pregnancy-Associated Malaria
Authors: Lambert Lester H. , Bullock Jeanee L. , Cook Sharma T. , Miura Kazutoyo , Garboczi David N. , Diakite Mahamadou , Fairhurst Rick M. , Singh Kavita , Long Carole A. 
Published: August 2014

ABSTRACT
Clinical immunity to pregnancy associated-malaria (PAM) in multigravida women has been attributed to antibodies that recognize VAR2CSA on the infected erythrocyte (IE) surface. The size and complexity of VAR2CSA have focused efforts on selecting one or more of its six Duffy binding-like (DBL) domains for vaccine development. Presently, however, there is no consensus as to which DBL domain(s) would be most effective in eliciting immunity. This is because antibodies to a number of the DBL domains have been found to block the adhesion of VAR2CSA-expressing erythrocytes to chondroitin sulfate A (CSA)—a major criterion for evaluating vaccine candidacy. Opsonization of IEs by cytophilic antibodies that recognize VAR2CSA represents an important yet understudied effector mechanism in acquired immunity to PAM. To date, no studies have sought to determine the targets of those antibodies. In this study, we found that IgGs from multigravida Malian women showed (i) higher reactivity to recombinant DBL domains by enzyme-linked immunosorbent assay (ELISA), (ii) more binding to VAR2CSA-expressing IEs, and (iii) greater opsonization of these IEs by human monocytic cells than IgGs from malaria-exposed Malian men and malaria-naive American adults. Preincubation of IgGs from multigravida women with recombinant DBL2χ, DBL3χ, or DBL5ε domains significantly diminished opsonization of VAR2CSA-expressing IEs by human monocytes. These data identify the DBL2χ, DBL3χ, and DBL5ε domains as the primary targets of opsonizing IgGs for the first time. Our study introduces a new approach to determining the antigenic targets of opsonizing IgGs in phagocytosis assays.
Discrepancy between subjectively reported symptoms and objectively measured clinical findings in dry eye: a population based analysis
Authors: Hua Rui , Yao Kai , Hu Yuedong , Chen Lei 
Published: August 2014

ObjectiveTo investigate the discrepancy between patient-reported symptoms and measured clinical findings and influencing factors in dry eye (DE).SettingA population-based, cross-sectional study was performed in July–August 2007 in northeast China. The study was performed on populations originating from two rural districts that are respectively located approximately 377 and 177 km from our hospital.Participants2600 eligible residents from 1300 households were identified; valid responses were obtained from 2262 residents (mean age 48 (range 12–88) years; 926 men and 1336 women; response rate 87%).Primary outcome measuresPatient-reported symptoms of DE, tear film break up time (BUT) and Schirmer scores (Schirmer II).ResultsSubjects with normal BUT and Schirmer scores without any DE symptoms were defined as the control group. Those with abnormal BUT and Schirmer scores and symptoms of DE were defined as the DE group. Subjects with disparities between the occurrence of DE symptoms and measured clinical findings were regarded as the discrepancy. Out of 2262 subjects, the discrepant group contained 960 subjects (42.44%) with significant difference (χ2=4.027, p=0.045<0.05). Factors that influenced the subjective reporting of DE symptoms included gender, smoking status, environment and age. Schirmer II test and tear film BUT values were remarkably different among control, DE and discrepant groups.ConclusionsDevelopment of DE can be related to many factors. It is of great importance to put forward the preclinical phase concept (patients who are symptomatic for DE and yet show no aqueous deficiency or evaporative signs) and to screen outpatients with DE-inducing features. Future interventions should focus on patients demonstrating a discrepancy between self-reported symptomology and measured clinical findings.
The performance of seven QPrediction risk scores in an independent external sample of patients from general practice: a validation study
Authors: Hippisley-Cox Julia , Coupland Carol , Brindle Peter 
Published: August 2014

ObjectivesTo validate the performance of a set of risk prediction algorithms developed using the QResearch database, in an independent sample from general practices contributing to the Clinical Research Data Link (CPRD).SettingProspective open cohort study using practices contributing to the CPRD database and practices contributing to the QResearch database.ParticipantsThe CPRD validation cohort consisted of 3.3 million patients, aged 25–99 years registered at 357 general practices between 1 Jan 1998 and 31 July 2012. The validation statistics for QResearch were obtained from the original published papers which used a one-third sample of practices separate to those used to derive the score. A cohort from QResearch was used to compare incidence rates and baseline characteristics and consisted of 6.8 million patients from 753 practices registered between 1 Jan 1998 and until 31 July 2013.Outcome measuresIncident events relating to seven different risk prediction scores: QRISK2 (cardiovascular disease); QStroke (ischaemic stroke); QDiabetes (type 2 diabetes); QFracture (osteoporotic fracture and hip fracture); QKidney (moderate and severe kidney failure); QThrombosis (venous thromboembolism); QBleed (intracranial bleed and upper gastrointestinal haemorrhage). Measures of discrimination and calibration were calculated.ResultsOverall, the baseline characteristics of the CPRD and QResearch cohorts were similar though QResearch had higher recording levels for ethnicity and family history. The validation statistics for each of the risk prediction scores were very similar in the CPRD cohort compared with the published results from QResearch validation cohorts. For example, in women, the QDiabetes algorithm explained 50% of the variation within CPRD compared with 51% on QResearch and the receiver operator curve value was 0.85 on both databases. The scores were well calibrated in CPRD.ConclusionsEach of the algorithms performed practically as well in the external independent CPRD validation cohorts as they had in the original published QResearch validation cohorts.
Early evidence about the predicted unintended consequences of standardised packaging of tobacco products in Australia: a cross-sectional study of the place of purchase, regular brands and use of illicit tobacco
Authors: Scollo Michelle , Zacher Meghan , Durkin Sarah , Wakefield Melanie 
Published: August 2014

ObjectivesTo test for early evidence whether, following the standardisation of tobacco packaging, smokers in Australia were—as predicted by the tobacco industry—less likely to purchase from small mixed business retailers, more likely to purchase cheap brands imported from Asia and more likely to use illicit tobacco.DesignSerial cross-sectional population telephone surveys in November 2011 (a year prior to implementation), 2012 (during roll-out) and 2013 (a year after implementation).Setting/participantsSmokers aged 18 years and over identified in an annual population survey in the Australian state of Victoria (2011: n=754; 2012: n=590; 2013: n=601).Main outcome measuresChanges between 2011 and 2013 in: proportions of current smokers who purchased their last cigarette from discount outlets such as supermarkets compared with small mixed business retail outlets; prevalence of regular use of low-cost brands imported from Asia and use of unbranded tobacco.ResultsThe proportion of smokers purchasing from supermarkets did not increase between 2011 (65.4%) and 2013 (65.7%; p=0.98), and the percentage purchasing from small mixed business outlets did not decline (2011: 9.2%; 2012: 11.2%; p=0.32). The prevalence of low-cost Asian brands was low and did not increase between 2011 (1.1%) and 2013 (0.9%; p=0.98). The proportion reporting current use of unbranded illicit tobacco was 2.3% in 2011 and 1.9% in 2013 (p=0.46). In 2013, 2.6% of cigarette smokers reported having purchased one or more packets of cigarettes in non-compliant packaging in the past 3 months; 1.7% had purchased one or more packets from an informal seller in the past year.ConclusionsOne year after implementation, this study found no evidence of the major unintended consequences concerning loss of smoker patrons from small retail outlets, flooding of the market by cheap Asian brands and use of illicit tobacco predicted by opponents of plain packaging in Australia.
High HIV seroprevalence, rectal STIs and risky sexual behaviour in men who have sex with men in Dar es Salaam and Tanga, Tanzania
Authors: Ross Michael W , Nyoni Joyce , Ahaneku Hycienth O , Mbwambo Jessie , McClelland R Scott , McCurdy Sheryl A 
Published: August 2014

ObjectivesTo assess HIV and sexually transmitted infection (STI) prevalence and associated risk factors in men who have sex with men (MSM) in two cities in mainland Tanzania.MethodsWe conducted respondent-driven sampling of 300 MSM in Dar es Salaam and Tanga.ResultsIn Dar es Salaam, 172 (86%) men (median age 23, IQR 21–28) consented to HIV/STI testing, and 30.2% were HIV seropositive. Only five reported a previous positive HIV test: >90% were new HIV detections. 2.5% were syphilis-exposed and none hepatitis B positive, but 21.4% had a curable STI. Over 90% of the gonorrhoea and chlamydia was rectal. In Tanga, 11.1% of MSM were HIV seropositive, 8% hepatitis B positive and 0% were syphilis-exposed, with 4.4% having a curable STI. Predictors of HIV infection were number of MSM known, city, identifying as gay and having first sex with a man. Predictors for STIs were recent unprotected receptive anal intercourse, and number of MSM seen in the last month. 30% of the sample reported that they sold sex. There was no significant association between HIV and STI infection.ConclusionsHIV and STI rates were substantially lower in MSM in a provincial city than in a large metropolis and rates appear to depend on larger numbers of MSM known. Most HIV detected were new cases, and there was a high burden of asymptomatic curable rectal STIs (>1 in 5 MSM). Owing to stigma, MSM may not report homosexuality and thus not have rectal STIs treated. High need for tailored HIV testing and STI screening and treatment of MSM in Tanzania is apparent.
Impact of smoking cessation therapy on health-related quality of life
Authors: Tomioka Hiromi , Sekiya Reina , Nishio Chihiro , Ishimoto Gakuji 
Published: August 2014

BackgroundSmoking is associated with poor health-related quality of life (HRQL); however, there are few data regarding effects of smoking cessation treatment on HRQL. The purpose of this study was to describe changes in HRQL after smoking cessation treatment and to elucidate factors influencing this improvement in HRQL.SettingSmoking cessation clinic at a 358-bed community teaching hospital in Japan.MethodsWe conducted a prospective cohort study of cigarette smokers who participated in a 3-month smoking cessation programme. HRQL was assessed at baseline and at the end of the programme using the St. George's Respiratory Questionnaire (SGRQ). The abstinence was subjected to verification by an exhaled CO level of ≤10 ppm.ResultsOf 570 participants in the programme, 277 (mean age: 60.9±12.2 y, male/female=180/97) were eligible; excluded were 277 participants who dropped out of the programme and 16 for whom SGRQs were not available or were incomplete. Initial prescribed pharmacotherapy was transdermal nicotine patches in 160 participants and varenicline in 117. At 12 weeks, SGRQ scores improved significantly as follows (mean±SD): Δ symptoms score, −5.7±16.0; Δ activity score, −4.4±18.3; Δ impact score, −5.3±13.5 and Δ total score, −5.1±12.2 (p<0.0001 in all cases). There were no significant differences in changes in SGRQ scores between quitters (n=183) and continuous smokers (n=94). In a multivariate analysis, only the average nicotine addiction level according to the Tobacco Dependence Screener test was associated with a clinically significant improvement in the SGRQ (OR 1.35 (95% CI 1.15 to 1.59)). Marked reduction in number of cigarettes smoked with a corresponding low median exhaled CO level of 7 ppm in continuous smokers following therapy was observed.ConclusionsSmoking cessation treatment improved HRQL regardless of quit status. Baseline nicotine addiction level was predictive of that improvement.
Rise in testing and diagnosis associated with Scotland's Action Plan on Hepatitis C and introduction of dried blood spot testing
Authors: McLeod Allan , Weir Amanda , Aitken Celia , Gunson Rory , Templeton Kate , Molyneaux Pamela , McIntyre Paul , McDonald Scott , Goldberg David , Hutchinson Sharon 
Published: August 2014

BackgroundA key aim of the Hepatitis C Action Plan for Scotland was to reduce the undiagnosed population through awareness-raising activities, for general practitioners and those at risk, and the introduction of dried blood spot (DBS) sampling in community drug services to overcome barriers to testing. This study evaluates the impact of these activities on testing and diagnosis.MethodsData on hepatitis C virus (HCV) testing undertaken between January 1999 and December 2011 in Scotland's four largest health boards were analysed. Segmented regression analysis was used to examine changes in testing following the (1) launch of the Action Plan and (2) introduction of DBS testing.ResultsBetween the pre-Action Plan and Action Plan periods, increases were observed in the average number of HCV tests (19 058–29 045), positive tests (1993–2405) and new diagnoses (1221–1367). Since July 2009, 26% of new diagnoses were made in drug services. The trend in the number of positive tests was raised during the Action Plan, compared to pre-Action Plan, particularly in drug services (rate ratio (RR)=1.4, p<0.001) and prisons (RR=1.2, p<0.001); no change was observed in general practice. Following introduction of DBS testing, there was a 3-fold increase in testing (RR=3.5, p<0.001) and 12-fold increase in positives (RR=12.1, p<0.001) in drug services.ConclusionsThe introduction of DBS sampling in community drug services has made an appreciable contribution to efforts to diagnose the HCV-infected population in Scotland. These findings are important to other countries, with injecting-related HCV epidemics, needing to scale-up testing/case-finding initiatives.
Micro Vascular Plug (MVP)-assisted vessel occlusion in neurovascular pathologies: technical results and initial clinical experience
Authors: Beaty Narlin B , Jindal Gaurav , Gandhi Dheeraj 
Published: August 2014

BackgroundDeconstructive approaches may be necessary to treat a variety of neurovascular pathologies. Recently, a new device has become available for endovascular arterial occlusion that may have unique applications in neurovascular disease. The Micro Vascular Plug (MVP, Reverse Medical, Irvine, California, USA) has been designed for vessel occlusion through targeted embolization.PurposeTo report the results from our initial experience with eight consecutive patients in whom the MVP was used to achieve endovascular occlusion of an artery in the head and neck.MethodsEight consecutive patients treated over a nine-month period were included. The patients’ radiographic and electronic medical records were retrospectively reviewed. Specifically demographic information, clinical indication, site of arterial occlusion, size of MVP, time to vessel occlusion, clinical complications, use of other secondary embolic agents, and clinical outcome were recorded. Follow-up information when available is presented.ResultsThe MVP was used in eight patients for the treatment of neurovascular disease. Indications for treatment included post-traumatic head/neck bleeding (n=3), carotid–cavernous fistula (1), vertebral–vertebral fistula (1), giant fusiform vertebral aneurysm (1), stump-emboli after carotid dissection (1), and iatrogenic vertebral artery penetrating injury (1). One device was used in five patients, two in two patients, and one patient with extensive vertebral–vertebral venous fistula required three plugs to effectively trap the fistula from proximal and distal aspects. Vessel occlusion was obtained in <2 min in each case and there were no procedural complications. Four patients were followed up and no incidence of plug migration or vessel recanalization was seen.ConclusionsTo the best of our knowledge, this is the first series reporting the use of MVP in neurovascular disease. Use of this device may be associated with shorter procedural times and cost savings in comparison with the use of microcoils for vessel occlusion. Our experience shows that MVP can have unique applications in neurovascular pathologies and it complements other occlusive devices.
Prognostic factors for survival in dogs with pituitary‐dependent hypercortisolism treated with trilostane
Authors: Fracassi F. , Corradini S. , Floriano D. , Boari A. , Aste G. , Pietra M. , Bergamini P. F. , Dondi F. 
Published: August 2014

Pituitary‐dependent hypercortisolism (PDH) is one of the most frequent endocrinopathies in dogs, but prognostic factors are largely unknown. The aim of this retrospective case series study was to determine the prognostic value of different clinical and clinicopathological variables evaluated in dogs newly diagnosed with PDH that were subsequently treated with trilostane. Medical records from one referral centre were evaluated. Eighty‐five dogs with PDH were included. The median survival time was 852 days (range 2–3210 days); 60/85 (70 per cent) and 25/85 (29 per cent) dogs survived more than one and three years, respectively. In multivariable model analysis the length of survival of older dogs (HR 1.24, 95% CI 1.09 to 1.40) and dogs with higher serum phosphate concentrations (HR 1.35, 95% CI 1.01 to 1.81) was shorter. Serum phosphate concentrations were above the reference range in 37/85 (44 per cent) of animals. Clinical signs, liver enzymes, serum cortisol concentrations of the endocrine tests, proteinuria, systolic hypertension, the presence of concomitant disorders, and the frequency of trilostane administration were not associated with survival time. Hyperphosphataemia is a common finding in dogs with newly diagnosed PDH and represents a negative prognostic factor.
Dsh Homolog DVL3 Mediates Resistance to IGFIR Inhibition by Regulating IGF-RAS Signaling
Authors: Gao Shan , Bajrami Ilirjana , Verrill Clare , Kigozi Asha , Ouaret Djamila , Aleksic Tamara , Asher Ruth , Han Cheng , Allen Paul , Bailey Deborah , Feller Stephan , Kashima Takeshi , Athanasou Nicholas , Blay Jean-Yves , Schmitz Sandra , Machiels Jean-Pascal , Upile Nav , Jones Terry M. , Thalmann George , Ashraf Shazad Q. , Wilding Jennifer L. , Bodmer Walter F. , Middleton Mark R. , Ashworth Alan , Lord Christopher J. , Macaulay Valentine M. 
Published: August 2014

Abstract
Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK–ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor–bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc–Grb2–SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition. Cancer Res; 74(20); 5866–77. ©2014 AACR.
HE4 Tissue Expression and Serum HE4 Levels in Healthy Individuals and Patients with Benign or Malignant Tumors: A Systematic Review
Authors: Karlsen Nikoline S. , Karlsen Mona A. , Høgdall Claus K. , Høgdall Estrid V.S. 
Published: August 2014

AbstractHuman epididymis protein 4 (HE4) has received major attention as a potential tumor marker in epithelial ovarian cancer; however, evidence of significant overexpression of HE4 in several other human cancers is expanding. To assess the possible limitations or benefits of HE4 in a clinical setting, this review aims to systematically outline published results of HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors. Our findings suggest scientific basis for a potential diagnostic ability of HE4 in gynecologic cancer and lung cancer, and further research is needed regarding other cancers. Yet, it is important to recognize that other malignancies can cause increased HE4 levels. Furthermore, attention should be paid to the influence of age and renal function on HE4 serum levels in future studies as well as in the clinic for proper interpretation of serum HE4 test results. Cancer Epidemiol Biomarkers Prev; 23(11); 2285–95. ©2014 AACR.
The Fibroblast Growth Factor Receptor Genetic Status as a Potential Predictor of the Sensitivity to CH5183284/Debio 1347, a Novel Selective FGFR Inhibitor
Authors: Nakanishi Yoshito , Akiyama Nukinori , Tsukaguchi Toshiyuki , Fujii Toshihiko , Sakata Kiyoaki , Sase Hitoshi , Isobe Takehito , Morikami Kenji , Shindoh Hidetoshi , Mio Toshiyuki , Ebiike Hirosato , Taka Naoki , Aoki Yuko , Ishii Nobuya 
Published: August 2014

Abstract
The FGF receptors (FGFR) are tyrosine kinases that are constitutively activated in a subset of tumors by genetic alterations such as gene amplifications, point mutations, or chromosomal translocations/rearrangements. Recently, small-molecule inhibitors that can inhibit the FGFR family as well as the VEGF receptor (VEGFR) or platelet-derived growth factor receptor (PDGFR) family displayed clinical benefits in cohorts of patients with FGFR genetic alterations. However, to achieve more potent and prolonged activity in such populations, a selective FGFR inhibitor is still needed. Here, we report the identification of CH5183284/Debio 1347, a selective and orally available FGFR1, FGFR2, and FGFR3 inhibitor that has a unique chemical scaffold. By interacting with unique residues in the ATP-binding site of FGFR1, FGFR2, or FGFR3, CH5183284/Debio 1347 selectively inhibits FGFR1, FGFR2, and FGFR3 but does not inhibit kinase insert domain receptor (KDR) or other kinases. Consistent with its high selectivity for FGFR enzymes, CH5183284/Debio 1347 displayed preferential antitumor activity against cancer cells with various FGFR genetic alterations in a panel of 327 cancer cell lines and in xenograft models. Because of its unique binding mode, CH5183284/Debio 1347 can inhibit FGFR2 harboring one type of the gatekeeper mutation that causes resistance to other FGFR inhibitors and block FGFR2 V564F–driven tumor growth. CH5183284/Debio 1347 is under clinical investigation for the treatment of patients harboring FGFR genetic alterations. Mol Cancer Ther; 13(11); 2547–58. ©2014 AACR.