bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormalities of serum-free light chain in patients with primary antibody deficiency in the absence of B lymphocyte clonality
Authors: Unsworth David Joseph , Wallage Michael John , Sarkar Esha , Lock Robert John 
Published: September 2012

AimsA review of practice to determine whether serum-free light chain (SFLC) assays are helpful in detecting underlying clonal B-cell disorders or amyloidosis in patients with primary antibody deficiency (PAD) and recurrent infection.MethodsSFLC were assayed by nephelometry (BN2 nephelometer, Siemens; FREELITE assay, Binding Site). We reviewed SFLC test results recorded in our regional laboratory over a 4-year time period; 20 adults with PAD were identified as having been tested on at least two occasions.ResultsOf 20 patients, 4 with PAD had abnormal serum-free kappa/lambda (K/L) ratios but no evidence of B-cell clonality. We also found extremely low levels of kappa and or lambda (below the limits of reliable detection) in 19/20 PAD cases (mostly common variable immunodeficiency), such that in many, ratios were not calculable.ConclusionsThe data suggest that the abnormal ratios are generated by an inability to produce and/or secrete SFLCs, particularly kappa FLC. In this small initial study, we seek to highlight PAD cases where a suspicious K/L ratio, typically with very low absolute quantities of SFLCs, most likely points to B-cell dysfunction, rather than to B lymphocyte clonality.
Immunohistochemistry in the era of personalised medicine
Authors: McCourt Clare Margaret , Boyle David , James Jacqueline , Salto-Tellez Manuel 
Published: September 2012

BackgroundImmunohistochemistry (IHC) plays a central role in the histopathological classification of diseases, including cancer. More recently, the importance of immunohistochemical staining is increasing. IHC usage in diagnostics is invaluable; however, the genetic and therapeutic significance of biomarker immunostaining has become equally relevant.ContentIn this article, we would like to analyse the three distinct roles of IHC and review their individual impacts on modern diagnostic pathology: (1) diagnostic IHC; (2) genetic IHC and (3) therapeutic IHC.SummaryThus, we will characterise the different analytical processes that are required in the three approaches to IHC usage stated above, as well as the clinical significance and overall importance in patient management. This will allow us to hypothesise on the most appropriate laboratory environment and detection methods for the future.
The role and status of evidence and innovation in the healthy towns programme in England: a qualitative stakeholder interview study
Authors: Goodwin Denise May , Cummins Steven , Sautkina Elena , Ogilvie David , Petticrew Mark , Jones Andy , Wheeler Katy , White Martin 
Published: September 2012

BackgroundIn 2008, the Healthy Community Challenge Fund commissioned nine ‘healthy towns’ in England to implement and evaluate community-based environmental interventions to prevent obesity. This paper examines the role of evidence in informing intervention development, innovation and the potential for programmes to contribute to the evidence base on the effectiveness of interventions that tackle population obesity.MethodTwenty qualitative interviews with local programme stakeholders and national policy actors were conducted. Interview transcripts were coded and thematically analysed. Initial analyses were guided by research questions regarding the nature and role of evidence in the development and implementation of the healthy towns programme and the capacity for evidence generation to inform future intervention design, policy and practice.FindingsStakeholders relied on local anecdotal and observational evidence to guide programme development. While the programme was considered an opportunity to trial new and innovative approaches, the requirement to predict likely health impacts and adopt evidence-based practice was viewed contradictory to this aim. Stakeholders believed there were missed opportunities to add to the existing empirical evidence base due to a lack of clarity and planning, particularly around timing, in local and national evaluations.ConclusionsA strong emphasis on relying on existing evidence-based practice and producing positive impacts and outcomes may have impeded the opportunity to implement truly innovative programmes because of fear of failure. Building more time for development, implementation and evaluation into future initiatives would maximise the use and generation of robust and relevant evidence for public health policy and practice.
Stent assisted embolization of 64 anterior communicating artery aneurysms
Authors: Johnson Andrew Kelly , Munich Stephan A , Heiferman Daniel M , Lopes Demetrius Klee 
Published: September 2012

IntroductionAnterior communicating artery (ACoA) aneurysms comprised over half of the ruptured aneurysms in the International Subarachnoid Trial. Endovascular treatment of ACoA aneurysms has provided good results, but until the introduction of intracranial stents, many ACoA aneurysms could not be treated without craniotomy. The current study analyzes the results of ACoA aneurysm treatment using stent assisted embolization.Methods64 patients with ACoA aneurysms underwent stent assisted aneurysm repair. Four were treated in the acute rupture phase and a fifth ruptured aneurysm was stented in a second procedure after initial coiling. Five aneurysms were 10 mm or more in greatest diameter. Follow-up angiography was performed 6 months after treatment; then, patients were followed with annual MR angiography. Technical, clinical, and long term radiographic results were analyzed.ResultsStents were successfully deployed in each case. One patient was eventually treated with a three stent construct and died of perioperative hemorrhage. One major stroke occurred during a separate procedure when a patient was taken off antiplatelet medications. These cases were the only aneurysm related morbidity (1.6%) and mortality (1.6%) events during the entire follow-up period. After stent assisted embolization, 32 (50.0%) ACoA aneurysms were completely occluded, 15 (23.4%) had residual neck, and 17 (26.6%) had residual filling. At first radiographic follow-up, 39 of 55 (70.9%) showed complete occlusion. Three (5.5%) total aneurysms required retreatment.ConclusionsStent assisted aneurysm treatment was a safe and effective option in this series of ACoA aneurysms with maximum diameter less than 15 mm. ACoA aneurysms may be more likely to recur regardless of treatment option, but stent assisted embolization may be durable after stable initial radiographic follow-up.
Management options for visual pathway compression from optic gliomas
Authors: Bessero Anne-Caroline , Fraser Clare , Acheson James , Davagnanam Indran 
Published: September 2012

Abstract
Optic pathway gliomas (OPGs) manifest with neuro-ophthalmic symptoms and signs; however, presentation can vary as their location and growth patterns are highly variable. An exophytic expansion of an OPG within the intracranial cavity can cause compression on neurological structures, warranting intervention. However, management guidelines are limited and the treatment itself may also cause neuro-ophthalmic complications. Therefore, clinical decision-making must include input from a multidisciplinary team that includes ophthalmology, neurosurgery, radiation oncology and neuroradiology.
Prevalence of HIV and other sexually transmitted infections and factors associated with syphilis among female sex workers in Panama
Authors: Hakre Shilpa , Arteaga Griselda , Núñez Aurelio E , Bautista Christian T , Bolen Aimee , Villarroel Maria , Peel Sheila A , Paz-Bailey Gabriela , Scott Paul T , Pascale Juan M ,   the Panama HIV EPI Group
Published: September 2012

ObjectivesBiological and behavioural surveillance of HIV and sexually transmitted infections (STIs) among populations at highest risk have been used to monitor trends in prevalence and in risk behaviours. Sex work in Panama is regulated through registration with the Social Hygiene Programme, Ministry of Health. We estimated prevalence of HIV and STIs, and factors associated with active syphilis among female sex workers (FSWs).MethodsA cross-sectional study using venue-based, time-space sampling was conducted among FSWs in Panama from 2009 to 2010. FSWs were interviewed about sociodemographic characteristics, sexual risk behaviour, health history and drug use using an anonymous structured questionnaire. Blood was collected for serological testing of HIV and other STIs. Factors associated with active syphilis were studied using logistic regression analysis.ResultsThe overall HIV-1 prevalence of 0.7% varied by FSW category; 1.6% in 379 unregistered, and 0.2% in 620 registered FSWs. Overall prevalence (and 95% CI) of STIs were: syphilis antibody, 3.8% (2.7% to 5.2%); herpes simplex virus type 2 antibody (anti-HSV-2), 74.2% (71.4% to 76.9%); hepatitis B surface antigen, 0.6% (0.2% to 1.3%); hepatitis B core antibody, 8.7% (7.0% to 10.6%); and hepatitis C antibody, 0.2% (0.0% to 0.7%). In multivariate analysis, registration (adjusted OR (AOR)=0.35; 95% CI 0.16 to 0.74), having a history of STI (AOR=2.37; 95% CI 1.01 to 5.58), forced sex (AOR=2.47; 95% CI 1.11 to 5.48), and anti-HSV-2 (AOR=10.05; 95% CI 1.36 to 74.38) were associated with active syphilis.ConclusionsAlthough HIV prevalence is low among FSWs in Panama, unregistered FSWs bear a higher burden of HIV and STIs than registered FSWs. Programmes aimed at overcoming obstacles to registration, and HIV, STI and harm reduction among unregistered FSWs is warranted to prevent HIV transmission, and to improve their sexual and reproductive health.
A pilot study of the feasibility of a vaginal washing cessation intervention among Kenyan female sex workers
Authors: Masese Linnet , McClelland R Scott , Gitau Ruth , Wanje George , Shafi Juma , Kashonga Francis , Ndinya-Achola Jeckoniah O , Lester Richard , Richardson Barbra A , Kurth Ann 
Published: September 2012

BackgroundIntravaginal practices including vaginal washing have been associated with HIV-1 acquisition. This association may be mediated by mucosal disruption, changes in vaginal flora or genital tract inflammatory responses. Reducing vaginal washing could lower women's risk of HIV-1 acquisition.Methods23 HIV-1 seronegative women who reported current vaginal washing were recruited from a prospective cohort study of high-risk women in Mombasa, Kenya. A theoretical framework including information–motivation–behavioural skills and harm reduction was implemented to encourage participants to reduce or eliminate vaginal washing. At baseline and after 1 month, we evaluated vaginal epithelial lesions by colposcopy, vaginal microbiota by Nugent's criteria and vaginal cytokine milieu using ELISA on cervicovaginal lavage specimens.ResultsThe most commonly reported vaginal washing substance was soap with water (N=14, 60.9%). The median frequency of vaginal washing was 7 (IQR 7–14) times per week. After 1 month, all participants reported cessation of vaginal washing (p=0.01). The probability of detecting cervicovaginal epithelial lesions was lower (OR 0.48; 95% CI 0.20 to 1.16; p=0.10) and the likelihood of detectingLactobacillusby culture was higher (OR 3.71, 95% CI 0.73 to 18.76, p=0.11) compared with baseline, although these results were not statistically significant. There was no change in the prevalence of bacterial vaginosis. Most cytokine levels were reduced, but these changes were not statistically significant.ConclusionsA theory-based intervention appeared to have a positive effect in reducing vaginal washing over 1 month. Larger studies with longer follow-up are important to further characterise the effects of vaginal washing cessation on biological markers.
Condom effectiveness against non-viral sexually transmitted infections: a prospective study using electronic daily diaries
Authors: Crosby Richard A , Charnigo Richard A , Weathers Chandra , Caliendo Angela M , Shrier Lydia A 
Published: September 2012

ObjectivesTo prospectively evaluate the protective value of consistent and correct use of latex condoms against the acquisition ofChlamydia trachomatis,Neisseria gonorrhoeaeandTrichomonas vaginalis.MethodsPatients (N=929) attending clinics that treat sexually transmitted infections (STIs) were prospectively followed for up to 6 months. Urine STI nucleic acid amplification testing was performed at baseline, 3 months and 6 months. Participants were instructed to respond to daily prompts from a handheld device by completing a report for each penile-vaginal sexual intercourse event. Generalised estimating equation models examined associations of consistent as well as consistent and correct condom use with STI incidence over 3-month intervals.ResultsConsistent condom use was not significantly associated with STI incidence (Estimated OR (EOR)=0.75; 95% CI (CI) 0.43 to 1.30; p=0.31). However, individuals who used condoms both correctly and consistently were estimated to have 59% lower odds of acquiring an STI (EOR=0.41; 95% CI 0.19 to 0.90; p=.026), compared to those who did not.ConclusionsThe correct as well as the consistent use of condoms greatly reduces the odds of non-viral STI acquisition.
Chemotherapeutic Sensitivity of Testicular Germ Cell Tumors Under Hypoxic Conditions Is Negatively Regulated by SENP1-Controlled Sumoylation of OCT4
Authors: Wu Yu-Chih , Ling Thai-Yen , Lu Shing-Hwa , Kuo Hung-Chih , Ho Hong-Nerng , Yeh Shauh-Der , Shen Chia-Ning , Huang Yen-Hua 
Published: September 2012

Abstract
Testicular germ cell tumors (TGCT) generally respond well to chemotherapy, but tumors that express low levels of the transcription factor OCT4 are associated with chemoresistance and poor prognosis. Hypoxia is known to induce drug resistance in TGCTs; however, the mechanistic basis for reduced expression of OCT4 and drug resistance is unclear. Here we show that hypoxia reduces OCT4 levels and increases the resistance of embryonal carcinoma (EC) cells to cisplatin and bleomycin. Furthermore, we show that the loss of OCT4 expression under hypoxia can be triggered by sumoylation, which was regulated by SUMO1 and the SUMO1 peptidase SENP1. Under hypoxic conditions, overexpression of SUMO1gg (the active form of SUMO1) not only increased the level of sumoylated OCT4 (Su-OCT4), but also decreased the stability of OCT4 protein. In addition, overexpression of SENP1 reduced the Su-OCT4 level induced by SUMO1gg overexpression, thereby maintaining OCT4 levels and enhancing chemosensitivity. Mechanistic investigations revealed that OCT4 sumoylation occurred at K123, as overexpression of an OCT4-K123R mutant effectively reduced the level of Su-OCT4 under hypoxic conditions. Taken together, our results showed that hypoxia reduces OCT4 expression levels in ECs to increase drug resistance and that these effects could be countered to ablate the suppressive effects of hypoxia on chemosensitivity. Our findings also highlight SENP1 as a potential therapeutic target for drug resistant TGCTs. Cancer Res; 72(19); 4963–73. ©2012 AACR.
Anti–IL-20 Monoclonal Antibody Alleviates Inflammation in Oral Cancer and Suppresses Tumor Growth
Authors: Hsu Yu-Hsiang , Wei Chi-Chen , Shieh Dar-Bin , Chan Chien-Hui , Chang Ming-Shi 
Published: September 2012

Abstract
Interleukin-20 (IL-20) is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, little is known about the role of IL-20 in oral cancer. We explored the function of IL-20 in the tumor progression of oral cancer. IL-20 expression levels in tumorous and nontumorous oral tissue specimens from 40 patients with four different stages oral cancer were analyzed with immunohistochemistry (IHC) staining and quantitative real-time PCR (qRT-PCR). Expression of IL-20 and its receptor subunits was higher in clinical oral tumor tissue than in nontumorous oral tissue. The role of IL-20 was examined in two oral cancer cell lines (OC-3 and OEC-M1). In vitro, IL-20 promoted TNF-α, IL-1β, MCP-1, CCR4, and CXCR4 and increased proliferation, migration, reactive oxygen species (ROS) production, and colony formation of oral cancer cells via activated STAT3 and AKT/JNK/ERK signals. To evaluate the therapeutic potential of anti–IL-20 monoclonal antibody 7E for treating oral cancer, an ex vivo tumor growth model was used. In vivo, 7E reduced tumor growth and inflammation in oral cancer cells. In conclusion, IL-20 promoted oral tumor growth, migration, and tumor-associated inflammation. Therefore, IL-20 may be a novel target for treating oral cancer, and anti–IL-20 monoclonal antibody 7E may be a feasible therapeutic. Mol Cancer Res; 10(11); 1430–9. ©2012 AACR.
TLR 2 Induces Vascular Smooth Muscle Cell Migration Through cAMP Response Element−Binding Protein−Mediated Interleukin-6 Production
Authors: Lee Guan-Lin , Chang Ya-Wei , Wu Jing-Yiing , Wu Meng-Ling , Wu Kenneth K. , Yet Shaw-Fang , Kuo Cheng-Chin 
Published: September 2012

Objective—
Migration of vascular smooth muscle cells (VSMCs) from the media into intima contributes to the development of atherosclerosis. Gene deletion experiments implicate a role for toll-like receptor 2 (TLR2) in atherogenesis. However, the underlying mechanisms remain unclear. We postulate that TLR2 promotes VSMC migration by enhancing interleukin (IL)-6 production.

Methods and Results—
Migration assays revealed that TLR2 agonists promoted VSMC migration but not cell proliferation or viability. TLR2 deficiency or inhibition of TLR2 signaling with anti-TLR2 antibody suppressed TLR2 agonist–induced VSMC migration and IL-6 production, which was mediated via p38 mitogen-associated protein kinase and extracellular signal–regulated kinase 1/2 signaling pathways. Neutralizing anti−IL-6 antibodies impaired TLR2-mediated VSMC migration and formation of filamentous actin fiber and lamellipodia. Blockade of p38 mitogen-associated protein kinase or extracellular signal–regulated kinase 1/2 activation inhibited TLR2 agonist pam3CSK4-induced phosphorylation of cAMP response element−binding protein, which regulates IL-6 promoter activity through the cAMP response element site. Moreover, cAMP response element−binding protein small interfering RNA inhibited pam3CSK4-induced IL-6 production and VSMC migration. Additionally, Rac1 small interfering RNA inhibited pam3CSK4-induced VSMC migration but not IL-6 production.

Conclusion—
Our results suggest that on ligand binding, TLR2 activates p38 mitogen-associated protein kinase and extracellular signal–regulated kinase 1/2 signaling in VSMCs. These signaling pathways act in concert to activate cAMP response element−binding protein and subsequent IL-6 production, which in turn promotes VSMC migration via Rac1-mediated actin cytoskeletal reorganization.
Analysis of Procedural Effects of Percutaneous Edge-to-Edge Mitral Valve Repair by 2D and 3D Echocardiography
Authors: Altiok Ertunc , Hamada Sandra , Brehmer Kathrin , Kuhr Kathrin , Reith Sebastian , Becker Michael , Schröder Jörg , Almalla Mohammad , Lehmacher Walter , Marx Nikolaus , Hoffmann Rainer 
Published: September 2012

Background—
Analysis of procedural effects in patients undergoing percutaneous mitral valve repair (PMVR) using the edge-to-edge technique is complex, and common methods to define mitral regurgitation severity based on 2-dimensional (2D) echocardiography are not validated for postprocedural double-orifice mitral valve. This study used 3D transesophageal echocardiography (TEE) to determine the functional and morphological effects of PMVR.

Methods and Results—

In 39 high-risk surgical patients with moderate to severe functional mitral valve regurgitation, 3D TEE with and without color Doppler as well as 2D transthoracic and TEE was performed before and after PMVR (MitraClip device). Mitral valve regurgitant volume by color Doppler 3D TEE was determined as the product of vena contracta areas defined by direct planimetry and velocity time integral using continuous-wave Doppler. Regurgitant volume was reduced from 84.1±38.3 mL preintervention to 35.6±25.6 mL postintervention. Patients in whom vena contracta area could be reduced >50% had a smaller preprocedural mitral annulus area compared with patients with ≤50% reduction (11.9±3.9 versus 16.1±8.5 cm
2
, respectively;

P

=0.036) and tended to have a smaller mitral annulus circumference (13.0±2.0 versus 14.8±4.1 cm, respectively;

P

=0.112). At 6 months follow-up, left atrial and left ventricular end-diastolic volumes were significantly more reduced in patients in whom regurgitant vena contracta area was reduced by >50% compared with those with less reduction (−11.4±5.2 versus −4.8±7.7%;

P

=0.005, and −11.0±7.2 versus −4.5±9.3%;

P

=0.028). The maximum diastolic mitral valve area decreased from 6.0±2.0 to 2.9±0.9 cm
2
(

P

<0.0001).

Conclusions—
Three dimensional TEE demonstrates significant reduction of regurgitant volume after PMVR. The unique visualization of the mitral valve by 3D TEE allows improved understanding of the morphological and functional changes induced by PMVR.
Cardiac Allograft Function During the First Year after Transplantation in Rejection-Free Children and Young Adults
Authors: Lunze Fatima I. , Colan Steven D. , Gauvreau Kimberlee , Chen Ming Hui , Perez-Atayde Antonio R. , Blume Elizabeth D. , Singh Tajinder P. 
Published: September 2012

Background—
Allograft dysfunction is a common finding early after heart transplant (HT). We sought to assess the recovery of left (LV) and right ventricular (RV) function during the first year after HT in children and young adults using pulsed-wave tissue Doppler imaging.

Methods and Results—

We analyzed serially performed echocardiography in 44 pediatric HT recipients (median age: 7.3 years at HT) who remained rejection-free during the first year post-transplant. Age-based normative values for systolic (
S
′), early-diastolic (
E
′), and late-diastolic (
A
′) velocities obtained using pulsed-wave tissue Doppler imaging in 380 healthy children were used to transform patient data into
z
scores. Pulsed-wave tissue Doppler imaging studies ≤10 days post-HT demonstrated biventricular systolic and diastolic dysfunction with most prominent impairment in RV systolic function (
S
′
z
score −2.7±0.8), RV early-diastolic filling (
E
′
z
score −2.3±1.1), and LV early-diastolic filling (
E
′
z
score −2.3±1.1). LV systolic function (
S
′
z
score) and late-diastolic filling (
A
′
z
score) improved to normal in 11 to 30 days, LV early-diastolic filling (
E
′
z
score) in 4 to 6 months, and RV early-diastolic filling in 6 to 9 months (
P
<0.001 for all on longitudinal analysis). However, RV systolic function (RV
S
′
z
score −1.2±1.1) remained impaired 1-year post-transplant. Analysis of serial cardiac catheterization studies showed that RV and LV filling pressures were elevated early post-HT and declined gradually during the first year post-transplant.

Conclusions—
Pediatric HT recipients have biventricular dysfunction using pulsed-wave tissue Doppler imaging early after HT with most significant impairment in RV systolic function and RV and LV early-diastolic filling. Although other aspects of LV and RV function normalize in 6 to 9 months, RV systolic function remains abnormal 1 year-post-transplant.