bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained Complete Responses in Patients With Lymphoma Receiving Autologous Cytotoxic T Lymphocytes Targeting Epstein-Barr Virus Latent Membrane Proteins
Authors: Bollard Catherine M. , Gottschalk Stephen , Torrano Vicky , Diouf Oumar , Ku Stephanie , Hazrat Yasmin , Carrum George , Ramos Carlos , Fayad Luis , Shpall Elizabeth J. , Pro Barbara , Liu Hao , Wu Meng-Fen , Lee Daniel , Sheehan Andrea M. , Zu Youli , Gee Adrian P. , Brenner Malcolm K. , Heslop Helen E. , Rooney Cliona M. 
Published: December 2013

Purpose Tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma express the type II latency Epstein-Barr virus (EBV) antigens latent membrane protein 1 (LMP1) and LMP2, which represent attractive targets for immunotherapy. Because T cells specific for these antigens are present with low frequency and may be rendered anergic by the tumors that express them, we expanded LMP–cytotoxic T lymphocytes (CTLs) from patients with lymphoma using autologous dendritic cells and EBV-transformed B–lymphoblastoid cell lines transduced with an adenoviral vector expressing either LMP2 alone (n = 17) or both LMP2 and ΔLMP1 (n = 33). Patients and Methods These genetically modified antigen-presenting cells expanded CTLs that were enriched for specificity against type II latency LMP antigens. When infused into 50 patients with EBV-associated lymphoma, the expanded CTLs did not produce infusional toxicities. Results Twenty-eight of 29 high-risk or multiple-relapse patients receiving LMP-CTLs as adjuvant therapy remained in remission at a median of 3.1 years after CTL infusion. None subsequently died as a result of lymphoma, but nine succumbed to complications associated with extensive prior chemoradiotherapy, including myocardial infarction and secondary malignancies. Of 21 patients with relapsed or resistant disease at the time of CTL infusion, 13 had clinical responses, including 11 complete responses. T cells specific for LMP as well as nonviral tumor-associated antigens (epitope spreading) could be detected in the peripheral blood within 2 months after CTL infusion, but this evidence for epitope spreading was seen only in patients achieving clinical responses. Conclusion Autologous T cells directed to the LMP2 or LMP1 and LMP2 antigens can induce durable complete responses without significant toxicity. Their earlier use in the disease course may reduce delayed treatment-related mortality.
Massive Solitary Fibrous Tumor (SFT) of the infratemporal and pterygomaxillary fossa treated by combined endoscopic approach
Authors: Cloutier François , Lapointe Geneviève , Nadeau Sylvie 
Published: December 2013

Solitary fibrous tumors (SFTs) were first described as spindle-cell tumors originating from the pleura. Until recently, there was some debate with regards to the name and origin of these tumors and the distinctions with the term haemangiopericytomas (HPCs), a rare type of vascular tumor.Morphological, immunohistochemical and clinical features of HPCs were not specific for one entity. With the exception of myopericytoma, infantile myofibromatosis and HPC-like lesions of the sinonasal tract showing myoid differentiation, all other HPC-like lesions are best considered as subtypes of SFT. Due to their mesenchymal origin, we are now aware that SFTs may involve several extrapleural sites including soft tissues or meninges. When SFTs involve the skull base and show malignant histological characteristics, they can be an important challenge for the surgical team.We report a case of a 54-year-old man complaining of poor vision and facial pain that had worsened over the last year. Computed tomography and magnetic resonance imaging indicated a large mass, involving the right infratemporal and pterygomaxillary fossa. A biopsy proved positive for a solitary fibrous tumor with malignant features. Surgery was performed using a combined approach of frontotemporal craniotomy and nasal endoscopy. The subtotal resection, conducted due to nodularity on the dura mater, was a success and was complemented by postoperative radiation therapy. Follow-up MRIs showed no recurrence of the tumor.To the authors’ knowledge, this is the first reported case of a massive SFT involving this region, treated with minimal invasive surgery without any facial osteotomies.
An Integrative Study of the Genetic, Social and Environmental Determinants of Chronic Kidney Disease Characterized by Tubulointerstitial Damages in the North Central Region of Sri Lanka
Authors: Nanayakkara Shanika , Senevirathna STMLD , Abeysekera Tilak , Chandrajith Rohana , Ratnatunga Neelakanthi , Gunarathne EDL , Yan Junxia , Hitomi Toshiaki , Muso Eri , Komiya Toshiyuki , Harada Kouji H. , Liu Wanyang , Kobayashi Hatasu , Okuda Hiroko , Sawatari Hideyuki , Matsuda Fumihiko , Yamada Ryo , Watanabe Takao , Miyataka Hideki , Himeno Seiichiro , Koizumi Akio 
Published: December 2013

An Integrative Study of the Genetic, Social and Environmental Determinants of Chronic Kidney Disease Characterized by Tubulointerstitial Damages in the North Central Region of Sri Lanka: Shanika NANAYAKKARA, et al. Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University—ObjectivesPrevious investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. Methods: We conducted a social‐environmental‐ and‐genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case‐series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha‐1 microglobulin in urine.Results and DiscussionNone of 18 metals measured (μg/l) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75.80% of total urinary As was in the form of arsenobetaine, which is non‐toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome‐wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome‐wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 ~ 10.9 in quantitative trait locus analysis; p=3.73 ~ 10.8 in dichotomous analysis) in SLC13A3 (sodium‐dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy male population suffers from non‐communicable diseases, suggesting their possible influence on CKDu progression.
Association Between Pediatric Clinical Trials and Global Burden of Disease
Authors: Bourgeois Florence T. , Olson Karen L. , Ioannidis John P.A. , Mandl Kenneth D. 
Published: December 2013

BACKGROUND:
The allocation of research resources should favor conditions responsible for the greatest disease burden. This is particularly important in pediatric populations, which have been underrepresented in clinical research. Our aim was to measure the association between the focus of pediatric clinical trials and burden of disease and to identify neglected clinical domains.

METHODS:
We performed a cross-sectional study of clinical trials by using trial records in ClinicalTrials.gov. All trials started in 2006 or after and studying patient-level interventions in pediatric populations were included. Age-specific measures of disease burden were obtained for 21 separate conditions for high-, middle-, and low-income countries. We measured the correlation between number of pediatric clinical trials and disease burden for each condition.

RESULTS:
Neuropsychiatric conditions and infectious diseases were the most studied conditions globally in terms of number of trials (874 and 847 trials, respectively), while intentional injuries (5 trials) and maternal conditions (4 trials) were the least studied. Clinical trials were only moderately correlated with global disease burden (r = 0.58, P = .006). Correlations were also moderate within each of the country income levels, but lowest in low-income countries (r = .47, P = .03). Globally, the conditions most understudied relative to disease burden were injuries (–260 trials for unintentional injuries and –160 trials for intentional injuries), nutritional deficiencies (–175 trials), and respiratory infections (–171 trials).

CONCLUSIONS:
Pediatric clinical trial activity is only moderately associated with pediatric burden of disease, and least associated in low-income countries. The mismatch between clinical trials and disease burden identifies key clinical areas for focus and investment.
Concentrated tea tree oil toxicosis in dogs and cats: 443 cases (2002–2012)
Authors: Khan Safdar A. , McLean Mary Kay , Slater Margaret R. 
Published: December 2013

Abstract
Objective—To determine the frequency, types, and severity of clinical signs; geographic distribution; and treatment information associated with toxicosis caused by 100% tea tree oil (TTO) in dogs and cats in the United States and Canada.
Design—Retrospective case series.
Animals—337 dogs and 106 cats with evidence of exposure to 100% TTO.
Procedures—10-year incident data were retrieved from the ASPCA Animal Poison Control Center database from January 2002 to December 2012. Only evidenced or witnessed incidents assessed as toxicosis or suspected toxicosis were included. Signalment, amount of TTO used, intention of use, and outcome information were evaluated. Severity of illness and correlations with breed, sex, age, and weight were determined.
Results—TTO was intentionally used in 395 of 443 (89%) animals. The amount used ranged from 0.1 to 85 mL. Incidents were reported from 41 states, the District of Columbia, and 4 Canadian provinces. Exposure route was cutaneous in 221 (50%) animals, cutaneous and oral in 133 (30%), and oral in 67 (15%). Clinical signs developed within 2 to 12 hours and lasted up to 72 hours. The most common signs were increased salivation or drooling, signs of CNS depression or lethargy, paresis, ataxia, and tremors. A significant association with severity of illness was found for age and weight, with higher prevalence of major illness in younger and smaller cats.
Conclusions and Clinical Relevance—Intentional or accidental use of 100% TTO in dogs or cats caused serious signs of CNS depression, paresis, ataxia, or tremors within hours after exposure and lasting up to 3 days. Younger cats and those with lighter body weight were at greater risk of developing major illness.
Prevalence of hepatitis B e antigen among human immunodeficiency virus and hepatitis B virus co-infected patients in Jos, Nigeria
Authors: Iroezindu Michael O , Daniyam Comfort A , Agbaji Oche O , Isa Ejiji S , Okeke Edith N , Imade Godwin E 
Published: December 2013

Introduction: Human immunodeficiency virus (HIV) negatively impacts the natural history of hepatitis B virus (HBV) infection, including replication. We determined the prevalence of HBeAg in HIV/HBV co-infected patients compared to HBV mono-infected controls and further investigated the relationship between HBeAg seropositivity and the degree of HIV-induced immunosuppression in co-infected patients. Methodology: The study design was cross-sectional. One hundred HBsAg-positive HIV-infected adults and 100 age and sex matched HBsAg-positive HIV negative controls were consecutively recruited between May and November 2010. Relevant demographic and HBV-related information was obtained. HBeAg was assayed by semi-quantitative third generation ELISA. The HIV/HBV co-infected patients also had CD4+ cell and HIV viral load quantification measured using flow cytometry and polymerase chain reaction techniques respectively. Results: In each group, the mean age was 34 ± 8 years and the majority (61%) was female. The prevalence of HBeAg was significantly higher among co-infected patients (n = 28; 28%) than in the controls (n = 15; 15%; p = 0.03). HBeAg seropositivity was independently associated with age < 40 years (AOR = 2.83, 95% = CI 1.29-6.17) and HIV seropositivity (AOR = 2.44, 95% C.I = 1.17-5.07). The prevalence of HBeAg was significantly higher in co-infected patients with CD4 cell count < 200 cell/µL (41.3%) compared to those with 200-499 cell/µL (18.6%) and ≥500 cell/µL (9.1%), p = 0.006. Conclusion: HIV/HBV co-infected patients have a significantly higher prevalence of HBeAg than HBV mono-infected individuals. HBV-infected patients should be routinely assessed for HBeAg, especially if they are co-infected with HIV.
Etiological diversity of diarrhoeal disease in Bangladesh
Authors: Das Sumon Kumar , Ahmed Shahnawaz , Ferdous Farzana , Farzana Fahmida Dil , Chisti Mohammod Jobayer , Latham Jonathan Ross , Talukder Kaisar Ali , Rahman Mustafizur , Begum Yasmin Ara , Qadri Firdausi , Faruque Abu Syed Golam , Ahmed Tahmeed 
Published: December 2013

Background: This study compared the diversity of common diarrhoeal pathogens and antimicrobial susceptibility in four hospitals in Bangladesh. Methodology: A total of 13,959 diarrhoea patients, comprising rural Mirzapur [2,820), rural Matlab (2,865), urban Dhaka (5,287) and urban Mirpur (2,987) were included under the diarrhoeal disease surveillance system of icddr,b during 2010-2011; stool specimens were tested for Shigella spp., Vibrio cholerae, enterotoxigenic Escherichia coli and rotavirus. Results: Rotavirus was highest in Mirzapur (28%) followed by Dhaka (24%), Matlab (19%) and Mirpur (18%). Overall, Shigella was significantly more prevalent in rural sites (Mirzapur 13% and Matlab 7%), than in urban sites (Dhaka 3% and Mirpur 3%). Vibrio cholerae was more common in the urban sites of Dhaka (14%) and Mirpur (12%). 72% of Shigella isolates were susceptible to ciprofloxacin in Mirzapur, and 88% to mecillinam. In Dhaka, the figures for Shigella were 65% and 50%, in Matlab 65% and 85%, and in Mirpur 59% and 92% respectively. Susceptibility of Shigella to azithromycin and ceftriaxone in Dhaka was 74% and 95%, and in Mirpur 88% and 92% respectively. Vibrio cholerae showed the highest resistance to trimethoprim-sulfamethoxazole (100% in Mirpur) and lowest resistance to ciprofloxacin (0% in Dhaka, Matlab and Mirpur) and azithromycin (30% in Dhaka to 7% in Mirzapur). Multidrug resistance (≥ 3 antibiotics) for Shigella were: Mirzapur (50%); Dhaka (36%); Matlab (23%) and Mirpur (37%); and for V. cholerae it was 26%, 37%, 49% and 23% respectively. Conclusion: The isolation rates and antimicrobial susceptibility of Shigella spp. and V. cholerae along with rotavirus differed significantly in certain geographical sites.
Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children
Authors: Ojurongbe Olusola , Lawal Olubunmi A , Abiodun Oyindamola O , Okeniyi John A , Oyeniyi Ayobami J , Oyelami Oyeku A 
Published: December 2013

Introduction: The development and spread of Plasmodium falciparum resistance to most commonly used antimalarials remain a major challenge in the control of malaria. Constant monitoring of drug efficacy is an important tool in establishing rational antimalarial drug policies. Methodology: A randomized comparative study was conducted at the Wesley Guild Hospital, Ilesa, Nigeria between February 2010 and September 2011 comparing the efficacy and safety of artemether-lumefantrine (Coartem) and fixed dose of artesunate plus amodiaquine (Larimal) in the treatment of uncomplicated P. falciparum malaria in children betweem 6 and 144 months of age. P. falciparum malaria parasitemia was assessed by microscopy and rapid diagnostic test. Drugs were administered according to age for three days under supervision. The primary efficacy endpoint was a day 28 PCR-corrected parasitological cure. Results: A total of 182 patients were enrolled in the two treatment groups, Coartem (n = 101) and Larimal (n = 81), and tested after 28 days. In the intention-to-treat population, Coartem (n= 101) and Larimal (n= 81) had a PCR-corrected cure rate of 98% and 100% respectively, while in the per-protocol population, Coartem (n = 89) and Larimal (n = 71) both had a PCR-corrected cure rate of 100% at day 28. Although parasite and fever clearance time was faster in the Larimal group, no significant difference was observed between the two drugs. No serious adverse effects were reported. Conclusion: Five years after being introduced in Nigeria, both Coartem and Larimal have been shown to be safe and highly effective in the treatment of uncomplicated P. falciparum malaria in children.
A Longterm Prospective Real-life Experience with Leflunomide in Juvenile Idiopathic Arthritis
Authors: Alcântara Antonia Célia de Castro , Leite Christiane Araújo Chaves , Leite Ana Caroline Rocha Melo , Sidrim José Julio Costa , Silva Francisco Saraiva , Rocha Francisco Airton Castro 
Published: December 2013

Objective.To describe a clinical practice with leflunomide (LEF) in juvenile idiopathic arthritis (JIA).Methods.Patients with JIA seen between May 2008 and May 2012 and considered nonresponsive to methotrexate (MTX) were given LEF and prospectively followed. Primary outcome was a 28-joint Disease Activity Score (DAS28) of low disease activity (< 3.2) in less than 6 months. Childhood Health Assessment Questionnaire (CHAQ) scores and safety data were recorded.Results.Forty-three patients (33 female) were included with 25 (58.1%) polyarticular, 10 oligoarticular (7 extended; 3 persistent), 6 systemic, and 2 enthesitis-related. Ten (23.2%) were rheumatoid factor–positive and 7 (16.3%) had antinuclear antibodies. Prior drugs other than MTX: 11 (25.5%) chloroquine diphosphate + MTX and 2 (4.6%) sulfasalazine + MTX; mean prednisone dose was 6.4 ± 9.3 mg. The MTX dose prior to LEF was 14.5 ± 4.5 mg/m2/week. LEF dose and duration of therapy were 16.6 ± 5.2 mg/d and 3.6 ± 2.2 years, respectively. Nineteen patients (44.2%) interrupted LEF: 1 entered remission, 11 were nonresponsive, and 7 were intolerant (16.2%). Baseline DAS28 (5.57 ± 0.7) dropped to 3.7 ± 1.2 at final analysis (p < 0.001) and 16 patients (37.2%) had a low DAS28 [< 3.2; 12 (27.9%) while taking LEF + MTX and 4 (9.3%) while taking monotherapy]. At last followup, the number of patients with DAS28 > 5.1 dropped from 34 (79%) to 9 (20.9%) and CHAQ scores from 0.86 ± 0.7 to 0.44 ± 0.5 (p < 0.001).Conclusion.LEF isolated or combined with MTX is effective and safe to treat JIA in patients refractory to MTX.
Deregulated NLRP3 and NLRP1 Inflammasomes and Their Correlations with Disease Activity in Systemic Lupus Erythematosus
Authors: Yang Qingrui , Yu Chengcheng , Yang Zhaowen , Wei Qing , Mu Kun , Zhang Ying , Zhao Wei , Wang Xiaofeng , Huai Wanwan , Han Lihui 
Published: December 2013

Objective.NOD-like receptor family, pyrin domain containing 3 and 1 (NLRP3 and NLRP1) inflammasomes are molecular platforms that sense the damage or danger signals of cells. We investigated whether NLRP3/NLRP1 inflammasomes are involved in the pathogenesis and progression of systemic lupus erythematosus (SLE).Methods.Expressions of inflammasome components at the mRNA and protein levels in the peripheral blood mononuclear cells (PBMC) from patients with SLE and healthy controls were investigated by quantitative real-time transcription PCR and Western blot, respectively. Correlations between NLRP3/NLRP1 inflammasome components’ expression and clinical disease progression were investigated. Expressions of NLRP3/NLRP1 inflammasomes before and after treatment in the patients with SLE were also analyzed and compared.Results.Our data showed that expressions of NLRP3/NLRP1 inflammasomes were significantly downregulated in PBMC from patients with SLE compared with PBMC from healthy controls. Further, expressions of NLRP3/NLRP1 inflammasomes were negatively correlated with the SLE Disease Activity Index, and regular glucocorticoid treatment significantly corrected this deregulation of these inflammasomes. Further analysis showed that type I interferon (IFN) level was significantly negatively correlated with expression of NLRP3/NLRP1 inflammasomes, which indicated that enhanced IFN-I level in patients with SLE was responsible, at least to a great degree, for the deregulation of inflammasomes.Conclusion.These results indicated deregulation of NLRP3/NLRP1 inflammasomes in patients with SLE, and suggested an important role for inflammasomes in the pathogenesis and progression of SLE.
Health Literacy Predicts Discrepancies Between Traditional Written Patient Assessments and Verbally Administered Assessments in Rheumatoid Arthritis
Authors: Hirsh Joel M. , Davis Lisa A. , Quinzanos Itziar , Keniston Angela , Caplan Liron 
Published: December 2013

Objective.Patient assessments of disease activity (PtGA) and general health (GH) measured by visual analog scale (VAS) are widely used in rheumatoid arthritis (RA) clinical practice and research. These require comprehension of the question’s wording and translation of disease activity onto a written VAS, which is problematic for patients with limited health literacy (HL) or difficulty completing forms. This study’s objective was to validate verbally administered versions of patient assessments and identify factors that might explain discrepancies between verbal and written measures.Methods.We enrolled patients with RA at the Denver Health rheumatology clinic (n = 300). Subjects were randomized to complete the traditional written PtGA and GH and one of the verbal assessments. Subjects provided a verbal numeric response after reading the question, having the question read to them in person, or hearing the question over the phone. Spearman and Lin correlations comparing written and verbal assessments were determined. Multivariate logistic regression was performed to explain any discrepancies.Results.The instruments administered verbally in-person showed good, but not excellent, correlation with traditional written VAS forms (Spearman coefficients 0.59 to 0.70; p < 0.001 for all correlations). Twenty-three percent of subjects were unable to complete 1 of the written VAS assessments without assistance. HL predicted missing written data and discrepancies between verbal and written assessments (p < 0.05 for all correlations).Conclusion.Providers should use verbal versions of PtGA and GH with caution while caring for patients unable to complete traditional written version. Limited HL is widely prevalent and a barrier to obtaining patient-oriented data.