bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of antigen testing for the diagnosis of ocular histoplasmosis in four cats: a case series and literature review
Authors: Smith Kathryn M , Strom Ann R , Gilmour Margi A , LaDouceur Elise , Reilly Christopher M , Byrne Barbara A , Affolter Verena K , Sykes Jane E , Maggs David J 
Published: August 2016

Case series summary This case series describes the clinical utility of antigen testing for the diagnosis of feline ocular histoplasmosis. Four cats with suspected (n = 2) or confirmed (n = 2) ocular histoplasmosis are described: three from Oklahoma and one from California. In one case, serial urine antigen tests, as well as a serum antigen test for Histoplasma capsulatum, were negative; however, light microscopy identified microorganisms consistent with H capsulatum in ocular tissues at necropsy. In a further two cats with recurrent ocular histoplasmosis following long-term systemic antifungal therapy, Histoplasma species urine antigen concentrations were negative, but both cats improved clinically following systemic antifungal therapy and remained in apparent clinical remission after treatment cessation (9–16 months). The final cat displayed profound bilateral endophthalmitis; however, Histoplasma species antigen testing of vitreous humor and subretinal fluid from the left eye was negative. Intralesional organisms were detected on histopathology of both eyes, and H capsulatum was subsequently isolated and sequenced from tissue of one eye. Relevance and novel information These cases highlight the potential difficulty in definitively diagnosing ocular histoplasmosis in cats when conducting antigen testing of serum, urine and even ocular fluids. Although antigen testing has previously proven useful in the diagnosis of disseminated feline histoplasmosis, it may not be adequate in cats with only ocular signs.
Is pruritus an indicator of aquaporin-positive neuromyelitis optica?
Authors: Netravathi Manjunath , Saini Jitender , Mahadevan Anita , Hari-Krishna Bollampalli , Yadav Ravi , Pal Pramod Kumar , Satishchandra Parthasarathy 
Published: August 2016

Background: Recently, pruritus has been recognised as an important association with neuromyelitis optica spectrum disorders (NMOSD). Objective: To determine the clinical and radiological characteristics of patients with NMOSD and pruritus. Methods and results: Among 57 consecutive patients with NMOSD, 15 (26.3% women) reported pruritus. All had aquaporin-4 (AQP4) antibodies. The mean age was 34.5 ± 9.1 years, age at onset was 31.3 ± 11.0 years and the duration of illness was 3.9 ± 3.1 years. Pruritus preceded the neurological disturbances in all the patients. Predominant patients experienced pruritus in the cervical dermatome (66.7%) followed by cervicothoracic region (13.3%), trigeminal nerve (13.3%) and lumbar region (6.7%). Lesions extending from cervicomedullary junction up to the thoracic segment was the most common site of affection (40%) followed by cervicothoracic (26.7%), cervicomedullary junction to cervical cord (13.3%), cervical cord (6.7%) and thoracic segment (6.7%). Conclusion: This report is one of the largest series reporting the close association of pruritus with onset of neurological symptoms in NMOSD. It highlights the importance of recognising this rare symptom which may help in making a correct diagnosis in a patient with suspected demyelinating disorder. In a patient with NMOSD, early treatment with immunomodulation during pruritus may prevent or minimise occurrence of neurological dysfunction.
Speaking in a second language but thinking in the first language: Language-specific effects on memory for causation events in English and Spanish
Authors: Filipović Luna 
Published: August 2016

Aims and objectives/purpose/research question: This paper’s objective is to offer new insights into the effects of language on memory for causation events in a second language (L2) context. The research was driven by the question of whether proficient L2 users acquired L2 thinking-for-speaking-and-remembering strategies along with the relevant expressions for different types of causation (intentional versus non-intentional). Design/methodology/approach: The cognitive domain of causation is an ideal platform for this investigation, since the lexicalisation of causation differs clearly in the two languages under consideration, English and Spanish. Spanish speakers always distinguish between intentional and non-intentional events through the use of different constructions. The English pattern of lexicalisation in this domain often leaves intentionality unspecified. Our methodology involves an experimental elicitation of event verbalisations and recall memory responses to video stimuli by English and Spanish monolinguals and bilinguals. Data and analysis: The analysis has shown that the Spanish monolinguals and first language (L1) Spanish/L2 English speakers always distinguished between intentional and non-intentional events, while the English monolinguals and L1 English/L2 Spanish speakers generally used expressions that were underspecified with regard to intentionality. Findings/conclusions: All populations used their habitual language patterns as an aid to memory. Spanish monolingual had better recall than their English peers. L2 speakers were mainly relying on the L1 in spite of speaking only the L2 during the experiment. Originality: Possible effects of these typological differences between an L1 and an L2 on speaker recall memory have not been investigated before. Significance/implications: The research presented in this paper informs the theoretical assumptions related to the thinking-for-speaking hypothesis by showing empirically that late bilinguals adhere to their L1 patterns as an aid to memory while speaking in their L2. This novel finding contributes to an improved understanding of language processing and language use among late bilinguals.
Direct sac puncture versus transarterial embolization of type II endoleaks: An evaluation and comparison of outcomes
Authors: Yang Roy Y , Tan Kong T , Beecroft J Robert , Rajan Dheeraj K , Jaskolka Jeffrey D 
Published: August 2016

Purpose To determine the outcomes of type II endoleak embolization with aneurysm sac obliteration and whether the approach – direct sac puncture or transarterial – affects outcome. Methods A retrospective review of patients who underwent endovascular aneurysm repairs and subsequent type II endoleak embolization over 10 years was performed. Twenty-three patients (median age: 73 years, range: 40–88 years) underwent 35 embolizations. Embolization was performed with the goal of obliterating both the endoleak sac and feeding vessels. Embolization agents used include cyanoacrylate glue only (48%), glue and coils (36%), coils only (13%), and other (3%). Results Mean follow-up was 21.8 months. Patients underwent an average of 1.5 embolizations, with 35% requiring more than one. Technical success rate was 89%. Freedom from aneurysm sac expansion was achieved in 91%. Freedom from type II endoleak was accomplished in 70%. There were no ruptured aneurysms during the follow-up period. Direct sac puncture and transarterial approaches had similar incidences of aneurysm sac growth ( p = 0.74), persistent type II endoleak ( p = 0.32), and complications ( p = 0.64). However, direct sac puncture had significantly shorter fluoroscopy ( p < 0.001) and total procedure times ( p < 0.001) than transarterial embolizations. Conclusion Direct sac puncture and transarterial embolization of type II endoleak with aneurysm sac obliteration are similarly effective for the prevention of aneurysm sac growth. However, direct sac puncture is our preferred approach given its significantly shorter fluoroscopic and procedural times.
Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal
Authors: Hennessy Kym , Woodburn James , Steultjens Martijn 
Published: August 2016

AbstractBackgroundClinical practice guidelines are recommendations systematically developed to assist clinical decision‐making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under‐represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA.MethodsGuidelines were identified electronically and through hand searching. Search terms ‘rheumatoid arthritis', ‘clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.ResultsTwenty‐four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an ‘other foot care treatments' domain.ConclusionsFoot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly ‘expert opinion’ or ‘good clinical practice’. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines.
Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device
Authors: Yen Meng-Hua , Wu Yuan-Yi , Liu Yi-Shiuan , Rimando Marilyn , Ho Jennifer Hui-Chun , Lee Oscar Kuang-Sheng 
Published: August 2016

Abstract
Background
Mesenchymal stromal cells (MSCs) are multipotent and have great potential in cell therapy. Previously we reported the differentiation potential of human MSCs into hepatocytes in vitro and that these cells can rescue fulminant hepatic failure. However, the conventional static culture method neither maintains growth factors at an optimal level constantly nor removes cellular waste efficiently. In addition, not only is the duration of differentiating hepatocyte lineage cells from MSCs required to improve, but also the need for a large number of hepatocytes for cell therapy has not to date been addressed fully. The purpose of this study is to design and develop an innovative microfluidic device to overcome these shortcomings.

Methods
We designed and fabricated a microfluidic device and a culture system for hepatic differentiation of MSCs using our protocol reported previously. The microfluidic device contains a large culture chamber with a stable uniform flow to allow homogeneous distribution and expansion as well as efficient induction of hepatic differentiation for MSCs.

Results
The device enables real-time observation under light microscopy and exhibits a better differentiation efficiency for MSCs compared with conventional static culture. MSCs grown in the microfluidic device showed a higher level of hepatocyte marker gene expression under hepatic induction. Functional analysis of hepatic differentiation demonstrated significantly higher urea production in the microfluidic device after 21 days of hepatic differentiation.

Conclusions
The microfluidic device allows the generation of a large number of MSCs and induces hepatic differentiation of MSCs efficiently. The device can be adapted for scale-up production of hepatic cells from MSCs for cellular therapy.
How Many Lymph Nodes Are Enough? Assessing the Adequacy of Lymph Node Yield for Papillary Thyroid Cancer
Authors: Robinson Timothy J. , Thomas Samantha , Dinan Michaela A. , Roman Sanziana , Sosa Julie Ann , Hyslop Terry 
Published: August 2016

Purpose Patients who undergo surgery for papillary thyroid cancer with only a limited lymph node examination are thought to be at risk for potentially harboring occult disease. However, this risk has not been objectively quantified and may have implications for subsequent management and surveillance. Methods Data from the National Cancer Database (1998 to 2012) were used to characterize the distribution of nodal positivity of adult patients diagnosed with localized ≥ 1-cm papillary thyroid cancer who underwent thyroidectomy with one or more lymph nodes (LNs) examined. A β-binomial distribution was used to estimate the probability of occult nodal disease as a function of total number of LNs examined and pathologic tumor stage. Results A total of 78,724 patients met study criteria; 38,653 patients had node-positive disease. The probability of falsely identifying a patient as node negative was estimated to be 53% for patients with a single node examined and decreased to less than 10% when more than six LNs were examined. To rule out occult nodal disease with 90% confidence, six, nine, and 18 nodes would need to be examined for patients with T1b, T2, and T3 disease, respectively. Sensitivity analyses limited to patients likely undergoing prophylactic central neck dissection resulted in three, four, and eight nodes needed to provide comparable adequacy of LN evaluation. Conclusion To our knowledge, our study provides the first empirically based estimates of occult nodal disease risk in patients after surgery for papillary thyroid cancer as a function of primary tumor stage and number of LNs examined. Our estimates provide an objective guideline for evaluating adequacy of LN yield for surgeons and pathologists in the treatment of papillary thyroid cancer, and especially intermediate-risk disease, for which use of adjuvant radioactive iodine and surveillance intensity are not currently standardized.
Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy
Authors: Tendulkar Rahul D. , Agrawal Shree , Gao Tianming , Efstathiou Jason A. , Pisansky Thomas M. , Michalski Jeff M. , Koontz Bridget F. , Hamstra Daniel A. , Feng Felix Y. , Liauw Stanley L. , Abramowitz Matthew C. , Pollack Alan , Anscher Mitchell S. , Moghanaki Drew , Den Robert B. , Stephans Kevin L. , Zietman Anthony L. , Lee W. Robert , Kattan Michael W. , Stephenson Andrew J. 
Published: August 2016

Purpose We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated in the contemporary era. Methods Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated. Results Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM). Conclusion Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.
Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors
Authors: Naing Aung , Papadopoulos Kyriakos P. , Autio Karen A. , Ott Patrick A. , Patel Manish R. , Wong Deborah J. , Falchook Gerald S. , Pant Shubham , Whiteside Melinda , Rasco Drew R. , Mumm John B. , Chan Ivan H. , Bendell Johanna C. , Bauer Todd M. , Colen Rivka R. , Hong David S. , Van Vlasselaer Peter , Tannir Nizar M. , Oft Martin , Infante Jeffrey R. 
Published: August 2016

Purpose Interleukin-10 (IL-10) stimulates the expansion and cytotoxicity of tumor-infiltrating CD8+ T cells and inhibits inflammatory CD4+ T cells. Pegylation prolongs the serum concentration of IL-10 without changing the immunologic profile. This phase I study sought to determine the safety and antitumor activity of AM0010. Patients and Methods Patients with selected advanced solid tumors were treated with AM0010 in a dose-escalation study, which was followed by a renal cell cancer (RCC) dose-expansion cohort. AM0010 was self-administered subcutaneously at doses of 1 to 40 μg/kg once per day. Primary end points were safety and tolerability; clinical activity and immune activation were secondary end points. Results In the dose-escalation and -expansion cohorts, 33 and 18 patients, respectively, were treated with daily subcutaneous injection of AM0010. AM0010 was tolerated in a heavily pretreated patient population. Treatment-related adverse events (AEs) included anemia, fatigue, thrombocytopenia, fever, and injection site reactions. Grade 3 to 4 nonhematopoietic treatment-related AEs, including rash (n = 2) and transaminitis (n = 1), were observed in five of 33 patients. Grade 3 to 4 anemia or thrombocytopenia was observed in five patients. Most treatment-related AEs were transient or reversible. AM0010 led to systemic immune activation with elevated immune-stimulatory cytokines and reduced transforming growth factor beta in the serum. Partial responses were observed in one patient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 μg/kg (overall response rate, 27%). Prolonged stable disease of at least 4 months was observed in four patients, including one with colorectal cancer with disease stabilization for 20 months. Conclusion AM0010 has an acceptable toxicity profile with early evidence of antitumor activity, particularly in RCC. These data support the further evaluation of AM0010 both alone and in combination with other immune therapies and chemotherapies.
Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ
Authors: Morrow Monica , Van Zee Kimberly J. , Solin Lawrence J. , Houssami Nehmat , Chavez-MacGregor Mariana , Harris Jay R. , Horton Janet , Hwang Shelley , Johnson Peggy L. , Marinovich M. Luke , Schnitt Stuart J. , Wapnir Irene , Moran Meena S. 
Published: August 2016

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.
A Systematic Review and Meta-Analysis of the Global Burden of Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: Trends in Heterogeneous Data and a Proposal for New Assessment Methods
Authors: Jackson Tracy , Thomas Sarah , Stabile Victoria , Shotwell Matthew , Han Xue , McQueen Kelly 
Published: August 2016

BACKGROUND:
The global burden of chronic pain is projected to be large and growing, in concert with the burden of noncommunicable diseases. This is the first systematic review and meta-analysis of the prevalence of chronic pain without clear etiology in general, elderly, and working populations of low- and middle-income countries (LMICs).

METHODS:
We collected and reported data using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, excluding acute pain or pain associated with a concurrent medical condition. One hundred nineteen publications in 28 LMICs were identified for systematic review; the 68 reports that focused on general adult populations (GP), elderly general populations (EGP), or workers (W) were evaluated using mixed-effects regression meta-analysis.

RESULTS:
Average chronic pain prevalence is reported as a percentage of the population, with 95% confidence interval for each pain type and population (GP, EGP, and W; NA is equal to not available): unspecified chronic pain (34[26–42], 62[41–81], and NA); low back pain (21[15–27], 28[16–42], and 52[26–77]); headache (42[27–58], 30[19–43], and 51[13–88]); chronic daily headache (5[3–7], 5[1–12], and 10[0–33]); chronic migraine (GP 12[6–19]); chronic tension type headache (GP 8[3–15]); musculoskeletal pain (25[19–33], 44[28–62], and 79[60–94]); joint pain (14[11–18], 34[16–54], and NA); chronic pelvic/prostatitis pain (GP 4[0–14]); temporomandibular disorder (35[4–78], 8[0–24], and NA); abdominal pain (EGP 17[6–32]); fibromyalgia (Combined GP, EGP, W 6[5–7]); and widespread pain (7[1–18], 19[8–32], and NA). Chronic low back pain and musculoskeletal pain were 2.50 (1.21–4.10) and 3.11 (2.13–4.37) times more prevalent among W, relative to a GP. Musculoskeletal, joint, and unspecified pain were 1.74 (1.03–2.69), 2.36 (1.09–4.02), and 1.83 (1.13–2.65) times more prevalent among the EGP, relative to a GP. There was significant heterogeneity among studies for all pain types (I
2 > 90%).

CONCLUSIONS:
Chronic pain is prevalent in LMICs, and where there was sufficient evidence, generally more prevalent in EGP and W. This meta-analysis reveals the spectrum of chronic pain without clear etiology in LMICs. Steps should be taken to reduce heterogeneity in the assessment of global chronic pain. Possible actions may include standardization of chronic pain definition, widespread adoption of validated questionnaires across cultures, attention to inequitably burdened populations, and inclusion of queries regarding known associations of chronic pain with social and psychological factors that, in combination, increase the global burden of noncommunicable disease and disability.