Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinal vascular injuries and intravitreal human embryonic stem cell‐derived haemangioblasts

To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen‐induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion.
CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia.

PURPOSE Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. PATIENTS AND METHODS A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry-based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. RESULTS Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry-based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. CONCLUSION In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry-based predictor of OS and TFS in CLL.
Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

PURPOSE Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. PATIENTS AND METHODS In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. RESULTS Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. CONCLUSION In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.
Misperceptions of harm among Natural American Spirit smokers: results from wave 1 of the Population Assessment of Tobacco and Health (PATH) study (2013–2014)

Introduction This study estimated differences in cigarette harm perceptions among smokers of the Natural American Spirit (NAS) brand—marketed as ‘natural’, ‘organic’ and ‘additive-free’—compared to other smokers, and examined correlates of NAS use. Methods Data were drawn from wave 1 of the Population Assessment of Tobacco and Health (PATH) study, a nationally representative study of US adults (2013–2014). Weighted analyses using a subset of current adult smokers (n=10 565) estimated the prevalence of NAS use (vs all other brands) and examined associations between NAS use and sociodemographics, tobacco/substance use, tobacco harm perceptions, quit intentions, quit attempts and mental/behavioural health. Results Overall, 2.3% of adult smokers (920 000 people in the USA) reported NAS as their usual brand. Nearly 64% of NAS smokers inaccurately believed that their brand is less harmful than other brands compared to 8.3% of smokers of other brands, after controlling for potential confounders (aOR 22.82). Younger age (18–34 vs 35+; aOR 1.54), frequent thinking about tobacco harms (aOR 1.84), past 30-day alcohol use (aOR 1.57), past 30-day marijuana use (aOR 1.87) and sexual orientation (lesbian, gay, bisexual, ‘other’ or ‘questioning’ vs heterosexual; aOR 2.07) were also associated with increased odds of smoking NAS. Conclusions The majority of NAS smokers inaccurately believes that their cigarettes are less harmful than other brands. Given the brand's rapid growth and its more common use in vulnerable groups (eg, young adults, lesbian, gay, bisexual, ‘other’ or ‘questioning’ adults), corrective messaging and enforcement action are necessary to correct harm misperceptions of NAS cigarettes.
The Anatomy of the Eye and Orbit.

More than eighty illustrations have been added to the third, and revised, edition of this popular anatomy. The majority of the illustrations were prepared from sections made in the pathologic laboratory of what is now the Westminster branch of the combined Royal and Westminster hospitals. The main changes in the text are in the description of the ciliary muscle, the substantia propria of the cornea, the vitreous, the zonule of Zinn, the distribution of the lacrimal fluid, the mucocutaneous junction of the lid margin, the precorneal film, the retinal capillaries and the central connections of the visual apparatus. The illustrations number 323, including 24 in color; these, in their clearness and selections, constitute a most important part, which with the excellence of the text, make this an important and essential book for study and reference. Though the book has been previously reviewed (Arch. Ophth. 25: 526 [March] 1941), it may
Evolution of root canal sealers: An insight story

Attainment of ideal root canal treatment comprises various essential factors such as proper instrumentation, biomechanical preparation, obturation, and ultimately depending upon the case, post-endodontic restoration. Main objective of the treatment is to get absolute rid of microbial entity and prevent any future predilection of re-infection. In order to achieve that, proper seal is required to cut down any chance of proliferation of bacteria and future occurrence of any pathology. Although gutta-percha has been the standard obturating material used in root canal treatment, it does not reinforce endodontically treated roots owing to its inability to achieve an impervious seal along the dentinal walls of the root canal. Gutta-percha does not from a monoblock even with the use of a resin-based sealer such as AH Plus because the sealer does not bind to gutta-percha. As a result, a monoblock is formed (consisting of Resilon core material, Resin sealer, bonding agent/primer, and dentin). Another reason of Resilon being a better obturating material could be that the removal of smear layer by ethylenediaminetetraacetic acid (EDTA) after biomechanical preparation may have allowed the root canal filling material and root canal sealers to contact the canal wall and penetrate in the dentinal tubules, which may increase the strength of roots. New silicone-based sealers like Roekoseal automix and the most recent GuttaFlow have some affirmative results regarding solubility and biocompatibility, as compared to other sealers. Methacrylate resin-based sealers and mineral trioxide aggregate (MTA)-based sealers have opened a new horizon for sealers.
Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

PURPOSE Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. PATIENTS AND METHODS We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. RESULTS Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. CONCLUSION A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed.
New p53 mutations in canine skin tumours

TUMOURS of the skin and subcutaneous tissue are the most common tumours affecting dogs; they represent about 35.4 to 46.5 per cent of all tumours diagnosed in this species (Gamlem and others 2008). Many types of primary tumours occur on the skin, and approximately 20 to 40 per cent of these are malignant (Kaldrymidou and others 2002, Gamlem and others 2008). Alterations of the p53 tumour suppressor gene have been implicated in the pathogenesis of a variety of types of human tumours and were found in 50 per cent of skin cancer cases (Giglia-Mari and Sarasin 2003). Moreover, p53 mutations are frequent in normal sun-exposed skin and are considered as an early genetic event in the development of UV-induced skin cancer in human beings (Melnikova and Ananthaswamy 2005). Most mutations are localised within a highly conserved region of this gene between codons 120 and 290 (Levine and others 1994, Giglia-Mari and Sarasin 2003). In canine skin neoplasms, alterations of the p53 gene have been reported in single cases, including papilloma (codon 284) (Mayr and others 1994), hepatoid gland adenoma (codon 249) (Mayr and others 1997), squamous cell carcinoma (codon 89) (Mayr and others 1999a), mast cell tumour (codon 266) (Kanaya and others 2002), leiomyosarcoma (codon 274) and malignant peripheral nerve sheath tumour (codons 259 and 261) (Nasir and others 2001). This short communication describes the results of examination of canine skin tumours for the presence of p53 gene mutations. One hundred dogs aged four-and-a-half months to 17 years with skin tumours were studied for the presence of alterations in the p53 gene. Tumour samples for the study were collected during surgery at a small animal practice. For histological examination and classification, 6 µm sections were prepared from formalin-fixed and paraffin-embedded specimens. The slides were stained with …
Pneumonia caused by influenza A H1N1 2009 virus in farmed American mink (Neovison vison)

IN 2009, a new pandemic influenza A H1N1 virus with gene segments from both North American and Eurasian swine influenza viruses emerged (Trifonov and others 2009). The outbreak started in Mexico, spread to the USA and then worldwide (Peiris and others 2009, Girard and others 2010). The influenza pandemic lasted for more than a year where after the pandemic (H1N1) 2009 virus subtype became a part of the seasonal influenza in human beings. In animals, most cases of pandemic (H1N1) 2009 virus influenza have been described in pigs (Howden and others 2009, Pereda and others 2010, Moreno and others 2010, Kim and others 2011), while there are case reports from other species such as turkeys, ferrets and cats (Patterson and others 2009, Mathieu and others 2010, Lohr and others 2010). In Norway, several pig farms got infected (Hofshagen and others 2009, Gjerset and others 2011). This short communication describes an outbreak of respiratory disease in farmed American mink ( Neovison vison ) where influenza A virus was detected by immunohistochemistry in the lung lesions and pandemic (H1N1) 2009 virus was confirmed using real-time RT-PCR. In the middle of May 2011, mink showed clinical signs of respiratory disease on a fur farm situated near Stavanger in southwestern Norway. …
Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial.

PURPOSE We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. PATIENTS AND METHODS TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). RESULTS Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). CONCLUSION Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
Differential Effect of a Bilateral Deep Cerebellar Nuclei Lesion on Externally and Internally Triggered Saccades in Humans

Visually guided saccades were recorded which occurred either at the onset of a peripheral target (externally triggered) or when scanning a static display (internally triggered) in a patient with a bilateral lesion of the nucleus fastigii and nucleus interpositus caused by a hemangioblastoma. The externally triggered saccades were hypermetric before and after surgery. In contrast, the internally triggered saccades (scanning saccades) were normometric. This finding supports the view that the midline cerebellum is involved in the control of saccades in a way that depends on the mode of saccade elicitation.
Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database.

PURPOSE To analyze factors that predict the use of trimodality treatment (chemotherapy, surgery, and radiation therapy [RT]) and evaluate the impact that trimodality treatment use has on survival for patients with inflammatory breast cancer (IBC). METHODS Using the National Cancer Data Base, patients who underwent surgical treatment of nonmetastatic IBC from 1998 to 2010 were identified. We collected demographic, tumor, and treatment data and analyzed treatment and survival trends over time. Logistic regression and Cox proportional hazard models were used to examine factors predicting treatment and survival. RESULTS We identified 10,197 patients who fulfilled study criteria. The use of trimodality therapy fluctuated annually (58.4% to 73.4%). Patients who were older, diagnosed earlier in the study period, lived in regions of the country outside of the Midwest, had lower incomes or public insurance, and had a higher comorbid score were significantly less likely to receive trimodality therapy (all P < .05). Five- and 10-year survival rates were highest among patients receiving trimodality treatment (55.4% and 37.3%, respectively) compared with patients who received the combination of surgery plus chemotherapy, surgery plus RT, or surgery alone. After adjusting for potential confounding variables, use of trimodality therapy remained a significant independent predictor of survival. CONCLUSION Underutilization of trimodality therapy negatively impacted survival for patients with IBC. The use of trimodality therapy increased marginally with time, but there remain significant factors associated with differences in use of trimodality treatment. We have identified specific barriers to care that may be targeted to improve treatment delivery and potentially improve patient outcomes.
Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study.

PURPOSE Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. PATIENTS AND METHODS Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. RESULTS In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). CONCLUSION R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.
Monitoring the bulk milk antibody response to BVDV: the effects of vaccination and herd infection status

Bovine Viral Diarrhoea Virus (BVDV) is a pestivirus in the flaviviridae family which affects cattle worldwide. Bulk milk (BM) antibody testing is frequently used as a relatively quick method of assessing herd BVDV exposure; however, an understanding of the effects of vaccination and historic infection is essential for test interpretation. This study investigated the trends exhibited by monthly BM antibody analysis in 14 herds split into three categories. Category 1 herds (vaccinating/no persistently infected (PI) animals) began the study with mid-positive BM antibody titres and experienced an estimated increase of 0.007 optical density (OD) units per month (equating to a rise of 0.35 OD units in 50 months). Category 2 herds (not vaccinating/no PI animals) began the study with mid-positive BM antibody titres and experienced an estimated decrease of 0.005 OD units per month with antibody levels in one category 2 herd taking 1290 days to decrease from mid-positive to negative. Category 3 herds (vaccinating/PI animals present) began the study with high BM antibody titres which plateaued within this range throughout the 50-month observation period. Vaccination was observed to cause transient increases in BM antibody in a number of herds in categories 1 and 3.
Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non-small-cell lung cancer.

PURPOSE Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single-agent activity in non-small-cell lung cancer (NSCLC). We evaluated linifanib with carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC. PATIENTS AND METHODS Patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). The primary end point was progression-free survival (PFS); secondary efficacy end points included overall survival (OS) and objective response rate. RESULTS One hundred thirty-eight patients were randomly assigned (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and 0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were associated with increased toxicity, including a higher incidence of adverse events known to be associated with VEGF/PDGF inhibition. Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. CONCLUSION Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGF/PDGF inhibitory effects.