bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate
Authors: Sisteré-Oró Marta , Pedersen Gabriel K. , Córdoba Lorena , López-Serrano Sergi , Christensen Dennis , Darji Ayub 
Published: April 2020

AbstractConserved epitopes are targets commonly researched to be part of universal vaccine candidates against influenza viruses (IV). These conserved epitopes need to be cross-protecting against distinct IV subtypes and to have a strong immunogenic potential. Nevertheless, subunit vaccines generally require a strong adjuvant to enhance their immunological effects. Herewith, we compare four different adjuvants differing in their immunological signatures that may enhance efficacy of a conserved hemagglutinin (HA)-epitope from IV, the NG-34, to define the most efficient combination of antigen/adjuvant to combat IV infections. Soluble NG-34 was mixed with adjuvants like aluminium hydroxide (AH) and AddaVax, known to induce Th2 and humoral responses; CAF01 which displays a biased Th1/Th17 profile and Diluvac Forte which augments the humoral response. Combinations were tested in different groups of mice which were subjected to immunological analyses. CAF01 + NG-34 induced a complete immune response with the highest IgG1, IgG2c titers and percentages of activated CD4 T cell promoting IFN-γ, IL-2 and TNF-α producing cells. Furthermore, in NG-34 stimulated mice splenocytes, cytokine levels of IFN-γ, IL-1β, IL-6, IL-10, IL-17 and TNF-α were also the highest in the CAF01 + NG-34 mouse group. This complete induced immune response covering the humoral and the cellular arms of the adaptive immunity promoted by CAF01 + NG-34 group suggests that CAF01 could be a good candidate as an adjuvant to combine with NG-34 for an efficacious vaccine against IV. However, more studies performed in IV hosts as well as studies with a challenge model are further required.
Semi-analytical solutions for the diffusive logistic equation with mixed instantaneous and delayed density dependence
Authors: Alfifi H. Y. 
Published: April 2020

AbstractIn this work, the semi-analytical solution is studied for the diffusive logistic equation with both mixed instantaneous and delayed density. The domain of reaction–diffusion in one dimension is shown. Delay partial differential equation is approximated with a delay ordinary differential equation system by using the Galerkin technique method. Steady-state solutions and stability analysis as well as bifurcation diagrams are derived. The effect of diffusion parameter and delay values is comprehensively studied; as a result, both parameters can destabilize or stabilize the model. We obtained that the decrease in values of the Hopf bifurcations for growth rate is associated with an increase in delay values, whereas the diffusion parameter is increased. Furthermore, comparisons between the numerical simulations and semi-analytical results present a good agreement for all examples and figures of the Hopf bifurcations. Examples of limit cycle and phase-plane map are plotted to confirm the benefits and accuracy of semi-analytical solutions result. For periodic solutions, an asymptotic method is studied after the Hopf bifurcation point for both one- and two-term semi-analytical systems.
How far is FDI relevant to India’s foreign trade growth? An empirical investigation
Authors: Jana Shib Sankar , Sahu Tarak Nath , Pandey Krishna Dayal 
Published: April 2020

AbstractThe study seeks to foster fresh empirical evidence on how FDI is relevant to the foreign trade growth in India under a time-varying parameter model with vector autoregressive specification. The Johansen’s cointegration test documents a significant and positive long-run co-movement between FDI and foreign trade in India. The vector error correction model suggests a unidirectional long-run causality from foreign trade to FDI. However, the Granger causality test confirms a bidirectional short-run causal relationship between these variables. Further, the variance decomposition analysis approves strong exogeneity of foreign trade. Again, the impulse response function analysis reveals that the responses generated from a positive shock of foreign trade to FDI and vice versa are small and initially negative and thereafter remain persistently positive at a constant level. The study finally concludes that the absence of long-run causality from FDI to export is the result of much domestic market orientation of foreign investors and less emphasis on the export-oriented sectors in India.
Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial
Authors: Subbiah Vivek , Dumbrava Ecaterina Ileana , Jiang Yunfang , Thein Kyaw Z. , Naing Aung , Hong David S. , Fu Siqing , Piha-Paul Sarina A. , Tsimberidou Apostolia M. , Janku Filip , Meric-Bernstam Funda , Kurzrock Razelle , Falchook Gerald 
Published: April 2020

Abstract
Background
Angiogenesis and activation of the epidermal growth factor (EGFR) pathway play an essential role in tumor proliferation and metastasis. Targeting angiogenesis or EGFR alone does not yield adequate tumor control in most solid tumors. Overcoming intrinsic and/or acquired resistance may need a doublet or triplet therapy strategy. Herein, we report the safety and feasibility of dual EGFR blockade with EGFR monoclonal antibody and EGFR tyrosine kinase inhibitor combined with anti-VEGF antibody in advanced solid tumors.

Methods
We conducted a phase I study combining erlotinib, cetuximab, and bevacizumab. Patients with advanced or metastatic solid tumors (excluding colorectal and non-small cell lung cancers) were analyzed for safety, toxicity profile, and response. Anti-tumor activity was evaluated per response evaluation criteria in solid tumors (RECIST 1.0).

Results
Thirty-six patients received treatment on a range of dose-levels. The most frequent tumor types enrolled were cervical (n = 10), head and neck squamous cell (n = 10), and follicular thyroid (n = 4) cancers. The most common treatment-related grade ≥ 2 adverse events were rash (56%), hypomagnesemia (17%), pruritus (11%), diarrhea (8%), and tumor-related bleeding (8%). Seventeen of 19 patients (89%) treated at the maximum tolerated dose did not present treatment-related dose-limiting toxicity. Fifteen (63%) of the 24 evaluable patients achieved a disease control (stable disease ≥ 4 months (n = 14) and partial response (n = 1). The median number of prior lines of therapies was 3 (range 1–10).

Conclusions
The triplet combination of erlotinib, cetuximab, and bevacizumab was well tolerated, conferring clinical benefit in heavily pretreated patients. Future studies are warranted with second or third-generation EGFR tyrosine kinase triplet combinations in the EGFR pathway aberrant patients.
Trial Registration: ClinicalTrials.gov Identifier: NCT00543504. Sponsor(s): National Cancer Institute (NCI), MD Anderson Cancer Center
Salvator Mundi: an investigation of the painting’s materials and techniques
Authors: Gutman Rieppi Nica , Price Beth A. , Sutherland Ken , Lins Andrew P. , Newman Richard , Wang Peng , Wang Ting , Tague Thomas J. 
Published: April 2020

Abstract
Before the start of its restoration in 2007, the Salvator Mundi was thought to be one of a number of copies of a long-lost Leonardo da Vinci painting, depicting Christ giving a blessing with his right hand while holding a crystal orb in his left. During the restoration treatment, a scientific examination of the painting was carried out to elucidate the painting’s materials and techniques. Microscopic sampling of the painting was necessarily limited, and nine out of ten samples were prepared and analyzed as cross-sections. A number of analytical methods were employed selectively, including stereomicroscopy, visible and fluorescent light microscopy, scanning electron microscopy with energy dispersive spectroscopy, Raman microspectroscopy, Fourier transform infrared microspectroscopy in transmission mode and with attenuated total reflection. The pigments characterized were lead white, vermilion, red iron oxide earth, red lake, natural ultramarine, lead–tin yellow, umber, and charcoal, carbon and bone blacks. Manganese-containing soda-lime glass was detected in the ground, imprimitura and paint layers, and a walnut oil medium was identified by pyrolysis gas chromatography-mass spectrometry. Cross-section studies revealed aspects of the painting’s stratigraphy: a size layer, white ground and off-white imprimitura, followed by a complex sequence of paint layers applied by the artist to achieve sophisticated visual effects.
Bochdalek hernia in an adult: two case reports and a review of perioperative cardiopulmonary complications
Authors: Akita Masayuki , Yamasaki Nobuaki , Miyake Taiichiro , Mimura Kazuya , Maeda Eri , Nishimura Tohru , Abe Koichiro , Kozuki Akihito , Yokoyama Kunio , Kominami Hiroaki , Tanaka Tomohiro , Takamatsu Manabu , Kaneda Kunihiko 
Published: April 2020

Abstract
Background
Bochdalek hernia in an adult is very rare and often needs an immediate surgical repair for the herniation. Although its etiology and surgical techniques have frequently been reported, perioperative complications, especially cardiopulmonary problems, remain unknown. We reported two adults with Bochdalek hernia and reviewed the published literatures with a focus on these issues.

Case presentation
We experienced two adult cases of Bochdalek hernia with gastrointestinal strangulation. One case had massive herniation of the stomach, colon, spleen, and pancreas in the left chest, causing repeated vomiting. The other had a right-side hernia with strangulation of the colon. We successfully performed emergency repairs of these diaphragmatic hernias without any postoperative complications.

Conclusions
Our literature review revealed that life-threatening cardiopulmonary complications, such as empyema or cardiac arrest caused by the tamponade effect of the herniated viscera, sometimes occurred in patients with Bochdalek hernia. These complications were found in Bochdalek hernia with gastrointestinal strangulation.
Free-breathing T2* mapping for MR myocardial iron assessment at 3 T
Authors: Nazarova E. E. , Tereshchenko G. V. , Kupriyanov D. A. , Smetanina N. S. , Novichkova G. A. 
Published: April 2020

Abstract
Background
Timely diagnosis of cardiac iron overload is important for children with transfusion-dependent anaemias and requires modern measure methods. Nowadays, myocardial iron quantification is performed by magnetic resonance (MR) breath-hold techniques, sensitive to respiratory motion and unfeasible in patients who are unable to hold their breath. Free-breathing T2* mapping sequences would allow to scan children who cannot hold their breath for a specified duration. Our aim was to test a free-breathing T2* mapping sequence, based on motion correction by multiple signal accumulation technique.

Methods
We used an electrocardiographically gated T2* mapping sequence based on multiple gradient echo at 3-T in 37 paediatric patients with haematologic disorders aged from 2 to 16. We compared T2* values of myocardium and signal-to-noise ratio of this new sequence with standard breath-holding T2* mapping sequence. T2* values were measured in the interventricular septum for both methods in studies with adequate image quality.

Results
All children were scanned without complications. Five patients were excluded from analysis because of the presence of respiratory artefacts on the T2* images with breath-holding technique due to patient’s inability to hold their breath. Breath-holding T2* was 19.5 ± 7.7 ms (mean ± standard deviation), free-breathing T2* was 19.4 ± 7.6 ms, with positive correlation (r = 0.99, R2 = 0.98; p < 0.001). The free-breathing sequence had a higher signal-to-noise ratio (median 212.8, interquartile range 148.5–566.5) than the breath-holding sequence (112.6, 71.1–334.1) (p = 0.03).

Conclusion
A free-breathing sequence provided accurate measurement of myocardial T2* values in children.
Formulation of Trichoderma asperellum TV190 for biological control of Rhizoctonia solani on corn seedlings
Authors: Herrera Wence , Valbuena Oscar , Pavone-Maniscalco Domenico 
Published: April 2020

AbstractEnvironmental conditions affect biocontrol agents in a field, being appropriate formulations an alternative to overcome this problem. Formulations based on Trichoderma asperellum TV190 were prepared by emulsified mineral or vegetable oils, which protected spores from ultraviolet radiation, showing greater viability of 37–43% (mineral) and 56–63% (vegetable) than the control (8–12%). These formulations improved an antagonism of T. asperellum on Rhizoctonia solani under greenhouse conditions, reducing infected corn seedlings by 72% (mineral) and 59% (vegetable). Necrotic spot size was reduced by 90.04% (mineral) and 87.29% (vegetable). A granular formulation, prepared with degreased corn germ and T. asperellum spores, protected the corn seedlings from R. solani under greenhouse conditions, with 73% reduction of infected plants and 93% reduction of necrotic spot size. Both granular and liquid formulations were able to improve T. asperellum antagonism, suggesting that these formulations could be included in agricultural pest control strategies.
Phase II study of erlotinib given daily for patients with metastatic melanoma (MM)
Authors: Wyman K. , Kelley M. , Puzanov I. , Sanders K. , Hubbard F. , Krozely P. , Sturgeon D. , Viar V. , Sosman J. A. 
Published: April 2020

18002 Background: Erlotinib is a small molecule tyrosine kinase inhibitor (TKI) that targets epidermal growth factor receptor (EGFr). The EGFr is a potential therapeutic target because it is expressed by a number of malignancies, including melanocytic lesions, and in some plays an important role in the biology of the cancer. Our aim was to conduct a phase II study evaluating erlotinib in patients (pts) with measurable metastatic melanoma. Methods: Eligibility criteria included measurable disease, ECOG PS = 0–1, and adequate organ function. Pts were eligible if they received up to one prior therapy for metastatic disease. Pts received a daily dose of erlotinib 150 mg. The primary outcomes were overall response rate and response duration. The study had a two-stage design with closure at 14 pts if there were no objective RECIST responses. Secondary outcomes included overall safety and tolerability of erlotinib. Results: Between August 2003 and August 2004, a total of 14 pts with MM were accrued. The majority of pts were male 12:2 = M, median age = 57.5 yrs (range 38 to 80 yrs). Stage of disease included M1a (n = 7), M1b (n = 5), M1c (n = 2) and performance status was equally divided between 0 and 1 (7 pts each). Seven pts (50%) had prior adjuvant therapy and six pts (43%) had at least one prior therapy for metastatic disease. Four pts (29%) had no prior therapy. No objective responses were observed. Four pts (29%) had stable disease at their initial 8-week evaluation of which only 2 had SD>6 months (228 and 365 days). One pt with SD withdrew from the study on day 68 for grade II toxicities. There were no Grade III/IV hematological or biochemical toxicities. Grade III toxicities were diarrhea and anorexia, each in a single patient. Most pts (n = 12) experienced at least a grade I dermatological toxicity manifested as an acneiform rash and/or pruritis. The median progression free survival (PFS) of all 14 pts was approximately 60 days with a range of 35 to 365 days. The median PFS of those with SD was 192.5 days. Conclusions: Erlotinib given daily at 150 mg is well tolerated in pts with MM. However, it has minimal to no single agent activity. Any further investigation of this drug should be pursued in combination with other agents only if a strong scientific/clinical rationale exists. No significant financial relationships to disclose.
DAB(389)IL2 (denileukin diftitox) suppresses growth of melanoma metastases
Authors: Chesney J. , Guarnaschelli J. , Telang S. , Miller D. 
Published: April 2020

18010 Background: CD4+CD25high regulatory T (Treg) cells have been found to suppress the activation of anti-tumor effector T cells. Depletion of Treg cells using anti-CD25 antibodies can induce a CD8+ T cell dependent rejection of melanoma in mice. Furthermore, Treg cells are increased in human lymph nodes containing melanoma metastases relative to adjacent benign lymph nodes. Taken together, these observations provide rationale for an examination of the effect of Treg cell depletion on the progression of metastatic melanoma in humans. Recombinant interleukin 2/diphtheria toxin conjugate (DAB[389]IL2; also termed ONTAK or denileukin diftitox) binds to CD25 and, following internalization, causes cell death. DAB(389)IL2 was recently reported to selectively deplete peripheral blood Treg cells in patients with renal cell carcinoma. Methods: The effect of DAB(389)IL2 on tumor growth was examined in 4 patients with Stage IV melanoma who had either progressed after biochemotherapy and/or high dose IL-2 or were ineligible for these treatments. DAB(389)IL2 (9 or 12 μg/kg) was administered daily x 4 days every three weeks for two cycles. FDG-PET/CT imaging was obtained just prior to DAB(389)IL2 administration and within 2 weeks of completion of the second cycle. In the setting of stable disease or tumor regression, DAB(389)IL2 was continued for two more cycles and a subsequent FDG-PET/CT imaging study was obtained. Results: Two patients received 9 μg/kg DAB(389)IL2 and, after two cycles, experienced overt progression consisting of a combination of tumor growth and newly detectable tumors. Two patients received 12 μg/kg DAB(389)IL2 and, after two cycles, experienced a combination of stable disease and marked regression of several metastatic tumors. In one patient, tumor volume of right and left axillary metastases shrunk by 33% and 43%, respectively, after two cycles of DAB(389)IL2. The second responding patient experienced resolution of several dermal metastases, reduction in the tumor volume of a left adrenal mass, and the complete regression of two hepatic metastases. Conclusions: We conclude that DAB(389)IL2 may provide a safe and effective treatment for stage IV melanoma. A phase II clinical trial is now underway to examine the efficacy of DAB(389)IL2 in this patient population. No significant financial relationships to disclose.
Effect of age on treatment and survival among patients with non-small cell lung cancer
Authors: Owusu O. , Owusu C. , Hankins M. 
Published: April 2020

18504 Background: Lung cancer is a disease of the elderly. Yet older patients are underrepresented in clinical trials resulting in scanty efficacy data. We sought to assess the relationship between age, treatment and overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective cohort study of patients with consecutively diagnosed NSCLC between 1999 and 2003 at the Boston Veterans Administration Medical Center (BVAMC). All patients with a biopsy proven NSCLC were included. Patients diagnosed at autopsy were excluded. Data sources included the BVAMC tumor registry and medical records. Deaths were ascertained from the Social Security Administration and VA databases. All patients were right censored at death from any cause or at 12/31/2004, whichever came first. Our primary endpoints were 1) receipt of surgery; 2) receipt of chemotherapy; and 3) three-year overall survival. Our independent variable was age, operationalized as 70 years and older versus less than 70 years. We used logistic regression analysis to assess the relationship between age and treatment and Kaplan-Meier curves and Cox proportional hazards modeling to determine the effect of age on survival. Results: We studied 410 patients. 211 (51%) of the cohort were ≥70 years and 199 (49%) were <70 years. Among those with localized disease (stages I and II) there was no significant difference in the odds of receiving surgery between the two age categories, (OR = 1.54, 95% CI, 0.72, 3.28). Among those with non-localized disease (stages III and IV) those who were ≥ 70 years were less likely to receive chemotherapy (OR = 0.46, 95% CI, 0.27, 0.79). There were 308 deaths from all causes: 167 in the ≥ 70 year group and 141 in the <70 year group. The three-year overall survival was 20.4% (95% CI, 14.5%, 26.3%) and 32.7% (95% CI, 25.3%, 39.5%) for the ≥70 and <70 year groups, respectively. The adjusted hazard ratio was 0.72 (95% CI, 0.57, 0.92), P = 0.03 by the log rank test in favor of those less than 70 years. Other significant predictors of overall survival included stage at diagnosis and treatment. Comorbidity was not a significant predictor of overall survival. Conclusion: The poorer survival outcome among older NSCLC patients at the BVAMC may be improved by more aggressive treatment with chemotherapy. No significant financial relationships to disclose.
Evaluation of predictive factors for response to darbepoetin alfa (DA): A prospective study
Authors: Steinmetz H. T. , Fandel F. , Hellmich M. , Neise M. , Aldaud A. , Lerchenmüller C. , Tsamaloukas A. , Weiligmann C. , Schmitz S. 
Published: April 2020

18514 Background: Therapy with erythropoiesis-stimulating factors (ESF) can ameliorate the anaemia associated with cancer and chemotherapy, reduce the need for transfusions and improve quality of life. However, as many as 30–50% of pts. do not respond, even to very high doses of ESF. Methods: In January 2003, we commenced a prospective phase-2 study to evaluate the value of predictive factors for response to DA. The following 5 factors, which had been previously determined as predictive factors in several retrospective studies, were investigated: serum erythropoietin < 100 mU/ml before therapy (Epo-d0); increase in reticulocytes > 40,000/μl (Reti-d14) and in soluble transferrin receptor ≥ 25% (sTfR-d14), both after 2 weeks; increase in reticulocytes > 40,000/μl (Reti-d28) and in Hb > 1 g/dl (Hb-d28), both after 4 weeks. Response was defined as Δ Hb > 2 g/dl or Hb ≥ 12 g/dl within 8–12 weeks. Pts. with solid tumours receiving chemotherapy, ECOG < 2 and Hb < 11g/dl or significant decrease in Hb > 1.5 g/dl within 4 weeks received DA 150 μg/QW or 300 μg/Q2W sc. and 300 μg/QW if Hb < 1 g/dl at d28. Results: Between 01/03 and 09/05 196 pts., 112 female and 84 male, median age 66 years, were treated and evaluated for response. 119 pts. (60.7%) had a response as defined (PP analysis: 68.3%). The predictive value of the 5 factors are given in the Table . In a multiple logistic regression analysis of all 5 factors the ROC has an AUC of 0.78 (95% CI 0.71–0.84). The reduced logistic classification rule (with cutoff 0.5) based on an increase in sTfR > 25% on day14, reticulocytes > 40,000/μl and Hb > 1 g/dl, both on day 28, had the same AUC and its positive / negative predictive value was 88.1% (=74/84) and 59.8% (=67/112) respectively. Conclusions: In contrast to observations made in pts. with lymphoproliferative malignancies, the pretherapeutic serum erythropoietin level has no or very little predictive value for response to DA in anaemic pts. with solid tumours. Supported by AMGEN, Germany with an unrestricted grant. [Table: see text] [Table: see text]