bluuebunny/crossref_metadata_2025_split huggingface dataset:
FPT155-001: A phase Ia/Ib study of FPT155 (CD80-FC) in patients with advanced solid tumors.
Authors: Millward Michael , Gan Hui Kong , Joshua Anthony M. , Kuo James Chun-Yen , Prawira Amy , Richardson Gary Edward , Barbee Susannah D. , Inamdar Sandeep P. , Pierce Kristen L. , Qureshi Mona , Horvath Lisa 
Published: July 2019

TPS42 Background: Despite recent advances in immunotherapy, many patients with advanced solid tumors are refractory to available therapies or eventually relapse. Novel immune therapies are needed with differentiated mechanisms of action that result in improved response rates and durability across a broad range of tumors. FPT155 is a first-in-class therapeutic being developed to meet this need. FPT155 is a recombinant fusion protein composed of the extracellular domain of human CD80 fused with the Fc domain of human immunoglobulin G1. It is designed to act as a potent stimulator of anti-tumor immunity through CD28 and thereby co-stimulate T cell responses only in the presence of antigenic T cell receptor (TCR) signaling. FPT155 alone does not induce spontaneous cytokine release by primary human immune cells, in contrast to a CD28 superagonist antibody that exerts TCR stimulus-independent activity. FPT155 also blocks CTLA-4 from competing for endogenous CD80, allowing CD28 signaling to prevail in T cell activation. A murine surrogate of FPT155 is a potent inhibitor of tumor growth that induces complete tumor regression in multiple tumor models, including models that are insensitive to anti-PD1 or anti-CTLA4. Methods: The FPT155-001 study is a Phase 1a/1b open-label, multicenter, dose escalation and expansion study to evaluate the safety and tolerability of FPT155 monotherapy. Phase 1a dose escalation includes an accelerated titration design followed by a standard 3+3 design until the recommended dose for Phase 1b is determined by evaluation of all available safety, pharmacokinetic (PK), and pharmacodynamic (PD) data. Eligible patients with advanced solid tumors who are refractory to all standard therapy for their malignancy will be enrolled in Phase 1a. Phase 1b dose expansion will enroll patients with select tumor types. The primary endpoint is safety in both phases. Key secondary endpoints in Phase 1a include characterization of the FPT155 PK profile and immunogenicity. Key secondary endpoints in Phase 1b include objective response rate, duration of response, progression free survival, and disease control rate. The FPT155-001 trial opened for enrollment in October 2018 and is in progress. Clinical trial information: Submitted - awaiting registration number.
Prevalence of PD-L1 expression in first-line (1L) locally advanced/unresectable or metastatic urothelial carcinoma (UC).
Authors: Grivas Petros , Morgans Alicia K. , Lotan Yair , Gregg Jeffrey P. , Geynisman Daniel M. , Friedlander Terence W. , Agarwal Piyush K. , Tesic-Schnell Marija , Bernstein Andrew , Makari Doris , Meeks Joshua J 
Published: July 2019

TPS67 Background: Treatments for 1L advanced/metastatic UC include platinum-based chemotherapy, an immune checkpoint inhibitor (ICI) or clinical trial enrollment. Not all patients benefit from, or are eligible for, specific therapies due to comorbidities and performance status. There is an urgent need for biomarker-directed strategies to enable patient selection and improve outcomes. Currently the only clinically used molecular biomarker is PD-L1 protein expression in tumor tissue. Although inconsistent and variable among assays, higher PD-L1 expression generally correlates with increased ICI response rate. Improved understanding of the prevalence and potential prognostic and/or predictive role of PD-L1 can further enhance its clinical utility and guide novel clinical trial designs. Methods: This observational study will enroll 250 patients with advanced UC prior to starting or during 1L therapy, as initiated at the discretion of participating clinicians, from 60 US community sites. The primary endpoint is prevalence of PD-L1 expression by VENTANA SP263 Assay (exact [Clopper-Pearson] 95% CI) on pre-treatment tumor tissue. Secondary endpoints include the association of pre-treatment PD-L1 expression with pre-treatment tumor tissue mutational burden (tTMB), descriptions of treatment response and outcomes (ORR based on RECIST 1.1, PFS, OS) and assessment of their correlations with PD-L1 expression. Exploratory endpoints include the association of pre-treatment tumor tissue PD-L1 with pre-treatment blood-based tumor mutational burden (bTMB), changes in circulating tumor DNA (ctDNA) levels at various timepoints, the correlation between tTMB and bTMB values, and the association of those biomarkers for outcomes of PFS and OS. Enrollment will take place over 24 months with follow-up to 30 months from study enrollment. With 250 patients, the 95% CI for 30%, 45%, and 60% observed prevalence of PD-L1 high are (24.4%, 36.1%), (38.9%, 51.2%), and (53.6%, 66.1%), respectively; the various secondary and exploratory analyses will be descriptive.
Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study
Authors: Herzog-Niescery Jennifer , Seipp Hans-Martin , Bellgardt Martin , Herzog Torsten , Belyaev Orlin , Uhl Waldemar , Gude Philipp , Weber Thomas P. , Vogelsang Heike 
Published: July 2019

BACKGROUND:
Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered.

METHODS:
SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·

JOURNAL/asag/04.03/00000539-202008000-00031/inline-graphic1/v/2023-07-21T062418Z/r/image-tiff

·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration;

JOURNAL/asag/04.03/00000539-202008000-00031/inline-graphic2/v/2023-07-21T062418Z/r/image-tiff

: respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches.

RESULTS:
Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L−1 (15.53 µg·L−1; median: 2.11 µg·L−1, interquartile range [IQR]: 4.58 µg·L−1) and in all postoperative samples (25.42 µg·L−1 [21.39 µg·L−1]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons’ breathing zones (β = 216.89; P < .001) and to the calculated masses of inhaled SEVO (β = 4.17; P = .018). The surgeon’s body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively.

CONCLUSIONS:
The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel’s individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting.
Total skin electron beam therapy rationalization and utility of in vivo dosimetry in a high-volume centre
Authors: Misson-Yates Sarah , Naeem Marium , Palmer Isabel , Holden Eleanor , Hedley Owen , McGovern Mark , Morris Stephen , Greener Anthony G 
Published: July 2019

Objective: This paper reports on the rationalization of a substantial pool of in vivo dosimetry (IVD) data from patients treated with total skin electron beam therapy (TSEBT) and the application of this to verify the accurate delivery of TSEBT when changing linac manufacturer. Methods: Thermoluminescent dosimeter IVD data from 149 patients were analyzed comparing the population mean and standard deviation for each site. The number of sites required to confirm the prescribed dose were reviewed considering both dosimetric and clinical relevance. The reduced sites were then used to assess the continued dosimetric accuracy on new equipment and the results were compared statistically using the Mann–Witney test. Results: The trunk dose measurement points were reduced from nine to six and five extra trunk sites were identified and reviewed clinically prior to removal. Following change in manufacturer the trunk dose points showed no statistically significant change and confirmed that patients had received within 1.3% of the intended mean trunk dose using both delivery methods. A statistically significant change in 4 out of the 13 extra trunk sites was seen following the move to the new centre. However, all but one site showed a change of less than 1 standard deviation. Conclusion: The total number of measurement points per patient were reduced from 27 to 19 which constituted a 25% saving in preparation and read out. Accurate delivery of prescribed dose was confirmed following measurement point reduction for treatments delivered on linacs from two different manufacturers. Advances in knowledge: Proven methodology for rationalization of IVD measurements for TSEBT
Elementos para la relación entre cultura organizacional y estrategia
Authors: Mendez Alvarez Carlos Eduardo 
Published: July 2019

Este trabajo tiene como objetivo identificar mediante el análisis conceptual los elementos que permiten correlacionar la cultura y estrategia en la organización. Mediante una matriz de impacto cruzado, establece relaciones y las sustenta con el propósito de señalar que la cultura es fundamental para la estrategia. Se fundamenta en la consulta bibliográfica de los conceptos planteados señalando 112 referencias de uno o más autores. Mediante la síntesis de los resultados obtenidos cumple con el objetivo propuesto y construye la matriz de relación que se constituye en el aporte a lectores interesados en este tema. Desde la perspectiva sociológica y de la administración explica y sustenta la relación en cada elemento identificado. Permite concluir por la relación establecida que la Cultura Organizacional actúa como condición para que la estrategia cumpla su propósito.
EVOLUTION AND PALEOENVIRONMENTAL RECONSTITUTION OF THE SOUTHERN ZONE OF THE RIO DE JANEIRO CITY (SE BRAZIL)
Authors: Potratz Guilherme Loriato , Souza e Almeida Felipe Saliba de , Castro João Wagner de Alencar , Alves Martins Maria Virginia , Geraldes Mauro Cesar 
Published: July 2019

Paleoenvironmental reconstructions in coastal environments have been carried out using indicators of relative sea level oscillation (RSL), among them, mollusk shells, beachrocks and sedimentary records. Data from eleven geological-geotechnical drilling cores (from 15 m to 30 m long) distributed along the Ipanema - Leblon coastline and on the edge of the Rodrigo de Freitas Lagoon and respective stratigraphic profiles were analyzed in this work. Eleven radiocarbon ages obtained from shell samples calibrated to eliminate the effect of reservoir were used to perform the time evolution of the study area.The obtained results allowed to identify five distinct stages on the sedimentary evolution of the Southern Zone of the Rio de Janeiro City related to the Holocene RSL variations: the first stage under continental environmental conditions, with sea level approximately 4.5 m below the current; the second stage corresponding to a paleo-cove formed due to the sea level rising; the third stage associated with the mid-Holocene maximum transgression, in which the entire study area was flooded; the fourth stage following the gradual lowering of the RSL and marked by the formation of a paleo-bay; the fifth stage corresponding to the current configuration of the coastline. EVOLUÇÃO E RECONSTITUIÇÃO PALEO-AMBIENTAL DA ZONA SUL DA CIDADE DO RIO DE JANEIRO (SE BRASIL) ResumoAs reconstruções paleoambientais em ambientes costeiros têm sido realizadas utilizando indicadores de oscilação relativa do nível do mar (NRM), entre eles, conchas de moluscos, beachrocks e registros sedimentares. Foram analisados neste trabalho, dados de onze testemunhos de perfuração geológico-geotécnica (de 15 m a 30 m de comprimento) distribuídos ao longo do litoral de Ipanema - Leblon e à beira da Lagoa Rodrigo de Freitas e respectivos perfis estratigráficos. Onze idades de radiocarbono calibradas obtidas em amostras de conchas foram utilizadas no estudo da evolução temporal da área de estudo.Os resultados obtidos permitiram identificar cinco etapas distintas da evolução sedimentar da Zona Sul da cidade do Rio de Janeiro, relacionadas com variações do NRM durante o Holoceno: a primeira etapa, sob a influência de condições ambientais continentais, está relacionada com um nível do mar aproximadamente 4,5 m abaixo do atual; a segunda etapa corresponde a uma paleo-enseada formada devido à elevação do nível do mar; o terceiro estágio associado à transgressão máxima do Holoceno médio, em que toda a área de estudo foi inundada; o quarto estágio, após o abaixamento gradual do NRM, é marcado pela formação de uma paleo-baía; a quinta etapa corresponde à configuração atual do litoral. Palavras-chave: Mudança relativa do nível do mar. Quaternário. Sedimentação Marinha. Evolução litoral. Modelo 2D.
BVD Stamp It Out initiative
Authors: Carter Neil 
Published: July 2019

In 2018, Defra announced a project focused on controlling bovine viral diarrhoea (BVD) in the national breeding herd in England. The project has become known as Stamp It Out. Run by SAC Consulting alongside Duchy College, Stamp It Out offers funding through the Rural Development Programme for England (RDPE) for cattle keepers in England to draw up plans to control the disease. The headline target for Stamp It Out is to engage 50% of the breeding herd in England in active BVD control planning; this equates to 911 764 breeding cattle. The overall budget for Stamp It Out is £5.7 million, of which £1.2 million is ring fenced for testing costs. This testing money is split into two available pots: £61.80 per herd to undertake a check test; £440 per SBI number to undertake a persistently infected (PI) animal hunt if check test shows active infection. With delivery having started in August 2018, as of May 2019, the following successes can be reported: 4187 farmers enrolled, 3483 of which have agreed to join BVDFree England, and their details have been sent across.
Effect of golimumab on endothelial vasomotor function and arterial stiffness in ankylosing spondylitis
Authors: Knyazeva L. A. , Damjanov N. , Knyazeva L. I. , Meshcherina N. S. , Goryainov I. I. , Stepchenko M. A. , Bobyntsev Ya. I. , Rudakov O. S. 
Published: July 2019

Objective: to evaluate the effect of golimumab (GLM) on endothelial vasomotor function and arterial stiffness in patients with ankylosing spondylitis (AS).Subjects and methods. A total of 42 patients with advanced-stage AS, who were older than 18 years and met the 1984 modified New York criteria with a disease duration of ≤5 years, were examined. The investigators visualized carotid arteries to determine local vascular wall stiffness, studied regional arterial stiffness to assess a pulse wave contour analysis, and a reactive hyperemia test before and after 104-week therapy.Results and discussion. RA patients without cardiovascular comorbidity were found to have signs of subclinical great artery involvement accompanied by endothelial vasoregulatory dysfunction in both the small resistance and large muscular arteries; by increases in common carotid artery (CCA) intima-media thickness (IMT) and stiffness index (SI); by rises in peripheral augmentation index (AIp), SI and reflection index (RI), the intensity of a change in which correlated with disease duration and activity assessed by ASDAS; as well as with the modified Schober test value, cervical rotation, and tragus-to-wall distance. In addition to a decrease in the Ankylosing Spondylitis Disease Activity Score (ASDAS), GML treatment in patients with AS caused a statistically significant increase in the amplitude occlusion index to the control values and a rise in the phase shift between the channels by an average of 2 times (p<0.01) as compared to the baseline values; a decrease in CCA IMT by an average by 20% (p=0.01) and in the local stiffness of the (carotid) vascular bed by 31% (p=0.01). The pulse wave contour analysis after 104-week GLM therapy revealed that AIp, SI and RI decreased by an average of 5 (р<0.001), 1.3 (р<0.01), and 2 (p<0.05) times, respectively, with the remaining statistically significant differences from the control values.Conclusion. In addition to the effectively reduced inflammatory activity, GLM therapy in patients with AS provides restoration of endothelial function in both the small resistance vessels (an increase in the amplitude occlusion index) and the large muscular arteries (a rise in the phase shift between the channels) and also has a vasoprotective effect on the wall of large elastic vessels (reductions in CCA IMT, SI, AIp, and SI) and small muscular arteries (a decrease in RI).
Global invertibility of Sobolev maps
Authors: Henao Duvan , Mora-Corral Carlos , Oliva Marcos 
Published: July 2019

AbstractWe define a class of SobolevW1,p⁢(Ω,ℝn){W^{1,p}(\Omega,\mathbb{R}^{n})}functions, withp>n-1{p>n-1}, such that its trace on∂⁡Ω{\partial\Omega}is also Sobolev, and do not present cavitation in the interior or on the boundary. We show that if a function in this class has positive Jacobian and coincides on the boundary with an injective map, then the function is itself injective. We then prove the existence of minimizers within this class for the type of functionals that appear in nonlinear elasticity.
Commutative cocycles and stable bundles over surfaces
Authors: Ramras Daniel A. , Villarreal Bernardo 
Published: July 2019

Abstract
Commutative K-theory, a cohomology theory built from spaces of commuting matrices, has been explored in recent work of Adem, Gómez, Gritschacher, Lind and Tillman.
In this article, we use unstable methods to construct explicit representatives for the real commutative K-theory classes on surfaces.
These classes arise from commutative

O
⁢

(
2
)

{O(2)}

-valued cocycles and are analyzed via the point-wise inversion operation on commutative cocycles.
Regulatory Perspectives for Streamlining HIV Prevention Trials
Authors: Murray Jeffrey Scott 
Published: July 2019

Abstract
Designing and conducting active-controlled trials of HIV pre-exposure prophylaxis (PrEP) therapeutics are becoming challenging due to inconsistency of adherence across trials and the need for increasingly larger trials to assess efficacy. In the United States (US), trials evaluating oral contraceptives (OC) use the Pearl Index to assess efficacy in single-arm trials. This article explores the possibility of using an index (“HIV Incidence Index”) analogous to the Pearl Index to assess preventive efficacy in active-controlled HIV prevention trials in sexually-acquired HIV. One proposal for constructing an HIV Incidence Index is to use the incidence of sexually transmitted infections (STIs) during a trial to serve as a marker for HIV risk behavior and to estimate what the HIV seroconversion rate would have been had the participants not been on efficacious PrEP. In addition, a consensus of expert opinion will be needed to define clinically acceptable HIV seroconversion rates for populations at risk of HIV-infection receiving active PrEP.
Role of O-GlcNAcylation and endoplasmic reticulum stress on obesity and insulin resistance
Authors: Sermikli Benan Pelin , Aydogdu Gulizar , Taghidizaj Afsar Abbasi , Yilmaz Erkan 
Published: July 2019

Abstract

Background
Obesity is a global public health problem. Obesity closely associated with various metabolic diseases such as; insulin resistance, hypertension, dyslipidemia and cardiovascular diseases. Endoplasmic reticulum (ER) stress is a critical factor for insulin resistance. O-linked N-acetyl-glucosamine (O-GlcNAc); is the post-translational modification which is has a vital role in biological processes; including cell signaling, in response to nutrients, stress and other extracellular stimuli.

Materials and methods
In this study, we aimed to investigate the role of O-GlcNAc modification in the context of obesity and obesity-associated insulin resistance in adipose tissue. For this purpose, first, the visceral and epididymal adipose tissues of obese and insulin resistant C57BL/6 Lepob/Lepob and wild-type mice were used to determine the O-GlcNAc modification pattern by western blot. Secondly, the external stimulation of O-GlcNAc modification in wild-type mice achieved by intraperitoneal 5 mg/kg/day glucosamine injection every 24 h for 5 days. The effect of increased O-GlcNAc modification on insulin resistance and ER stress investigated in adipose tissues of glucosamine challenged wild-type mice through regulation of the insulin signaling pathway and unfolded protein response (UPR) elements by western blot. In addition to that, the O-GlcNAc status of the insulin receptor substrate-1 (IRS1) investigated in epididymal and visceral adipose tissues of ob/ob, wild-type and glucosamine challenged mice by immunoprecipitation.

Results
We found that reduced O-GlcNAc levels in visceral and epididymal adipose tissues of obese and insulin-resistant ob/ob mice, although interestingly we observed that increased O-GlcNAc modification in glucosamine challenged wild-type mice resulted in insulin resistance and ER stress. Furthermore, we demonstrated that the IRS1 was modified with O-GlcNAc in visceral and epididymal adipose tissues in both ob/ob mice and glucosamine-injected mice, and was compatible with the serine phosphorylation of this modification.

Conclusion
Our results suggest that O-GlcNAcylation of proteins is a crucial factor for intracellular trafficking regulates insulin receptor signaling and UPR depending on the cellular state of insulin resistance.
FARKLI YÖNTEMLERLE ELDE EDİLEN KAMKAT (FORTUNELLA MARGARITA Swing.) TOZLARININ FONKSİYONEL ÖZELLİKLERİNİN BELİRLENMESİ
Authors: YILDIZ TURGUT Demet , ÇINAR Orçun , SEÇMEN Tuba 
Published: July 2019

Bu çalışmada farklı yöntemlerle elde edilen kamkat
tozlarının fonksiyonel kalite parametrelerinin belirlenmesi amaçlanmıştır. Bu
kapsamda, %10 maltodekstrin ilavesi ve maltodekstrinsiz olarak sıcak hava ile
kurutma ve dondurarak kurutma yöntemi ile elde edilen kamkat tozu örneklerinde
toplam fenolik madde, flavonoid, karetonoid miktarı, askorbik asit, antioksidan
aktivite ve flavonoid bileşen analizleri gerçekleştirilmiştir. Toplam fenolik
madde, flavonoid ve karotenoid miktarı, antioksidan aktivite ve flavonoid
kompozisyonu açısından en yüksek değerler maltodekstrinsiz dondurarak kurutma
yöntemi ile elde edilen toz örneğinde tespit edilmiştir. En yüksek askorbik
asit içeriği ise %10 maltodekstrin
ilaveli dondurarak kurutma yöntemi ile elde edilen toz örneğinde
belirlenmiştir. Maltodekstrin ilavesinin sıcak hava kurutma yönteminde
flavonoid bileşenlerin miktarını olumlu etkilediği gözlenmiştir. Elde edilen
kamkat tozlarının çeşitli gıda ürünlerinde duyusal ve fonksiyonel özelliklerin
geliştirilmesinde katkı maddesi olarak kullanılabileceği öngörülmektedir.