bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial with safety lead-in to evaluate the addition of APX005M, a CD40 agonistic monoclonal antibody, to standard-of-care doxorubicin chemotherapy for the treatment of advanced soft tissue sarcoma.
Authors: Ingham Matthew , Lee Shing Mirn , Doshi Sahil , Hernandez Susana , Singh-Kandah Shahnaz V. , Singer Zoe , Trifan Ovidiu C. , Schwartz Gary K. 
Published: February 2020

TPS85 Background: Soft tissue sarcoma (STS) is a biologically heterogeneous disease for which existing immunotherapy approaches (e.g. anti-PD-1) have shown limited clinical activity. Cytotoxic chemotherapy with doxorubicin (D), an anthracycline, remains standard-of-care treatment for most advanced STS. Combining chemotherapy with immunomodulatory treatments may enhance antigen presentation and favorably impact the immune microenvironment (iME). APX005M (Apexigen; San Carlos, CA) is a novel CD40 agonistic antibody. Preclinically, CD40 ligation plus chemotherapy induced expression of costimulatory and major histocompatibility complex molecules on antigen presenting cells (APCs), shifted the myeloid compartment towards an M1 phenotype and expanded T-cell receptor clonality, which are characteristics in which the sarcoma iME is deficient (2,3). In phase 1, APX005M showed dose-dependent activation of APCs in peripheral blood and favorable tolerability. We designed a phase II study evaluating D+A as a novel combination for STS. Methods: This is a single-arm, open-label, Simon 2 stage phase II study with safety lead-in evaluating D+A among 27 patients with STS. Pts have advanced STS (excluding GIST and Kaposi sarcoma) for which doxorubicin is appropriate and any prior lines of therapy, including none. Pts receive D 75 mg/m2 and A 0.3 mg/m2 IV day 1 in 21 day cycles. Doxorubicin is stopped after cycle 8 but APX005M may continue. The primary endpoint is the objective response rate (ORR). The study design has power of 85% to show an improvement in ORR from 10% (inactive) to 30% (active) with α = 0.04. Secondary endpoints include PFS and safety. Pts undergo collection of stool specimens at baseline and cycle 3 to evaluate composition of the gut microbiome including effects on clinical outcomes and modulation of microbiome by treatment. Pts undergo paired tumor biopsies at baseline and cycle 2 which are evaluated with gene expression and multiplex immunohistochemistry to evaluate effects of D+A on iME. The study opened in 1/2019. Clinical trial information: NCT03719430.
NANORAY-1100: A phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with anti-PD-1 therapy.
Authors: Shen Colette J. , Jameson Katherine LaRoque , Weiss Jared , Hackman Trevor , Dixon Robert , Akulian Jason A. , Pearson Alexander T. , Frakes Jessica , Said Patricia , Seiwert Tanguy Y. 
Published: February 2020

TPS86 Background: Most cancer patients present resistance to immune therapy; only approximately 15% of patients respond to immune checkpoint inhibitors (ICI). Strategies able to increase ICI response are thus of great interest. Radiotherapy (RT), by acting as an immunomodulator is a good candidate to increase the proportion of ICI responders. However, RT dose and ultimate efficacy are limited by potential toxicity to healthy tissues. NBTXR3, a first in class radioenhancer administered by intratumoral injection, has been designed at the nanoscale to increase RT energy dose deposition within the tumor. The result is increased radiation-dependent tumor cell killing, without increasing radiation exposure of healthy tissues. Preclinical and early clinical data suggest NBTXR3 activated by RT can increase the anti-tumor response yielding both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect while also producing a systemic effect sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods: NANORAY-1100 [NCT03589339] is a multicenter, open-label, phase 1 study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregionally recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases from any primary cancer eligible for anti-PD-1, or (3) Liver metastases from any primary cancer eligible for anti-PD-1. Approximately two-thirds of each cohort will be composed of anti-PD-1 non-responders. NBTXR3 injection volume is based on a percentage of gross tumor volume (GTV) determined by central review. The primary objective is to determine R3/RT/PD-1 RP2D. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR) of R3/RT/PD-1, safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, mRNA and cytokine immune marker profiling. Clinical trial information: NCT03589339.
The Association Between Heart Rate and Glycemic Status in the National Health and Nutrition Examination Surveys
Authors: Casagrande Sarah S , Cowie Catherine C , Sosenko Jay M , Mizokami-Stout Kara , Boulton Andrew J M , Pop-Busui Rodica 
Published: February 2020

Abstract

Context
Evidence suggests that heart rate (HR) is a prognostic factor for cardiovascular disease (CVD), for which persons with diabetes are at increased risk.

Objective
The objective of this article is to determine the association between HR and glycemic status in a nationally representative sample of US adults, and, among adults with diagnosed diabetes, the association between HR and hemoglobin A1c (HbA1c) level.

Design
A cross-sectional study was conducted.

Setting
The setting of this study is the National Health and Nutrition Examination Surveys, 2011 to 2016.

Participants
US general adult (age ≥ 20 years) population who had information on glycemic status based on self-report, HbA1c, and fasting plasma glucose (N = 8562).

Intervention
There was no intervention.

Main outcome measure
The main outcome measure of this study was mean HR (beats per minute).

Results
After adjustment for examination time, age, other demographic characteristics, health insurance, health behaviors, body mass index, CVD and kidney disease, and taking antihypertensive medications, mean HR was significantly higher for those with diagnosed (75 bpm), undiagnosed diabetes (75 bpm), and prediabetes (73 bpm) compared to those with normoglycemia (71 bpm, P &lt; .05 for all); this association was robust both for men and women. Mean HR increased with increasing HbA1c level among individuals with diagnosed diabetes independent of other risk factors (HbA1c &lt; 7.0% [&lt; 53 mmol/mol], 73 bpm vs A1c ≥ 11.0% [≥ 97mmol/mol], 79 bpm, P &lt; .001); this association was most pronounced for women.

Conclusions
Adjusted mean HR was higher among individuals with diabetes and increased glycemia, which may reflect underlying autonomic and/or myocardial dysfunction among those with diabetes.
Parathyroidectomy in First Trimester of Pregnancy
Authors: Sharma Sonia G , Levine Steven N , Yatavelli Rajini K , Shaha Manish A , Nathan Cherie Ann O 
Published: February 2020

Abstract
Primary hyperparathyroidism is not commonly diagnosed during pregnancy. For pregnant women with mild, asymptomatic disease, surgery can be avoided unless the degree of hypercalcemia becomes more severe or they develop complications. However, there are no evidence-based guidelines to assist clinicians regarding the management of primary hyperparathyroidism during pregnancy. When surgery is deemed necessary during pregnancy, the second trimester is generally considered to be the optimal time. We report the case of a 31-year-old female G1P0 who presented at 6 weeks gestation with symptoms of nausea, vomiting, polyuria, and corrected calcium of 14.8 mg/dL. Due to the extreme degree of hypercalcemia and refractory to medical treatment, it was decided that surgery could not be delayed until the second trimester. At 7w3d gestational age the patient had resection of a 37 gram, 5 × 4 × 3 cm right inferior parathyroid adenoma.
Study of the 193Ir(n,2n)192Ir Reaction Cross Section
Authors: Patronis N. , Kalamara A. , Harissopulos S. , Kokkoris M. , Lagoyannis A. , Vlastou R. 
Published: February 2020

The 193Ir(n,2n)192Ir reaction cross section was measured relative to the 27Al(n,a)24Na and 197Au(n,2n)196Au reactions by means of the activation technique at two neutron beam energies: 10.0 and 10.5 MeV. The neutron beam was produced via the 2H(d,n)3Ηe reaction. The deuteron beam was provided by the 5.5 MV Tandem Van de Graaff accelerator of the N.C.S.R. “Demokritos”. After the irradiations the induced activity of the samples was measured through a 56% relative efficiency HPGe detector. The total reaction cross section for the population of the ground state (4+) and the first isomeric state (1-) was determined. The adopted method for the correction concerning the population of the product nucleus 192Ir through the 191Ir(n,γ)192Ir reaction is also presented.
Ormianie kamienieccy w ostatniej ćwierci XVII wieku – próba rekonstrukcji spisu imiennego
Authors: Agopsowicz Monika 
Published: February 2020

Armenians in Kamieniec Podolski in the Last Quarter of the 17th Century − An Attempt to Reconstruct the Census Records
By examining the manuscript sources created by Armenian community in Kamieniec Podolski (Kamianets-Podilskyi), Jazłowiec (Yazlovets), Lwów (Lviv) and Stanisławów (now: Ivano-Frankivsk), the author reconstructs the names and surnames of Armenians who lived in Kamieniec Podolski before the Turkish invasion of 1672 and those who resided there immediately after 1700.
The current state of bionic limbs from the surgeon’s viewpoint
Authors: Bumbaširević Marko , Lesic Aleksandar , Palibrk Tomislav , Milovanovic Darko , Zoka Milan , Kravić-Stevović Tamara , Raspopovic Stanisa 
Published: February 2020

Amputations have a devastating impact on patients’ health with consequent psychological distress, economic loss, difficult reintegration into society, and often low embodiment of standard prosthetic replacement. The main characteristic of bionic limbs is that they establish an interface between the biological residuum and an electronic device, providing not only motor control of prosthesis but also sensitive feedback. Bionic limbs can be classified into three main groups, according to the type of the tissue interfaced: nerve-transferred muscle interfacing (targeted muscular reinnervation), direct muscle interfacing and direct nerve interfacing. Targeted muscular reinnervation (TMR) involves the transfer of the remaining nerves of the amputated stump to the available muscles. With direct muscle interfacing, direct intramuscular implants record muscular contractions which are then wirelessly captured through a coil integrated in the socket to actuate prosthesis movement. The third group is the direct interfacing of the residual nerves using implantable electrodes that enable reception of electric signals from the prosthetic sensors. This can improve sensation in the phantom limb. The surgical procedure for electrode implantation consists of targeting the proximal nerve area, competently introducing, placing, and fixing the electrodes and cables, while retaining movement of the arm/leg and nerve, and avoiding excessive neural damage. Advantages of bionic limbs are: the improvement of sensation, improved reintegration/embodiment of the artificial limb, and better controllability. Cite this article: EFORT Open Rev 2020;5:65-72. DOI: 10.1302/2058-5241.5.180038
A review of informed consent and how it has evolved to protect vulnerable participants in emergency care research
Authors: Nandra Rajpal , Brockie Alan F. , Hussain Faisal 
Published: February 2020

A vulnerable participant in research lacks capacity to consent or may be exposed to coercion to participate. Capacity may be temporarily impaired due to loss of consciousness, hypoxia, pain and the consumption of alcohol or elicit substances. To advance emergency care, providing life-threatening measures in life-threatening circumstances, vulnerable patients are recruited into research studies. The urgent need for time-critical treatment conflicts with routine informed consent procedures. This article reviews ethical considerations and moral obligations to safeguard these participants and preserve their autonomy. A particular focus is given to research methodology to waive consent, and the role of ethics committees, research audits, research nurses and community engagement. Research on the acutely unwell patient who lacks capacity is possible with well-designed research trials that are led by investigators who are sufficiently trained, engage the community, gain ethical approval to waive consent and continuously audit practice. Cite this article: EFORT Open Rev 2020;5:73-79. DOI: 10.1302/2058-5241.5.180051
Enhancing sensing capacity of terahertz metamaterial absorbers with a surface-relief design
Authors: Wang Wei , Yan Fengping , Tan Siyu , Li Haisu , Du Xuemei , Zhang Luna , Bai Zhuoya , Cheng Dan , Zhou Hong , Hou Yafei 
Published: February 2020

Metamaterial absorbers (MAs) serve as important electromagnetic wave-absorbing devices that have captured the attention of researchers for a long term. Functioning as sensitive detectors to determine perturbations in an ambient environment is another significant subsidiary function. Here, we theoretically propose an optimized fabrication method to implement terahertz MAs with fewer steps and also evaluate both absorption and sensing performances of such MAs realized by the new method. Simulation findings demonstrate that such MAs can basically maintain the original absorption features perfectly, including near-complete absorption at resonance as well as strong robustness to wide incident angles. Specifically, the full width at half-maximum and quality factor of the absorption resonances attenuate less than 26% and 8% with this new method, remaining in the ranges of

∼
0.03
–
0.04

THz

and

∼
20
–
27

for two selected example MAs. More significantly, sensing capacities of this type of MA, in terms of maximum detection range (enhancing at least 9%), observable spectral modulation (increasing at least 6.3%), and refractive index sensitivity, are improved to a large extent because of more intense coupling between resonant field and matter in the case of surface-relief MAs. This stronger coupling results from exposing more spots of the resonantly high field to direct contact with an approaching analyte, which is illustrated by field profiles of the MAs at resonance in this work. Additionally, other desirable absorber features are also explored with such MAs, like functioning as building blocks to configure multiband MAs and strong robustness against fabrication errors. Such new-style terahertz MAs shown in the paper, acting as good examples, not only prove that terahertz MAs can be fabricated by the proposed time- and cost-saving route in contrast to the traditional MA fabrication process, but also can serve as novel platforms to explore other intriguing terahertz photonic effects, such as the field enhancement effect.
Implikationen von Machine Learning auf das Datenmanagement in Unternehmen
Authors: Kessler René , Gómez Jorge Marx 
Published: February 2020

ZusammenfassungMachine Learning ist ein Forschungsfeld mit großen Potenzialen und weitreichenden Anwendungspotenzialen. Big Data kann dabei als Enabler angesehen werden, da große und qualitativ hochwertige Daten stets die Grundlage für erfolgreiche Machine Learning-Algorithmen und -Modelle darstellen. Aktuell gibt es noch keinen voll etablierten Standardprozess für den Machine Learning-Life Cycle, wie es im Data Mining mit dem CRISP-DM beispielsweise der Fall ist, was zur Folge hat, dass gerade die Operationalisierung von Machine Learning-Modellen Unternehmen vor große Herausforderungen stellen kann. In diesem Beitrag werden anhand der Sicht auf die Beschaffenheit der Daten, die verschiedenen Rollen in Machine Learning-Teams und den Lebenszyklus von Machine Learning-Modellen Implikationen für das Datenmanagement in Unternehmen herausgearbeitet.
Die Zukunft der Bushaltestelle vor dem Hintergrund von Mobility-as-a-Service – Eine qualitative Betrachtung des öffentlichen Personennahverkehrs in Deutschland
Authors: Hahn Andreas , Pakusch Christina , Stevens Gunnar 
Published: February 2020

ZusammenfassungDie Bundesrepublik Deutschland erlebt in jüngster Vergangenheit verstärkt Dieselfahrverbote in Großstädten. Gleichzeitig erfahren Großstädte als Lebensmittelpunkt eine steigende Beliebtheit. Für Verkehrsunternehmen gilt es, der Bevölkerung nachhaltige Mobilitätslösungen zu bieten, die ein Höchstmaß an Flexibilität ermöglichen. Moderne Mobility-as-a-Service-Konzepte und Innovationen in der Mobilität stellen den klassischen, planorientierten, öffentlichen Personennahverkehr und damit auch die Existenz von Bushaltestellen infrage. Mittels qualitativer Experten-Interviews lässt sich feststellen, dass sich die Bushaltestelle in den Innenstädten vor dem Hintergrund zunehmender digitaler Vernetzung von Mobilitätsanbietern und daraus resultierender modernen Mobility-as-a-service-Konzepte verändern wird. Die Ergebnisse deuten darauf hin, dass die Bushaltestelle in den Innenstädten auch in Zukunft bestehen bleibt und um „on demand“-Verkehre ergänzt wird. Ein radikaler Wandel, wie eine flächendeckende Einführung von autonom fahrenden Bussen, könnte langfristig eine Runderneuerung der Haltestelle zur Folge haben.
The Binding Force of International Legal Standards in the Face of the Recurrent Practice of Soft Law
Authors: Boubacar Sidi Diallo 
Published: February 2020

Soft law facilitates cooperation between international actors. Already, the elaboration of international law is a matter of shared competence between States, traditionally recognized as the only subjects of international law, international organizations and the typical actors. International organizations have initiated a movement towards the adoption of flexible forms of regulation of international relations. They will profoundly change the way in which international law will be created and presented to the recipients of the rule of law. From the very beginning of their activities, organizations preferred a method other than hierarchical command to encourage international cooperation. They will develop a consistent legal technique, aimed at persuading and not compelling their Member States to adopt conduct consistent with the legally binding standard. This article proposes a reflection on soft law and the results of its increasing use in international practices.
Why Legal Reasoning has to be Unique
Authors: Koszowski Maciej 
Published: February 2020

This article addresses the issue of the uniqueness of legal reasoning and, specifically, the author advances the thesis that what makes legal reasoning different from the reasoning employed in demonstrative and empirical sciences and matters of everyday life is not the actual form (scheme) of this reasoning but the legal milieu. Thus, he tries to demonstrate that some features of law – such as its normative and prescriptive nature, difficulties with the verification of its content on empirical grounds, its limitations stemming from the physical world and dependence on humans and their minds, as well as the ‘unspecialized’ character of law agents and the extraordinary role of authority – influence legal reasoning as well. At the same time these features also allow this reasoning to be unique, despite its adoption of forms of inference that are present elsewhere.
The prevalence of virulence genes and multidrug resistance in thermophilic Campylobacter spp. isolated from dogs
Authors: Selwet Marek 
Published: February 2020

AbstractThe aim of the study was to determine the role of dogs as a potential reservoir of Campylobacter spp. At the next stage of the research the frequency of occurrence of selected virulence genes, i.e. cadF, flaA and iam as well as genes responsible for the formation the cytolethal distending toxin (CDT), i.e. cdtA, cdtB and cdtC was determined. The isolates obtained in the research were tested for their resistance to selected antibiotics: ciprofloxacin (CIP), enrofloxacin (EF), erythromycin (E) and tetracycline (TE). Campylobacter spp. was found in 63 (12.6%) out of a total number of 500 isolates. 61 (12.2%) isolates were identified as C. jejuni. The number of C. jejuni isolates found in the younger animals was smaller (p <0.05) than in the older ones. The frequency of occurrence of virulence genes and the genes responsible for the formation of CDT was significantly (p <0.05) higher in the older dogs. A comparison of the effect of antibiotics showed that the isolates obtained from both age groups exhibited low resistance to erythrosine (13.5% in the group aged under 1 year and 8.6% in the group aged over 1 year). Both groups exhibited the highest resistance to ciprofloxacin and enrofloxacin.
Biogenesis pathways of α-helical mitochondrial outer membrane proteins
Authors: Drwesh Layla , Rapaport Doron 
Published: February 2020

Abstract
Mitochondria harbor in their outer membrane (OM) proteins of different topologies. These proteins are encoded by the nuclear DNA, translated on cytosolic ribosomes and inserted into their target organelle by sophisticated protein import machineries. Recently, considerable insights have been accumulated on the insertion pathways of proteins into the mitochondrial OM. In contrast, little is known regarding the early cytosolic stages of their biogenesis. It is generally presumed that chaperones associate with these proteins following their synthesis in the cytosol, thereby keeping them in an import-competent conformation and preventing their aggregation and/or mis-folding and degradation. In this review, we outline the current knowledge about the biogenesis of different mitochondrial OM proteins with various topologies, and highlight the recent findings regarding their import pathways starting from early cytosolic events until their recognition on the mitochondrial surface that lead to their final insertion into the mitochondrial OM.
Basics and use of continuous glucose monitoring (CGM) in diabetes therapy
Authors: Freckmann Guido 
Published: February 2020

Abstract

Background
For a long time, self-monitoring of blood glucose (SMBG) was widely viewed as the essential glucose measurement procedure in the therapy of insulin-treated people with diabetes. With increasing accuracy and simplified handling of continuous glucose monitoring (CGM) systems, this evolving technology challenges and at least partly replaces SMBG systems.

Content
Sensors of all currently available CGM systems measure glucose levels in the subcutaneous interstitial fluid for 6–14 days. The only available implantable sensor facilitates a measurement span of up to 6 months. Depending on the used system, glucose levels are either shown in real time (rtCGM systems) or after scanning (iscCGM systems). Functions such as alerts, alarms and trend arrows and data presentation encourage independent self-management of diabetes therapy. The high frequency of glucose data and the multitude of existing functions require an extensive training of people with diabetes and their caregivers.

Summary
CGM systems provide a much more detailed picture of glycemia in people with diabetes. Educated patients can use these data to react adequately to their glucose levels and therefore avoid hypoglycemic and hyperglycemic events. Studies showed that glycated hemoglobin (HbA1c) levels and hypoglycemic events can be significantly reduced by frequent use of CGM systems.