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Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.

Lancet Oncol 2021 May 11. Epub 2021 May 11.

Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Background: Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC.

Methods: This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Read More

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Hierarchies, markets, and collaborative networks in energy governance: Multilevel drivers of renewable energy deployment.

J Environ Manage 2021 May 4;290:112614. Epub 2021 May 4.

Florida State University Askew School of Public Administration, USA. Electronic address:

State renewable portfolio standard (RPS) mandates, competitive wholesale electricity markets, and cooperative regional transmission planning have all been identified as potential drivers of RE production. However, these factors are typically studied in isolation, and studies come to mixed conclusions about their actual effects on RE deployment. In this article, we a) use a novel "networks of action situations" (NAS) approach to examine the way that state RPS mandates, competitive markets, and regional transmission planning interact to jointly affect RE production; and b) ask whether these patterns differ across traditionally regulated and "deregulated" jurisdictions. Read More

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Effects of hatching enzymes on egg envelope digestion in the male-brooding seahorse.

Mol Reprod Dev 2021 May 7. Epub 2021 May 7.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Innovation Academy of South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences, Guangzhou, China.

In the present study, we aimed to evaluate the effects of hatching enzymes on the egg envelope digestion during the hatching period in the male brooding seahorse. The complementary DNAs encoding two hatching-enzyme genes, high choriolytic enzyme (HCE) and low choriolytic enzyme (LCE), were cloned and functionally characterized from the lined seahorse (Hippocampus erectus). The genomic-synteny analysis confirmed that teleosts shared LCE gene synteny. Read More

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First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study.

Eur J Cancer 2021 May 3;151:14-24. Epub 2021 May 3.

St John of God Subiaco Hospital, Subiaco, WA, Australia.

Background: This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX).

Methods: Patients (aged ≥18 years) had locally advanced/metastatic pancreatic ductal adenocarcinoma (mPDAC), with an Eastern Cooperative Oncology Group performance status score of 0/1 and adequate organ function. Primary objectives were to determine the maximum tolerated dose (MTD) and to evaluate safety and tolerability. Read More

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Supramolecular structures of Ni and Cu with the sterically demanding Schiff base dyes driven by cooperative action of preagostic and other non-covalent interactions.

IUCrJ 2021 May 1;8(Pt 3):351-361. Epub 2021 May 1.

University of Tyumen, Volodarskogo Street 6, Tyumen, 625003, Russian Federation.

This work reports on synthesis and extensive experimental and theoretical investigations on photophysical, structural and thermal properties of the Ni and Cu discrete mononuclear homoleptic complexes [Ni()] and [Cu()] fabricated from the Schiff base dyes -HOCH-CH=N--CH (H) and -HOCH-CH=N--CH (H), containing the sterically crowding cyclo-hexyl units. The six-membered metallocycles adopt a clearly defined envelope conformation in [Ni()], while they are much more planar in the structures of [Ni()] and [Cu()]. It has been demonstrated by in-depth bonding analyses based on the ETS-NOCV and Interacting Quantum Atoms energy-decomposition schemes that application of the bulky substituents, containing several C-H groups, has led to the formation of a set of classical and unintuitive intra- and inter-molecular interactions. Read More

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MAP-kinase and JAK-STAT pathways dysregulation in plasmablastic lymphoma.

Haematologica 2021 May 6. Epub 2021 May 6.

Hematopathology Unit, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid.

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large cell morphology and plasmacytic differentiation. The differential diagnosis with Burkitt lymphoma (BL), plasma cell myeloma (PCM) and some variants of diffuse large B-cell lymphoma (DLBCL) may be challenging due to the overlapping morphological, genetic and immunophenotypic features. Furthermore, the genomic landscape in PBL is not well known. Read More

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DNA Binding to the Silica: Cooperative Adsorption in Action.

Langmuir 2021 May 5. Epub 2021 May 5.

Bioseparation Engineering Group, Department of Mechanical Engineering, Technical University of Munich (TUM), Munich 85748, Germany.

The adsorption and desorption of nucleic acid to a solid surface is ubiquitous in various research areas like pharmaceutics, nanotechnology, molecular biology, and molecular electronics. In spite of this widespread importance, it is still not well understood how the negatively charged deoxyribonucleic acid (DNA) binds to the negatively charged silica surface in an aqueous solution. In this article, we study the adsorption of DNA to the silica surface using both modeling and experiments and shed light on the complicated binding (DNA to silica) process. Read More

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The impact of resveratrol on skin wound healing, scarring, and aging.

Int Wound J 2021 May 5. Epub 2021 May 5.

COREMED-Cooperative Centre for Regenerative Medicine, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Graz, Austria.

Resveratrol is a well-known antioxidant that harbours many health beneficial properties. Multiple studies associated the antioxidant, anti-inflammatory, and cell protective effects of resveratrol. These diverse effects of resveratrol are also potentially involved in cutaneous wound healing, scarring, and (photo-)aging of the skin. Read More

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The End of the Profession as a Sociological Category? Systems-theoretical Remarks on the Relationship between Profession and Society.

Authors:
Thomas Kurtz

Am Sociol 2021 Apr 30:1-18. Epub 2021 Apr 30.

DHGE, University of Cooperative Education, Campus Gera, Weg der Freundschaft 4, 07546 Gera, Germany.

Following reflections by Talcott Parsons and Niklas Luhmann, this paper is concerned with the changing meaning of the profession as a sociological category for analyzing modern society. Professions are practical academic occupational groups oriented to certain social values, to which a special significance for society was attributed in the social sciences for a long time, thus marking a connection between professions' research and theory of society. This paper now describes that the causal relationship between profession and society is limited to a historically relatively early period. Read More

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IMCC: A Novel Quantitative Approach Revealing Variation of Global Modular Map and Local Inter-Module Coordination Among Differential Drug's Targeted Cerebral Ischemic Networks.

Front Pharmacol 2021 16;12:637253. Epub 2021 Apr 16.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Stroke is a common disease characterized by multiple genetic dysfunctions. In this complex disease, detecting the strength of inter-module coordination (genetic community interaction) and subsequent modular rewiring is essential to characterize the reactive biosystematic variation (biosystematic perturbation) brought by multiple-target drugs, whose effects are achieved by hitting on a series of targets (target profile) jointly. Here, a quantitative approach for inter-module coordination and its transition, named as IMCC, was developed. Read More

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Gaze-Based Intention Estimation for Shared Autonomy in Pick-and-Place Tasks.

Front Neurorobot 2021 16;15:647930. Epub 2021 Apr 16.

Honda Research Institute Europe, Offenbach, Germany.

Shared autonomy aims at combining robotic and human control in the execution of remote, teleoperated tasks. This cooperative interaction cannot be brought about without the robot first recognizing the current human intention in a fast and reliable way so that a suitable assisting plan can be quickly instantiated and executed. Eye movements have long been known to be highly predictive of the cognitive agenda unfolding during manual tasks and constitute, hence, the earliest and most reliable behavioral cues for intention estimation. Read More

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Mood States and Performance in Elite Canoe Polo Players: The Mediating Role of Stress.

Int J Environ Res Public Health 2021 Apr 23;18(9). Epub 2021 Apr 23.

Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

Sport performance is characterized by competitive stressful conditions that elicit emotional states. The purpose of the study was to examine whether stress mediated the relationship between mood states and performance. Thirty-two elite canoe polo players from four different Italian teams (16 senior males and 16 senior females), aged between 29 and 38 years old (M = 32. Read More

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Polyphenols and Fish Oils for Improving Metabolic Health: A Revision of the Recent Evidence for Their Combined Nutraceutical Effects.

Molecules 2021 Apr 22;26(9). Epub 2021 Apr 22.

Instituto de Investigaciones Marinas-Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain.

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. Read More

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Fungal and Bacterial Endophytes as Microbial Control Agents for Plant-Parasitic Nematodes.

Int J Environ Res Public Health 2021 Apr 17;18(8). Epub 2021 Apr 17.

University of California Cooperative Extension, 2156 Sierra Way, Ste. C, San Luis Obispo, CA 93401, USA.

Endophytes are symbiotic microorganisms that colonize plant tissues and benefit plants in multiple ways including induced systemic resistance to biotic and abiotic stresses. Endophytes can be sustainable alternatives to chemical nematicides and enhance plant health in a variety of cropping and natural environments. Several in vitro and in vivo studies demonstrated the potential of multiple species of and against plant-parasitic nematodes in horticultural, agricultural, and fodder crops and in forestry. Read More

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Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?

Diseases 2021 Apr 10;9(2). Epub 2021 Apr 10.

Centro Militar de Farmacia de la Defensa (CEMILFARDEF), Base Logística de San Pedro, Colmenar Viejo, 28770 Madrid, Spain.

Blister or vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood. Sulfur and nitrogen mustard exert toxic effects not only through the alkylation of thiol-bearing macromolecules, such as DNA and proteins, but also produce free radicals that can develop direct toxic effects in target organs such as the eyes, skin, and respiratory system. Read More

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Alternatives to Antibiotics: A Symposium on the Challenges and Solutions for Animal Health and Production.

Antibiotics (Basel) 2021 Apr 21;10(5). Epub 2021 Apr 21.

Office of National Programs, USDA-Agricultural Research Service, Beltsville, MD 20705, USA.

Antibiotics have improved the length and quality of life of people worldwide and have had an immeasurable influence on agricultural animal health and the efficiency of animal production over the last 60 years. The increased affordability of animal protein for a greater proportion of the global population, in which antibiotic use has played a crucial part, has resulted in a substantial improvement in human quality of life. However, these benefits have come with major unintended consequences, including antibiotic resistance. Read More

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Mechanical Properties of Al Matrix Composite Enhanced by In Situ Formed SiC, MgAlO and MgO via Casting Process.

Materials (Basel) 2021 Apr 2;14(7). Epub 2021 Apr 2.

Shaanxi Key Laboratory of Green Preparation and Functionalization for Inorganic Materials, School of Materials Science and Engineering, Shaanxi University of Science & Technology, Xi'an 710021, China.

Al matrix composite, reinforced with the in situ synthesized 3C-SiC, MgAlO and MgO grains, was produced via the casting process using phenolic resin pyrolysis products in flash mode. The contents and microstructure of the composites' fracture characteristics were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Mechanical properties were tested by universal testing machine. Read More

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Rapid exploration of the epitope coverage produced by an Ebola survivor to guide the discovery of therapeutic antibody cocktails.

Antib Ther 2020 Jul 1;3(3):167-178. Epub 2020 Aug 1.

ImmunoPrecise Antibodies Ltd., Fargo, ND 58104, USA.

Background: Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences.

Methods And Results: A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. Read More

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Association Between Finger-to-Nose Kinematics and Upper Extremity Motor Function in Subacute Stroke: A Principal Component Analysis.

Front Bioeng Biotechnol 2021 12;9:660015. Epub 2021 Apr 12.

Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Kinematic analysis facilitates interpreting the extent and mechanisms of motor restoration after stroke. This study was aimed to explore the kinematic components of finger-to-nose test obtained from principal component analysis (PCA) and the associations with upper extremity (UE) motor function in subacute stroke survivors.

Methods: Thirty-seven individuals with subacute stroke and twenty healthy adults participated in the study. Read More

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Comprehensive characterization of the chemical constituents in Yiganmingmu oral liquid and the absorbed prototypes in cynomolgus monkey plasma after oral administration by UPLC-Q-TOF-MS based on the self built components database.

Chin Med 2021 Apr 28;16(1):35. Epub 2021 Apr 28.

College of Pharmacy and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, Jinan University, Guangzhou, 510632, China.

Background: Yiganmingmu oral liquid (YGMM), a well known over-the-counter (OTC) drug in China, is composed of 12 types of valuable herbal medicines and has been widely used in clinical for the treatment of soreness and weakness of waist and knees, dizziness, memory loss, and fatigue. However, the chemical compositions of YGMM and its absorbed compounds in plasma remain unclear.

Methods: Since chemical investigation is the first important step to reveal effects and action mechanisms of traditional Chinese medicine (TCM), in this study, based on the self built components database, systematic characterization of the chemical profile of YGMM in vitro was carried out by using a reliable UPLC-Q-TOF-MS method. Read More

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Collective reflections on the first cycle of a collaborative learning platform to strengthen rural primary healthcare in Mpumalanga, South Africa.

Health Res Policy Syst 2021 Apr 19;19(1):66. Epub 2021 Apr 19.

Department of Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Background: Frontline managers and health service providers are constrained in many contexts from responding to community priorities due to organizational cultures focused on centrally defined outputs and targets. This paper presents an evaluation of the Verbal Autopsy with Participatory Action Research (VAPAR) programme-a collaborative learning platform embedded in the local health system in Mpumalanga, South Africa-for strengthening of rural primary healthcare (PHC) systems. The programme aims to address exclusion from access to health services by generating and acting on research evidence of practical, local relevance. Read More

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The Emotional States Elicited in a Human Tower Performance: Case Study.

Front Psychol 2021 1;12:611279. Epub 2021 Apr 1.

Motor Action Research Group (GIAM), INDEST, National Institute of Physical Education of Catalonia (INEFC), University of Lleida (UdL), Lleida, Spain.

Human Towers are one of the most representative traditional sporting games in Catalonia, recognized in 2010 as Intangible Cultural Heritage by the United Nations Organization for Education, Science and Culture (UNESCO). The objective of this research was to study the emotional states (well-being, discomfort, and affectivity) elicited by a representative performance of the de Castellers de Lleida. This research is based on an ethnographic case study, with mixed methods in which 17 key informants () voluntarily participated. Read More

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Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels.

J Headache Pain 2021 Apr 13;22(1):23. Epub 2021 Apr 13.

Institute of Physiology and Pathophysiology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 17, 91054, Erlangen, Germany.

Background: Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Read More

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New Visualization Models of Designation Pathway and Group Categorization of Device-Drug and Device-Biologic Combination Products Classification in the United States: Analysis of FDA Capsular Decisions.

Ther Innov Regul Sci 2021 Apr 12. Epub 2021 Apr 12.

Joint Graduate School of Tokyo Women's Medical University and Waseda University (TWIns), Cooperative Major in Advanced Biomedical Sciences, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.

Objective: The developer and sponsor of new combination products in US needs to forecast which classification and designation to the regulatory scheme of drug, biological product, or device would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization.

Method: We searched the website of the FDA on 15 November, 2020 to identify the regulatory scheme of the FDA's 129 capsular decision cases of device-drug and device-biologics combination products and other publicly available cases the FDA designated to the drug/biologic or device regulatory scheme. Read More

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Cognitive enrichment device provides evidence for intersexual differences in collaborative actions in Indo-Pacific bottlenose dolphins (Tursiops aduncus).

Anim Cogn 2021 Apr 12. Epub 2021 Apr 12.

Department of Ethology, Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary.

Social living, long lifespan and advanced cognitive skills provided favourable conditions for the development of pro-social behaviours and cooperative activities in cetacean. Dolphins have been observed to collaborate for various purposes, finding food, finding mates or raising and teaching younger individuals. This study investigated the potential impact of demographic factors (sex and age), social factors (relatedness and group size), and individual experience in a cooperative problem solving task. Read More

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Challenges to Interprofessional Education: will e-Learning be the Magical Stick?

Adv Med Educ Pract 2021 1;12:329-336. Epub 2021 Apr 1.

Department of Family Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: In Egypt, the main challenges to interprofessional education (IPE) implementation are complexity of the required curricular design, the attitudinal barriers between professions, and the needed resources. Action research work was planned and implemented to identify alternative solutions to overcome barriers to IPE in the local Egyptian context.

Methods: -An 8-week e-learning elective course was developed, implemented, and evaluated. Read More

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New methods for quantifying rapidity of action potential onset differentiate neuron types.

PLoS One 2021 8;16(4):e0247242. Epub 2021 Apr 8.

School of Biomedical Engineering, Colorado State University, Fort Collins, CO, United States of America.

Two new methods for quantifying the rapidity of action potential onset have lower relative standard deviations and better distinguish neuron cell types than current methods. Action potentials (APs) in most central mammalian neurons exhibit sharp onset dynamics. The main views explaining such an abrupt onset differ. Read More

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Targeted RNA sequencing reveals differential patterns of transcript expression in geographically discrete, insecticide resistant populations of Leptinotarsa decemlineata.

Pest Manag Sci 2021 Apr 5. Epub 2021 Apr 5.

Department of Entomology, University of Wisconsin-Madison, Madison, WI, USA.

Background: The Colorado potato beetle (Leptinotarsa decemlineata Say) is a major agricultural pest of commercial potatoes, partially due to its ability to rapidly develop resistance to multiple insecticide modes of action. Patterns of L. decemlineata insecticide resistance in the contiguous United States have been linked to geographic location and regional management practices. Read More

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Insulin Action, Glucose Homeostasis and Free Fatty Acid Metabolism: Insights From a Novel Model.

Front Endocrinol (Lausanne) 2021 16;12:625701. Epub 2021 Mar 16.

Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States.

Glucose and free fatty acids (FFA) are essential nutrients that are both partly regulated by insulin. Impaired insulin secretion and insulin resistance are hallmarks of aberrant glucose disposal, and type 2 diabetes (T2DM). In the current study, a novel model of FFA kinetics is proposed to estimate the role insulin action on FFA lipolysis and oxidation allowing estimation of adipose tissue insulin sensitivity ( ). Read More

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