bluuebunny/crossref_metadata_2025 huggingface dataset:
NRG-HN003: Phase I and Expansion Cohort Study of Adjuvant Pembrolizumab, Cisplatin and Radiation Therapy in Pathologically High-Risk Head and Neck Cancer
Authors: Bauman Julie E. , Harris Jonathan , Uppaluri Ravindra , Yao Min , Ferris Robert L. , Chen Josephine , Jordan Richard C. , Joshi Nikhil P. , Jujjuvaparu Srinivas , Blakaj Dukagjin M. , Henson Christina , Sheqwara Jawad , Mell Loren K. , Sen Neilayan , Clump David A. , Garg Madhur K. , Yilmaz Emrullah , Torres-Saavedra Pedro , Le Quynh-Thu
Published: June 2021

The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin–radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III–IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted.
Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems
Authors: Wang Peiyu , Zhou Renwu , Thomas Patrick , Zhao Liqian , Zhou Rusen , Mandal Susmita , Jolly Mohit , Richard Derek , Rehm Bernd , Ostrikov Kostya , Dai Xiaofeng , Williams Elizabeth , Thompson Erik
Published: June 2021

Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies. The same trend was seen in luminal muscle-invasive bladder cancer model (TSU-Pr1/B1/B2) and the non-muscle-invasive basal 5637 bladder cancer cell line. Three-dimensional spheroid cultures of the bladder cancer cell lines were less sensitive to the PAM treatment compared to their two-dimensional counterparts; however, incrementally better responses were again seen in more mesenchymally-shifted cell lines. This study provides evidence that PAM preferentially inhibits mesenchymally-shifted carcinoma cells, which have been associated with resistance to other therapies. Thus, PAM may represent a novel treatment that can selectively inhibit triple-negative breast cancers and a subset of aggressive bladder cancers, which tend to be more mesenchymal. Our approach may potentially be utilized for other aggressive cancers exhibiting EMT and opens new opportunities for CAP and PAM as a promising new onco-therapy.
From Pathways to Practice: Impact of Implementing Mobilization Recommendations in Head and Neck Cancer Surgery with Free Flap Reconstruction
Authors: Twomey Rosie , Matthews T. Wayne , Nakoneshny Steven C. , Schrag Christiaan , Chandarana Shamir P. , Matthews Jennifer , McKenzie David , Hart Robert D. , Li Na , Dort Joseph C. , Sauro Khara M.
Published: June 2021

One of the foundational elements of enhanced recovery after surgery (ERAS) guidelines is early postoperative mobilization. For patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction, the ERAS guideline recommends patients be mobilized within 24 h postoperatively. The objective of this study was to evaluate compliance with the ERAS recommendation for early postoperative mobilization in 445 consecutive patients who underwent HNC surgery in the Calgary Head and Neck Enhanced Recovery Program. This retrospective analysis found that recommendation compliance increased by 10% despite a more aggressive target for mobilization (from 48 to 24 h). This resulted in a decrease in postoperative mobilization time and a stark increase in the proportion of patients mobilized within 24 h (from 10% to 64%). There was a significant relationship between compliance with recommended care and time to postoperative mobilization (Spearman’s rho = −0.80; p < 0.001). Hospital length of stay was reduced by a median of 2 days, from 12 (1QR = 9–16) to 10 (1QR = 8–14) days (z = 3.82; p < 0.001) in patients who received guideline-concordant care. Engaging the clinical team and changing the order set to support clinical decision-making resulted in increased adherence to guideline-recommended care for patients undergoing major HNC surgery with free flap reconstruction.
Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany
Authors: Heimes Diana , Müller Lena Katharina , Schellin Alexandra , Naujokat Hendrik , Graetz Christian , Schwendicke Falk , Goedecke Maximilian , Beck-Broichsitter Benedicta , Kämmerer Peer W.
Published: June 2021

(1) Background: In response to the global COVID-19 pandemic, governmental measures have been undertaken. The impact of the crisis on the healthcare of patients with cancer is largely unexplored. This multicenter cohort study aimed to investigate a potential screening delay and its consequences in patients with oral cancer (OC) during the pandemic. (2) Material and Methods: Data of patients who were first diagnosed with OC during different periods were collected, especially in terms of OC incidence, tumor stage/entity and time to intervention. The periods lockdown (LD) (13 March–16 June 2020), post-lockdown (PLD) (17 June–1 November 2020), and the corresponding equivalents in 2018/19 were differentiated and compared. (3) Results: There was no obvious trend towards a higher incidence of OC or higher tumor stages, whereas a trend towards a shorter time to intervention during the LD2020 could be observed. Subgroup analyses revealed an increased incidence in OC within the PLD2020 in Mainz, which might be explained by the partial closure of dental practices in this federal state during LD. (4) Conclusions: While there was no overall higher incidence of OC, we found closure of practices during LD to possibly delay cancer diagnosis. Therefore, measures must be taken to identify patients at risk and to ensure basic healthcare, especially in the context of dental screening measures.
Salmonella Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma
Authors: Pangilinan Christian R. , Wu Li-Hsien , Lee Che-Hsin
Published: June 2021

Targeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a Salmonella-based treatment to address metastasis. The potential of Salmonella as an anticancer agent has been extensively studied; however, the mechanism through which it affects metastasis remains unclear. This study found that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly reduced in Salmonella-treated melanoma cells, as revealed by immunoblotting. Furthermore, wound healing and transwell assays showed a reduced in vitro cell migration following Salmonella treatment. Transfection experiments confirmed that Salmonella acted against metastasis by suppressing protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited SNAI1 expression. Since it is known that metastasis is also influenced by inflammation, we partly characterized the immune infiltrates in melanoma as affected by Salmonella treatment. We found through tumor-macrophage co-culture that Salmonella treatment increased high mobility group box 1 (HMGB1) secretion in tumors to coax the polarization of macrophages in favor of an M1-like phenotype, as shown by increased inducible nitric oxide synthase (iNOS) expression and Interleukin 1 Beta (IL-1β) secretion. Data from our animal study corroborated the in vitro findings, wherein the Salmonella-treated group obtained the lowest lung metastases, longer survival, and increased iNOS-expressing immune infiltrates.
Effect of COVID-19 on Thoracic Oncology Surgery in Spain: A Spanish Thoracic Surgery Society (SECT) Survey
Authors: Martínez-Hernández Néstor , Caballero Silva Usue , Cabañero Sánchez Alberto , Campo-Cañaveral de la Cruz José , Obeso Carillo Andrés , Jarabo Sarceda José , Sevilla López Sebastián , Cilleruelo Ramos Ángel , Recuero Díaz José , Call Sergi , Couñago Felipe , Hernando Trancho Florentino ,   on behalf of the Scientific Committee of the Spanish Thoracic Surgery Society
Published: June 2021

After the first wave of COVID-19, the Spanish Society of Thoracic Surgeons (SECT) surveyed its members to assess the impact of the pandemic on thoracic oncology surgery in Spain. In May 2020, all SECT members were invited to complete an online, 40-item, multiple choice questionnaire. The questionnaire was developed by the SECT Scientific Committee and sent via email. The overall response rate was 19.2%. The respondents answered at least 91.5% of the items, with only one exception (a question about residents). Most respondents (89.3%) worked in public hospitals. The reported impact of the pandemic on routine clinical activity was considered extreme or severe by 75.5% of respondents (25.5% and 50%, respectively). Multidisciplinary tumour boards were held either with fewer members attending or through electronic platforms (44.6% and 35.9%, respectively). Surgical activity decreased by 95.7%, with 41.5% of centers performing surgery only on oncological patients and 11.7% only in emergencies. Nearly 60% of respondents reported modifying standard protocols for early-stage cancer and in the preoperative workup. Most centers (≈80%) reported using full personal protective equipment when operating on COVID-19 positive patients. The COVID-19 pandemic severely affected thoracic oncology surgery in Spain. The lack of common protocols led to a variable care delivery to lung cancer patients.
Riluzole Administration to Rats with Levodopa-Induced Dyskinesia Leads to Loss of DNA Methylation in Neuronal Genes
Authors: Pagliaroli Luca , Fothi Abel , Nespoli Ester , Liko Istvan , Veto Borbala , Devay Piroska , Szeri Flora , Hengerer Bastian , Barta Csaba , Aranyi Tamas
Published: June 2021

Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the phenotype. The rat model of Levodopa-Induced Dyskinesia is a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle, followed by the repeated administration of levodopa. The molecular pathomechanism of Levodopa-Induced Dyskinesia is still not deciphered; however, the implication of epigenetic mechanisms was suggested. In this study, we investigated the striatum for DNA methylation alterations under chronic levodopa treatment with or without co-treatment with Riluzole. Our data show that the lesioned and contralateral striata have nearly identical DNA methylation profiles. Chronic levodopa and levodopa + Riluzole treatments led to DNA methylation loss, particularly outside of promoters, in gene bodies and CpG poor regions. We observed that several genes involved in the Levodopa-Induced Dyskinesia underwent methylation changes. Furthermore, the Riluzole co-treatment, which improved the phenotype, pinpointed specific methylation targets, with a more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for Levodopa-Induced Dyskinesia.
Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue Dysfunction in Mice
Authors: Proniewski Bartosz , Bar Anna , Kieronska-Rudek Anna , Suraj-Prażmowska Joanna , Buczek Elżbieta , Czamara Krzysztof , Majka Zuzanna , Czyzynska-Cichon Izabela , Kwiatkowski Grzegorz , Matyjaszczyk-Gwarda Karolina , Chlopicki Stefan
Published: June 2021

Hyperglycemia linked to diabetes results in endothelial dysfunction. In the present work, we comprehensively characterized effects of short-term hyperglycemia induced by administration of an insulin receptor antagonist, the S961 peptide, on endothelium and perivascular adipose tissue (PVAT) in mice. Endothelial function of the thoracic and abdominal aorta in 12-week-old male C57Bl/6Jrj mice treated for two weeks with S961 infusion via osmotic pumps was assessed in vivo using magnetic resonance imaging and ex vivo by detection of nitric oxide (NO) production using electron paramagnetic resonance spectroscopy. Additional methods were used to analyze PVAT, aortic segments and endothelial-specific plasma biomarkers. Systemic disruption of insulin signaling resulted in severe impairment of NO-dependent endothelial function and a loss of vasoprotective function of PVAT affecting the thoracic as well as abdominal parts of the aorta, however a fall in adiponectin expression and decreased uncoupling protein 1-positive area were more pronounced in the thoracic aorta. Results suggest that dysfunctional PVAT contributes to vascular pathology induced by altered insulin signaling in diabetes, in the absence of fat overload and obesity.
Memory Layout Extraction and Verification Method for Reliable Physical Memory Acquisition
Authors: Jung Seungwon , Seo Seunghee , Kim Yeog , Lee Changhoon
Published: June 2021

Physical memory acquisition is a prerequisite when performing memory forensics, referring to a set of techniques for acquiring and analyzing traces associated with user activity information, malware analysis, cyber incident response, and similar areas when the traces remain in the physical RAM. However, certain types of malware have applied anti-memory forensics techniques to evade memory analysis strategies or to make the acquisition process impossible. To disturb the acquisition process of physical memory, an attacker hooks the kernel API, which returns a map of the physical memory spaces, and modifies the return value of the API, specifically that typically used by memory acquisition tools. Moreover, an attacker modifies the kernel object referenced by the kernel API. This causes the system to crash during the memory acquisition process or causes the memory acquisition tools to incorrectly proceed with the acquisition. Even with a modification of one byte, called a one-byte modification attack, some tools fail to acquire memory. Therefore, specialized countermeasure techniques are needed for these anti-memory forensics techniques. In this paper, we propose a memory layout acquisition method which is robust to kernel API hooking and the one-byte modification attack on NumberOfRuns, the kernel object used to construct the memory layout in Windows. The proposed acquisition method directly accesses the memory, extracts the byte array, and parses it in the form of a memory layout. When we access the memory, we extract the _PHYSICAL_MEMORY_DESCRIPTOR structure, which is the basis of the memory layout without using the existing memory layout acquisition API. Furthermore, we propose a verification method that selects a reliable memory layout. We realize the verification method by comparing NumberOfRuns and the memory layout acquired via the kernel API, the registry, and the proposed method. The proposed verification method guarantees the reliability of the memory layout and helps secure memory image acquisition through a comparative verification with existing memory layout acquisition methods. We also conduct experiments to prove that the proposed method is resistant to anti-memory forensics techniques, confirming that there are no significant differences in time compared to the existing tools.
Open-Loop Class-BD Audio Amplifiers with Balanced Common-Mode Output
Authors: Kołodziejski Wojciech , Kuta Stanisław , Jasielski Jacek
Published: June 2021

This paper presents new architectures and implementations of original open-loop Class-BD audio amplifiers with balanced Common-Mode output. The output stage of each proposed amplifier includes the typical H-bridge with four MOSFETs and four additional MOSFET switches that balance and keep the Common-Mode output constant. The presented amplifiers employ the extended NBDD PWM or PSC PWM modulation scheme. When the output stage is built only on NMOSFET transistors, gate drivers require a floating power supply, using a self-boost charge pump with capacitive isolation of the control signal. The use of complementary MOSFETs in the output stage greatly simplifies gate control systems. The proposed amplifiers were compared to the typical Class-BD configuration, using the optimal NBDD modulation with respect to audio performance of the Differential-Mode (DM) and Common-Mode (CM) outputs. Basic SPICE simulations and experimental studies have shown that the proposed Class-BD amplifiers have similar audio performance to the prototype with the optimal NBDD modulation scheme, while at the same time having a balanced constant voltage CM output, thus eliminating the main contributor to radiation emission. As a result, the filtering of the DM output signals can be greatly simplified, while the filtering of the CM output signals can be theoretically eliminated. Practically, due to the timing errors added by the gate drivers, spikes are generated at the CM output, which are very easy to filter out by the reduced LC output filter, even at very low L.
0.5-V Frequency Dividers in Folded MCML Exploiting Forward Body Bias: Analysis and Comparison
Authors: Centurelli Francesco , Scotti Giuseppe , Palumbo Gaetano
Published: June 2021

Two frequency divider architectures in the Folded MOS Current Mode Logic which allow to operate at ultra-low voltage thanks to forward body bias are presented, analyzed, and compared. The first considered architecture exploits nType and pType divide-by-two building blocks (DIV2s) without level shifters, whereas the second one is based on the cascade of nType DIV2s with input level shifter. Both the architectures have been previously proposed by the same authors with higher supply voltages, but are able to work at a supply voltage as low as 0.5 V due to the threshold lowering allowed by forward body bias. For each architecture, analytical design strategies to optimize the divider under different operation scenarios are considered and a comparison among all the treated case studies is presented. Simulation results considering a commercial 28 nm FDSOI CMOS process are reported to confirm the advantages and features of the different architectures and design strategies. The analysis show that the use of the forward body bias allows to design frequency dividers which have the best efficiency. Moreover, we have found that the frequency divider architecture based on nType and pType DIV2s without level shifter provides always better performance both in terms of speed and power consumption approaching about 17 GHz of maximum operating frequency with less than 30 μW power consumption.
Two-Dimensional Monte Carlo Filter for a Non-Gaussian Environment
Authors: Qiang Xingzi , Xue Rui , Zhu Yanbo
Published: June 2021

In a non-Gaussian environment, the accuracy of a Kalman filter might be reduced. In this paper, a two- dimensional Monte Carlo Filter is proposed to overcome the challenge of the non-Gaussian environment for filtering. The two-dimensional Monte Carlo (TMC) method is first proposed to improve the efficacy of the sampling. Then, the TMC filter (TMCF) algorithm is proposed to solve the non-Gaussian filter problem based on the TMC. In the TMCF, particles are deployed in the confidence interval uniformly in terms of the sampling interval, and their weights are calculated based on Bayesian inference. Then, the posterior distribution is described more accurately with less particles and their weights. Different from the PF, the TMCF completes the transfer of the distribution using a series of calculations of weights and uses particles to occupy the state space in the confidence interval. Numerical simulations demonstrated that, the accuracy of the TMCF approximates the Kalman filter (KF) (the error is about 10−6) in a two-dimensional linear/ Gaussian environment. In a two-dimensional linear/non-Gaussian system, the accuracy of the TMCF is improved by 0.01, and the computation time reduced to 0.067 s from 0.20 s, compared with the particle filter.
Optimising Energy Flexibility of Boats in PV-BESS Based Marina Energy Systems
Authors: Jozwiak Dawid , Pillai Jayakrishnan Radhakrishna , Ponnaganti Pavani , Bak-Jensen Birgitte , Jantzen Jan
Published: June 2021

Implementation of alternative energy supply solutions requires the broad involvement of local communities. Hence, smart energy solutions are primarily investigated on a local scale, resulting in integrated community energy systems (ICESs). Within this framework, the distributed generation can be optimally utilised, matching it with the local load via storage and demand response techniques. In this study, the boat demand flexibility in the Ballen marina on Samsø—a medium-sized Danish island—is analysed for improving the local grid operation. For this purpose, suitable electricity tariffs for the marina and sailors are developed based on the conducted demand analysis. The optimal scheduling of boats and battery energy storage system (BESS) is proposed, utilising mixed-integer linear programming. The marina’s grid-flexible operation is studied for three representative weeks—peak tourist season, late summer, and late autumn period—with the combinations of high/low load and photovoltaic (PV) generation. Several benefits of boat demand response have been identified, including cost savings for both the marina and sailors, along with a substantial increase in load factor. Furthermore, the proposed algorithm increases battery utilisation during summer, improving the marina’s cost efficiency. The cooperation of boat flexibility and BESS leads to improved grid operation of the marina, with profits for both involved parties. In the future, the marina’s demand flexibility could become an essential element of the local energy system, considering the possible increase in renewable generation capacity—in the form of PV units, wind turbines or wave energy.
Energy Community Flexibility Solutions to Improve Users’ Wellbeing
Authors: Mar Adriana , Pereira Pedro , Martins João
Published: June 2021

Energy communities, mostly microgrid based, are a key stakeholder of modern electrical power grids. Operating a microgrid based energy community is a challenging topic due to the involved uncertainties, complexities and often conflicting objectives. The aim of this paper is to present a novel methodology demonstrating that energy community flexibility can contribute to each community member’s wellbeing when a grid fault occurs. A three-house energy community will be modelled considering as consumption sources non-controllable and controllable devices in each house. As power supply sources, PV systems installed in a community’s houses are considered, as well as the power obtained from main grid. Each house’s flexibility inside the community will be studied to improve the management of loads during a fault occurrence. Moreover, three different scenarios will be considered with different available power in the community. With these simulations, it was possible to understand that houses’ energy flexibility can be used under a fault situation, either to maintain the users’ wellbeing or to change the energy flow. Furthermore, energy flexibility can be used to create better energy price markets, to improve the resilience of the grid, or even to consider electrical vehicles’ connection to a community’s grid.
Employee Behaviors toward Using and Saving Energy at Work. The Impact of Personality Traits
Authors: Szostek Dawid
Published: June 2021

The purpose of the article is to determine how personality traits (extraversion, neuroticism, conscientiousness, agreeableness and openness to experience) affect organizational citizenship behaviors for the environment (OCBE), especially in the context of energy saving. The purpose is also to verify the hypothesis that this impact is significantly moderated by individuals’ demographic characteristic (sex, age, length of service, work type and economic sector of employment). To achieve the purposes, a survey was conducted in 2020 on 454 working people from Poland. The analysis was based on structural equation modeling (SEM). The research model assumed that particular types of personality affect direct and indirect OCBEs, including energy-saving patterns. The model also included the aforementioned demographic characteristics of respondents. I proved that personality traits have a significant impact on direct and indirect organizational citizenship behaviors for the environment. In the case of direct OCBEs, the energy-saving items that were most significantly affected by employee personality were: I am a person who turns off my lights when leaving my office for any reason; I am a person who turns off the lights in a vacant room; I am a person who makes sure all of the lights are turned off if I am the last to leave. The strongest predicators were Neuroticism (negative relationship) and Agreeableness (positive relationship) for direct OCBE, but Extraversion (positive relationship) and Agreeableness (negative relationship) for indirect OCBE. The impact of an individual’s personality on OCBE was significantly moderated mainly for indirect behaviors. This applied to all the analyzed demographic variables, but it was stronger for women, employees aged up to 40 years, those with 10 years or more experience, office/clerical workers, and public sector employees. The article discusses the theoretical framework, research limitations, future research directions and practical implications.
Co-Management of Sewage Sludge and Other Organic Wastes: A Scandinavian Case Study
Authors: Fernando-Foncillas Clara , Estevez Maria M. , Uellendahl Hinrich , Varrone Cristiano
Published: June 2021

Wastewater and sewage sludge contain organic matter that can be valorized through conversion into energy and/or green chemicals. Moreover, resource recovery from these wastes has become the new focus of wastewater management, to develop more sustainable processes in a circular economy approach. The aim of this review was to analyze current sewage sludge management systems in Scandinavia with respect to resource recovery, in combination with other organic wastes. As anaerobic digestion (AD) was found to be the common sludge treatment approach in Scandinavia, different available organic municipal and industrial wastes were identified and compared, to evaluate the potential for expanding the resource recovery by anaerobic co-digestion. Additionally, a full-scale case study of co-digestion, as strategy for optimization of the anaerobic digestion treatment, was presented for each country, together with advanced biorefinery approaches to wastewater treatment and resource recovery.
The Effects of the Management Strategies on Spruce Bark Beetles Populations (Ips typographus and Pityogenes chalcographus), in Apuseni Natural Park, Romania
Authors: Fora Ciprian George , Balog Adalbert
Published: June 2021

The population densities of I. typographus and P. chalcographus inside the Carpathian Mountains increasing mostly because of the non-synchronized and divers management strategies. The growing loss of trees from one year to another indicates assessment to determine the influence of the current management practices (or the absence of such) on bark beetle densities. A comprehensive tree-year assessment were made inside the Apuseni Natural Park, with a surface of 75,784 ha, to assess the population density of bark beetles. High abundance of both species were detected from one year to another, both in managed and unmanaged forests, the latter explained by the presence of scattered wind falling trees which represent favorable places for oviposition. General linear modelling revealed that the effect of environmental variables (forest mean age, forest density, altitude and slope) on I. typographus density were only significant under management systems, and only forest age has significantly negative effect on bark beetles densities. Overall, we conclude that there is little difference in population between non-intervention and intervention areas and even over a relatively short period of time (2011–2013), the population of both species expanded, and new uninfected habitats were infected both in unmanaged and managed forests, therefore a synchronized management system has to be developed. Climate variables as temperature and precipitations has more significant effects on population density than management.
From Rigidity to Exuberance: Evolution of News on Online Newspaper Homepages
Authors: Peña-Fernández Simón , Casado-del-Río Miguel Ángel , García-González Daniel
Published: June 2021

Since their emergence in the mid-90s, online media have evolved from simple digital editions that merely served to dump content from print newspapers, to sophisticated multi-format products with multimedia and interactive features. In order to discover their visual evolution, this article conducts a longitudinal study of the design of online media by analyzing the front pages of five general-information Spanish newspapers (elpais.com, elmundo.es, abc.es, lavanguardia.com, and elperiodico.com) over the past 25 years (1996–2020). Moreover, some of their current features are listed. To this end, six in-depth interviews were conducted with managers of different online media outlets. The results indicate that the media analysed have evolved from a static, rigid format, to a dynamic, mobile, and multi-format model. Regarding the language used, along with increased multimedia and interactive possibilities, Spanish online media currently display a balance between text and images on their front pages. Lastly, audience information consumption habits, largely superficial and sporadic, and the increasing technification and speed of production processes, means that news media have lost in terms of the design part of the individual personality they had in their print editions. However, they maintain their index-type front pages as one of their most characteristic elements, which are very vertical and highly saturated.
High Hydrostatic Pressure Treatment Ensures the Microbiological Safety of Human Milk Including Bacillus cereus and Preservation of Bioactive Proteins Including Lipase and Immuno-Proteins: A Narrative Review
Authors: Billeaud Claude
Published: June 2021

Breast milk is the nutritional reference for the child and especially for the preterm infant. Breast milk is better than donated breast milk (DHM), but if breast milk is not available, DHM is distributed by the Human Milk Bank (HMB). Raw Human Milk is better than HMB milk, but it may contain dangerous germs, so it is usually milk pasteurized by a Holder treatment (62.5 °C 30 min). However, Holder does not destroy all germs, and in particular, in 7% to 14%, the spores of Bacillus cereus are found, and it also destroys the microbiota, lipase BSSL and immune proteins. Another technique, High-Temperature Short Time (HTST 72 °C, 5–15 s), has been tried, which is imperfect, does not destroy Bacillus cereus, but degrades the lipase and partially the immune proteins. Therefore, techniques that do not treat by temperature have been proposed. For more than 25 years, high hydrostatic pressure has been tried with pressures from 100 to 800 MPa. Pressures above 400 MPa can alter the immune proteins without destroying the Bacillus cereus. We propose a High Hydrostatic Pressure (HHP) with four pressure cycles ranging from 50–150 MPa to promote Bacillus cereus germination and a 350 MPa Pressure that destroys 106 Bacillus cereus and retains 80–100% of lipase, lysozyme, lactoferrin and 64% of IgAs. Other HHP techniques are being tested. We propose a literature review of these techniques.
Digested Civet Coffee Beans (Kopi Luwak)—An Unfortunate Trend in Specialty Coffee Caused by Mislabeling of Coffea liberica?
Authors: Lachenmeier Dirk W. , Schwarz Steffen
Published: June 2021

In the context of animal protection, the trend of digested coffees such as Kopi Luwak produced by civet cats in captivity should not be endorsed. Previous studies on such coffees may have been flawed by sample selection and misclassification. As wild civets may prefer Coffea liberica beans, due to their higher sugar content, the chemical differences may be caused by the Coffea species difference combined with a careful selection of ripe, defect-free cherries by the animals, rather than changes caused by digestion. This may also explain the observed differences between Kopi Luwak from wild civets (mainly C. liberica) compared to the one from animals in captivity (typically fed with C. arabica and/or C. canephora).
Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (HTR1B, HTR1E, and HTR1F) in Chickens
Authors: Sun Caiyun , Qiu Yang , Ren Qin , Zhang Xiao , Cao Baolong , Zou Yi , Li Juan , Zhang Jiannan , Wang Yajun
Published: June 2021

The serotonin (5-hydroxytryptamine, 5-HT) signaling system is involved in a variety of physiological functions, including the control of cognition, reward, learning, memory, and vasoconstriction in vertebrates. Contrary to the extensive studies in the mammalian system, little is known about the molecular characteristics of the avian serotonin signaling network. In this study, we cloned and characterized the full-length cDNA of three serotonin receptor genes (HTR1B, HTR1E and HTR1F) in chicken pituitaries. Synteny analyses indicated that HTR1B, HTR1E and HTR1F were highly conserved across vertebrates. Cell-based luciferase reporter assays showed that the three chicken HTRs were functional, capable of binding their natural ligands (5-HT) or selective agonists (CP94253, BRL54443, and LY344864) and inhibiting intracellular cAMP production in a dose-dependent manner. Moreover, activation of these receptors could stimulate the MAPK/ERK signaling cascade. Quantitative real-time PCR analyses revealed that HTR1B, HTR1E and HTR1F were primarily expressed in various brain regions and the pituitary. In cultured chicken pituitary cells, we found that LY344864 could significantly inhibit the secretion of PRL stimulated by vasoactive intestinal peptide (VIP) or forskolin, revealing that HTR1F might be involved in the release of prolactin in chicken. Our findings provide insights into the molecular mechanism and facilitate a better understanding of the serotonergic modulation via HTR1B, HTR1E and HTR1F in avian species.
Metaproteomics to Decipher CF Host-Microbiota Interactions: Overview, Challenges and Future Perspectives
Authors: Hardouin Pauline , Chiron Raphael , Marchandin Hélène , Armengaud Jean , Grenga Lucia
Published: June 2021

Cystic fibrosis (CF) is a hereditary disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, triggering dysfunction of the anion channel in several organs including the lung and gut. The main cause of morbidity and mortality is chronic infection. The microbiota is now included among the additional factors that could contribute to the exacerbation of patient symptoms, to treatment outcome, and more generally to the phenotypic variability observed in CF patients. In recent years, various omics tools have started to shed new light on microbial communities associated with CF and host–microbiota interactions. In this context, proteomics targets the key effectors of the responses from organisms, and thus their phenotypes. Recent advances are promising in terms of gaining insights into the CF microbiota and its relation with the host. This review provides an overview of the contributions made by proteomics and metaproteomics to our knowledge of the complex host–microbiota partnership in CF. Considering the strengths and weaknesses of proteomics-based approaches in profiling the microbiota in the context of other diseases, we illustrate their potential and discuss possible strategies to overcome their limitations in monitoring both the respiratory and intestinal microbiota in sample from patients with CF.
Impact of Alzheimer’s Dementia on Caregivers and Quality Improvement through Art and Music Therapy
Authors: Popa Laura-Cristina , Manea Mihnea Costin , Velcea Diana , Șalapa Ion , Manea Mirela , Ciobanu Adela Magdalena
Published: June 2021

Dementia is a general term for a series of medical conditions that affect the brain and evolve progressively. According to the literature, there are over 200 subtypes and causes of dementia, with Alzheimer’s disease (AD) being the most common in elderly people. AD is an irreversible progressive neurodegenerative condition that leads to a decline in mental function, enough to disrupt daily life. Thinking skills slowly deteriorate, which, in advanced stages, makes it impossible to perform simple tasks. Besides the change in the quality of life of AD patients and their families, there is a considerable alteration in the quality of life of their caregivers, whose health can be negatively affected by the development of mental and somatic disorders. This article reviews the literature in order to reveal the benefits of applying non-pharmacological interventions such as music and art therapy to improve quality of life. This article also aims to shed light on the impact of this disease on the caregiver’s life. Music and art therapy have produced reliable results in the treatment of patients with AD, and the best effects are related to increased socialization and the maintenance of social status.
Musculoskeletal Changes in Hemophilia Patients Subsequent to COVID−19 Lockdown
Authors: Cuesta-Barriuso Rubén , Meroño-Gallut Javier , Pérez-Llanes Raúl , Ucero-Lozano Roberto
Published: June 2021

(1) Background. The lockdown period due to the COVID−19 pandemic has drastically decreased levels of physical activity in the population. Hemophilia is characterized by hemarthrosis that leads to chronic, progressive and degenerative joint deterioration. (2) Methods. This observational study recruited 27 patients with hemophilia and arthropathy. Knee, ankle and elbow joints were assessed. The frequency of clinical hemarthrosis, pain intensity, pressure pain threshold, and joint ROM were evaluated. (3) Results. Following lockdown, a significant deterioration of joint condition, perceived joint pain and range of motion was noted in all joints. There were no changes in the frequency of knee hemarthrosis, while the frequency of ankle hemarthrosis significantly reduced. However, the frequency of elbow hemarthrosis increased. Depending on the degree of hemophilia severity, there were changes in pressure pain threshold in the elbow and in pain intensity and range of motion of the ankle joint. According to the type of treatment, i.e., prophylaxis vs. on-demand treatment, there were differences in the joint condition in elbows and the plantar flexion movement of the ankle. There were no differences in the knee joint based on the severity of the disease, the type of treatment or the development of inhibitors (4). Conclusions. Because of the COVID−19 lockdown, the musculoskeletal status of patients with hemophilia deteriorated. Joint condition, perceived pain, and range of motion were significantly affected. The frequency of clinical hemarthrosis did not increase during this period. A more active therapeutic model could prevent rapid deterioration in patients with hemophilic arthropathy during prolonged sedentary periods.
Prevalence, Demographic, and Clinical Correlates of Likely PTSD in Subscribers of Text4Hope during the COVID-19 Pandemic
Authors: Shalaby Reham , Adu Medard K. , Andreychuk Taelina , Eboreime Ejemai , Gusnowski April , Vuong Wesley , Surood Shireen , Greenshaw Andrew J. , Agyapong Vincent I. O.
Published: June 2021

Background: During the COVID-19 pandemic, people may experience increased risk of adverse mental health, particularly post-traumatic stress disorder (PTSD). Methods: A survey measured stress, anxiety, depression, and PTSD symptoms in Text4Hope subscribers using the Perceived Stress Scale, Generalized Anxiety Disorder 7-Item Scale, Patient Health Questionnaire-9, and PTSD Checklist for DSM-5 Part 3, respectively. A Chi-square test and multivariate logistic regression were employed. Results: Most respondents were 41–60 years old (49.5%), Caucasian (83.3%), with post-secondary education (92.1%), employed (70.3%), married/cohabiting/partnered (64.9%), and homeowners (71.7%). Likely PTSD was reported in 46.8% of the respondents. Those who were afraid to contract the coronavirus had a history of depression before the pandemic, and those who received counselling during the pandemic exhibited a high prevalence of likely PTSD (OR (1.7 to 2.2)). Significant lower odds of likely PTSD were observed among subscribers who received absolute support from family/friends. Conclusions: This paper presents findings on the prevalence of likely PTSD and identified vulnerable groups during the COVID-19 pandemic. Our results support the proposal that public health advice should incorporate mental health wellness campaigns aiming to reduce the psychological impact of pandemics.
Using Machine Learning Algorithms to Develop a Clinical Decision-Making Tool for COVID-19 Inpatients
Authors: Vepa Abhinav , Saleem Amer , Rakhshan Kambiz , Daneshkhah Alireza , Sedighi Tabassom , Shohaimi Shamarina , Omar Amr , Salari Nader , Chatrabgoun Omid , Dharmaraj Diana , Sami Junaid , Parekh Shital , Ibrahim Mohamed , Raza Mohammed , Kapila Poonam , Chakrabarti Prithwiraj
Published: June 2021

Background: Within the UK, COVID-19 has contributed towards over 103,000 deaths. Although multiple risk factors for COVID-19 have been identified, using this data to improve clinical care has proven challenging. The main aim of this study is to develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, thus enabling risk-stratification and earlier clinical decision-making. Methods: Anonymised data consisting of 44 independent predictor variables from 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case–control analysis. Primary outcomes included inpatient mortality, required ventilatory support, and duration of inpatient treatment. Pulmonary embolism sequala was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were then learned and constructed using Bayesian networks. Results: The proposed probabilistic models were able to predict, using feature selected risk factors, the probability of the mentioned outcomes. Overall, our findings demonstrate reliable, multivariable, quantitative predictive models for four outcomes, which utilise readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as risk stratification and clinical decision-making tools.
The Perception of Primary School Teachers Regarding the Pharmacotherapy of Attention Deficit Hyperactivity Disorder
Authors: Gregório João , Ferreira Raquel , Fernandes Ana Sofia
Published: June 2021

Attention Deficit Hyperactivity Disorder (ADHD) is raising concerns across health systems, affecting about 5% of the school-age population. Therapy usually involves psychostimulants, which are prone to adverse drug reactions (ADRs). Teachers have many contact hours with children and can easily detect behavioral changes upon the beginning of medication. However, few studies have focused on the role of teachers in the management of ADHD children and detection of ADRs. The present work aimed to characterize the perception of primary school teachers regarding the impact of ADHD therapeutics. A questionnaire was constructed focused on teachers’ training regarding ADHD and its therapy; experience with students with ADHD; changes upon beginning of medication; and observation of ADRs. A total of 107 completed questionnaires were obtained. The results indicate that more than 40% of the inquired teachers have received training in ADHD, but in most cases, the theme of therapeutics was absent from that training. The vast majority of teachers (91.6%) have had students with ADHD and observed mood alterations associated with medications. More than 60% of the teachers answered that they are aware of the ADRs and of these, 24% have already detected them in their students. The teachers reported the observed ADRs to parents in 93% of the cases and to doctors in 28% of the cases. In conclusion, the results show the need to reinforce teachers’ training in ADHD and its therapeutics.
What Is Commensality? A Critical Discussion of an Expanding Research Field
Authors: Jönsson Håkan , Michaud Maxime , Neuman Nicklas
Published: June 2021

Commensality (the act of eating together) is studied in a range of disciplines and often considered important for social communion, order, health and well-being, while simultaneously being understood as in decline (especially the family meal). However, such claims are also contested in various ways. In this paper, we discuss the expanding field of commensality research and critically reflect on the debates surrounding its social functions, including its role in public health. We illuminate the deep social and cultural significance of commensality, through time and space, and conclude that whether or not commensality is the preferred social form of eating for any given individual, it is difficult to escape its sociocultural desirability and idealization. As a cross-cultural phenomenon in both past, present, and future, we suggest that commensality deserves further research. This includes commensality as a research topic in itself and as an entry point to unveil different dimensions of social relations between people, as well as interactions between humans and material objects.