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Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

Fraudulent papers from paper mills are a serious threat to the entire scientific community. Naunyn-Schmiedeberg’s Archives of Pharmacology has become the target of a massive attack of fraudulent papers originating from paper mills. This editorial highlights 20 important features we observed with paper mills and explains how the journal is responding to this serious threat to restore the integrity of science. Hopefully, this editorial is also helpful for editors of other scientific journals.

Continuous manufacturing is an indicator of a maturing industry, as can be seen by the example of the petrochemical industry. Patent expiry promotes a price competition between manufacturing companies, and more efficient and cheaper processes are needed to achieve lower production costs. Over the last decade, continuous biomanufacturing has had significant breakthroughs, with regulatory agencies encouraging the industry to implement this processing mode. Process development is resource and time consuming and, although it is increasingly becoming less expensive and faster through high‐throughput process development (HTPD) implementation, reliable HTPD technology for integrated and continuous biomanufacturing is still lacking and is considered to be an emerging field. Therefore, this paper aims to illustrate the major gaps in HTPD and to discuss the major needs and possible solutions to achieve an end‐to‐end Integrated Continuous Biomanufacturing, as discussed in the context of the 2019 Integrated Continuous Biomanufacturing conference. The current HTPD state‐of‐the‐art for several unit operations is discussed, as well as the emerging technologies which will expedite a shift to continuous biomanufacturing., With an ever‐growing interest in shifting to integrated continuous biomanufacturing (ICB), the major gaps and state‐of‐the‐art perceived by academia and industry members in high‐throughput process development (HTPD) technologies for the development and implementation of this type of operation (ICB) are debated in this paper, with a special focus on the HT tools for the different unit operations in a typical biopharmaceutical process. The current needs in ICB and possible solutions to fulfill these needs are also highlighted

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.

Allergo journal international 30(5), 155-168 (2021). doi:10.1007/s40629-021-00178-2, Published by Urban & Vogel, München

Up to 90% of the human genome is transcribed into Long-noncoding RNAs (lncRNAs) that longer than 200 nucleotides but do not code for proteins. LncRNAs play a vital role in a broad range of biological process, it’s dysregulations and mutations are linked to the development and progression of various complex human diseases. Given the dramatic changes and growing scientific outputs in lncRNAs field, using a quantitative measurement to analyze and characterize the existing studies has become imperative.Bibliometric analysis is a widely used tool to assess the academic influence of a publication or a country in a specific field. However, a bibliometric analysis of the top 100 most-cited papers in lncRNAs area has not been conducted. Thus, we executed a bibliometric study to identify the authors, journals, countries and institutions that contributed most to the top 100 lncRNAs list, characterize the key words and focus of top 100 most-cited papers, and detect the factors related to their successful citation. This study provides a comprehensive list of the most influential papers on lncRNAs research and demonstrates the important advances in this field, which might be benefit to researchers in their paper publication and scientific cooperation.

BackgroundChronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. MethodsThe current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. ResultsBased on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. ConclusionIntranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.

Phenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Analyses of the molecular foundations of phenotypic plasticity are challenging, however, especially in the case of complex social phenotypes. Here we apply a machine learning approach to tackle this challenge by analyzing individual-level gene expression profiles of Polistes dominula paper wasps following the loss of a queen. We find that caste-associated gene expression profiles respond strongly to queen loss, and that this change is partly explained by attributes such as age but occurs even in individuals that appear phenotypically unaffected. These results demonstrate that large changes in gene expression may occur in the absence of outwardly detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic level but not at the levels of ovarian development or behavior., Connecting genotypes to complex social behaviour is challenging. Taylor et al. use machine learning to show a strong response of caste-associated gene expression to queen loss, wherein individual wasp’s expression profiles become intermediate between queen and worker states, even in the absence of behavioural changes.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Paper mulberry (Broussonetia papyrifera) is a perennial woody plant used as source material for Cai Lun paper making, in traditional Chinese medicine, and as livestock feed. To identify the presence of viruses in paper mulberry plants affected by a disease with leaf curl symptoms, high-throughput sequencing of total RNA was performed. Analysis of transcriptome libraries allowed the reconstruction of two geminivirus-like genomes. Rolling-circle amplification and PCR with back-to-back primers confirmed the presence of two geminiviruses with monopartite genomes in these plants, with the names paper mulberry leaf curl virus 1 and 2 (PMLCV-1 and PMLCV-2) proposed. The genomes of PMLCV-1 (3,056 nt) and PMLCV-2 (3,757 to 3,763 nt) encode six proteins, with the V4 protein of PMLCV-1 and the V3 proteins of both viruses having low similarities to any known protein in databases. Alternative splicing of an intron, akin to that of mastre-, becurto-, capula-, and grabloviruses, was identified by small RNA (sRNA)-seq and RNA-seq reads mapping to PMLCV-1 and PMLCV-2 antisense transcripts. Phylogenetic analyses and pairwise comparisons showed that PMLCV-1 and PMLCV-2 are most closely related to, but distinct from, two unassigned geminiviruses, citrus chlorotic dwarf associated virus and mulberry mosaic dwarf associated virus, suggesting that they are two new members of the family Geminiviridae. Field investigation confirmed the close association of the two viruses with leaf curl symptoms in paper mulberry plants and that coinfection can aggravate the symptoms.

The gut microbiota is recognized as having major impact in health and disease. Sample storage is an important aspect to obtain reliable results. Mostly recommended is immediate freezing, however, this is not always feasible. Faecal occult blood test (FOBT) papers are an appealing solution in such situations, and most studies find these to be applicable, showing no major changes within 7 days storage at room temperature (RT). As fieldwork often requires RT storage for longer periods, evaluation of this is warranted. We performed 16S rRNA gene sequencing of 19 paired faecal samples immediately frozen or kept five weeks and five months at RT on FOBT papers. Alpha-diversity evaluation revealed no effect of FOBT storage, and evaluation of beta-diversity showed that host explained 65% of community variation, while storage method explained 5%. Evaluation of community dispersion and the Firmicutes/Bacteroidetes ratio revealed a larger effect of storage time for fresh-frozen samples. Single taxa evaluation (order-to-genus level) showed significant alterations of four (of 37) genera after five weeks and five genera after five months. When comparing the two timepoints, alterations were only detectable for fresh-frozen samples. Our findings reveal that long term storage on FOBT papers is an applicable approach for microbiota research.

The main objective of this study is the evaluation of RPPW anaerobic digestion feasibility at laboratory scale under Mesophilic condition. The experiment is conducted using a two-stage biofilm digester of 5 L capacity with mobile support material. Anaerobic treatment of wastewater from recycled pulp and paper industry in Morocco was tested using a laboratory-scale anaerobic biofilm digester that operated under mesophilic conditions over a 70-day. Chemical oxygen demand (COD) efficiency, volatile and total solid (VS, TS) elimination of the substrate during the process were: 78%, 52% and 48% respectively. The system was stable throughout its operating cycle with an optimum pH (7.24), alkalinity (1750 mg CaCO3/L) and a volatile fatty acid value (760 mg/L). The experimental daily biogas production measured reaches a value of 5 L/day with a composition of 71% methane, 27.6% carbon dioxide, 0.2 oxygen and 7713 ppm of the H2S. The study results show that the anaerobic biofilm reactor is a suitable technique for recycled pulp and paper wastewater (RPPW) treatment. The reactor shows high performances in terms of process stability, removal efficiency (> 70%) and biogas production. Anaerobic digestion is an efficient waste treatment technology that uses natural anaerobic decomposition to reduce the volume of waste while producing biogas. However, research is needed to strengthen microbial metabolism, biochemistry and the functioning of the rector to improve biogas production. The RPPW AD experiment with biofilm digester technology was stable throughout the operation period. The digester knows an overloaded in the last phase of the experiment which leads to an inhibition of biogas production.

PTDC/EPH-PAT/0224/2014. POCI-01-0145-FEDER-PTDC/EPHPAT/3345/2014. The action of fungi on books, documents, maps, and works of art on paper can result in inestimable cultural losses. Plus, some of the fungi present in paper documents, surfaces and air from archives, libraries and museums are also a threat to human health. This work aims to review the literature on the most important and frequent microfungal populations found in paper-based collections all over the world, and correlate these data with human health risks. A total of 71 studies, dating between 1997 and 2018 were reviewed and organized. From 27 different countries, 207 fungal genera and 580 species were reported. Chaetomium sp. and Fusarium sp. were found to be special contaminants in the air of archives and have been associated with paper biodeterioration. The most common fungi reported (e.g. Penicillium, Aspergillus, and Alternaria species) have an impact on paper conservation but can also cause adverse human health effects. The most frequent fungal species retrieved from discoloured paper materials are discussed in greater detail. Considerations on methods of identification and quantification of fungal contamination are also presented. Finally, the authors acknowledge an urgent need for standardizing research in this area and further studies are proposed. publishersversion published

Background: Asia Pacific Initiative on Reproduction (ASPIRE) aims to improve knowledge and awareness of Assisted Reproductive Technology (ART) and infertility-related services, with the aim of improving the quality of patient care. Methods: A survey was developed and responded by a group of 10 ASPIRE board members to gather in-depth information about current practices, recommendations, and perceptions about SARS-CoV-2 and ART. The collected data were summarized and individual responses pooled among questions requiring voting. The overall rates were computed by response category. The group discussed the summary evidence, until a consensus was reached concerning a series of recommendation on how to make decisions concerning ART service provision during the current (and any future) pandemic. A two-tier recommendation was developed based on agreement rate and implementation priority. Tier 1 comprises recommendations in which the rate of “absolutely agree” responses were [Formula: see text]60%, whereas tier 2 refers to recommendations in which the rate of “absolutely agree” plus “agree” was >60%, but the rate of “absolutely agree” was [Formula: see text]50%. Results: The survey was responded by all participants between July 24 and July 30, 2020. Nine tier 1 and five tier 2 recommendations are provided concerning prevention, testing, personal protective equipment, informed consent, and quality management. The former indicates the situations in which most individuals should receive the intervention/procedure, whereas the latter relates to those that may be suitable for individual clinics and patients. Conclusions: This document provides the ASPIRE viewpoint on better managing infertile patients seeking ART during the COVID-19 pandemic. This expert opinion guide aims to help both competent authorities and healthcare providers to deliver quality and safe ART.

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field. ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsråd, Kreftforeningen and Helse Sør-Øst RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05.

Why workers forfeit direct reproduction is a crucial question in eusocial evolution. Worker reproduction provides an excellent opportunity to understand the mechanism of kin conflict resolution between the queen and workers. We evaluated behavioral and physiological differences among females in the paper wasp Polistes chinensis antennalis to examine why some workers reproduce under queenright conditions. Reproductive workers were old and foraged less early in the season; their cuticular hydrocarbon (CHC) profiles overlapped with those of queens but were significantly different. The distinct CHC profile of the eggs of the queen likely represented a cue for policing against those by workers. Juvenile hormone (JH) and dopamine seemed to be associated with gonadotropic function, and the JH level of reproductive workers was similar to that of the queen. The high JH level of reproductive workers likely facilitated their reproduction even under queenright conditions. Gene expression levels of the queen and reproductive workers differed only in vitellogenin. These results suggest that worker reproduction is facilitated by an increase in JH level; however, CHC is not a fertility-linked signal, but a queen-linked signal; consequently, reproductive workers without a queen-linked signal might be allowed to stay within the colony.

The term sarcopenia was introduced in 1988. The original definition was a “muscle loss” of the appendicular muscle mass in the older people as measured by dual energy x‐ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC‐F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease‐related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age‐related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age‐related and disease‐related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

This is a pre-copyedited, author-produced version of an article accepted for publication in Cardiovascular Research (CVR) following peer review. The version of record Perrino, Ferdinandy, Bøtker, Brundel, Collins, Davidson, Den Ruijter, Engel, Gerdts, Girao, Gyöngyösi, Hausenloy, Lecour, Madonna, Marber, Murphy, Pesce, Regitz-Zagrosek, Sluijter, Steffens, Gollmann-Tepeköylü, Van Laake, Van Linthout, Schulz, Ytrehus. Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: Position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research (CVR). 2021;117(2):367-385, is available online at: https://doi.org/10.1093/cvr/cvaa155. Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

The health risks associated with acute and prolonged exposure to estrogen receptor (ER) modulators has led to a concerted effort to identify and prioritize potential disruptors present in the environment. ER agonists and antagonists are identified with end-point assays, quantifying changes in cellular proliferation or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+) cells upon exposure. While these monolayer cultures can be prepared, dosed, and analyzed in a highly parallelized manner, they are unable to predict the potencies of ER modulators in vivo accurately. Physiologically relevant model systems that better predict tissue- or organ-level responses are needed. To address this need, we describe here a screening platform capable of quantitatively assessing ER modulators in 96 chemically isolated 3D cultures. These cultures are supported in wax-patterned paper scaffolds whose design has improved performance and throughput over previously described paper-based setups. To highlight the potential of paper-based cultures for toxicity screens, we measured the potency of known ER modulators with a luciferase-based reporter assay. We also quantified the proliferation and invasion of two ER+ cell lines in the presence of estradiol. Despite the inability of the current setup to better predict in vivo potencies of ER modulators than monolayer cultures, the results demonstrate the potential of this platform to support increasingly complex and physiologically relevant tissue-like structures for environmental chemical risk assessment.

Synthetic organic compounds (SOCs) are reported as xenobiotics compounds contaminating the environment from various sources including waste from the pulp and paper industries: Since the demand and production of paper is growing increasingly, the release of paper and pulp industrial waste consisting of SOCs is also increasing the SOCs’ pollution in natural reservoirs to create environmental pollution. In pulp and paper industries, the SOCs viz. phenol compounds, furans, dioxins, benzene compounds etc. are produced during bleaching phase of pulp treatment and they are principal components of industrial discharge. This review gives an overview of various biotechnological interventions for paper mill waste effluent management and elimination strategies. Further, the review also gives the insight overview of various ways to restrict SOCs release in natural reservoirs, its limitations and integrated approaches for SOCs bioremediation using engineered microbial approaches. Furthermore, it gives a brief overview of the sustainable remediation of SOCs via genetically modified biological agents, including bioengineering system innovation at industry level before waste discharge.

In this study, polyacrylic acid modified filter paper (FP/PAA) was synthesized by in-situ polymerization of acrylic acid, which was used as a matrix to chelate nano-scale zero valent iron (nZVI). The loading content of nZVI in the filter paper reached 24.8%. The fabricated composite FP/PAA/nZVI was characterized by SEM, FT-IR and TGA respectively. Moreover, it was used for the removal of methyl blue and methylene blue as model anionic and cationic dyes. The effect of initial dye concentration on decolorization efficiency was investigated. The results showed that FP/PAA/nZVI enhanced the removal of dye from the simulated dye wastewater and the decolorization efficiency exceeded 95% for the dye solutions lower than 20 mg/L. More importantly, the filter paper supported nZVI realized the continuous treatment of simulated dye wastewater by a simple filtration process. This study hopes to serve as a basis for the application of nZVI in textile wastewater treatment.

Metal oxides based graphene nanocomposites were used for ammonia vapour sensing. The self-assembly process was adopted to prepare freestanding flexible pure rGO, CeO2-rGO and SnO2-rGO composite papers. The structural studies confirmed the formation of rGO composite papers. The ammonia vapor sensing was demonstrated using an impedance analyzer at different humidity levels as well as concentration. The CeO2-rGO composite paper achieved a sensitivity of 51.70 ± 1.2%, which was higher than that of pure rGO and SnO2-rGO composite paper. Both the surfaces (top and bottom) of the papers are active in efficiently sensing ammonia, which makes the present work unique. The results reveal that metal oxide/rGO papers can be effectively utilized in real time sensor application.

Thermophilic methane fermentation was a valid approach for handling the stillage eluted from ethanol fermentation of waste paper and kitchen waste. The wide organic loading rate (OLR) range (2-14 g VTS/(L d)) for stable performance and relatively high energy recovery efficiency (79.0%) were achieved, and OLR of 8 g VTS/(L d) was optimum for achievement of highest biogas evolution and VTS removal efficiency. Microbial community analysis revealed that hydrolysis of cellulose was the critical step for methane production from the stillage.

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. © Published on behalf of the European Society of Cardiology. All rights reserved.

Many paper products are coated with plastic to improve their quality and stability. However, this limits recycling and recovery options and the plastic-coated waste paper is mostly disposed in landfills. Such practices are uneconomical and contrary to sustainable waste management. In this work enzymes of the white rot fungus Dichomitus squalens were investigated for possible delamination of plastic-coated waste paper. Enzymes were found capable to release the polyethylene foil from plastic-coated paper which resulted in 88.6-91.5% mass loss. The delamination rate, however, was depended on the ratio between plastic-coated paper and volume of enzyme filtrate. Results of a consequent experiment showed that enzymes are also efficient when plastic-coated paper is treated in a sequencing batch reactor resulting in 88.2-90.6% mass loss. The system was fully functional up to the 5th cycle; afterwards, the delamination rate reduced due to high thickness of the waste paper sludge. The enzyme activity, however, was still very high; with the laccase activity at the end of the experiment above 900 U/L and manganese peroxidase above 250 U/L. Our results demonstrated, that plastic-coated waste paper has the potential to be efficiently recovered instead of being disposed in landfills.

Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions. ispartof: CARDIOVASCULAR RESEARCH vol:117 issue:1 pages:43-59 ispartof: location:England status: published

In Italy, recent legislation (Law No. 10/2020) has tuned regulations concerning the donation of one's postmortem body and tissues for study, training, and scientific research purposes. This study discusses several specific issues to optimise the applicability and effectiveness of such an important, novel regulatory setting. Some of these unsolved issues may involve the grantees of teaching and training activities, the role of academic anatomical institutes, the role of family members in the donation process, the universal time limit indicated for any donation, the handling of corpses, and the limited body donation and its subordination to the donation of organs and tissues. Critical issues arise concerning the learners, the type of training and teaching activities that can be planned, the position of academic anatomy institutes, the role of family members in the donation process, the time frame of the donation process, the eligibility of partial donation, or the simultaneous donation of organs and tissues to patients awaiting transplantation. In particular, a universal time limit for donations (i.e., one year) makes it impossible to plan the long-term use of specific body parts, which could be effectively preserved for the advanced teaching and training of medical students and surgeons. The abovementioned conditions lead to the limited use of corpses, thus resulting in the inefficiency of the whole system of body donation. Overall, the donors' scope for the donation of their body could be best honoured by a more flexible and tuneable approach that can be used on a case-by-case basis. Furthermore, it is deemed necessary to closely monitor the events scheduled for corpses in public nonacademic institutions or private enterprises. This paper presents useful insights from Italian anatomists with the hope of providing inspiration for drafting the regulations. In conclusion, this paper focuses on the critical issues derived from the recently introduced Italian law on the donation and use of the body after death and provides suggestions to lawmakers for future implementations.

Paper production generates large quantities of a solid waste known as papermaking sludge (PS), which needs to be handled properly for final disposal. The high amount of this byproduct creates expensive economical costs and induces environmental and ecological risks. Therefore, it is necessary to search uses for PS, in order to reduce the negative environmental impact and to generate a more valuable byproduct. Due to the cellulolytic composition of PS, this work evaluated a solid state fermentation process using it as substrate to obtain spores of the fungus Trichoderma asperellum. Optimal conditions to obtain T. asperellum spores were: 60% water content, 3% (w/w) salts (Nutrisol P® and Nutrisol K®), inoculum concentration at 1x105 spores/g, and pasteurized or sterilized PS. Under these conditions it was possible to obtain 2.37x109 spores/g. T. asperellum spores applied directly to pepper (Capsicum anuum) seeds without PS increased significantly seedling dry mass in greenhouse assays. This work suggests an alternative, economic and abundant substrate for production of T. asperellum spores.

Oteros, Jose/0000-0002-9369-8633; Fonseca, Joao Almeida/0000-0002-0887-8796; Alvarez-Perea, Alberto/0000-0001-7417-7309; Oteros, Jose/0000-0002-9369-8633; Gevaert, Philippe/0000-0002-1629-8468; Antolin, Dario/0000-0001-5699-4022; Apfelbacher, Christian/0000-0003-3805-8219; Buters, Jeroen/0000-0003-3581-5472; Berger, Uwe E./0000-0002-9265-2131; Blank, Simon/0000-0002-5649-1078; Cardona, Victoria/0000-0003-2197-9767; Dramburg, Stephanie/0000-0002-9303-3260 WOS: 000486665800001 PubMed: 31230373 Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

Background In Software Engineering (SE), conference publications have high importance both in effective communication and in academic careers. Researchers actively discuss how a paper should be organized to be accepted in mainstream conferences. Aiming This work tackles the problem of generalizing and characterizing the type of papers accepted at SE conferences. Method The paper offers a new perspective in the analysis of SE literature: a categorization scheme for SE papers is obtained by merging, extending and revising related proposals from a few existing studies. The categorization scheme is used to classify the papers accepted at three top-tier SE conferences during five years (2012–2016). Results While a broader experience is certainly needed for validation and fine-tuning, preliminary outcomes can be observed relative to what problems and topics are addressed, what types of contributions are presented and how they are validated. Conclusions The results provide insights to paper writers, paper reviewers and conference organizers in focusing their future efforts, without any intent to provide judgments or authoritative guidelines.

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), “lower is better for longer”, and the recent data have strongly emphasized the need of also “the earlier the better”. In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual’s calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an ‘Extremely High Risk’ group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardio-vascular risk in these patients.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.

We present a rapid (

Reject fines, a waste stream of short lignocellulosic fibers produced from paper linerboard recycling, are a cellulose-rich paper mill byproduct that can be hydrolyzed enzymatically into fermentable sugars. In this study, the use of hydrolyzed reject fines as a carbon source for bacterial biosynthesis of poly(R-3-hydroxyalkanoate) (PHA) and poly(γ-glutamic acid) (PGA) was investigated. Recombinant Escherichia coli harboring PHA biosynthesis genes were cultivated with purified sugars or crude hydrolysate to produce both poly(R-3-hydroxybutyrate) (PHB) homopolymer and medium chain length-containing copolymer (PHB-co-MCL). Wild-type Bacillus licheniformis WX-02 were cultivated with crude hydrolysate to produce PGA. Both PHB and short chain-length-co-medium chain-length (SCL-co-MCL) PHA yields from crude hydrolysate were a 2-fold improvement over purified sugars, and the MCL monomer fraction was decreased slightly in copolymers produced from crude hydrolysate. PGA yield from crude hydrolysate was similarly increased 2-fold. The results suggest that sugars from hydrolyzed reject fines are a viable carbon source for PHA and PGA biosynthesis. The use of crude hydrolysate is not only possible but beneficial for biopolymer production, eliminating the need for costly separation and purification techniques. This study demonstrates the potential to divert a lignocellulosic waste stream into valuable biomaterials, mitigating the environmental impacts of solid waste disposal.

Civil Construction Industry impacts significantly the environment, being one of the most critic factors related to elevated production of Civil Construction Residue (CCR). Among CCR produced, the Kraft paper package acquires notoriety, due their large use on material packaging, such as Portland cement and lime, then, present a high production rate and offer contamination potential, lack of collection logistics and nearly any reuse. In this scenario, the study and development of alternative constructive materials which applies the sustainability concept and CCR recycling have acquired great relevance in the sector. It is highlighted the residue incorporation on masonry soil-cement blocks, due its block are not submitted to the sintering process. Then, the present research intend to study adobe blocks mechanical properties based on soil-cement reinforced with cellulose fibers obtained from Kraft paper recycling. The bricks were confectioned with 7% Portland cement content and with 0%, 8%, 10% e 12% Kraft paper fiber addition, being submitted to compressive strength test, water absorption test, durability test with wetting and drying and retraction analysis. It was verified the confectioned composites presented as a viable and interesting alternative on technical and environment range. All studied researches presented null retraction and compressive strength increase on cracked state, toughness increase and good performance about durability.

Aim: Since 2014, enzyme replacement therapy (ERT) has been available for treatment of Morquio A syndrome. During clinical trials, urinary keratan sulfate (KS) has been a useful biomarker and showed a marked decrease in patients on ERT, demonstrating therapy efficacy. Unfortunately, quantitative urinary KS testing is not widely available in biochemical genetics laboratories for efficient monitoring and follow-up of treated patients. Materials & methods: A tandem mass spectrometry methodology was devised to analyze KS disaccharides and creatinine in urine specimens collected on filter paper. Results: All Morquio A patients presented abnormal results pretreatment compared with reference values. Conclusion: This collection procedure can be performed by patients at home and filter papers sent by regular mail to a specialized laboratory, facilitating follow-up of patients.

Introduction: Brain Ichemic-Reperfusion Injury (IRI) activates different pathophysiological processes. It also changes physiological parameters such as Blood Glucose (BG) level. An increase in BG after stroke is associated with poor clinical outcomes. Erythropoietin has been shown to be effective on both reducing inflammation and BG level. Therefore, in this study the erythropoietin pretreatment effect on BG and its relationship with inflammatory markers after brain IRI was investigated. Methods: Thirty adult male Wistar rats were randomly divided into 5 groups: sham, control and 3 pretreatment groups: single dose, double dose, and triple dose that received 1000 U/kg of erythropoietin before stroke induction in different times intraperitoneally. A rat model of IRI was established by Middle Cerebral Artery Occlusion (MCAO) for 60 minutes. Infarct volume, neurological defects, Interleukin-1α (IL-1α) and IL-6 serum levels were evaluated 24 hours after reperfusion. Also BG was measured after 1, 6, and 24 hours. Results: Single dose of erythropoietin significantly decreased infarct volume and improved neurological defects which was associated with decreased serum level of IL-1α and IL-6 but higher doses of erythropoietin administration had adverse effects on histological, neurological, and inflammatory results. In addition, erythropoietin significantly increased BG in a dose- dependent manner. Conclusion: Erythropoietin could reduce brain IRI by reducing inflammation and BG stabilization. The results of the present study demonstrated a relationship between inflammatory factors and hyperglycemia after IRI and suggested that erythropoietin may be useful for preventing brain IRI, but its higher doses should be used with caution due to possible side effects.

Although nucleic acid amplification test (NAT) is widely used for pathogen detection, rapid NAT systems that do not require special and expensive instruments must be developed in order to enable point of care (POC)-NATs, which contribute to early initiation of treatment. As a POC-NAT system, Kaneka DNA chromatography chip (KDCC), developed using DNA tag-bound primer through modified substance, was shown to be suitable for POC testing, due to the rapid detection time, simple procedures, and low manufacturing costs. However, owing to some modifications in primer, the detection performance and amplification speed were shown to be reduced when using KDCC, counteracting the increased speed of detection. To solve these issues and improve the speed of this NAT system, we investigated a better modification substance for KDCC. Here, azobenzene-modified primers were shown to have the highest amplification speed and detection performance in KDCC, of all modifications tested in this study, showing 10-100-fold lower detection limit but maintaining the same reaction time. Additionally, rapid herpes simplex virus detection system with azobenzene modified primers was developed. We believed that this breakthrough will contribute toward enabling greater utilization of POC-NATs for medical care, especially in developing countries and clinics.

The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances.

Bisphenol A (BPA) was commonly used as color developer for thermal paper such as cash register receipts, labels or tickets. Therefore, thermal paper was considered by the European Food Safety Authority (EFSA) as the main source of human exposure to BPA beside epoxy based food contact materials. In this study, a German market analysis on the use of BPA and alternative color developers in thermal paper receipts is provided for the years 2015, 2016 and 2017.114 (2015), 98 (2016) and 99 (2017) samples were randomly collected and analyzed by HPLC-DAD. In summary, BPA was still the most frequently found color developer (48.2% in 2015, 46.9% in 2016 and 52.5% in 2017). The most commonly used alternative was the phenol-free substance Pergafast® 201 (34.2%, 33.7%, 40.4%). The bisphenol analogs bisphenol S (BPS; 11.4%, 9.2%, 6.1%) and D8 (6.1%, 7.1%, 1.0%) were less common. Another phenol-free substituent, a urea urethane compound (UU), was also detected (3.1% in 2016). Concentrations of color developers in thermal paper ranged from 1.4 to 32.4 mg/g (median values between 2.5 and 15.9 mg/g). Concentrations of BPA were found to be highest followed by BPS, UU, Pergafast® 201 and D8. In addition, two pharmacologically active substances, dapsone (6.0 mg/g) and tolbutamide (5.5 mg/g), were detected in a non-marketed thermal paper, that was supposed to use ascorbic acid as initial color developer. Different release experiments of the detected color developers were performed. Sensitizers 1,2-diphenoxy-ethane, 1-phenylmethoxy-naphthalene and diphenylsulfone, used frequently in the thermal paper processes, were quantified.

Scientific writing is an important skill in both academia and clinical practice. The skills for writing a strong scientific paper are necessary for researchers (comprising academic staff and health-care professionals). The process of a scientific research will be completed by reporting the obtained results in the form of a strong scholarly publication. Therefore, an insufficiency in scientific writing skills may lead to consequential rejections. This feature results in undesirable impact for their academic careers, promotions and credits. Although there are different types of papers, the original article is normally the outcome of experimental/epidemiological research. On the one hand, scientific writing is part of the curricula for many medical programs. On the other hand, not every physician may have adequate knowledge on formulating research results for publication adequately. Hence, the present review aimed to introduce the details of creating a strong original article for publication (especially for novice or early career researchers).

The paper concerns the current position of the Polish Society of Allergology Food Allergy Section on the diagnosis and management of food allergies. The aim of this position is to provide evidence-based recommendations on the diagnosis and management of patients with allergic hypersensitivity to foods. This position statement includes a systematic review of studies in three areas, namely, the epidemiology, diagnosis and management of food allergies. While taking into account the specific Polish setting, in this publication we also used the current European Academy of Allergy and Clinical Immunology (EAACI) position paper and other current position statements, including those of the United States National Institute of Allergy and Infectious Diseases (NIAID).

The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.

Abstract Mechanical stimuli play important roles on the growth, development, and behavior of tissue. A simple and novel paper-based in vitro tissue chip was developed that can deliver two types of mechanical stimuli—local compression and shear flow—in a programmed manner. Rat vascular endothelial cells (RVECs) were patterned on collagen-coated nitrocellulose paper to create a tissue chip. Localized compression and shear flow were introduced by simply tapping and bending the paper chip in a programmed manner, utilizing an inexpensive servo motor controlled by an Arduino microcontroller and powered by batteries. All electrical compartments and a paper-based tissue chip were enclosed in a single 3D-printed enclosure, allowing the whole device to be independently placed within an incubator. This simple device effectively simulated in vivo conditions and induced successful RVEC migration in as early as 5 h. The developed device provides an inexpensive and flexible alternative for delivering mechanical stimuli to other in vitro tissue models. Graphical abstract

To study the possible roles of type-2C protein phosphatases (PP2Cs) which have been confirmed to play roles in the response to diverse abiotic stresses in paper mulberry, we launched a series of genomic and functional studies of BpPP2Cs. Sixty-three PP2C proteins in paper mulberry (Broussonetia papyrifera) were classified into 13 clades. Four BpPP2Cs with kinase domains were verified to be highly conserved in organisms ranging from algae to dicots. Seven pairs of BpPP2C genes were found to be expanding, and 18 BpPP2C genes had orthologues in Arabidopsis. BpPP2Cs showed broad expression in different tissues; the expression levels of 18 BpPP2Cs were changed and the phosphorylation levels of seven BpPP2C proteins increased at low temperature. Cold-response elements were found in the promoter region of 31 BpPP2Cs. Finally, Bp01g0320 was found to act as a hub protein and Bp01g0512 and Bp09g1278 played key roles in the ABA-signaling pathway and MAPK cascades, respectively. These results suggest that the PP2C gene family of paper mulberry is evolutionarily conserved and participates the regulation of the response to cold stress, which will play a vital role in further research on phosphatases in paper mulberry.

Paper sludge is an attractive biomass feedstock for bioconversion to ethanol due to its low cost and the lack of pretreatment required for its bioprocessing. This study assessed the use of a recombinant cellulase cocktail (mono-components: S. cerevisiae-derived PcBGL1B (BGL), TeCel7A (CBHI), ClCel6A (CBHII) and TrCel5A (EGII) mono-component cellulase enzymes) for the efficient saccharification of softwood-derived paper sludge to produce fermentable sugars. The paper sludge mainly contained 74.3% moisture and 89.7% (per dry mass (DM)) glucan with a crystallinity index of 91.5%. The optimal protein ratio for paper sludge hydrolysis was observed at 9.4: 30.2: 30.2: 30.2% for BGL: CBHI: CBHII: EGII. At a protein loading of 7.5 mg/g DW paper sludge, the yield from hydrolysis was approximately 80%, based on glucan, with scanning electron microscopy micrographs indicating a significant alteration in the microfibril size (length reduced from &ge, 2 mm to 93 &micro, m) of the paper sludge. The paper sludge hydrolysis potential of the Opt CelMix (formulated cellulase cocktail) was similar to the commercial Cellic CTec2&reg, and Celluclast&reg, 1.5 L cellulase preparations and better than Viscozyme&reg, L. Low enzyme loadings (15 mg/g paper sludge) of the Opt CelMix and solid loadings ranging between 1 to 10% (w/v) rendered over 80% glucan conversion. The high glucose yields attained on the paper sludge by the low enzyme loading of the Opt CelMix demonstrated the value of enzyme cocktail optimisation on specific substrates for efficient cellulose conversion to fermentable sugars.

The current international pharmaceutical scenario encompasses several steps for drug production with complex and extremely long procedures. In the last few decades, scientific research has been trying to offer valid and reliable solutions to replace or support conventional techniques, in order to facilitate drug development procedures. These innovative approaches may have extremely positive effects in the production chain supplying fast and cost-effective quality and safety tests on active pharmaceutical ingredients and their excipients. In this context, the exploitation of electrochemical paper-based analytical devices (ePADs) is still in its infancy, but particularly promising for its fascinating properties in the detection of active pharmaceutical ingredients and excipients in tablets, capsules, suppositories, and injections, as well as for pharmacokinetic bioanalysis in real samples.