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Patients with the dual burden of chronic kidney disease (CKD) and cardiovascular disease (CVD) experience unacceptably high rates of morbidity and mortality, which also entail unfavorable effects on healthcare systems. Currently, concerted efforts to identify, prevent and treat CVD in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this position paper endorse the need for a dedicated interdisciplinary team of subspecialists in cardio-nephrology that manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for training programs, guidelines and best clinical practice models, and research funding from nephrology, cardiology and other professional societies, to support the development of the subspecialty of cardio-nephrology. This position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology (S.E.N.) is intended to be the starting point to develop the subspecialty of cardio-nephrology within the S.E.N.. The implementation of the subspecialty in day-to-day nephrological practice will help to diagnose, treat, and prevent CVD in CKD patients in a precise, clinically effective, and health cost-favorable manner. Resumen: Los pacientes con enfermedad renal crónica (ERC) que presentan enfermedad cardiovascular (ECV) tienen índices de morbilidad y mortalidad inaceptablemente elevados, que impactan desfavorablemente sobre los sistemas de salud. En la actualidad, se requieren actuaciones multidisciplinares para identificar, prevenir y tratar la ECV en los pacientes con ERC, debiendo pues superarse la época de las actuaciones de las especialidades individuales. Los autores de este artículo respaldan la necesidad de un equipo interdisciplinar de subespecialistas en cardionefrología que gestione las intervenciones clínicas adecuadas en el entorno hospitalario y en el ambulatorio. Existe una gran necesidad de programas de formación, de guías y modelos de práctica clínica, y de fondos para la investigación en las sociedades de nefrología, cardiología y otras, para apoyar el desarrollo de la subespecialidad de cardio-nefrología. Este documento de opinión del comité coordinador del Grupo de Trabajo de Medicina Cardiorenal de la Sociedad Española de Nefrología (S.E.N.) pretende ser el inicio del desarrollo de la subespecialidad de Cardionefrología en el marco de la S.E.N. La implementación de la subespecialidad en la práctica nefrológica diaria contribuirá a diagnosticar, tratar y prevenir la ECV en los pacientes con ERC de una manera precisa, clínicamente efectiva y sanitariamente rentable.

BackgroundThe analysis of the quality of food is important to protect humans from food-borne or food-based illnesses caused by pathogens, such as bacteria, fungi, viruses, and protozoa. Rapid identification of these pathogens is critical to ensure food safety. Various detection and identification strategies exist; however, they are laborious and time consuming and hence the detection takes longer time. The aim of this study was to develop the specific and fast method for the detection of contaminants in milk.ResultsIn this study, we have developed a simple paper-based PCR method with minimum sample preparation process. The 16S rDNA universal primers were used for the detection of bacterial contaminants. LacZ primers were used for coliform detection which causes serious illness and hence their detection is crucial. ITS region primers were used for fungal detection. The most unique thing about this study is use of Whatman paper no. 1 as sample carrier material. We developed and validated the paper-based PCR method and used it for the detection of microbes and coliforms using milk as a representative sample.ConclusionWe evaluated this method for its suitability in the detection of contaminant microbes using different milk samples. The paper-based method could successfully detect contaminants in the milk samples and the results were comparable to the traditional microbial detection method. The traditional microbiological method takes at least 18–20 h for detecting the presence of microbes in any sample but the developed paper-based PCR method can confirm the microbial presence in 2–3 h. This is very promising especially in the testing where sample sterility is crucial.

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.

Background Lysine succinylation is a naturally occurring post-translational modification (PTM) that is ubiquitous in organisms. Lysine succinylation plays important roles in regulating protein structure and function as well as cellular metabolism. Global lysine succinylation at the proteomic level has been identified in a variety of species; however, limited information on lysine succinylation in plant species, especially paper mulberry, is available. Paper mulberry is not only an important plant in traditional Chinese medicine, but it is also a tree species with significant economic value. Paper mulberry is found in the temperate and tropical zones of China. The present study analyzed the effects of lysine succinylation on the growth, development, and physiology of paper mulberry. Results A total of 2097 lysine succinylation sites were identified in 935 proteins associated with the citric acid cycle (TCA cycle), glyoxylic acid and dicarboxylic acid metabolism, ribosomes and oxidative phosphorylation; these pathways play a role in carbon fixation in photosynthetic organisms and may be regulated by lysine succinylation. The modified proteins were distributed in multiple subcellular compartments and were involved in a wide variety of biological processes, such as photosynthesis and the Calvin-Benson cycle. Conclusion Lysine-succinylated proteins may play key regulatory roles in metabolism, primarily in photosynthesis and oxidative phosphorylation, as well as in many other cellular processes. In addition to the large number of succinylated proteins associated with photosynthesis and oxidative phosphorylation, some proteins associated with the TCA cycle are succinylated. Our study can serve as a reference for further proteomics studies of the downstream effects of succinylation on the physiology and biochemistry of paper mulberry.

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

Background Since the COVID-19 pandemic has occurred, nations showed their unpreparedness to deal with a mass casualty incident of this proportion and severity, which resulted in a tremendous number of deaths even among healthcare workers. The World Society of Emergency Surgery conceived this position paper with the purpose of providing evidence-based recommendations for the management of emergency surgical patients under COVID-19 pandemic for the safety of the patient and healthcare workers. Method A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) through the MEDLINE (PubMed), Embase and SCOPUS databases. Synthesis of evidence, statements and recommendations were developed in accordance with the GRADE methodology. Results Given the limitation of the evidence, the current document represents an effort to join selected high-quality articles and experts’ opinion. Conclusions The aim of this position paper is to provide an exhaustive guidelines to perform emergency surgery in a safe and protected environment for surgical patients and for healthcare workers under COVID-19 and to offer the best management of COVID-19 patients needing for an emergency surgical treatment. We recommend screening for COVID-19 infection at the emergency department all acute surgical patients who are waiting for hospital admission and urgent surgery. The screening work-up provides a RT-PCR nasopharyngeal swab test and a baseline (non-contrast) chest CT or a chest X-ray or a lungs US, depending on skills and availability. If the COVID-19 screening is not completed we recommend keeping the patient in isolation until RT-PCR swab test result is not available, and to manage him/she such as an overt COVID patient. The management of COVID-19 surgical patients is multidisciplinary. If an immediate surgical procedure is mandatory, whether laparoscopic or via open approach, we recommend doing every effort to protect the operating room staff for the safety of the patient.

Purpose To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. Methods Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. Results Twenty-four sections on HNC-specific OD topics. Conclusion This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Approximately 10 years have passed since the Peritoneal Dialysis Guidelines were formulated in 2009. Much evidence has been reported during the succeeding years, which were not taken into consideration in the previous guidelines, e.g., the next peritoneal dialysis PD trial of encapsulating peritoneal sclerosis (EPS) in Japan, the significance of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the effects of icodextrin solution, new developments in peritoneal pathology, and a new international recommendation on a proposal for exit-site management. It is essential to incorporate these new developments into the new clinical practice guidelines. Meanwhile, the process of creating such guidelines has changed dramatically worldwide and differs from the process of creating what were “clinical practice guides.” For this revision, we not only conducted systematic reviews using global standard methods but also decided to adopt a two-part structure to create a reference tool, which could be used widely by the society’s members attending a variety of patients. Through a working group consensus, it was decided that Part 1 would present conventional descriptions and Part 2 would pose clinical questions (CQs) in a systematic review format. Thus, Part 1 vastly covers PD that would satisfy the requirements of the members of the Japanese Society for Dialysis Therapy (JSDT). This article is the duplicated publication from the Japanese version of the guidelines and has been reproduced with permission from the JSDT.

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.

This White Paper by the European Society for Swallowing Disorders (ESSD) reports on the current state of screening and non-instrumental assessment for dysphagia in adults. An overview is provided on the measures that are available, and how to select screening tools and assessments. Emphasis is placed on different types of screening, patient-reported measures, assessment of anatomy and physiology of the swallowing act, and clinical swallowing evaluation. Many screening and non-instrumental assessments are available for evaluating dysphagia in adults; however, their use may not be warranted due to poor diagnostic performance or lacking robust psychometric properties. This white paper provides recommendations on how to select best evidence-based screening tools and non-instrumental assessments for use in clinical practice targeting different constructs, target populations and respondents, based on criteria for diagnostic performance, psychometric properties (reliability, validity, and responsiveness), and feasibility. In addition, gaps in research that need to be addressed in future studies are discussed. The following recommendations are made: (1) discontinue the use of non-validated dysphagia screening tools and assessments; (2) implement screening using tools that have optimal diagnostic performance in selected populations that are at risk of dysphagia, such as stroke patients, frail older persons, patients with progressive neurological diseases, persons with cerebral palsy, and patients with head and neck cancer; (3) implement measures that demonstrate robust psychometric properties; and (4) provide quality training in dysphagia screening and assessment to all clinicians involved in the care and management of persons with dysphagia.

The entire world seems to have responded to COVID-19 pandemic in a knee-jerk manner with a short mindset without building on the existing strengths of public health infrastructure. National governments cannot be blamed for this as we are dealing with a crisis that comes once in a lifetime. Realising this, the Organized Medicine Academic Guild (OMAG) an association of major health associations in this country has suggested measures for long-term solutions to COVID-19-like pandemics in the form of a policy paper by OMAG.

Background The outpatient setting is a key scenario for the implementation of antimicrobial stewardship (AMS) activities, considering that overconsumption of antibiotics occurs mainly outside hospitals. This publication is the result of a joint initiative by the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks, which is aimed at formulating a set of target actions for linking surveillance data with AMS activities in the outpatient setting. Methods A scoping review of the literature was carried out in three research areas: AMS leadership and accountability; antimicrobial usage and AMS; antimicrobial resistance and AMS. Consensus on the actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine or public health, from 18 low-, middle- and high-income countries. Results Evidence was retrieved from 38 documents, and an initial 25 target actions were proposed, differentiating between essential or desirable targets according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for all targets. Further to a second review, 6 statements were re-considered and 3 were deleted, leading to a final list of 22 target actions in the form of a practical checklist. Conclusions This White Paper is a pragmatic and flexible tool to guide the development of calibrated surveillance-based AMS interventions specific to the outpatient setting, which is characterized by substantial inter- and intra-country variability in the organization of healthcare structures, maintaining a global perspective and taking into account the feasibility of the target actions in low-resource settings.

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

BACKGROUND: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups. METHODS: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists). RESULTS: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries. CONCLUSIONS: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.

Background The implementation of an electronic health record (EHR) with structured and standardized recording of patient data can improve data quality and reusability. Whether and how users perceive these advantages may depend on the preimplementation situation. Objective To determine whether the influence of implementing a structured and standardized EHR on perceived EHR use, data quality, and data reuse differed for users working with paper-based records versus a legacy EHR before implementation. Methods We used an electronic questionnaire to measure users' perception before implementation (2014), expected change, and perceived change after implementation (2016) on three themes. We included all health care professionals in two university hospitals in the Netherlands. Before jointly implementing the same structured and standardized EHR, one hospital used paper-based records and the other a legacy EHR. We compared perceptions before and after implementation for both centers. Additionally, we compared expected benefit with perceived benefit. Results We received 7,611 responses (4,537 before and 3,074 after implementation) of which 5,707 (75%) were from professionals reading and recording patient data. A total of 975 (13%) professionals responded to both before and after implementation questionnaires. In the formerly paper-based center staff perceived improvement in all themes after implementation. The legacy EHR center experienced deterioration of perceived EHR use and data reuse, and only one improvement in EHR use. In both centers, for half of the aspects at least 45% of responders experienced results worse than expected preimplementation. Conclusion Our results indicate that the preimplementation recording practice impacts the perceived effect of the implementation of a structured and standardized EHR. For almost half of the respondents the new EHR did not meet their expectations. Especially legacy EHR centers need to investigate the expectations as these might be different and less clear cut than those in paper-based centers. These expectations need to be addressed appropriately to achieve a successful implementation.

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.

BACKGROUND The recent rise in the incidence of hepatitis B virus (HBV) infections in a densely populated city of eastern India (“mixing vessel” of people of varied socio-economic and immune status) prompted this study. Applying saliva on fingers for enumerating bank notes is a common practice in the Indian subcontinent. Paper notes may be a potential source of “horizontal” transmission of this virus, especially if there are cuts/bruises on the oral mucous membrane or skin. AIM To investigate whether paper currencies could be a plausible mode of horizontal transmission of HBV infection. METHODS Polymerase chain reactions (PCR) followed by nucleotide sequencing was done for the detection of HBV. Hepatitis B virus surface antigen enzyme-linked immunosorbent assay(HBsAg ELISA) was performed on all HBV deoxyribonucleic acid-positive samples to check the detectability of the virus. Atomic force microscopy (AFM) was carried out for visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings. RESULTS HBV-specific PCRs on pellets obtained after ultracentrifugation/ immunoprecipitation of the currency paper washings detected potentially intact/viable HBV (genotype D2) in 7.14% of samples (n = 70). AFM gave the visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings. However, HBV isolates from the currency notes could not be detected by HBsAg ELISA. CONCLUSION It is a common practice in the Indian subcontinent to count paper currencies by applying saliva on fingertips. Paper notes may be a potential source of “horizontal” transmission of this virus, especially if there are cuts/bruises on the oral mucous membrane or skin, but it was practically not possible to demonstrate experimentally such transmission. Detection of potentially intact/viable and “occult” HBV from currency poses potential risk of silent transmission of this virus among the general population.

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning for COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which are described in this paper to face the emergency.

Background Adequately measuring resilience is important to support young people and children who may need to access resources through social work or educational settings. A widely accepted measure of youth resilience has been developed previously and has been shown to be suitable for vulnerable youth. While the measure is completed by the young person on paper, it has been designed to be worked through with a teacher or social worker in case further clarification is required. However, this method is time consuming and, when faced with large groups of pupils who need assessment, can be overwhelming for schools and practitioners. This study assesses app software with a built-in avatar that can guide young persons through the assessment and its interpretation. Objective Our primary objective is to compare the reliability and psychometric properties of a mobile software app to a paper version of the Child and Youth Resilience measure (CYRM-28). Second, this study assesses the use of the CYRM-28 in a Scottish youth population (aged 11-18 years). Methods Following focus groups and discussion with teachers, social workers, and young people, an avatar was developed by a software company and integrated into an android smartphone app designed to ask questions via the device’s inbuilt text-to-voice engine. In total, 714 students from 2 schools in North East Scotland completed either a paper version or app version of the CYRM-28. A cross-sectional design was used, and students completed their allocated version twice, with a 2-week period in between each testing. All participants could request clarification either from a guidance teacher (paper version) or from the in-built software glossary (app version). Results Test and retest correlations showed that the app version performed better than the paper version of the questionnaire (paper version: r303=0.81; P Conclusions ALEX, an avatar with an integrated voice guide, had higher reliability when measuring resilience than a paper version with teacher assistance. The CFA reports similar structure using the avatar when compared against the original validation.

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.

Background The development of new genetic testing methods and the approval of the first treatments raises questions regarding when and how to perform screening for inherited neuromuscular conditions. Screening directives and access to the different techniques is not uniform across Europe. The patient advisory board of the European reference network for rare neuromuscular diseases (NMD) conducted a qualitative study to understand the state of play of screening for inherited NMD in Europe and patients’ needs. Results We collected answers from 30 patient organisations (POs) from 18 European countries. Fifteen acknowledge the existence of pre-implantation genetic diagnosis in their country. Regarding prenatal screening, we had 25 positive answers and 5 negative ones. Twenty-four POs mentioned that newborn screening was available in their country. We had some contradictory answers from POs from the same country and in some cases; diseases said to be part of the screening programmes were not hereditary disorders. Twenty-eight organisations were in favour of screening tests. The reasons for the two negative answers were lack of reimbursement and treatment, religious beliefs and eventual insurance constrains. Most POs (21) were in favour of systematic screening with the option to opt-out. Regarding the timing for screening, “at birth”, was the most consensual response. The main priority to perform screening for NMDs was early access to treatment, followed by shorter time to diagnostic, preventive care and genetic counselling. Conclusions This is the first study to assess knowledge and needs of POs concerning screening for NMDs. The knowledge of POs regarding screening techniques is quite uneven. This implies that, even in communities highly motivated and knowledgeable of the conditions they advocate for, there is a need for better information. Differences in the responses to the questions “how and when to screen” shows that the screening path depends on the disease and the presence of a disease modifying treatment. The unmet need for screening inherited NMDs should follow an adaptive pathway related to the fast moving medical landscape of NMDs. International coordination leading to a common policy would certainly be a precious asset tending to harmonize the situation amongst European countries.

Smartphone technology has spread rapidly around the globe. According to a report released by the Korea Information Society Development Institute, about 95% of Koreans aged more than 30 years old owned smartphones. Recently, blood pressure (BP) measurement using a photoplethysmography-based smartphone algorithm paired with the smartwatch is continuously evolving. In this document, the Korean Society of Hypertension intends to remark the current results of smartphone / smartwatch-based BP measurement and recommend optimal BP measurement methods using a smartphone device. We aim to increase the likelihood of success in implementing these new technologies into improved hypertension awareness, diagnosis, and control.

Paper mulberry (Broussonetia papyrifera) is a tree species that has many economic, ecological, and social uses. This study developed an efficient protocol for regenerating shoots from leaf explants using Murashige and Skoog (MS) medium supplemented with different concentrations of plant growth regulators (PGRs), which play vital roles in shoot regeneration. The best result, 86.67% induction frequency and 4.35 shoots per explant, was obtained in the MS medium containing 2.0 mg/L N6-benzyladenine (BA) and 0.05 mg/L indole-3-butyric acid. The effects of explant age, orientation, and genotype were also investigated. Explants from young leaves had a greater regeneration frequency than those from old leaves, and the results were better when the distal end of the leaf explant contacted the medium versus the proximal end. Approximately 70.96% of the shoots rooted well in the MS medium containing 0.4 mg/L α-naphthalene acetic acid (NAA). Although some genotypes achieved poorer results, the regeneration protocol is still applicable for mass multiplication and genetic transformation.

Purpose: Data papers are a promising genre of scholarly communication, in which research data are described, shared, and published. Rich documentation of data, including adequate contextual information, enhances the potential of data reuse. This study investigated the extent to which the components of data papers specified by journals represented the types of contextual information necessary for data reuse.Methods: A content analysis of 15 data paper templates/guidelines from 24 data journals indexed by the Web of Science was performed. A coding scheme was developed based on previous studies, consisting of four categories: general data set properties, data production information, repository information, and reuse information.Results: Only a few types of contextual information were commonly requested by the journals. Except data format information and file names, general data set properties were specified less often than other categories of contextual information. Researchers were frequently asked to provide data production information, such as information on the data collection, data producer, and related project. Repository information focused on data identifiers, while information about repository reputation and curation practices was rarely requested. Reuse information mostly involved advice on the reuse of data and terms of use.Conclusion: These findings imply that data journals should provide a more standardized set of data paper components to inform reusers of relevant contextual information in a consistent manner. Information about repository reputation and curation could also be provided by data journals to complement the repository information provided by the authors of data papers and to help researchers evaluate the reusability of data.

BackgroundThe EAPC White Paper addresses the issue of spiritual care education for all palliative care professionals. It is to guide health care professionals involved in teaching or training of palliative care and spiritual care; stakeholders, leaders and decision makers responsible for training and education; as well as national and local curricula development groups.MethodsEarly in 2018, preliminary draft paper was written by members of the European Association for Palliative Care (EAPC) spiritual care reference group inviting comment on the four core elements of spiritual care education as outlined by Gamondi et al. (2013) in their paper on palliative care core competencies. The preliminary draft paper was circulated to experts from the EAPC spiritual care reference group for feedback. At the second stage feedback was incorporated into a second draft paper and experts and representatives of national palliative care organizations were invited to provide feedback and suggest revisions. The final version incorporated the subsequent criticism and as a result, the Gamondi framework was explored and critically revised leading to updated suggestions for spiritual care education in palliative care.ResultsThe EAPC white paper points out the importance of spiritual care as an integral part of palliative care and suggests incorporating it accordingly into educational activities and training models in palliative care. The revised spiritual care education competencies for all palliative care providers are accompanied by the best practice models and research evidence, at the same time being sensitive towards different development stages of the palliative care services across the European region.ConclusionsBetter education can help the healthcare practitioner to avoid being distracted by their own fears, prejudices, and restraints and attend to the patient and his/her family. This EAPC white paper encourages and facilitates high quality, multi-disciplinary, academically and financially accessible spiritual care education to all palliative care staff.

International audience; Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective. Recent papers, provide important guidance on regulatory aspects of pharmaceutical development, defining EVs for therapeutic applications and critical considerations for the development of potency tests. In addition, the ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics as well as the Exosomes Committee from the ISCT are expected to contribute in an active way to the development of EV-based medicinal products by providing update on the scientific progress in EVs field, information to patients and expert resource network for regulatory bodies. The contribution of our work group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France", created in 2020, can be positioned in complement to all these important initiatives. Based on complementary scientific, technical, and medical expertise, we provide EV-specific recommendations for manufacturing, quality control, analytics, non-clinical development, and clinical trials, according to current European legislation. We especially focus on early phase clinical trials concerning immediate needs in the field. The main contents of the investigational medicinal product dossier, marketing authorization applications, and critical guideline information are outlined for the transition from research to clinical development and ultimate market authorization.

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance., Graphical Abstract Graphical Abstract

Simple Summary Although secondary enucleation (SE) is the treatment of choice for retinoblastoma eyes that did not respond favorably to conservative therapies, clear criteria for its indication are, however, currently missing. In this position paper on behalf of the European Retinoblastoma Group (EURbG), we discuss the available literature on SE, including its influence on metastases rate and survival, and propose guidelines to assist decision-making to interrupt eye-preserving therapies depending on the availabilities of advanced diagnostic and therapeutic modalities. Absolute indications to SE may be restricted to eyes with refractory tumor activity resisting all salvage treatments or eyes under apparent tumor control but no visual potential and irreducible complications. In contrast, eyes with an obscured optic nerve head and/or ocular complications amenable to specific surgical or medical management can be considered relative indications, provided that appropriate follow-up can be implemented and that parents are fully aware of a residual risk. Abstract Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.

The present study investigated the effects of dietary paper mulberry (Broussonetia Papyrifera, BP) on growth performance, muscle quality and muscle growth-related mRNA expressions of grass carp. Fish (initial weight: 50.0 ± 0.5 g) were fed diets supplemented with 0% (control diet), 5%, 10%, 15% and 20% BP for 8 weeks. The results showed that increasing levels of paper mulberry linearly and quadratically decreased the special gain rate (SGR) and increased the feed conversion rate (FCR) of grass carp (p &lt, 0.05). Significantly positive quadratic trends were found between paper mulberry levels and muscle crude fat or crude protein of grass carp (p &lt, 0.05). In comparison to the control diet, the 10%BP and 15%BP groups had significantly decreased muscle crude fat and increased crude protein (p &lt, 0.05). The levels of paper mulberry resulted in a linear and quadratic increase in water loss of grass carp muscle (p &lt, 0.05), and all groups with paper mulberry supplementation were significantly higher than the control group (p &lt, 0.05). Significant positive linear and quadratic trends were found between the paper mulberry levels and muscle fiber diameter or density of grass carp (p &lt, 0.05). In comparison to the control diet, the significant differences were found in the 15%BP and 20%BP groups (p &lt, 0.05). The muscle adhesiveness and hardness linearly and quadratically increased with the increasing levels of paper mulberry (p &lt, 0.05), and both of which increased significantly when the level of paper mulberry reached 10% (p &lt, 0.05). In addition, the increase in paper mulberry linearly and quadratically improved the expressions of myoblast determination protein (MyoD), myogenin (MyoG), paired box protein 7 (Pax7) and myostatin 1 (MSTN1) (p &lt, 0.05). When the supplementation of paper mulberry reached 15%, the expressions of all these mRNAs were significantly higher than those of the control group (p &lt, 0.05). In summary, adding 5% paper mulberry did not affect the growth of grass carp. However, the supplementation of 10% paper mulberry could improve muscle quality through improving muscle hardness, reducing fat accumulation and muscle fiber diameter, at the cost of reducing growth performance.

Urine bags are commonly used to collect urine samples from neonates. However, the sample can be contaminated by stool, or detachment of the bag due to body movement can lead to failure of the collection. A qualitative urine collection kit containing ten filter papers of 3.2 mm diameter was developed and clinically verified among 138 neonates. During a single diaper change (approximately 3 h), the rate of urine collection was calculated. Urine collection was considered to be successful if any filter paper in the urine collection sheet turned from blue to white. Of the 127 neonates who passed urine, 122 had a change in the filter paper. The urine collection rate was 96%, with changes in all 10 filter papers observed in 98 neonates (80%). Urine collection rate was not influenced by sex (p = 1.00), age at collection (p = 0.72), preterm birth (p = 1.00), low birth weight (p = 0.92), or fecal contamination (p = 1.00). The incidence of dermatitis was not higher than in the group in which urine bags were used (urine collection kit: 2/68 [3%]; urine bag: 5/68 [7%]; p = 0.44). Novel urine collection kits using filter paper can collect samples from neonates safely and with a high probability of success.

Lactic acid bacteria occupy an important position in silage microorganisms, and the effects of exogenous lactic acid bacteria on silage quality have been widely studied. Microbial metabolism has been proved as an indicator of substrate utilization by microorganisms. Paper mulberry is rich in free carbohydrate, amino acids, and other components, with the potential to be decomposed and utilized. In this study, changes in the microbial metabolism characteristics of paper mulberry silage with Lactiplantibacillus plantarum (LP) and Lentilactobacillus buchneri (LB) were studied along with a control (CK) using BIOLOG ECO microplates. The results showed that average well-color development (AWCD), Shannon diversity, Shannon evenness, and Simpson diversity exhibited significant temporal trends. LB and LP responded differently in the early ensiling phase, and the AWCD of LB was higher than LP at 7 days. Principal component analysis revealed that CK, LB, and LP samples initially clustered at 3 days and then moved into another similar cluster after 15 days. Overall, the microplates methodology applied in this study offers important advantages, not least in terms of accuracy.

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.

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a 'new normal' are discussed in this article.

The acute and long-lasting side effects of modern multimodal tumour therapy significantly impair quality of life and survival of patients afflicted with malignancies. The key components of this therapy include radiotherapy, conventional chemotherapy, immunotherapy and targeted therapies. In addition to established tumour therapy strategies, up to 30 new therapies are approved each year with only incompletely characterised side effects. This consensus paper discusses the risk factors that contribute to the development of a potentially adverse reaction to tumour therapy and, in addition, defines specific side effect profiles for different treatment groups. The focus is on novel therapeutics and recommendations for the surveillance and treatment of specific patient groups.

The World One Health Congresses are biennial gatherings of approximately 1500 professionals from relevant international organisations, OIE, FAO, WHO, World Bank, leading scientific experts and researchers in the field of One Health, animal production and trade, food safety, animal health, human health and environmentology/ecology, government representatives in public health, human health, food safety, environmental health and global health security. The Congress is organized by the One Health Platform.This white paper summarizes highlights of the 5th International One Health Congress in Saskatoon, Canada, June 2018 and serves as a roadmap for the future, detailing several concrete action points to be carried out in the run-up to the 6th World One Health Congress in Edinburgh, Scotland, June 2020.

Urgent care practice (UCP) is a novel concept for India. Urgent care primarily deals with injuries or illnesses requiring immediate care. Medical emergency and urgency can happen anywhere unannounced. Research has shown that 90% of the morbidities can be resolved within the community by primary care physicians lead teams. Given the changing professional demands, non-specialists tend to refer away far too many cases to specialists, undermining generalist medical care, particularly in Indian settings. The spillover of the patient load from the primary care setting to the tertiary care centers is enormous leading to resource mismatch. Family physicians and other primary care providers are best positioned to develop practices and provide good quality urgent care to society. Family physicians, general practitioners, and medical officers are already functioning as the frontline care providers for any emergency or medical urgency arising within communities. Urgent care is essentially ambulatory care or outpatient care outside of a traditional hospital emergency room. "UCP aims to provide timely support, which is easily accessible with a focus on good clinical outcomes, e.g. survival, recovery, lack of adverse events, and complications. Core interventions of urgent care are centered on the 4Rs - Rescue, Resuscitate, Relate, and Refer. At present, there are no available, established training model for future faculty, residents, and medical students on "UCP" in India.

Major depression is a highly prevalent condition, affecting approximately 10% of the population. It is also a growing global problem, and has been consistently associated with increased risk of coronary heart disease (CHD). It is therefore not surprising that depression is highly comorbid with CHD, being two to three times more common among patients with CHD than in the general population. The prevalence of depression is 15–30% in patients with CHD, and is approximately twice as high in women than men, especially affecting young women in the aftermath of acute myocardial infarction (MI). Depression as a risk factor for CHD has been characterized from mild depressive symptoms to a clinical diagnosis of major depression. As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), clinical depression, or major depression, is characterized by depressed mood or anhedonia (loss of interest or pleasure) for at least 2 weeks accompanied by significant functional impairment and additional somatic or cognitive symptoms. Most epidemiological studies of depression and incidence of CHD have used depressive symptom scales, and have frequently demonstrated a dose–response pattern, with higher levels of depressive symptoms being associated with higher risk. The exact mechanisms linking depression to increased CHD risk are complex and multifactorial, and still incompletely understood. Although adverse lifestyle behaviours and traditional CHD risk factors, such as smoking and sedentary lifestyle, largely contribute to the risk, they do not explain it entirely. In CHD patients, depression is also associated with severity of functional impairment, lower adherence to therapy and lower participation in cardiac rehabilitation. Whether and to what extent these factors explain the relationship between depression and CHD deserves future study. The present paper summarizes key aspects in our current knowledge linking depression and CHD within the intersecting fields of neuroscience, cardiovascular physiology, and behavioural medicine, with the objective of bringing attention to this area and stimulating interdisciplinary research, clinical awareness, and improved care.

For many patients, notably among elderly nursing home residents, no plans about end-of-life decisions and palliative care are made. Consequently, when these patients experience life-threatening events, decisions to withhold or withdraw life-support raise major challenges for emergency healthcare professionals. Emergency department premises are not designed for providing the psychological and technical components of end-of-life care. The continuous inflow of large numbers of patients leaves little time for detailed assessments, and emergency department staff often lack training in end-of-life issues. For prehospital medical teams (in France, the physician-staffed mobile emergency and intensive care units known as SMURs), implementing treatment withholding and withdrawal decisions that may have been made before the acute event is not the main focus. The challenge lies in circumventing the apparent contradiction between the need to make immediate decisions and the requirement to set up a complex treatment project that may lead to treatment withholding and/or withdrawal. Laws and recommendations are of little assistance for making treatment withholding and withdrawal decisions in the emergency setting. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and French Society of Emergency Medicine (Société Française de Médecine d’Urgence, SFMU) tasked a panel of emergency physicians and intensivists with developing a document to serve both as a position paper on life-support withholding and withdrawal in the emergency setting and as a guide for professionals providing emergency care. The task force based its work on the available legislation and recommendations and on a review of published studies.

Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID‐19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID‐19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a ‘long COVID‐19’ illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a ‘post‐COVID’ patient during follow‐up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID‐19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post‐COVID patient and how to integrate in our standard of care the new information on COVID‐19, possibly in a multidisciplinary view. Dealing with the increased COVID‐associated CV risk burden and becoming acquainted with potential new e‐cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.

Sustainability appears to be increasingly important to consumers. In order for companies to reach their sustainability targets and offer more environmentally friendly solutions to consumers, food producers and retailers have begun to change their packaging to more recyclable, bio-based and biodegradable packaging. This study evaluated the sensory characteristics of paper-based prototype packages developed for two product categories (biscuit and meat packages) using a trained sensory panel. Consumer liking, preference and purchase intent were assessed by 130 participants. For the biscuit packages, no significant differences were observed for the liking of any of the four dimensions assessed (appearance, design, feel or overall liking). However, consumer segmentation identified three relatively homogeneous groups of consumers exhibiting differences in the hedonic reaction to the three packages. For the meat packages, significant differences and preference were observed between the original and paper-based packages. For both categories, the purchase intent was low, indicating that further work needed to be done to improve several quality characteristics (e.g., design, size and strength of the package), which would lead to better consumer acceptability.

Objectives Bisphenol A (BPA) is the most used colour developer in thermal paper for cashiers receipts, labels, and tickets. BPA can migrate onto the skin and be absorbed when handling these papers. BPA is a known endocrine disruptor and is therefore being replaced in thermal paper by some alternatives such as Bisphenol S (BPS), D-8, and Pergafast 201® (PF201). To our knowledge, no studies have characterized skin permeation of these BPA alternatives. Methods We measured/characterized skin absorption for BPA, BPS, D-8, and PF201 through ex vivo human skin using flow-through diffusion cells according to OECD guideline 428. Skin samples were 7–12 per test substance from three different skin donors. Skin metabolism was studied for BPA. Dermal absorption was expressed as the amount of the BPA alternatives in the receptor fluid over applied dose in percent (%). Results The absorbed dose after 24 h of exposure was 25% for BPA, 17% for D-8, 0.4% for BPS, and Conclusions Skin absorption was in decreasing order: BPA > D-8 >> BPS > PF201. These results are in agreement with their log Kow and molecular weights. We provided here the necessary data to estimate the extent of skin absorption of BPA analogues, which is a necessary step in risk assessment, and ultimately evaluate public health risks posed by D-8, BPS, and PF201.

BACKGROUND Breast cancer remains the most common neoplasm diagnosed among women in China and globally. Health-related questionnaire assessments in research and clinical oncology settings have gained prominence. The National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy–Breast Cancer Symptom Index (NFBSI-16) is a rapid and powerful tool to help evaluate disease- or treatment-related symptoms, both physical and emotional, in patients with breast cancer for clinical and research purposes. Prevalence of individual smartphones provides a potential web-based approach to administrating the questionnaire; however, the reliability of the NFBSI-16 in electronic format has not been assessed. OBJECTIVE This study aimed to assess the reliability of a web-based NFBSI-16 questionnaire in breast cancer patients undergoing systematic treatment with a prospective open-label randomized crossover study design. METHODS We recruited random patients with breast cancer under systematic treatment from the central hospital registry to complete both paper- and web-based versions of the questionnaires. Both versions of the questionnaires were self-assessed. Patients were randomly assigned to group A (paper-based first and web-based second) or group B (web-based first and paper-based second). A total of 354 patients were included in the analysis (group A: n=177, group B: n=177). Descriptive sociodemographic characteristics, reliability and agreement rates for single items, subscales, and total score were analyzed using the Wilcoxon test. The Lin concordance correlation coefficient (CCC) and Spearman and Kendall τ rank correlations were used to assess test-retest reliability. RESULTS Test-retest reliability measured with CCCs was 0.94 for the total NFBSI-16 score. Significant correlations (Spearman ρ) were documented for all 4 subscales—Disease-Related Symptoms Subscale–Physical (ρ=0.93), Disease-Related Symptoms Subscale–Emotional (ρ=0.85), Treatment Side Effects Subscale (ρ=0.95), and Function and Well-Being Subscale (ρ=0.91)—and total NFBSI-16 score (ρ=0.94). Mean differences of the test and retest were all close to zero (≤0.06). The parallel test-retest reliability of subscales with the Wilcoxon test comparing individual items found GP3 (item 5) to be significantly different (P=.02). A majority of the participants in this study (255/354, 72.0%) preferred the web-based over the paper-based version. CONCLUSIONS The web-based version of the NFBSI-16 questionnaire is an excellent tool for monitoring individual breast cancer patients under treatment, with the majority of participants preferring it over the paper-based version.

Infections by SARS CoV2 - COVID-19 have become in a short time a worldwide health emergency. Due to cardiovascular implications of COVID-19 and to very frequent previous cardiovascular disorders of COVID-19 patients, it is presently crucial that Cardiologists are fully aware of COVID-19 related epidemiological, pathophysiological and therapeutic problems, in order to manage at best the present emergency by appropriate protocols developed on the basis of the competences acquired and shared on the field. The aim of this document is to propose algorithms for the management of cardiovascular diseases during COVID-19 emergency with the objective of providing patients with optimal care, minimizing contagion risk and appropriately managing personal protective equipment.

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of this statement is that sUPAR is a non-specific marker associated with a high negative predictive value for unfavourable outcomes; levels < 4 ng/ml indicate that it is safe to discharge the patient, whereas levels > 6 ng/ml are an alarming sign of risk for unfavourable outcomes. However, the suPAR levels should always be interpreted in light of the patient's history.

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.

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Fungi have the ability to transform organic materials into a rich and diverse set of useful products and provide distinct opportunities for tackling the urgent challenges before all humans. Fungal biotechnology can advance the transition from our petroleum-based economy into a bio-based circular economy and has the ability to sustainably produce resilient sources of food, feed, chemicals, fuels, textiles, and materials for construction, automotive and transportation industries, for furniture and beyond. Fungal biotechnology offers solutions for securing, stabilizing and enhancing the food supply for a growing human population, while simultaneously lowering greenhouse gas emissions. Fungal biotechnology has, thus, the potential to make a significant contribution to climate change mitigation and meeting the United Nation’s sustainable development goals through the rational improvement of new and established fungal cell factories. The White Paper presented here is the result of the 2nd Think Tank meeting held by the EUROFUNG consortium in Berlin in October 2019. This paper highlights discussions on current opportunities and research challenges in fungal biotechnology and aims to inform scientists, educators, the general public, industrial stakeholders and policymakers about the current fungal biotech revolution.

International audience; Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably 12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (

This research studied the strategies that players use in sequential adversarial games. We took the Rock-Paper-Scissors (RPS) game as an example and ran players in two experiments. The first experiment involved two humans, who played the RPS together for 100 times. Importantly, our payoff design in the RPS allowed us to differentiate between participants who used a random strategy from those who used a Nash strategy. We found that participants did not play in agreement with the Nash strategy, but rather, their behavior was closer to random. Moreover, the analyses of the participants’ sequential actions indicated heterogeneous cycle-based behaviors: some participants’ actions were independent of their past outcomes, some followed a well-known win-stay/lose-change strategy, and others exhibited the win-change/lose-stay behavior. To understand the sequential patterns of outcome-dependent actions, we designed probabilistic computer algorithms involving specific change actions (i.e., to downgrade or upgrade according to the immediate past outcome): the Win-Downgrade/Lose-Stay (WDLS) or Win-Stay/Lose-Upgrade (WSLU) strategies. Experiment 2 used these strategies against a human player. Our findings show that participants followed a win-stay strategy against the WDLS algorithm and a lose-change strategy against the WSLU algorithm, while they had difficulty in using an upgrade/downgrade direction, suggesting humans’ limited ability to detect and counter the actions of the algorithm. Taken together, our two experiments showed a large diversity of sequential strategies, where the win-stay/lose-change strategy did not describe the majority of human players’ dynamic behaviors in this adversarial situation.