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The Mediterranean Diet Foundation, in collaboration with the International Menarini Foundation, organized the “International Conference on Mediterranean Diet and Health: A Lifelong Approach.” The Conference was held in Ostuni (Puglia, Italy) from March 30 to April 1, 2017. The event received the endorsement of the American Federation for Aging Research, the Research Consortium “Luigi Amaducci,” the European Nutrition for Health Alliance, the European Union Geriatric Medicine Society, the Clinical Section of the International Association of Gerontology and Geriatrics—European Region, the National Research Council Research Project on Aging, the Italian Society of Gerontology and Geriatrics, and the Italian Society of Clinical Nutrition and Metabolism. During the conference, results were presented from major studies on dietary interventions aiming to assess the efficacy of the Mediterranean diet in the prevention of chronic diseases and the potential underlying mechanisms. Twenty-six international speakers, in seven different sessions, discussed the biological basis, clinical impact, health policy, and behavioral implications of the Mediterranean diet, and its use in potential interventions for health promotion. © 2018 Elsevier Inc.

This study provides the first molecular phylogeny of the social wasp subgenus Polistella (Hymenoptera: Vespidae: Polistes) from Vietnam. Fragments of the mitochondrial COI and 16S rRNA genes were used to reconstruct the phylogenetic trees among 38 Polistes species plus two out-group species (Vespa soror du Buysson and Ropalidia fasciata (Fabricius)). Our results support the existence of several species-groups, including two that are congruent with the previous stigma and Stenopolistes groups defined on the basis of morphology. Moreover, we recovered a clade including the stigma group and the two species P. humilis and P. variabilis that was sister to all other species of Polistella. However, the results also challenged the definition of other groups of Polistella based on morphological data, as well as the definition of two species: P. brunus and P. affinis. This first study calls for further analyses including morphological characters to clarify the taxonomy and the classification of the group.

Nutrition is an integral component of medical care for people living with human immunodeficiency virus (HIV)/autoimmune deficiency syndrome (AIDS) (PLWHA). The Academy of Nutrition and Dietetics supports integration of medical nutrition therapy into routine care for this population. Fewer PLWHA experience wasting and undernutrition, while the prevalence of obesity and other chronic diseases has increased significantly. Improved understanding of HIV infection's impact on metabolism and chronic inflammation has only increased the complexity of managing chronic HIV infection. Nutrition assessment should encompass food insecurity risk, changes in body composition, biochemical indices, and clinical indicators of comorbid disease. Side effects from current antiretroviral therapy regimens are less prevalent than with previous generations of therapy. However, micronutrient deficiencies and chronic anemia also remain significant nutritional risks for PLWHA, making vitamin and mineral supplementation necessary in cases of acute deficiency or food insecurity. Additional factors can impact HIV-related nutrition care among the pediatric population, older adults, minority groups, those co-infected with tuberculosis or hepatitis, and PLWHA in rural or underserved areas. Registered dietitian nutritionists and nutrition and dietetic technicians, registered should participate in multidisciplinary care to incorporate nutrition into the medical management of PLWHA.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders.

Background Infection control professionals (ICPs) are critical in maintaining high standards of quality patient care. Until recently, little was known about the scope of practice, structures, resources and priorities for ICPs and infection control units more generally. Over the past three years we have undertaken a program of work to explore these issues. The purpose of this discussion paper is to synthesise these results and outline implications for the Australian infection control community. Methods We undertook a survey of individual ICPs in Australian and New Zealand and a survey of hospital infection control units within Australia. To understand how our research program could be used to inform and be of value, we also convened a stakeholder workshop to discuss how data from our studies could be translated into meaningfully constructed findings. A synthesis of the findings from the two surveys and the workshop was undertaken and this formed the basis of this discussion paper. Results We were able for the first time, to comprehensively report on infection control staffing levels, priorities and barriers within Australia. We identified considerable variability in the scope, experience and expertise of ICPs and the potential value that credentialing has with respect to effective infection control programs. We were however, unable to develop recommendations with respect to staffing. Conclusion The findings of our work may be used in designing and justifying business cases for infection prevention and control resources. There is also a need to undertake a similar study in settings other than hospitals.

A deacidifying/antifungal mixture composed of calcium propionate, methylparaben and propylparaben was tested against Aspergillus niger, Cladosporium cladosporioides, Chaetomium globosum, Penicillium chrysogenum and Penicillium corylophilum. The preventive treatment of paper samples resulted in a complete fungal growth inhibition on 4 of the 5 tested species. The antifungal properties of the formulation remained unaffected for a minimum period of one year. The disinfecting treatment with the mixture led to a total elimination of all tested fungal species. The effects of the tested formulation on paper were evaluated in terms of pH, colourimetry, folding endurance, FTIR and XRD, using moist heat artificial ageing. Aside from plain paper, paper previously colonized by A. niger was tested to evaluate the potential of the formulation in preventing deterioration caused by fungal metabolites. In plain paper, an effective deacidification and long-term prevention of mechanical resistance loss were achieved, although a slight paper discoloration occurred. On previously colonized by fungi, the treatment effectively prevented the deterioration caused by fungal metabolites.

Polymorphisms are usually associated with defenses and mating strategies, affecting the individual’s fitness. Coexistence of different morphs is, therefore, not expected, since the fittest morph should outcompete the others. Nevertheless, coexistence is observed in many natural systems. For instance, males of the side-blotched lizards ( Uta stansburiana ) present three morphs with throat colors orange, yellow and blue, which are associated with mating strategies and territorial behavior. The three male morphs compete for females in a system that is well described by the rock-paper-scissors dynamics of game theory. Previous studies have modeled the lizards as hermaphroditic populations whose individual’s behavior were determined only by their phenotypes. Here we consider an extension of this dynamical system where diploidy and sexual reproduction are explicitly taken into account. Similarly to the lizards we represent the genetic system by a single locus with three alleles, o, y , and b in a diploid chromosome with dominance of o over y and of y over b . We show that this genotypic description of the dynamics results in the same equilibrium phenotype frequencies as the phenotypic models, but affects the stability of the system, changing the parameter region where coexistence of the three morphs is possible in a rock-paper-scissors game.

Clotrimazole is a well-known antimycotic agent, listed in the World Health Organization List of essential medicines, with minimal health side effects acknowledged throughout a long certification period. In this study, clotrimazole in isopropanol was tested as a potential antifungal treatment for paper objects. The antifungal properties of this azole compound were evaluated against five of the most common fungal species affecting paper collections. The addition of a deacidifying agent, calcium hydroxide nanoparticles, resulted in a multipurpose formulation also aimed at neutralizing the deleterious effects of acids excreted by fungi. Clotrimazole showed antifungal activity against all tested fungal species and its effectiveness followed the ascending order: Chaetomium globosum Cladosporium cladosporioides Penicillium chrysogenum Aspergillus niger Penicillium corylophilum . The best relationship between minimal concentration and fungal inhibition was achieved for 0.05% clotrimazole. The impact of the tested formulation on paper preservation was evaluated in terms of pH, colour and folding endurance, using moist heat artificial ageing. Clotrimazole and calcium hydroxide nanoparticles protected the paper from acidification and loss of folding endurance in the long term, thus representing a non-aqueous alternative treatment for paper affected by fungi.

Background The expansion of scientific publications makes more difficult the mining of relevant information necessary for a productive appraisal of authors' work, scientific interaction and exchange. Papers over-citation is unproductive, under-citation of innovative research generates delay and inefficiency. The extraction of information from the literature is mostly based on keywords (KWs). Methods I computed the chances of citation of one paper as 1/number of papers retrieved by the KWs published in that paper, and compared them with the chances obtained by selecting different KWs. Results Using generic KWs the chances are smaller, at times practically nil, as compared to those calculated with more specific KWs and their association. Conclusions Selecting scientifically-analyzed KWs, specific for the message conveyed by a paper and computing beforehand the theoretical chances of citation, might increase the citations obtained, the retrieval of important scientific and innovative information, optimize scientific exchange and qualitative productivity. Learning points • Retrieval of useful scientific information leaves many important data unrecognized when the KWs selected display a large number of papers. • Redundant information yielded by generic KWs discourages searching and favors the citation of articles published on established and well reputed journals. • A more rational use of KWs narrows the target, offering more selected information, while optimizing the exchange of scientific data and hypothesis. • Appropriately selected KWs might improve the access to, and the diffusion-citation of relevant scientific knowledge. • Trial and error reshaping of KWs allows their best selection to improve the chances of citation, that can be computed by appropriate formulas.

The emergence of Zika virus (ZIKV) infections in Latin America and Southeast Asia has created an urgent need for new, simple, yet sensitive, diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect ZIKV RNA as a new approach to achieve rapid development and deployment of field-ready diagnostics for emerging infectious diseases.

Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a second time. This is caused by a phenomenon called antibody-dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever-Dengvaxia. The trials in this meta-analysis have been used to campaign for mass vaccination programs in developing countries. We discuss the results of this paper and point out problems in the analyses. Reporting the findings in an Asian trial (CYD14), the authors show a sevenfold rise in one outcome-hospitalization for dengue fever in children

When applying for funding, researchers must demonstrate their productivity. For most funding organizations, a key measure of productivity is the number of papers published. The road to publication is rarely straightforward; few journals provide practical guidance to researchers who are struggling to publish their data. Here, we outline the sections of a research paper and describe practical steps in each part of the publication process as an aid to newer authors.

Due to the presence of antibiotics in environmental water and their potential influence on the occurrence of antibiotic-resistant bacteria, development of a detection method suitable for the screening of environmental water for antibiotics is required. In this study, we developed a simple colorimetric paper-based biosensor based on a novel principle for the detection of antibiotics inhibiting bacterial protein synthesis, including aminoglycosides, tetracycline, chloramphenicol, and macrolides. This biosensor is based on the detection of a color change induced by β-galactosidase, which is synthesized on freeze-dried paper discs containing an in vitro transcription/translation system. When a water sample without antibiotics is applied to the paper discs, β-galactosidase can be synthesized, and it hydrolyzes a colorimetric substrate, resulting in a color change from yellow to purple. By contrast, in the presence of antibiotics, the color change can be hampered due to an inhibition of β-galactosidase synthesis. We investigated the effect of the incubation temperature and pH of water samples and confirmed that the paper discs showed the color change to purple in the ranges of 15-37°C and pH 6-10. We observed concentration-dependent color variations of the paper discs by the naked eye and further estimated detection limits to be 0.5, 2.1, 0.8, and 6.1 μg/mL for paromomycin, tetracycline, chloramphenicol, and erythromycin, respectively, using digitized pictures. The paper-based biosensor proved to detect 0.5 μg/mL paromomycin, spiked in real environmental water samples, by the naked eye.

Genome-wide (exome or whole genome) sequencing with appropriate genetic counseling should be considered for any patient with a suspected Mendelian disease that has not been identified by conventional testing. Clinical genome-wide sequencing provides a powerful and effective means of identifying specific genetic causes of serious disease and improving clinical care.

Hydrogen sulfide (H 2 S) has recently been recognized as the third important physiologically gasotransmitter after carbon monoxide and nitrogen monoxide. The challenge of accurate measurement of H 2 S at micromolar levels in biological samples represents a major impediment to the investigation of H 2 S. Here a light emitting diode-based photometer was fabricated for the rapid and point of care measurement of sulfide in human serum samples via marriage of gas separation with paper enrichment. Sulfide in the sample was converted into H 2 S by the addition of diluted H 3 PO 4 and liberated from the sample matrix by the bubble of nitrogen gas (N 2 ). The liberated H 2 S was subsequently captured by a methyl green-impregnated paper filter placed at front of the detector. Upon reaction with H 2 S, the paper filter decolorized that was real-time monitored in transmission mode. With 0.2 mL sample, serum sulfide level within the range 10.0–200.0 μmol/L can be accurately measured in less than 2.5 min. The bubble of N 2 into the matrix promotes the mixing of sample with the added acid and helps the liberation of H 2 S. The addition of defoaming agent SE-15 into the matrix effectively prevented the frothing during aeration. The device was applied to the determination of sulfide in human serum and compared satisfactory with that of methylene blue method implemented on a commercial spectrophotometer.

Recently, scholars have applied network science, which examines interconnected systems, to the study of food recipes. By examining the current literature, this review paper analyses the contribution of network science to recipes, and finds evidence of two main contributions. First, the pioneer studies showed the potential of network science for reducing the complexity of recipes and proposing theories to model ingredient pairings and recipe evolution. The second contribution built upon the previous theories and expanded them to cover different regions of the world as the field moved towards understanding the granularity of human culture with rich and detailed studies that examine different cuisines as more recipe datasets became available. Network science studies of recipes allowed researchers to discover insights in recipes to explain sociocultural aspects of cuisines, and include large numbers of recipes in the analysis, which would be nearly impossible using other techniques.

Background Tuberculosis (TB) and non-small cell lung cancer (NSCLC) are two of the major contributor to mortality and morbidity worldwide. TB has symptoms identical to malignancy, therefore, sometimes its diagnosis confused with lung cancer. Several biologic pathways have been identified to be involved in these diseases. The miRNAs are biological molecules that were shown to play essential roles in TB and NSCLC through targeting the related genes. Methods In this research paper we evaluated the expression pattern of common miRNAs between TB and NSCLC and compared them with healthy controls. MiR-155 and miR-146a were examined using RT-qPCR and mir-16 were used as a reference gene. Additionally, the bioinformatics analysis was performed to confirm the role of miR-155 and miR-146a in signaling pathways of TB and NSCLC through targeting related genes. Results mir-155 showed higher expression in TB and NSCLC patients than healthy controls (P value = 0.0221 and 0.0214 respectively), whereas mir-146a showed lower expression in TB and NSCLC patients than healthy controls (P value ≤ 0.0001 and 0.0056 respectively). Conclusions The results demonstrated that miR-155 and miR-146a can be used as a biomarker for early detection, screening, treatment strategies and clinical management of TB and NSCLC.

Fungal stains affect documents and artworks on paper all over the world, diminishing their chemical stability and compromising their readability. The present paper studies the suitability of agarose and gellan gum hydrogels to remove fungal stains from paper, using paper impregnated with alizarin as a model system to simulate the most common colorant molecules produced by fungi - polyketide quinones. The effect of pH variation on the efficacy of the gels was evaluated by UV spectrometry. The results show that the cleaning efficacy of the gels greatly depends on the gel matrix, the colorant molecules, and the pH balance of the process.

Prostate cancer is the most significant reason for deaths in men, outside of lung cancer. The clinical examination of cancer proteins or biomarkers is extremely significant in early examination and monitoring of recurrence of disease after treatment. Biomarkers have expanded great clinical significance owing to their extensive spectra in the identification, elimination, early diagnosis and cure of cancer. In this work, novel, ultrasensitive sandwich-type portable bio device based on citrate-capped silver nanoparticles (Citrate-AgNPs) modified graphene quantum dots (GQDs) nano ink for detection of Prostate specific antigen (PSA) was fabricated. Functionalized cysteamine with gold nanoparticles (Cys-AuNPs) was also utilized to amplify the signal. It provides a good and high external area for the immobilization biotinylated antibody of PSA in the large amount. For the first time, citrate-AgNPs-GQDs nano ink was directly written on the cellulose paper surface (ivory sheet and photographic paper) and modified by Cys-AuNPs. So, final structure of the immunodevices was completed after including of Ab1 and PSA (antigen). The immunosensors were used for the recognition of PSA by using DPVs (differential pulse voltammetry) technique. The obtained low limit of quantification (LLOQ) of the first immunodevice (ivory sheet/Citrate AgNPs-GQDs nano-ink/CysA-Au NPs/Ab1/BSA/PSA/Ab2) was 0.07 μg/L and the linear range for the calibration plot was from 0.07 to 60 μg/L. Also, the achieved LLOQ of the second immunodevice (photographic paper/Citrate AgNPs-GQDs nano-ink/Cys-Au NPs/Ab1/BSA/PSA/Ab2) was 0.05 μg/L with the linear range of 10 to 0.05 μg/L. It is noteworthy that, proposed immunoassay was effectively utilized to the monitoring of PSA glycoprotein in unprocessed human plasma sample. Obtained results show that the constructed immunosensor is able to apply as portable bio device for the clinical analysis of PSA in human plasma samples., Electrochemistry; Biomedical engineering; Cancer research; Immunology; Nanotechnology; Conductive ink; Affinity binding; Biomedical analysis; Immunodevice; Prostate cancer; Nanostructure

Rock-paper-scissors games metaphorically model cyclic dominance in ecology and microbiology. In a static environment, these models are characterized by fixation probabilities obeying two different "laws" in large and small well-mixed populations. Here, we investigate the evolution of these three-species models subject to a randomly switching carrying capacity modeling the endless change between states of resources scarcity and abundance. Focusing mainly on the zero-sum rock-paper-scissors game, equivalent to the cyclic Lotka-Volterra model, we study how the ${\it coupling}$ of demographic and environmental noise influences the fixation properties. More specifically, we investigate which species is the most likely to prevail in a population of fluctuating size and how the outcome depends on the environmental variability. We show that demographic noise coupled with environmental randomness "levels the field" of cyclic competition by balancing the effect of selection. In particular, we show that fast switching effectively reduces the selection intensity proportionally to the variance of the carrying capacity. We determine the conditions under which new fixation scenarios arise, where the most likely species to prevail changes with the rate of switching and the variance of the carrying capacity. Random switching has a limited effect on the mean fixation time that scales linearly with the average population size. Hence, environmental randomness makes the cyclic competition more egalitarian, but does not prolong the species coexistence. We also show how the fixation probabilities of close-to-zero-sum rock-paper-scissors games can be obtained from those of the zero-sum model by rescaling the selection intensity., 31 pages, 15 figures: Main text (18 pages, 9 figures) followed by Supplementary Material (13 pages, 6 figures). Supplementary Information and resources available at https://doi.org/10.6084/m9.figshare.8858273.v1

The study included isolation and diagnosis of some types of anaerobic and aerobic bacteria capable of decomposition and fermentation of waste papers cellulose. Forty samples were collected from different environments (agricultural soil, wastewater, and normal soil) and three types of bacteria were diagnosis and isolated ( Clostridium phytofermentous , Eschrichia coli , and Pseudomonas aeruginosa ). The ability of studied bacteria on the production of cellulose decomposing enzymes was evaluated using UV absorbance method. Highest activity was obtained via Clostridium phytofermentous bacteria with maximum value of 2.52 IU/mL, while Pseudomonas aeroginosa gave 2.21 IU/mL and Eschrichia coli unit gave 2.09 IU/ml. The results showed the effect of some environmental conditions on the effectiveness of the production of the enzyme cellulose. Optimum temperature range was 35–40 °C and pH ranges of 7–9. Ethyl alcohol concentration was measured using titration method, maximum concentration of alcohol produced by Eschrichia coli , which reached 8.28 g/L, while in case of Pseudomonas aeroginosa reached 7.86 g/l, and Clostridium phytofermentous reached 6.62 g/L.

We identified vespid chemotactic peptide (VCP) and vespakinin (Vespk) from the lesser paper wasp, Parapolybia varia . The cDNA, genomic DNA, and mature peptide sequences of P. varia VCP ( Pv VCP) and Vespk ( Pv Vespk) were determined. To investigate the pharmacological and toxicological properties of Pv VCP and Pv Vespk, their hemolytic, anti-microbial, anti-fungal, and anti-tumor activities were evaluated and compared with those of Vespa mandarina VCP ( Vm VCP) and Vespk ( Vm Vespk). Pv VCP, Pv Vespk, and Vm Vespk showed little to low hemolytic activities. Only Vm VCP showed hemolytic activity at a high concentration. Among the four peptides tested, Vm VCP showed both anti-microbial and anti-fungal activities, whereas Pv VCP showed only anti-fungal activity to Candida albicans . Interestingly, Pv VCP showed significantly stronger anti-tumor activities to two ovarian cancer cell lines compared with Vm VCP. Vespks only showed anti-tumor activity to SK-OV-3 cells but not to NIH-OVCAR-3 cells. These differences in anti-tumor activity might have been caused by the differences in secondary structure among peptides. A circular dichroism spectrometry analysis revealed that VCPs have more amphiphilic α-helix structures than Vespks. Taken together, the low hemolytic but strong anti-tumor activities of Pv VCP suggest that this peptide could be a candidate for developing a new anti-tumor peptide drug or drug carrier in the future.

In their Commentary to our paper recently published in Zoology (Righi et al., 2021a), Tilic and Bartolomaeus question our findings that the chaetae of Hermodice carunculata (Annelida) are hollow and able to store and deliver venoms. They sustain the idea that inflammatory chemicals are secreted through epidermal glands and possibly exposed to predator trough wounds caused by the brittle chaetae. We provide evidence-based arguments in support of our considerations. The sample preparation procedures did not affect the native inner structure of unfixed fireworm chaetae, which is clearly hollow as supported by both ultrastructure observation and crystal-chemical analysis of constituents. Furthermore, our previous and more recent feeding bioassays and chemical analysis indicate both that chaetae retain strong deterrent capacities even when isolated from the body of H. carunculata, and that they contain venoms. The cellular mechanisms involved in fireworm chaeta storage and deliver of chemicals are still unstudied. We strongly believe that this lack of knowledge should draw further attention on H. carunculata biology, pursuing new hypotheses and studies based on the noteworthy information which has been obtained so far.

Plastic film (PF) is the primary material applied for soil mulching, but it may also cause heat and drought stresses to crops in the summer season. In a previous study, we revealed that biodegradable paper (BP) was a potential mulching material for summer crop production, because it could not only decrease soil temperature, but also increase soil moisture during the summer season. However, it is still unclear whether different colored BPs have various efficiencies in improving soil environment, when used as soil mulching materials. Therefore, in this study, gray PF and different colors (red, dark, blue and yellow) of BPs were used as soil mulching materials to explore their influences on soil temperature and moisture, spectral and photosynthetic characteristics, plant growth, and fruit quality and yield of tomato in the summer season. The non-mulching (NM) served as control. In general, PF exhibited the highest illuminance and photosynthetic irradiance, and thereby led to the highest soil temperature. However, soil temperature decreased on average of 5.73% and 20.28% in BPs as compared to NM and PF, respectively. Soil moisture increased on average of 8.15%, 5.41%, and 10.98% in dark, red, and blue BPs, respectively, as compared to NM. The ratio of blue-violet to red-orange irradiance were 1:2, 2:3, 1:4, 1:3, and 1:1 in NM, PF, yellow BP, red BP, and blue BP, respectively. The red and blue BPs generally enhanced root growth, and thereby increased total fruit yield by 36.56% and 41.64% on average, respectively, as compared to PF. In addition, an overall improvement in fruit quality (vitamin C, soluble sugar, and sugar-acid ratio) was observed in red and blue BPs as compared to PF and other colored BPs. Our results demonstrated that red and blue BPs can be applied to improve soil environment and spectral characteristics, and thereby enhance fruit yield and quality, during the summer crop production.

Nobel laureate Aziz Sancar writes about his decades-long relationship with the Journal of Biological Chemistry. Since 1984, he has published 100 papers in JBC, including this "Reflections."

The recent ESMO position paper on biosimilars in oncology1 was timely, given the rapidly increasing range of biologic medicines and the potential to develop biosimilar medicines in this area. As the position paper clearly states, biosimilar medicines can positively impact the financial sustainability of healthcare systems around the world.1 The paper also correctly highlights the importance of providing accurate information to all stakeholders involved. This is essential in order to avoid misunderstanding and misconceptions about biosimilar medicines. Biologic medicines, whether reference biologics or biosimilars, are recognised as being much more complex than traditional, chemically-synthesised drugs. A biosimilar, as defined by the EMA, is a biologic medicine that is similar to another biologic medicine that has already been authorised for use.2 A science-based regulatory framework has been established in the European Union (EU) since 2005 to ensure the development and approval of high-quality biosimilars; this framework is regularly reviewed and updated.3–5 The requirements for biosimilar development and approval are based on those that are in place for any biologic medicine; the manufacturer is required to demonstrate similarity to the reference medicine in terms of safety, efficacy and quality. This contrasts with the requirements for approval of generic versions of chemically synthesised, small-molecule drugs, which typically only require demonstration of identical structure and pharmacological …

This paper deals with the development and identification of a simple mass balance model for plant growth. Further to previous studies, this paper deals with modeling of growth of Arabidopsis thaliana , for which a detailed experimental design has been performed with the objective to address some of the limitations of the previously developed plant growth models, largely in terms of data availability, while accounting for the practical experimental constraints.

In this paper a robotic boat setup for research and education in control is presented. It was designed for students to develop their practical experience and validate theoretical results at the course “Control Methods for Robotic Applications”, which is being taught at the Department of Control Systems and Informatics of ITMO University. Four use cases of this setup are suggested in the paper. They are aimed to design controllers of various structures.

In this paper a series of practical tasks on control for manipulators is presented. This series represents a laboratory part of the course "Control Methods for Robotic Applications" included in the curriculum of the master’s degree program at the Department of Control Systems and Informatics of ITMO University. The exercises are aimed to attract and motivate students, improve their practical competency and simplify their understanding of theoretical background. The tasks are focused on such problems as path and trajectory planning, automatic code generation and design of a tracking system for moving target.

Next generation genomic sequencing (NGS) technologies-whole genome and whole exome sequencing-are now cheap enough to be within the grasp of many health care organizations. To many, NGS is symbolic of cutting edge health care, offering the promise of "precision" and "personalized" medicine. Historically, research and clinical application has been a two-way street in clinical genetics: research often driven directly by the desire to understand and try to solve immediate clinical problems affecting real, identifiable patients and families, accompanied by a low threshold of willingness to apply research-driven interventions without resort to formal empirical evaluations. However, NGS technologies are not simple substitutes for older technologies and need careful evaluation for use as screening, diagnostic, or prognostic tools. We have concerns across three areas. First, at the moment, analytic validity is unknown because technical platforms are not yet stable, laboratory quality assurance programs are in their infancy, and data interpretation capabilities are badly underdeveloped. Second, clinical validity of genomic findings for patient populations without pre-existing high genetic risk is doubtful, as most clinical experience with NGS technologies relates to patients with a high prior likelihood of a genetic etiology. Finally, we are concerned that proponents argue not only for clinically driven approaches to assessing a patient's genome, but also for seeking out variants associated with unrelated conditions or susceptibilities-so-called "secondary targets"-this is screening on a genomic scale. We argue that clinical uses of genomic sequencing should remain limited to specialist and research settings, that screening for secondary findings in clinical testing should be limited to the maximum extent possible, and that the benefits, harms, and economic implications of their routine use be systematically evaluated. All stakeholders have a responsibility to ensure that patients receive effective, safe health care, in an economically sustainable health care system. There should be no exception for genome-based interventions.

How many of the authors who publish in Cell Stem Cell dream that their work will eventually wind up in the clinic? Probably quite a few. In the 10 years since its launch, Cell Stem Cell has featured many innovative discoveries, and several of them have gone on to become the seeds of burgeoning biotechnology companies with therapeutic aspirations. Two scientists who have seen that happen are Benjamin Reubinoff (Figure 1) and Derrick Rossi (Figure 2), both of whom led the clinical translation of technologies that made their public debut in Cell Stem Cell.

Antimicrobial resistance is an important global issue that impacts the efficacy of established antimicrobial therapy. This is true globally and within the Arab countries of the Middle East, where a range of key Gram-negative pathogens pose challenges to effective therapy. There is a need to establish effective treatment recommendations for this region given specific challenges to antimicrobial therapy, including variations in the availability of antimicrobials, infrastructure and specialist expertise. This consensus provides regional recommendations for the first-line treatment of hospitalized patients with serious infections caused by World Health Organization critical priority Gram-negative pathogens Acinetobacter baumannii and Pseudomonas aeruginosa resistant to carbapenems, and Enterobacteriaceae resistant to carbapenems and third-generation cephalosporins. A working group comprising experts in infectious disease across the region was assembled to review contemporary literature and provide additional consensus on the treatment of key pathogens. Detailed therapeutic recommendations are formulated for these pathogens with a focus on bacteraemia, nosocomial pneumonia, urinary tract infections, skin and soft tissue infections, and intra-abdominal infections. First-line treatment options are provided, along with alternative agents that may be used where variations in antimicrobial availability exist or where local preferences and resistance patterns should be considered. These recommendations take into consideration the diverse social and healthcare structures of the Arab countries of the Middle East, meeting a need that is not filled by international guidelines. There is a need for these recommendations to be updated continually to reflect changes in antimicrobial resistance in the region, as well as drug availability and emerging data from clinical trials.

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations.

We enjoyed our colleagues' paper, and see ourselves as pursuing the same goal: the application of NGS technologies to improve clinical care and promote better health outcomes, particularly where alternative approaches are often inadequate. We find we agree on some points, but on others, regrettably, we're still far apart.

A recent article in Gene highlighted potential function of miR-346 in human breast cancer (Yang et al., 2017). We request an explanation or correction of the report. In its current state, the text will certainly create confusion in the field and lead to incorrect assumptions. The authors made several critical errors. The abstract stated "we found that the expression of miR-346 was higher in breast cancer tissues than in their paired corresponding non-cancerous tissues" and the main text and legend for Fig. 1A stated "miR-346 expression was significantly higher in breast cancer tissues than in their paired corresponding non-cancerous tissues (Fig. 1A, Yang et al., 2017)" and "miR-346 was upregulated in breast cancer tissues and cell lines. (A)", respectively. It was also stated that "SRCIN1 expression levels were significantly down-regulated in breast cancer compared to the adjacent normal tissues (Fig. 5B, Yang et al., 2017)". The problem with these statements is that they contradict the actual data presented in the paper! This misrepresentation of the effects of miR-346 in breast cancer could prove harmful by sidetracking future research. Further, clinical trials may be incorrectly directed towards lowering miR-346 without a complete and fair assessment of the internal contradictions in the data. Inaccurately-presented data impede progress of biomedical research, deplete scientific resources and compromise public trust.

In micro-arrayed compound screening (µARCS), an agarose gel is used as a reaction vessel that maintains humidity and compound location as well as being a handling system for reagent addition. Two or more agarose gels may be used to bring test compounds, targets, and reagents together, relying on the pore size of the gel matrix to regulate diffusion of reactants. It is in the microenvironment of the agarose matrix that all the components of an enzymatic reaction interact and result in inhibitable catalytic activity. In an effort to increase the throughput of µARCS-based screens, reduce the effort involved in manipulating agarose gels, and reduce costs, blotter paper was used rather than a second agarose gel to introduce a substrate to a gel contain ing a target enzyme. In this assay, the matrix of the blotter paper did not prevent the substrate from diffusing into the enzyme gel. The compound density of the µARCS format, the ease of manipulating sheets of paper for reagent addition, and a scheduled protocol for running multiple gels allowed for a throughput capacity of more than 200,000 tests per hour. A protease assay was developed and run in the µARCS format at a rate of 200,000 tests per hour using blotter paper to introduce the substrate. Picks in the primary screen were retested in the µARCS format at a density of 384 compounds per sheet. IC 50 values were confirmed in a 96-well plate format. The screen identified several small molecule inhibitors of the enzyme. The details of the screening format and the analysis of the hits from the screen are presented. ( Journal of Biomolecular Screening2003: 668-675)

Background Improving access to health information can empower patients and improve patient outcomes. Internet availability has seen the rise of so-called e-patients, especially those with chronic disease who seek information from primary sources. Our objective was to assess the readability of papers in online medical journals from a lay e-patient perspective. Methods We focused on diabetes mellitus as a chronic disease. Review of scripts from a weekly diabetes mellitus tweet chat (#gbdoc) found that sport was of high interest to participants. Search questions were then formulated by review of a Facebook diabetes mellitus sports forum and entered into Google UK and Google Scholar, with the aim of replicating a lay e-patient adept with Web 2.0 and active online searching for primary research. The first ten pages of Google UK/Google Scholar results (n=100–110 electronic documents) were reviewed for eligible papers for eight search questions (appendix). The readability of abstracts from all extracted papers was calculated with the Flesch Reading Ease (FRE) formula. ANOVA was used to compare scores according to type of paper (randomised controlled trial, meta-analysis, review, other original research). Findings 25 open-access abstracts met the inclusion criteria. They had a mean FRE score of 18·95 (SD 11.24) and a median score of 17·2 (IQR 12-25·5), indicating that they would require a university degree level of education to read. The ANOVA found no statistically significant difference in means between type of paper. Interpretation The readability level of abstracts in a sample of online medical papers on sport with diabetes mellitus was beyond the reading level of most people with that condition. We suggest that medical journals try to meet the challenge of disseminating primary research that e-patients want to access in a more readable way. We propose increasing the adoption of lay summaries and the use of patient rapporteurs—namely, people with chronic disease, Web 2.0 skills, and the medical knowledge to assist publications in the online dissemination of readable primary research to lay e-patients. Funding None.