mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer.

Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the "cancer vs. control" comparison, and 1,260 DEGs were recorded in the "cancer vs. neoplasia" comparison. Only two genes were observed to be differentially expressed in the "neoplasia vs. control" comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.

Fetal Exposure to Tobacco Metabolites and Depression During Adulthood: Beyond Binary Measures.

BACKGROUND: Sibling studies of maternal smoking during pregnancy and subsequent risk of depression have produced mixed results. A recent study identified not considering amount of maternal smoking and age of onset as potentially masking a true association. We examine these issues and also the relevance of maternal smoking during pregnancy as a determinant of severity of depressive symptoms. METHODS: We analyzed data from the community-based National Longitudinal Survey of Youth (U.S., 1994-2016). Mothers reported smoking during pregnancy (none, <1 pack/day, ≥1 pack/day). We assessed offspring's lifetime depression (i.e., ≥8 symptoms) and symptom counts with the Centers for Epidemiologic Studies Depression scale. We estimated the risk of these two outcomes in the full sample (n=7172) and among siblings (n=6145) using generalized linear mixed-effects models with random intercepts by family and family-averaged means for sibling analyses. RESULTS: Among siblings, we observed dose-dependent elevations for both risk of depression (smoking during pregnancy <1 pack/day aRR=1.18; 95% CI 1.07, 1.30; smoking ≥1 aRR=1.36; 95% CI 1.19, 1.56) and severity of depressive symptoms (smoking<1 pack/day aRR=1.12 (95% CI 1.08, 1.16); smoking ≥1 pack/day aRR=1.25 (95% CI 1.18, 1.31). Among both samples, the P for trend was <0.01. In analysis limited to offspring diagnosed prior to age 18, results for severity were attenuated. CONCLUSIONS: This evidence supports the existence of an independent association between maternal smoking during pregnancy and both risk of depression and severity of depressive symptoms. The results highlight the utility of considering the amount of smoking, severity of symptoms, and age of onset.

Four-bar Geometry is Shared among Ecologically DivergentFish Species.

Understanding the factors that influence morphological evolution is a major goal in biology. One such factor is the ability to acquire and process prey. Prey hardness and evasiveness are important properties that can impact evolution of the jaws. Similar diets and biomechanical systems have repeatedly evolved among fish lineages, providing an opportunity to test for shared patterns of evolution across distantly related organisms. Four-bar linkages are structures often used by animals to transmit force and motion during feeding and that provide an excellent system to understand the impact of diet on morphological and biomechanical evolution. Here, we tested how diet influences the evolutionary dynamics of the oral four-bar linkage system in wrasses (Family: Labridae) and cichlids (Family: Cichlidae). We found that shifts in prey hardness/evasiveness are associated with limited modifications in four-bar geometry across these two distantly related fish lineages. Wrasse and cichlid four-bar systems largely exhibit many-to-one mapping in response to dietary shifts. Across two iconic adaptive radiations of fish, an optimal four-bar geometry has largely been co-opted for different dietary functions during their extensive ecological diversification. Given the exceptional jaw diversity of both lineages, many-to-one mapping of morphology to mechanical properties may be a core feature of fish adaptive radiation.

Entender los factores que influyen en la evolución morfológica es un objetivo principal en biología. Uno de esos factores es la capacidad para atrapar y procesar presas. La dureza y evasividad de las presas son propiedades importantes que pueden impactar la evolución de las mandíbulas. Dietas y sistemas biomecánicos similares han evolucionado repetidamente entre linajes de peces, proporcionando una oportunidad para evaluar patrones evolutivos compartidos entre organismos lejanamente emparentados. Los mecanismos de cuatro barras en animales, usados usualmente para transmitir fuerza y movilidad durante la alimentación, proveen un sistema excelente para entender el efecto de la dieta en la evolución morfológica y biomecánica. Aquí, evaluamos cómo la dieta influye en las dinámicas evolutivas del mecanismo oral de cuatro barras en lábridos (Familia: Labridae) y cíclidos (Familia: Cichlidae). Encontramos que los cambios en la dureza y evasividad de las presas están asociados con modificaciones limitadas de la geometría de las cuatro barras entre esos dos linajes de peces lejanamente emparentados. Los mecanismos de cuatro barras de los lábridos y cíclidos muestran en gran medida diferentes estructuras que conducen a un mismo resultado funcional en respuesta a cambios de dieta. A lo largo de dos radiaciones adaptativas icónicas de peces, una geometría óptima de cuatro barras ha sido en gran medida adaptada para diferentes funciones dietéticas durante una diversificación ecológica extensa. Dada la excepcional diversidad de mandíbulas en ambos linajes, estructuras que conducen a un mismo resultado en morfología y propiedades mecánicas podrían ser características esenciales durante la radiación adaptativa de peces.Translated by Saúl Dominguez-Guerrero, Postdoctoral Associate- Yale University.

Comprendre les facteurs qui influencent l'évolution morphologique est un objectif majeur en biologie. L'un de ces facteurs est la capacité d'acquérir et de traiter des proies. La dureté et le caractère évasif des proies sont des propriétés importantes qui peuvent avoir un impact sur l'évolution des mâchoires. Des régimes alimentaires et des systèmes biomécaniques similaires ont évolué à plusieurs reprises parmi les lignées de poissons, offrant ainsi l'occasion de tester des modèles d'évolution partagés entre des organismes éloignés. Les liaisons à quatre barres sont des structures souvent utilisées par les animaux pour transmettre la force et le mouvement pendant l'alimentation, et qui constituent un excellent système pour comprendre l'impact du régime alimentaire sur l'évolution morphologique et biomécanique. Ici, nous avons testé comment le régime alimentaire influence la dynamique évolutive du système de liaison orale à quatre barres chez les labres (famille : Labridae) et les cichlidés (famille : Cichlidae). Nous avons constaté que les changements dans la dureté/le caractère évasif des proies sont associés à des modifications limitées de la géométrie à quatre barres dans ces deux lignées de poissons éloignées. Les systèmes à quatre barres de labres et de cichlidés présentent en grande partie une cartographie plusieurs-à-un en réponse aux changementsde régime alimentaire. Pour deux radiations adaptatives emblématiques de poissons, une géométrie optimale à quatre barres a été largement adoptée pour différentes fonctions alimentaires au cours de leur vaste diversification écologique. Compte tenu de la diversité exceptionnelle des mâchoires des deux lignées, la cartographie plusieurs-à-un de la morphologie aux propriétés mécaniques peut être une caractéristique essentielle du rayonnement adaptatif des poissons.Translated by Pauline Raimondeau, Postdoctoral Associate, Yale University.

Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T-cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma.

Not available.

Viral Genomic DNA Packaging Machinery.

Tailed double-stranded DNA bacteriophage employs a protein terminase motor to package their genome into a preformed protein shell-a system shared with eukaryotic dsDNA viruses such as herpesviruses. DNA packaging motor proteins represent excellent targets for antiviral therapy, with Letermovir, which binds Cytomegalovirus terminase, already licensed as an effective prophylaxis. In the realm of bacterial viruses, these DNA packaging motors comprise three protein constituents: the portal protein, small terminase and large terminase. The portal protein guards the passage of DNA into the preformed protein shell and acts as a protein interaction hub throughout viral assembly. Small terminase recognises the viral DNA and recruits large terminase, which in turn pumps DNA in an ATP-dependent manner. Large terminase also cleaves DNA at the termination of packaging. Multiple high-resolution structures of each component have been resolved for different phages, but it is only more recently that the field has moved towards cryo-EM reconstructions of protein complexes. In conjunction with highly informative single-particle studies of packaging kinetics, these structures have begun to inspire models for the packaging process and its place among other DNA machines.

PEMOCS: Evaluating the effects of a concept-guided, PErsonalised, MOtor-Cognitive exergame training on cognitive functions and gait in chronic Stroke-study protocol for a randomised controlled trial.

BACKGROUND: Many stroke survivors remain with residual cognitive and motor impairments despite receiving timely acute and sub-acute rehabilitation. This indicates that rehabilitation following stroke should be continuous to meet the needs of individual stroke patients. Both cognitive and motor functions are essential for mastering daily life and, therefore, should be aimed at with rehabilitation. Exergames, motor-cognitive exercises performed using video games, are an auspicious method to train both motor and cognitive functions and at the same time may foster the long-term motivation for training. This study aims to assess the effect of concept-guided, personalised, motor-cognitive exergame training on cognitive and motor functions in chronic stroke survivors. METHODS: This study is a single-blinded, randomised controlled trial. Assessments are performed at baseline, after a 12-week intervention, and at a 24-weeks follow-up. Chronic stroke patients (≥ 18 years old, ≥ 6 months post-stroke) able to stand for 3 min, independently walk 10 m, follow a two-stage command, and without other neurological diseases apart from cognitive deficits or dementia are included. Participants in the intervention group perform the exergame training twice per week for 30 (beginning) up to 40 (end) minutes additionally to their usual care programme. Participants in the control group receive usual care without additional intervention(s). Global cognitive functioning (total Montreal Cognitive Assessment (MoCA) score) is the primary outcome. Secondary outcomes include health-related quality of life, specific cognitive functions, single- and dual-task mobility, and spatiotemporal gait parameters. The target sample size for this trial is 38 participants. Linear mixed models with the post-outcome scores as dependent variables and group and time as fixed effects will be performed for analysis. DISCUSSION: Superior improvements in global cognitive functioning and in the abovementioned secondary outcomes in the intervention group compared to the control group are hypothesised. The results of this study may guide future design of long-term rehabilitation interventions after stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05524727). Registered on September 1, 2022.

Assessment of the Acute Toxicity of Chlorophyllin and Trolox for the Possibility of Studying Their Radioprotective Properties.

The acute toxicity of chlorophyllin and trolox upon intraperitoneal injection of their solutions was studied in male ICR (CD-1) mice. The LD50 of chlorophyllin was found to be 633±37.2 µg/g body weight, which is lower than the LD50 of established radioprotectors. Trolox is technically non-toxic under the conditions of our study. The results obtained highlight the need for a detailed study of the radioprotective properties of trolox and chlorophyllin.

Ecosystem services-based mangrove forest with management model strategies, sustainability of coastal natural resources.

The purpose of this research is to examine; Ecosystem Services Based Mangrove Forest with Management Model Strategies, Sustainability of Coastal Natural Resources. This research design uses systematic review namely library research that examines quality and critical journals, which have been filtered with inclusion criteria and uses several Google Scholar, Pubmed, Science Direct and Research gate databases as literacy in this study. A search of 2018-2023 articles returned 17,000 keyword results. Ecosystem Services Based Mangrove Forest with Management Strategies, which were filtered into 10 journals according to the theme and analyzed by reviewing them. Ecosystem Services Based Mangrove Forest with Management Strategies. The research results show that mangrove ecosystem services with an area of 88,556 ha was Rp 6,961,126,186,194 year-1 (US$ 467,974,555.06 year-1) or Rp 78,607,444 ha-1-1 (US$ 5,284.5 ha-1year-1). Ecosystem Services Based Mangrove Forest with Management Strategies, that there are three main components that must be considered in efforts to manage and utilize mangrove ecosystems and coastal natural resources, namely; 1) social activity(social processes) provide socialization or understanding to the community about the importance of protecting mangrove forests and the benefits that the community will receive 2) the economy(economic processes) take advantage of the existing potential by planting mangrove trees, and 3) the natural resources themselves(natural processes) Mangrove forest management includes establishing protected forest areas for mangrove forest conservation so that they are well maintained and sustainable. From the socio-economic, cultural and human aspects, natural resources are needed to be able to continue their lives, on the other hand, the existence or sustainability of coastal natural resources is very dependent on human activities as the main users of natural resources.

Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study.

BACKGROUND: A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the third-line and later setting of follicular lymphoma. METHODS: EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20+ follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing. FINDINGS: Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome. INTERPRETATION: Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile. FUNDING: Genmab and AbbVie.

CMR characterization of patients with heart failure and left bundle branch block.

Aims: We aimed to identify the distinctive cardiovascular magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. The secondary aim was to determine whether these individuals exhibit characteristics that could potentially serve as predictors of left ventricular ejection fraction (LVEF) recovery as compared with patients without LBBB. Methods and results: We prospectively recruited patients with HFrEF (LVEF ≤ 40%) on echocardiography who were referred for early CMR examination. Patients with an established diagnosis of coronary artery disease and known structural or congenital heart disease were excluded. LV recovery was defined as achieving ≥10% absolute improvement to ≥40% in LVEF between baseline evaluation to CMR. A total of 391 patients were recruited including 115 (29.4%) with LBBB. Compared with HF patients without LBBB, those with LBBB exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8 ± 12 vs. 38 ± 12%, P = 0.105). The overall rate of LV recovery from baseline echocardiogram to CMR (70 [42-128] days) was not significantly different between LBBB and non-LBBB patients (27.8% vs. 31.5%, P = 0.47). Reduced LVEF remained an independent predictor of LV non-recovery only in patients with LBBB. Conclusion: Patients presenting with HFrEF and LBBB had larger LV cavities and smaller RV cavities than those without LBBB but no difference in prevalence of scar or ischaemia. The rates of LV recovery were similar between both groups, which supports current guidelines to defer device therapy until 3-6 months of guideline-directed medical therapy, rather than early CMR and device implantation.

Efficiently recording and processing data from arbuscular mycorrhizal colonization assays using AMScorer and AMReader.

Arbuscular mycorrhizal (AM) fungi engage with land plants in a widespread, mutualistic endosymbiosis which provides their hosts with increased access to nutrients and enhanced biotic and abiotic stress resistance. The potential for reducing fertiliser use and improving crop resilience has resulted in rapidly increasing scientific interest. Microscopic quantification of the level of AM colonization is of fundamental importance to this research, however the methods for recording and processing these data are time-consuming and tedious. In order to streamline these processes, we have developed AMScorer, an easy-to-use Excel spreadsheet, which enables the user to record data rapidly during from microscopy-based assays, and instantly performs the subsequent data processing steps. In our hands, AMScorer has more than halved the time required for data collection compared to paper-based methods. Subsequently, we developed AMReader, a user-friendly R package, which enables easy visualization and statistical analyses of data from AMScorer. These tools require only limited skills in Excel and R, and can accelerate research into AM symbioses, help researchers with variable resources to conduct research, and facilitate the storage and sharing of data from AM colonization assays. They are available for download at https://github.com/EJarrattBarnham/AMReader, along with an extensive user manual.

Gender differences in outcomes following endoscopic sinus surgery: a systematic review and meta-analysis.

BACKGROUND: The extent to which gender affects outcomes in chronic rhinosinusitis (CRS) is unclear. The objective of this study was to examine differential outcomes between genders following endoscopic sinus surgery (ESS) among CRS patients. METHODS: PubMed/Ovid, Embase and Cochrane databases were queried. Outcomes included disease burden on imaging and endoscopy, patient-reported outcome measures (PROMs) including the Sinonasal Outcome Test (SNOT-22), revision rates, and olfactory outcomes. Meta-analysis was performed using the Mantel-Haenszel method with random effects model. RESULTS: Of 4,656 articles screened, 32 (n=103,499) were included for qualitative analysis and four (n=2,602) for meta-analysis. On qualitative analysis, 19 of the 32 studies noted a significant gender difference in post-operative outcomes, with five studies favoring women and 14 favoring men. Nine of 18 studies with PROMs noted a difference between genders, all favoring men. Olfactory outcomes were mixed with studies divided on favoring men vs women. No studies noted significant gender differences of disease burden on imaging or endoscopy. Across four studies included in the meta-analysis, women had higher preoperative and post-operative SNOT-22 scores. CONCLUSION: Meta-analysis shows that women patients have worse pre and postoperative SNOT-22 scores. Postoperative gender differences are most apparent in studies that examined PROMs. Further research is needed to investigate the underlying causes and to mitigate disparities between genders.

Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models.

INTRODUCTION: KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301. METHODS: C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations. RESULTS: KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection. CONCLUSIONS: Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.

Effect of colloidal magnetite (Fe3O4) nanoparticles on the electrical characteristics of the azolectin bilayer in a static inhomogeneous magnetic field.

This work is devoted to the study of the combined effects of applied magnetic field and MNPs on the electrical characteristics of bilayer lipid membranes. We present results of the study of electrical parameters of azolectin membranes in a static inhomogeneous magnetic field at the one-sided addition of positively charged quasi-spherical superparamagnetic magnetite nanoparticles with a diameter of about 4 nm. The magnet was located at different distances from the membrane, and the magnetic field attracted the nanoparticles to the membrane surface with different strengths. We observed three pronounced effects that depended on the external magnetic field. Firstly, after addition of nanoparticles in a magnetic field, the conductance of the membranes increased. A smooth increase in conductance was accompanied in some cases by the appearance of current jumps, which can be associated with the formation of through pores with a radius of no more than 1 nm. The conductance increased with increasing magnetic field gradient. Secondly, at zero command voltage, a negative current through the membrane was observed. Although our experiments did not allow us to unambiguously determine which particles create this current, we believe that this current is associated with the penetration of particles through the membrane. This effect intensified with increasing magnetic field gradient. Thirdly, we observed a sharp change in the nonlinear dependence of capacitance on voltage associated both with the change in the surface potential of the azolectin membrane and with the effect of MNP binding to the membrane surface on the apparent membrane capacitance.

Framework for evaluation of food safety in the circular food system.

In order to minimise food waste, side streams from feed and food production are increasingly being (re-) used in food supply chains. Such reuse contributes to the desire to implement circularity in food and agricultural systems. However, the reuse of side products in circular food systems may impact food safety, for instance, contaminant residues present at low levels in biomass may accumulate when reusing streams. In order to assess potential food safety issues related to circular food systems, a framework has been developed in this study. Based on this framework, appropriate actions can be taken to prevent from human health risks. The framework consists of three steps: 1. Describing the changes in the food supply chain as a result of the circularity transition; 2. Identifying potential food safety hazards related to the change; and 3. Prioritising food safety hazards related to the circularity transition. For the prioritisation, both the presence of the hazards in final foods and the effects of the hazards on human health need to be assessed. Persistence of the hazard in the environment and potential transfer from the environment to the final food product are relevant elements to include. The framework was tested in three case studies, showing that it allows for a prioritisation between hazards. Based on the case study results, circularity not so much influences the health effects of the hazards, but rather their presence depending on the persistence and transfer of food safety hazards in a circular system.

The chemical and microbiological safety of emerging alternative protein sources and derived analogues: A review.

Climate change and changing consumer demand are the main factors driving the protein transition. This shift toward more sustainable protein sources as alternatives to animal proteins is also reflected in the rapid upscaling of meat and dairy food analogues. Such changes could challenge food safety, as new food sources could result in new and unexpected food safety risks for consumers. This review analyzed the current knowledge on chemical and microbiological contamination of emerging alternative protein sources of plant origin, including soil-based (faba bean, mung bean, lentils, black gram, cowpea, quinoa, hemp, and leaf proteins) and aquatic-based (microalgae and duckweeds) proteins. Moreover, findings on commercial analogues from known alternative protein sources were included. Overall, the main focus of the investigations is on the European context. The review aimed to enable foresight approaches to food safety concerning the protein transition. The results indicated the occurrence of multiple chemical and microbiological hazards either in the raw materials that are the protein sources and eventually in the analogues. Moreover, current European legislation on maximum limits does not address most of the "contaminant-food" pairs identified, and no legislative framework has been developed for analogues. Results of this study provide stakeholders with a more comprehensive understanding of the chemical and microbiological safety of alternative protein sources and derived analogues to enable a holistic and safe approach to the protein transition.

[Prognosis of a high risk of non-alcoholic fatty liver disease in the long-term period of laparoscopic cholecystectomy in the elderly and senile.]

After cholecystectomy, elderly patients require special attention, due to the influence of involution processes in the body on the formation of complications. To identify prognostic criteria for the formation of fatty liver degeneration in the long-term period of minimally invasive cholecystectomy, 159 men were examined. Dysregulation of the biliary tract was determined using magnetic resonance cholangiopancreatography, elastography and magnetic resonance imaging of the liver. Microbial markers of the wall microbiome of the intestine were determined using chromatography-mass spectrometry. The relationship between an increase in body mass index and a decrease in the amount of obligate microbiome (r=-0,43, p<0,050), as well as with the formation of fatty liver degeneration in elderly patients, was revealed. The features of vegetative regulation in elderly people with fatty liver degeneration have been determined. It has been proven that in old age, a decrease in the number of obligate anaerobic association of microorganisms of the small intestine (on average from 15 659 to 7 630 in persons of the 2nd age subgroup and from 1 457 to 17 837 in the 3rd) is a predictor of fatty liver degeneration. The prognostic algorithm developed on the basis of the analysis of highly informative signs makes it possible to identify with an accuracy of at least 75% a high risk of fatty liver degeneration in the long-term period of cholecystectomy.

Isolated Roux-en-Y versus single loop pancreaticojejunal reconstruction after pancreaticoduodenectomy - a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Pancreaticoduodenectomy is a complex intra-abdominal operation used for the treatment of benign and malignant disease of the pancreatic head or periampullary region. Despite developments in surgical techniques, pancreaticoduodenectomy is still associated with high rate of postoperative complications. We performed this systematic review and meta-analysis to compare the surgical outcomes of isolated Roux-en-Y pancreaticojejunostomy (IRYPJ), and conventional pancreaticojejunostomy(CPJ). METHODS: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We searched the following electronic databases - PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical-Trials.gov. Published trials comparing the efficacy and safety of IRYPJ and CPJ after pancreaticoduodenectomy were evaluated. The search terms were "pancreaticoduodenectomy," "Whipple," "pylorus-preserving pancreaticoduodenectomy," "pancreaticojejunostomy," "Roux-en-Y," and "isolated Roux loop pancreaticojejunostomy." Only randomised controlled trials comparing outcome of IRYPJ and CPJ after pancreaticoduodenectomy were included. The analysed outcome measures were postoperative pancreatic fistula (POPF), clinically relevant POPF (CR-POPF), bile leak and delayed gastric emptying (DGE). RESULTS: The initial search yielded 342 results but only four randomised control trials fulfilled the inclusion criteria and were included for data synthesis and meta-analysis. Meta-analysis of POPF revealed that IRYPJ is associated with less POPF compared to CPJ but the difference was not statistically significant (risk ratio = 0.58, p = 0.56). A similar finding was also observed with CR-POPF (risk ratio = 0.17, p = 0.87) and DGE (risk ratio = 0.74, p = 0.46). CONCLUSION: Isolated Roux-en-Y pancreaticojejunostomy is not associated with a superior outcome when compared to CPJ.

Integrated plant conservation through the Global Conservation Consortia.

The 2020 State of the World's Plants and Fungi report revealed that two in five plant species are threatened with extinction. Despite their diverse ecosystem services and myriad human uses, plants receive a fraction of the conservation resources directed at animal taxa. Several existing frameworks-including International Union for Conservation of Nature (IUCN) Specialist Groups, the American Public Gardens Association Plant Collections Network, and the Center for Plant Conservation National Collection of Endangered Plants-have spurred conservation action, but there remains an urgent need to scale up conservation efforts for the world's plants. Here, a new approach to coordinated conservation action for plant taxa is described: the Global Conservation Consortia (GCC). GCC catalyze institutions and experts to collaboratively develop and implement comprehensive strategies to prevent extinction of threatened plant groups. This review focuses on three tree-focused, U.S.-led consortia: cycads, magnolias, and oaks, but the GCC framework is applicable to other taxonomic groups. This review covers consortia design and implementation, provides conservation action case studies, and shares preliminary successes and challenges as this new and exciting approach to conservation is developed.