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It is difficult to separate an age-dependent fall in nitrogen use efficiency (NUE; N balance/N intake) in growing ruminants from a progressively decrease in animal protein requirements over time. This study examined the effect of dietary protein content on N partitioning, digestibility and N isotopic discrimination between the animal and its diet (Δ15Nanimal-diet) evaluated at two different fattening periods (early v. late). Twenty-four male Romane lambs (age: 19 ± 4.0 days; BW: 8.3 ± 1.39 kg) were equally allocated to three dietary CP treatments (15%, 17% and 20% CP on a DM basis). Lambs were reared with their mothers until weaning, thereafter housed in individual pens until slaughter (45 kg BW). During the post-weaning period, lambs were allocated twice (early fattening (30 days post-weaning) and late fattening (60 days post-weaning)) to metabolic cages for digestibility and N balance study. When diet CP content increased, the average daily gain of lambs increased (P < 0.05) while the age at slaughter decreased (P = 0.01), but no effect was observed on feed efficiency (P > 0.10). Diet CP content had limited effect on lamb carcass traits. Higher fibre digestibility was observed at the early v. late fattening period (P < 0.001). The N intake and the urinary N excretion increased when diet CP content increased (P < 0.001) and when shifting from early to late fattening period (P < 0.001). Faecal N excretion (P = 0.14) and N balance (P > 0.10) were not affected by diet CP content. Nitrogen digestibility increased (P < 0.001) as the diet CP content increased and on average it was greater at late v. early fattening period (P = 0.02). The NUE decreased (P = 0.001) as the diet CP content increased and as the lamb became older (P < 0.001). However, the age-dependent fall in NUE observed was lower at high v. low dietary CP content (CP × age interaction; P = 0.04). The Δ15Nanimal-diet was positively correlated (P < 0.05) with N intake (r = 0.59), excretion of faecal N (r = 0.41), urinary N (r = 0.69) and total manure N (r = 0.64), while negatively correlated with NUE (r = −0.57). Overall, the experiment showed NUE was lower in older lambs and when lambs were fed high diet CP content, and that Δ15Nanimal-diet was a useful indicator not only for NUE but also for urinary N excretion, which is a major environmental pollution factor on farm.

There is a lot of evidence that chicory could be a highly palatable and nutritious source of forage for ruminants, well adapted to climate change and dry conditions in summer, thanks to its resistance to drought and high water content. This study aimed to describe the effect of incorporating chicory to ryegrass or to a ryegrass–white clover mixture on feeding behaviour, digestive parameters, nitrogen (N) balance and methane (CH4) emissions in sheep. In total, three swards of ryegrass, white clover and chicory were established and managed in a manner ensuring the forage use at a constant vegetative stage throughout the experiment. In all, four dietary treatments (pure ryegrass; binary mixture: 50% ryegrass–50% chicory; ternary mixture: 50% ryegrass–25% white clover–25% chicory; and pure chicory) were evaluated in a 4×4 replicated Latin square design with eight young castrated Texel sheep. Each experimental period consisted of an 8-day diet adaptation phase, followed by a 6-day measuring phase during which intake dynamics, chewing activity, digestibility, rumen liquid passage rate, fermentation end-products, N balance and CH4 emissions were determined. Data were analysed using a mixed model and orthogonal contrasts were used to detect the potential associative effects between ryegrass and chicory. The daily voluntary dry matter intake was lower for pure ryegrass than for diets containing chicory (P

Summary: Background: Carbapenems are a family of end line antibiotics with increasing levels of resistance that are a cause for concern. Aim: To ascertain whether the CPE screening programme employed in an acute tertiary hospital is fit for purpose. Method: We outlined the current working algorithm employed using a universal screening programme over a 26-month screening period. Rectal swabs are cultured on arrival. Those with suspicious growth are further investigated using NG-Carba 5 lateral flow tests and Vitek 2.0 sensitivity cards. These practices were compared with NHS guidelines. Findings & Conclusions: In all, 53 true positives were detected from 45 patients since the screening was implemented in early 2018 (46 OXA-48, 6 KPC, 1 NDM). As the rate of screening increased, the number of positive screens decreased over time. There were a lot of similarities between the HSE guidelines and the published NHS CPE toolkit. It was evident that there is no standard practice being employed across all hospitals. Comparing the MUH to national guidelines it appears to be quicker and more effective with universal screening in place at reducing the potential contacts and identifying carriers. Cost analysis indicates that the need to confirm all positive strains in a reference lab is costly, unnecessary and time consuming. There are adequate confirmatory tests available in-house for routine positive screens. It was concluded that infection prevention and control are key to identifying and controlling possible outbreaks in a hospital setting.

Stress changes in GeTe thin films on silicon have been studied in situ as a function of temperature by optical curvature measurements. Crystallization of the initially amorphous layers is evidenced by a steep tensile stress buildup. The crystallization temperature is shown to be thickness-dependent for the thinner films. Various annealing conditions, such as cooling/re-heating steps and isothermal stages, allow exploring the thermo-mechanical behavior of the films. A non-thermoelastic temperature-dependent behavior is observed in the amorphous phase before crystallization. Keywords: Phase-change materials, GeTe, Thin films, Stress measurements, Thermomechanical behaviour

Probiotics offer potential as an approach for the prevention and control of poultry intestinal diseases, but external factors can influence the birds’ response. Combining data from multiple trials provides greater confidence around efficacy under varying production conditions. Therefore, this study combined data from three separate trials analyzing the effect of a dual-strain probiotic comprising Lactobacillus acidophilus AG01 and Bifidobacterium animalis subspecies lactis AG02 on broilers during a mild necrotic enteritis (NE) challenge. In each, 1,440 broilers were assigned to floor-pens (40 birds/pen, 12 pens/treatment) in a completely randomized design. Treatments in each trial were a non-challenged control (C); challenged control (10 x dose of Eimeria/bird on d 14 and 1.0 x ∼109 colony forming units (CFU)/bird of C. perfringens on d 16-20; CC); and CC supplemented daily via the waterline with 1 × 109 CFU/bird of probiotic (CC+Probiotic). Birds were fed corn-soybean mealbased diets by phase (starter: 0 to 14, grower: 15 to 28, finisher: 29 to 42 d of age) ad libitum. Growth performance was monitored over 42 d, NE lesion scoring performed on d 21 and 28 in all trials, and, in Trial 3 only, cecal microbiota composition was analyzed on d 28. From d 1 to 42, CC birds exhibited reduced BW, BW gain (BWG), and feed intake (FI) (-9.2 %, -9.5 %, -5.0 %, respectively; P < 0.05), increased FCR and mortality (+8.5 points and 1.3 % points, respectively; P < 0.05) compared to C, and increased NE induction on d 28 (67.8 vs. 9.4 %, P

ABSTRACT: Pressure to reduce the use of antibiotics in the poultry industry has intensified research on alternative solutions to support intestinal health, including but not limited to direct fed microbials (DFM). Heat stress is known to impact intestinal health and function. The aim of this study was to determine efficacy of a water applied DFM product on broiler performance during the summer period. One of two treatments were randomly allocated to 12 replicate floor pens each: a control treatment and a treatment provided daily with a dual strain DFM comprised of Lactobacillus acidophilus AG01 and Bifidobacterium animalis AG02 at 1 × 108 CFU/bird/d. Each pen contained 20 Ross 308 broilers. All birds were fed the same three-phased wheat- and soybean meal-based diets. Body weight, feed intake, feed conversion ratio, and mortality were measured at d 0, 10, 24, 35, and 42. Due to natural extreme external temperature conditions, all birds were subject to heat stress during the end of the grower phase up to and including the finisher phase. Temperature was on average 5°C higher compared to industry recommendation. No significant differences were found in growth performance between the control and DFM treatment, yet BW at d 42 in both treatments was reduced by 19% compared to the breed standard. The DFM treatment significantly reduced mortality among the birds. Overall mortality from d 1 to d 35 was reduced from 4.58% to 0.42% (P = 0.023) and overall mortality from d 1 to d 42 was reduced from 5.83 to 0.83% (P = 0.027). This was driven by the difference in heat-stress related mortality in the finisher phase from d 25 to d 42, where mortality reached only 0.44% in the DFM treatment versus 2.88% in the unsupplemented control treatment. Post-mortem analysis confirmed heat-stress related hypoxia. In conclusion, the dual strain DFM may have provided improved (intestinal) homeostasis and barrier function allowing increased resilience to heat stress in broilers.

Introduction: Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center. Methods: We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol. Results: 27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR. Conclusions: aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS.

Purpose: We describe the design and development of the European Platform to Promote health and wellbeing in the workplace (EMPOWER) digital intervention that provides an integrative user programme meeting the needs of employees and employers in addressing work stress. Results: A user-centred design process was followed from January 2020 until November 2021. A tailored algorithm was developed to provide support at the individual employee level and the company level. Each element of the digital intervention was developed in English and then translated in Spanish, English, Polish and Finnish. The digital intervention consists of a website and a mobile application (app) that provides algorithm-based personalised content after assessing a user's somatic and psychological symptoms, work functioning, and psychosocial risk factors for work stress. It has a public section and an employer portal that provides recommendations to reduce psychosocial risks in their company based upon clustered input from employees. Usability testing was conducted and showed high ease of use and completion of tasks by participants. Conclusion: The EMPOWER digital intervention is a tailored multimodal intervention addressing wellbeing, work stress, mental and physical health problems, and work productivity. This will be used in a planned RCT in four countries to evaluate its effectiveness.

This is a study of two populations of learners/teachers: Pre-service teacher students (i.e., formal education for teaching certification) and In-service teachers (i.e., engaged in professional development), and involves an examination of their use of internet-based instructional applications. In these studies, the technologies are: a) Online Learning [OL]; b) Blended Learning [BL] and c) Flipped Classrooms [FC]. Treatments were compared to standard face-to-face classroom instruction (CI) on three dependent measures analysed separately to produce 77 achievement measures in the first meta-analysis, 21 attitude/satisfaction measures in the second, and 22 studies of self-efficacy in the third. Achievement data yielded a statistically significant, moderate effect size (i.e., g+= 0.44) in favor of the combined OL, BL and FC approaches versus CI, although OL showed only a small positive effect versus CI. Attitude yielded a non-significant effect size comparing CI with technology-supported strategies (g+= 0.12). Interestingly, self-efficacy produced a significant and moderate average random effect size of g+ = 0.45. Perhaps the most impactful finding of this analysis is related to improved performance of BL/FC when contrasted with OL, yielding significantly positive differences in all three measures. This confirms that improved outcomes are the result of better pedagogy, not the mere presence of technology. Finally, self-efficacy was found to be meaningfully improved when using BL/FC. This is the first meta-analysis with this target population implicating self-efficacy. These two outcomes offer important implications for institutions regarding the future design of instructional delivery for both pre- and in-service teachers.

Summary: Despite increasing threats of extinction to Elasmobranchii (sharks and rays), whole genome-based conservation insights are lacking. Here, we present chromosome-level genome assemblies for the Critically Endangered great hammerhead (Sphyrna mokarran) and the Endangered shortfin mako (Isurus oxyrinchus) sharks, with genetic diversity and historical demographic comparisons to other shark species. The great hammerhead exhibited low genetic variation, with 8.7% of the 2.77 Gbp genome in runs of homozygosity (ROH) > 1 Mbp and 74.4% in ROH >100 kbp. The 4.98 Gbp shortfin mako genome had considerably greater diversity and 1 Mbp. Both these sharks experienced precipitous declines in effective population size (Ne) over the last 250 thousand years. While shortfin mako exhibited a large historical Ne that may have enabled the retention of higher genetic variation, the genomic data suggest a possibly more concerning picture for the great hammerhead, and a need for evaluation with additional individuals.

Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.

Lipid droplets (LD) are storage sites for neutral lipids that can be used as a source of energy during nutrient starvation, but also function as hubs for fatty acid (FA) trafficking between organelles. In the yeast Saccharomyces cerevisiae, the absence of LD causes a severe disorganization of the endomembrane network during starvation. Here we show that cells devoid of LD respond to amino acid (AA) starvation by activating the serine/threonine phosphatase calcineurin and the nuclear translocation of its target protein Crz1. This activation was inhibited by treatments that restore a normal endomembrane organization, i.e. inhibition of FA synthesis with cerulenin or deletion of the inhibitory transcription factor Opi1. Activation of calcineurin increased the lifespan of LD-deficient cells during AA starvation. Indeed, deletion of its regulatory or catalytic subunits accelerated cell death. Surprisingly, calcineurin activation appeared to be calcium-independent. An increase in intracellular calcium was observed in LD-deficient cells during AA starvation, but its inhibition by genetic deletion of MID1 or YVC1 did not affect calcineurin activity. In contrast, calcineurin activation required the direct regulator of calcineurin Rcn1 and its activating (GSK-3)-related protein kinase Mck1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease, caused by mutations in the dystrophin gene and resulting in premature death. As a major secondary event, an abnormal elevation of the intracellular calcium concentration in the dystrophin-deficient muscle contributes to disease progression in DMD. In this study, we investigated the specific functional features of induced pluripotent stem cell-derived muscle cells (hiPSC-skMCs) generated from DMD patients to regulate intracellular calcium concentration. As compared to healthy hiPSC-skMCs, DMD hiPSC-skMCs displayed specific spontaneous calcium signatures with high levels of intracellular calcium concentration. Furthermore, stimulations with electrical field or with acetylcholine perfusion induced higher calcium response in DMD hiPSC-skMCs as compared to healthy cells. Finally, Mn2+ quenching experiments demonstrated high levels of constitutive calcium entries in DMD hiPSC-skMCs as compared to healthy cells. Our findings converge on the fact that DMD hiPSC-skMCs display intracellular calcium dysregulation as demonstrated in several other models. Observed calcium disorders associated with RNAseq analysis on these DMD cells highlighted some mechanisms, such as spontaneous and activated sarcoplasmic reticulum (SR) releases or constitutive calcium entries, known to be disturbed in other dystrophin-deficient models. However, store operated calcium entries (SOCEs) were not found to be dysregulated in our DMD hiPSC-skMCs model. These results suggest that all the mechanisms of calcium impairment observed in other animal models may not be as pronounced in humans and could point to a preference for certain mechanisms that could correspond to major molecular targets for DMD therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In the recent years, the number of Point-Of-Care-Tests (POCTs) available for clinical diagnostic has steadily increased. POCTs provide a near-patient testing with the potential to generate a result quickly so that appropriate treatment can be implemented, leading to improved clinical outcomes compared to traditional laboratory testing. Technological advances, such as miniaturization of sensors and improved instrumentation, have revolutionized POCTs, enabling the development of smaller and more accurate devices. In this context, it has also gained increasing importance the screening of various analytes simultaneously to increase specificity and improve the characterization of the disease. This study is aimed at developing and characterizing a photonic integrated circuit for multiple markers detection, which represents the functional core towards a full developed POCT device for clinical pathology applications. The photonic sensor, based on microring resonators (MRRs), is functionalized by immobilizing specific antibodies on a copolymer layer deposited on the MRR's surfaces. Surface chemical techniques were employed to analyse the surface chemical characteristics while fluorescence microscopy was involved to analyse the resulting bioreceptor surface density. The photonic sensor is characterized for the parallel detection of two biomarkers, the C-Reactive Protein (CRP) and the Creatine-Kinase-MB (CK-MB). The analyte-antibody binding curves were obtained both in buffer and in filtered un-diluted artificial saliva showing promising results both in terms of sensitivity, with limit of detection (LOD) of 103 pM for CRP and 140 pM for CK-MB, and in terms of specificity. These encouraging results let the assembly of a highly sensitive POC device for molecular diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of either IL-10 signaling or δOR triggered relapsing pain. Overall, our findings, from electrophysiology, genetic manipulation, flow cytometry, pharmacology, and behavioral approaches, indicate that remission of pain is not simply a return to the naïve state. Instead, remission is an adapted homeostatic state associated with lasting pain vulnerability resulting from persisting neuroimmune interactions within the nociceptive system. Broadly, this sheds light on the elusive mechanisms underlying recurrence a common aspect across various chronic pain conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The quality control of serological assays remains controversial. The aim of this project was to describe the problems associated with a working model for controlling these assays and solutions, including using a source of well-defined targets and acceptable limits, a process to identify lot-to-lot reagent variation and an interpretation of the result that accounted for the clinical situation. False-negative results are problematic but can be reduced by identifying and comparing reagent lot variation with previous results., Methods: The components of the Quality Assurance strategy are the following: Lot-to-lot reagent and calibrator variation assessment; dynamic, big-data approach to determine accurate targets and acceptable limits for manufacturer-provided QC material; negative QC monitoring process; use of commutable EQA with a sufficient method subgroup size to assess bias; clinical assessment of any statistically flagged error; and provision of support to the clinician for the interpretation of results., Results: The model described has been used for twelve months, and acceptable variation has been maintained., Conclusions: The paper presents a solution that emphasizes the early detection of reagent lot variation and patient risk rather than instrument control. Reducing the risk of a false result to patients requires optimal assay quality control and an effective mechanism to support the clinician's use of these results in diagnosis and monitoring. The problems of serological assays are well-known, but there remain few integrated solutions in the literature., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Placentitis is an important cause of reproductive losses in the equine industry. Many cases of clinical placentitis are not diagnosed until late in the course of the disease, and for this reason there is variability in the timing of intervention, diagnostic measurements, and treatment protocols. An 8-year-old multiparous Dutch Warmblood mare that was recently exposed to EHV-1 in the herd of origin presented for routine foaling management. Placentitis was diagnosed upon intake, and medical treatment was initiated. The mare delivered a term foal, and diagnostics for infectious etiology were unrewarding. While there were obvious clinical signs supporting a diagnosis of placentitis, histopathologic examination did not reveal active inflammatory lesions in the chorioallantois; however, severe funisitis was present. This report reviews early diagnosis and management of placentitis, demonstrates an array of classic and subtle pathologic lesions seen on microscopic examination, and discusses pathophysiology of placentitis., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to explore the non-volatile metabolomic variability of a large panel of strains (44) belonging to the Saccharomyces cerevisiae and Saccharomyces uvarum species in the context of the wine alcoholic fermentation. For the S. cerevisiae strains flor, fruit and wine strains isolated from different anthropic niches were compared. This phenotypic survey was achieved with a special focus on acidity management by using natural grape juices showing opposite level of acidity. A 1 H NMR based metabolomics approach was developed for quantifying fifteen wine metabolites that showed important quantitative variability within the strains. Thanks to the robustness of the assay and the low amount of sample required, this tool is relevant for the analysis of the metabolomic profile of numerous wines. The S. cerevisiae and S. uvarum species displayed significant differences for malic, succinic, and pyruvic acids, as well as for glycerol and 2,3-butanediol production. As expected, S. uvarum showed weaker fermentation fitness but interesting acidifying properties. The three groups of S. cerevisiae strains showed different metabolic profiles mostly related to their production and consumption of organic acids. More specifically, flor yeast consumed more malic acid and produced more acetic acid than the other S. cerevisiae strains which was never reported before. These features might be linked to the ability of flor yeasts to shift their metabolism during wine oxidation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marullo Philippe reports financial support was provided by Biolaffort. Vion Charlotte reports financial support was provided by Biolaffort. Maitena Muro reports financial support was provided by Biolaffort. Margaux Bernard reports financial support was provided by Biolaffort., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As highly effective modulator therapy improves the lives of many people with cystic fibrosis (pwCF), more are considering or pursuing parenthood. This study explores the interplay between having CF and being a parent., Methods: We recruited pwCF with >1 child ≤10 years from CF Foundation Community Voice and participating CF centers to complete interviews exploring their decision-making process to become a parent, adjustment to parenthood with CF, the impact of CF on parenting, and the impact of parenting on CF care/adherence. We transcribed and thematically analyzed interviews using a deductive approach., Results: Twenty-one mothers and 16 fathers participated (age 22-46 years). Key themes included: 1) The responsibilities of parenthood and the responsibilities of CF care often conflict, requiring creative multitasking and alterations to other aspects of life; 2) Delegating tasks to partners/family can alleviate conflicts between parenting and CF care; 3) While CF teams do not play a major role in decisions to become a parent, pwCF desire support/resources specific to parenting from their CF team; 4) It is logistically and emotionally difficult to avoid illnesses transmitted from children, but some parents use precautions to mitigate risk; and 5) Parents with CF desire clinic-facilitated connections with other parents with CF to share strategies and for emotional support., Conclusions: Parents with CF have unique challenges both as pwCF and as parents, and the intersection of these roles can impact their health outcomes and care adherence. Identifying common challenges may allow CF care teams to improve support of parents with CF., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Cardiovascular disease (CVD) is known to be linked with metabolic associated fatty liver disease and type 2 diabetes, but few studies assessed this relationship in prediabetes, especially among women, who are at greater risk of CVD. We aimed to evaluate cardiac alterations and its relationship with hepatic lipid metabolism in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS)., Methods and Results: Wistar female rats were divided into 2 groups fed for 5 months with standard or HFS diet. We analyzed cardiac morphology, function, perfusion and fibrosis by Magnetic Resonance Imaging. Hepatic lipid contents along with inflammation and lipid metabolism gene expression were assessed. Five months of HFS diet induced glucose intolerance (p < 0.05), cardiac remodeling characterized by increased left-ventricular volume, wall thickness and mass (p < 0.05). No significant differences were found in left-ventricular ejection fraction and cardiac fibrosis but increased myocardial perfusion (p < 0.01) and reduced cardiac index (p < 0.05) were shown. HFS diet induced hepatic lipid accumulation with increased total lipid mass (p < 0.001) and triglyceride contents (p < 0.05), but also increased mitochondrial (CPT1a, MCAD; (p < 0.001; p < 0.05) and peroxisomal (ACO, LCAD; (p < 0.05; p < 0.001) β-oxidation gene expression. Myocardial wall thickness and perfusion were correlated with hepatic β-oxidation genes expression. Furthermore, myocardial perfusion was also correlated with hepatic lipid content and glucose intolerance., Conclusion: This study brings new insights on the relationship between cardiac sub-clinical alterations and hepatic metabolism in female prediabetic rats. Further studies are warranted to explore its involvement in the higher CVD risk observed among prediabetic women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: We aimed to quantify how the vaccine efficacy of BNT162b2, messenger RNA-1273, AD26.COV2-S, and ChAdOx1 nCoV-19 against detected infection by the SARS-CoV-2 Delta and Omicron variants varied by time since the last dose, vaccine scheme, age, and geographic areas., Methods: We analyzed 3,261,749 community polymerase chain reaction tests conducted by private laboratories in France from December 2021 to March 2022 with a test-negative design comparing vaccinated to unvaccinated individuals., Results: Efficacy against detected infection by Delta was 89% (95% confidence interval, 86-91%) at 2 weeks, down to 59% (56-61%) at 26 weeks and more after the second dose. Efficacy against Omicron was 48% (45-51%) at 2 weeks, down to 4% (2-5%) at 16 weeks after the second dose. A third dose temporarily restored efficacy. Efficacy against Omicron was lower in children and the elderly. Geographical variability in efficacy may reflect variability in the ratio of the number of contacts of vaccinated vs unvaccinated individuals. This ratio ranged from 0 to +50% across departments and correlated with the number of restaurants and bars per inhabitant (beta = 15.0 [0.75-29], P-value = 0.04), places that only vaccinated individuals could access in the study period., Conclusion: SARS-CoV-2 vaccines conferred low and transient protection against Omicron infection., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs., Methods: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting., Findings: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group., Interpretation: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission., Funding: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie., Competing Interests: Declaration of interests AdM reports research funding from Innate, Almirall, and Kyowa Kirin; travel expenses from Kyowa Kirin, Recordati Rare Diseases and Orphan Europe, and Janssen-Cilag; and fees from Takeda. MB-B reports consultancy at Kyowa Kirin and Recordati; and research funding from Celgene and Roche. SD reports institutional grants from Bristol Myers Squibb and Merck Sharp & Dohme. SI-H-O reports consultancy for Takeda and Recordati. CO reports honoraria from Novartis. JA reports honoraria from Roche and Janssen. OD reports consultancy from Bristol Myers Squibb, Kyowa Kirin, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, Recordati Rare Diseases, Sanofi, and Sun Pharma; honoraria from Bristol Myers Squibb, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, Recordati Rare Diseases, Sanofi, and Sun Pharma; registration to meetings from Bristol Myers Squibb, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, and Pierre Fabre; grants from Pierre Fabre; research funding from Kyowa Kirin, Novartis, and Pierre Fabre; and travel expenses from Bristol Myers Squibb, Janssen, Kyowa Kirin, LeoPharma, Merck, Sharpe & Dohme, Novartis, Pierre Fabre, and Sanofi. SBa reports consultancy at Amgen and Blueprint Medicines; and honoraria from Novartis, Leo Laboratories, and AbbVie. EW-H reports consultancy at Novartis, Bristol Myers Squibb, Pierre Fabre, BluePrint, Sun Pharma, AbbVie, and Sanofi; research funding from AbbVie; and honoraria from Bristol Myers Squibb, Novartis, AbbVie, Sanofi, and Pierre Fabre. FA reports consultancy at AbbVie, Almirall, Amgen, Bristol Myers Squibb, Janssen-Cilag, Leo, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, and Union Chimique Belge; honoraria from AbbVie, Almirall, Amgen, Bristol Myers Squibb, Janssen-Cilag, Leo, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, and Union Chimique Belge; and research funding from Galderma, Janssen, and Pfizer. RH reports honoraria from Kite and Gilead, Novartis, Incyte, Janssen, Merck Sharp & Dohme, Takeda, and Roche; and consultancy at Kite and Gilead, Novartis, Bristol Myers Squibb and Celgene, ADC Therapeutics, Incyte, and Miltenyi. AP-L reports honoraria from Bristol Myers Squibb and Novartis; and travel accommodation and meeting participation from Kyowa Kirin, Recordati, Novartis, and Bristol Myers Squibb. DM reports honoraria from Novartis, Incyte, CSL Behring, and Jazz Pharmaceuticals. J-DB reports being on a speaker or advisory board member for Boehringer-Ingelheim, Janssen, Novartis, Union Chimique Belge, Leo, AbbVie, Eli Lilly, Pfizer, Sanofi, and Almirall. FG reports consultancy at Recordati Rare Disease, Kyowa Kirin, Novartis, Pierre Fabre, Bristol Myers Squibb, and Merck Sharp & Dohme. HM-T reports consultancy at Innate; and research funding from Kyowa Kirin. SMo reports honoraria from Novartis, Pierre Fabre, Roche and Biocartis; and research funding from Novartis and Bristol Myers Squibb. MBat reports consultancy at Bristol Myers Squibb and Quantum Genomics; honoraria from Innate, Kyowa Kirin, Takeda, Meccellis Biotech, Cerba Research, and Sanofi; research funding from Kyowa Kirin; and grants from Takeda. ED reports grants from Pfizer and Mallinckrodt; and consultancy at Swedish Orphan Biovitrum. ML reports honoraria from Novartis, Pfizer, Alexion Pharmaceuticals, Sandoz, Novartis, Sanofi, Swedish Orphan Biovitrum, Gilead, and Bristol Myers Squibb. AP reports consultancy and honoraria from Novartis, Pierre-Fabre, Bristol Myers Squibb, Merck Sharp & Dohme, and Sun Pharma. AH reports consultancy at Novartis, Astellas, Jazz Pharmaceuticals, and Pfizer; and honoraria from Novartis, Astellas, Jazz Pharmaceuticals, and Pfizer. YLC reports consultancy at Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, and Pierre Fabre Oncologie; and honoraria from Novartis, Leo, AbbVie, Pfizer, and Pierre Fabre Oncologie. EF reports participation in advisory board at Gilead, GSK, and Sanofi; speakers bureau from Novartis and Alexion; honoraria from Novartis; and travel grants from Gilead, Merck Sharp & Dohme, Jazz Pharmaceuticals, and Novartis. GS reports consultancy at Novartis and Alexion Pharmaceuticals; honoraria from Novartis, Incyte, and Alexion Pharmaceuticals; and research funding from Alexion Pharmaceuticals. RPdL reports consultancy at Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; honoraria from Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; research funding from Novartis, Pfizer, Amgen, and Alexion Pharmaceuticals; and grants from Alexion Pharmaceuticals, Amgen, Novartis, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the context of climate change, the chemical composition of wines is characterized by a massive drop of malic acid concentration in grape berries. Then wine professionals have to find out physical and/or microbiological solutions to manage wine acidity. The aim of this study is to develop wine Saccharomyces cerevisiae strains able to produce significant amount of malic acid during the alcoholic fermentation. By applying a large phenotypic survey in small scale fermentations, the production level of malic acid in seven grape juices confirmed the importance of the grape juice in the production of malic acid during the alcoholic fermentation. Beside the grape juice effect, our results demonstrated that extreme individuals able to produce up to 3 g/L of malic acid can be selected by crossing together appropriate parental strains. A multivariate analysis of the dataset generated illustrate that the initial the amount of malic acid produced by yeast is a determining exogenous factor for controlling the final pH of wine. Interestingly most of the acidifying strains selected are particularly enriched in alleles that have been previously reported for increasing the level of malic acid at the end of the alcoholic fermentation. A small set of acidifying strains were compared with strains able to consume a large amount of malic acid previously selected. The total acidity of resulting wines was statistically different and a panelist of 28 judges was able to discriminate the two groups of strains during a free sorting task analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marullo Philippe reports financial support was provided by Biolaffort. Vion Charlotte reports financial support was provided by Biolaffort. Maitena Muro reports financial support was provided by Biolaffort. Margaux Bernanrd reports financial support was provided by Biolaffort., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: This study evaluates the possibility for replacing conventional 3 slices, 3 breath-holds MOLLI cardiac T1 mapping with single breath-hold 3 simultaneous multi-slice (SMS3) T1 mapping using blipped-CAIPIRINHA SMS-bSSFP MOLLI sequence. As a major drawback, SMS-bSSFP presents unique artefacts arising from side-lobe slice excitations that are explained by imperfect RF modulation rendering and bSSFP low flip angle enhancement. Amplitude-only RF modulation (AM) is proposed to reduce these artefacts in SMS-MOLLI compared to conventional Wong multi-band RF modulation (WM)., Materials and Methods: Phantoms and ten healthy volunteers were imaged at 1.5 T using a modified blipped-CAIPIRINHA SMS-bSSFP MOLLI sequence with 3 simultaneous slices. WM-SMS3 and AM-SMS3 were compared to conventional single-slice (SMS1) MOLLI. First, SNR degradation and T1 accuracy were measured in phantoms. Second, artefacts from side-lobe excitations were evaluated in a phantom designed to reproduce fat presence near the heart. Third, the occurrence of these artefacts was observed in volunteers, and their impact on T1 quantification was compared between WM-SMS3 and AM-SMS3 with conventional MOLLI as a reference., Results: In the phantom, larger slice gaps and slice thicknesses yielded higher SNR. There was no significant difference of T1 values between conventional MOLLI and SMS3-MOLLI (both WM and AM). Positive banding artefacts were identified from fat neighbouring the targeted FOV due to side-lobe excitations from WM and the unique bSSFP signal profile. AM RF pulses reduced these artefacts by 38%. In healthy volunteers, AM-SMS3-MOLLI showed similar artefact reduction compared to WM-SMS3-MOLLI (3 ± 2 vs 5 ± 3 corrupted LV segments out of 16). In-vivo native T1 values obtained from conventional MOLLI and AM-SMS3-MOLLI were equivalent in LV myocardium (SMS1-T1 = 935.5 ± 36.1 ms; AM-SMS3-T1 = 933.8 ± 50.2 ms; P = 0.436) and LV blood pool (SMS1-T1 = 1475.4 ± 35.9 ms; AM-SMS3-T1 = 1452.5 ± 70.3 ms; P = 0.515). Identically, no differences were found between SMS1 and SMS3 postcontrast T1 values in the myocardium (SMS1-T1 = 556.0 ± 19.7 ms; SMS3-T1 = 521.3 ± 28.1 ms; P = 0.626) and the blood (SMS1-T1 = 478 ± 65.1 ms; AM-SMS3-T1 = 447.8 ± 81.5; P = 0.085)., Conclusions: Compared to WM RF modulation, AM SMS-bSSFP MOLLI was able to reduce side-lobe artefacts considerably, providing promising results to image the three levels of the heart in a single breath hold. However, few artefacts remained even using AM-SMS-bSSFP due to residual RF imperfections. The proposed blipped-CAIPIRINHA MOLLI T1 mapping sequence provides accurate in vivo T1 quantification in line with those obtained with a single slice acquisition., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Left atrial appendage (LAA) occlusion devices provided an acceptable and valid alternative to anticoagulation among patients with atrial fibrillation who carry high bleeding risk. Watchman device is non-inferior to oral anticoagulation to prevent cerebrovascular accidents. The presence of a longer distal portion of the older generation Watchman led to exclusion of patients with prohibitive anatomy of the LAA such as chicken-wing morphology or shallow LAA. Watchman FLX provides a wider range of sizes and can be implanted with complex anatomy or shallow LAA. In the case series, we discuss 3 patients with challenging LAA anatomy that underwent successful Watchman FLX implantation., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Diabetes affects the lives of patients and their close relatives. Considering the proven benefit of patient education programs, DiaLife was elaborated as the first German education program addressing the needs of relatives. The objective of this study was to investigate its efficacy., Methods: The evaluation was implemented in the form of a cRCT with longitudinal design and waiting list condition.In total, 179 relatives were recruited. Participants' diabetes-related knowledge was defined as the primary outcome. Diabetes-related strains, family interaction and other psychosocial factors were determined as secondary outcomes., Results: A generalized estimating equation model showed a persistent increase of diabetes-related knowledge in the intervention group compared to the control group regardless of the type of diabetes. Concerning secondary outcomes, mixed linear models showed an improvement for relatives of people with type 2 diabetes who participated in the DiaLife program., Conclusion: This study provides evidence of DiaLife's efficacy regarding a persistent increase of diabetes-related knowledge and a positive effect on psychosocial outcomes in relatives of people with type 2 but not in type 1 diabetes. Adding (an)other psychosocial module(s) might improve their well-being and psychosocial outcomes., Practice Implications: Diabetes centers should consider implementing an education program for relatives, such as DiaLife, in their curriculum., Trial Registration: The study was registered at the German Clinical Trials Register (DRKS00015157; date of registration: 24.08.2018)., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: New modulator therapies have markedly improved the health of people with cystic fibrosis (CF), allowing an increased focus on quality-of-life improvements for men with CF, including those related to sexual and reproductive health (SRH). This study explored CF providers' attitudes and experiences with addressing men's health in CF., Methods: We interviewed geographically diverse adult and pediatric United States (U.S.) CF program directors via semi-structured telephone interviews exploring their perspectives and practices related to men's SRH in CF. Two coders analyzed transcribed interviews and created a codebook to identify key themes., Results: We interviewed 20 providers and identified the following themes: 1) Men's SRH is important to address within CF care, but there is no standardization around this aspect of care; 2) There is no consensus about the recommendation or utilization of semen analysis to assess men's infertility; 3) There are many barriers to men's SRH care provision in CF centers, including the low priority of SRH concerns and provider discomfort and lack of expertise in SRH; 4) Providers desire clear evidence-based guidelines and patient resources related to men's SRH in CF; and 5) Providers believe future research should focus on testosterone and the impact of modulators on men's SRH., Conclusions: CF center directors acknowledge the importance of addressing SRH with men with CF, but there is a lack of standardization and research in this aspect of care. Existing barriers to optimal SRH care and identified facilitators in this study can serve as targets for interventions in the CF care model., Competing Interests: Declaration of Competing Interest There are no conflicts of interest regarding the publication of this data., (Copyright © 2021. Published by Elsevier B.V.)

Background: As people with cystic fibrosis (CF) are living longer, men with CF increasingly face both general and disease-specific sexual and reproductive health (SRH) concerns. This study explored the SRH experiences and preferences of men with CF in health care in the era of widespread use of highly effective CF modulator therapies., Methods: We recruited men with CF aged 18 years and older to participate in a qualitative descriptive study using semi-structured telephone interviews to explore experiences and preferences related to CF SRH care. Two independent researchers coded interview transcripts and conducted content and thematic analysis using an inductive approach., Findings: We interviewed 24 participants (mean age 33.7 ± 11.8 years, range 19-60) and identified five major themes: 1) CF SRH concerns, specifically infertility, can have negative impacts on men's perceptions of masculinity, relationships, and mental health; 2) As life expectancy increases, addressing male SRH is increasingly important in CF care; 3) Men with CF experience lack of SRH counseling and care; 4) Conversations about SRH should begin in early adolescence and be addressed regularly by CF providers in a stepwise fashion; 5) Men with CF value peer support and SRH information featuring the experiences of other men with CF., Conclusions: Men with CF acknowledge the need for comprehensive CF care that includes SRH and value early, stepwise, provider-initiated SRH conversations. Future work should seek a broader understanding of the impact of SRH on the mental health of men with CF as these concerns can have significant effects on the lives and self-identities of men with CF., Competing Interests: Declaration of Competing Interest There are no conflicts of interest regarding the publication of this data., (Copyright © 2022. Published by Elsevier B.V.)

In clinical applications, using erroneous segmentations of medical images can have dramatic consequences. Current approaches dedicated to medical image segmentation automatic quality control do not predict segmentation quality at slice-level (2D), resulting in sub-optimal evaluations. Our 2D-based deep learning method simultaneously performs quality control at 2D-level and 3D-level for cardiovascular MR image segmentations. We compared it with 3D approaches by training both on 36,540 (2D) / 3842 (3D) samples to predict Dice Similarity Coefficients (DSC) for 4 different structures from the left ventricle, i.e., trabeculations (LVT), myocardium (LVM), papillary muscles (LVPM) and blood (LVC). The 2D-based method outperformed the 3D method. At the 2D-level, the mean absolute errors (MAEs) of the DSC predictions for 3823 samples, were 0.02, 0.02, 0.05 and 0.02 for LVM, LVC, LVT and LVPM, respectively. At the 3D-level, for 402 samples, the corresponding MAEs were 0.02, 0.01, 0.02 and 0.04. The method was validated in a clinical practice evaluation against semi-qualitative scores provided by expert cardiologists for 1016 subjects of the UK BioBank. Finally, we provided evidence that a multi-level QC could be used to enhance clinical measurements derived from image segmentations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A patent including the present QC method was registered: Smart Heart, DSO2019018721. Steffen E. Petersen (SEP) provides consultancy to and owns stock of Cardiovascular Imaging Inc, Calgary, Alberta, Canada., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: The will to live (WTL) is an important indicator of subjective well-being. It may enable a deeper understanding of the well-being of nursing home residents., Objectives: To evaluate the intensity of WTL, its association with various factors, and its temporal evolution among residents ≥ 65 years old; we also aimed to compare it with proxy assessments of WTL., Methods: A cross-sectional study was conducted in five nursing homes in Switzerland. Participants with decisional capacity were asked to rate the intensity of their WTL on a single-item numerical rating scale ranging from 0-10. A short-term follow-up was conducted among a sub-sample of 17 participants after three and six weeks. Proxy assessment by residents' next of kin and professional caregivers was conducted, and inter-rater agreement was calculated., Results: Data from 103 participants (75.7% women, 87.3 ± 8.0 years) was analyzed. The median intensity of WTL was 8. Higher WTL was significantly associated with better physical mobility and shorter duration of daily care but not with age, gender, pre-admission care setting, or prognosis. Significant independent predictors of WTL were physical mobility and provenance from rehabilitative care. In the short-term follow-up assessment, WTL remained highly stable. Intraclass correlation coefficients were moderate for residents' next of kin and nurse assistants but poor for physicians and nurses; all proxy assessments underestimated the participants' WTL., Conclusion: Nursing home residents expressed a very strong WTL and proxy aents underestimated residents' WTL. It seems pivotal to proactively communicate with residents about their WTL., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: To improve access to palliative care, identification of patients in need of general or specialized palliative care is necessary. To our knowledge, no available identification instrument makes this distinction. ID-PALL is a screening instrument developed to differentiate between these patient groups., Objective: To assess the structural and criterion validity and the inter-rater agreement of ID-PALL., Methods: In this multicenter, prospective, cross-sectional study, nurses and physicians assessed medical patients hospitalized for 2 to 5 days in two tertiary hospitals in Switzerland using ID-PALL. For the criterion validity, these assessments were compared to a clinical gold standard evaluation performed by palliative care specialists. Structural validity, internal consistency and inter-rater agreement were assessed., Results: 2232 patients were assessed between January and December 2018, 97% by nurses and 50% by physicians. The variances for ID-PALL G and S are explained by two factors, the first one explaining most of the variance in both cases. For ID-PALL G, sensitivity ranged between 0.80 and 0.87 and specificity between 0.56 and 0.59. ID-PALL S sensitivity ranged between 0.82 and 0.94, and specificity between 0.35 and 0.64. A cut-off value of 1 delivered the optimal values for patient identification. Cronbach's alpha was 0.78 for ID-PALL G and 0.67 for ID-PALL S. The agreement rate between nurses and physicians was 71.5% for ID-PALL G and 64.6% for ID-PALL S., Conclusion: ID-PALL is a promising screening instrument allowing the early identification of patients in need of general or specialized palliative care. It can be used by nurses and physicians without a specialized palliative care training. Further testing of the finalized clinical version appears warranted., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Orchestrated recruitment of neutrophils to inflamed tissue is essential during the initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it remains unclear how these factors influence the migration of neutrophils to and at the site of inflammation during their transmigration through the blood-endothelial cell barrier, as well as their motility in the interstitial space. Here, we reveal that activation of hypoxia-inducible factor 2 (HIF2α) as a result of a deficiency in HIF prolyl hydroxylase domain protein 2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNA sequencing analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2α-dependent neutrophil motility. Thus, we propose that the novel PHD2-HIF2α-RhoA axis is vital to the initial stages of inflammation because it promotes neutrophil movement through highly confined tissue landscapes., (© 2021 by The American Society of Hematology.)

Context: The will to live (WTL) is an important factor to consider in the context of providing resource-oriented palliative care. Until now, there has been no major review of the existing research on this subject., Objectives: The primary objective of this study is to summarize the state of research concerning instruments that assess the WTL. The secondary objective is to explore the theoretical models and psychometric properties of these instruments, in studies where these instruments were initially presented. The tertiary objective is to identify, among all studies where these instruments have been used, the intensity of the WTL, and factors associated with it., Methods: We conducted a scoping review, including studies that were designed to assess the WTL among participants in all settings. Records were systematically searched from seven bibliographic databases with no date limitations up to August 2020., Results: Of the 3078 records screened, 281 were examined in detail and 111 were included in the synthesis. A total of 25 different instruments quantitatively assessing the WTL are presented. Most are single-question tools and rate intensity. The underlying concepts and psychometric properties are incompletely explained. Lack of crossreferencing is apparent. The intensity of the WTL is high, even among people with significant health impairment, and is frequently associated with different factors, such as resilience and quality of life., Conclusion: A considerable yet unconnected body of studies assesses the WTL. Its assessment in clinical routine could promote resource-oriented and patient-centered care., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cellular senescence, cancer and aging are highly interconnected. Among many important molecular machines that lie at the intersection of this triad, the mechanistic (formerly mammalian) target of rapamycin (mTOR) is a central regulator of cell metabolism, proliferation, and survival. The mTOR signaling cascade is essential to maintain cellular homeostasis in normal biological processes or in response to stress, and its dysregulation is implicated in the progression of many disorders, including age-associated diseases. Accordingly, the pharmacological implications of mTOR inhibition using rapamycin or others rapalogs span the treatment of various human diseases from immune disorders to cancer. Importantly, rapamycin is one of the only known pan-species drugs that can extend lifespan. The molecular and cellular mechanisms explaining the phenotypic consequences of mTOR are vast and heavily studied. In this review, we will focus on the potential role of mTOR in the context of cellular senescence, a tumor suppressor mechanism and a pillar of aging. We will explore the link between senescence, autophagy and mTOR and discuss the opportunities to exploit senescence-associated mTOR functions to manipulate senescence phenotypes in age-associated diseases and cancer treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rivers are representative of the overall contamination found in their catchment area. Contaminant concentrations in watercourses depend on numerous factors including land use and rainfall events. Globally, in Mediterranean regions, rainstorms are at the origin of fluvial multipollution phenomena as a result of Combined Sewer Overflows (CSOs) and floods. Large loads of urban-associated microorganisms, including faecal bacteria, are released from CSOs which place public health - as well as ecosystems - at risk. The impacts of freshwater contamination on river ecosystems have not yet been adequately addressed, as is the case for the release of pollutant mixtures linked to extreme weather events. In this context, microbial communities provide critical ecosystem services as they are the only biological compartment capable of degrading or transforming pollutants. Through the use of 16S rRNA gene metabarcoding of environmental DNA at different seasons and during a flood event in a typical Mediterranean coastal river, we show that the impacts of multipollution phenomena on structural shifts in the particle-attached riverine bacteriome were greater than those of seasonality. Key players were identified via multivariate statistical modelling combined with network module eigengene analysis. These included species highly resistant to pollutants as well as pathogens. Their rapid response to contaminant mixtures makes them ideal candidates as potential early biosignatures of multipollution stress. Multiple resistance gene transfer is likely enhanced with drastic consequences for the environment and human-health, particularly in a scenario of intensification of extreme hydrological events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)