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BACKGROUND: Climbing places high loads through the hands and fingers, and climbers may benefit from specific finger strength training (hangboarding) protocols. The purpose of this study was to evaluate the effect of a 10-minute low intensity hangboard finger strengthening protocol (Abrahangs), compared with the generally accepted Max Hangs protocol for training maximal grip strength. METHODS: We retrospectively evaluated the change in grip strength and Strength: Weight following Max Hangs, Abrahangs, or the two protocols performed concurrently in rock climbers who used the Crimpd app to log their training. Users who had completed two finger strength tests within a 4-16-week period were included. Climbers were grouped by the number of training sessions into: Climbing Only, Abrahangs Only, Max Hangs Only and Both Max Hangs and Abrahangs. RESULTS: Frequent low intensity finger loading was as effective at improving grip strength in climbers as training with maximal loads. Additionally, combining low intensity and maximal load training resulted in additive strength gains. CONCLUSIONS: These results suggest that low-intensity long duration holds provide a promising training paradigm for training finger strength that is gentle enough to incorporate into existing training programs.

Fish oils rank among the world's most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

Cultivated meat production requires bioprocess optimization to achieve cell densities that are multiple orders of magnitude higher compared to conventional cell culture techniques. These processes must maximize resource efficiency and cost-effectiveness by attaining high cell growth productivity per unit of medium. Microcarriers, or carriers, are compatible with large-scale bioreactor use, and offer a large surface-area-to-volume ratio for the adhesion and proliferation of anchorage-dependent animal cells. An ongoing challenge persists in the efficient retrieval of cells from the carriers, with conflicting reports on the effectiveness of trypsinization and the need for additional optimization measures such as carrier sieving. To surmount this issue, edible carriers have been proposed, offering the advantage of integration into the final food product while providing opportunities for texture, flavor, and nutritional incorporation. Recently, a proof of concept (POC) utilizing inactivated mycelium biomass derived from edible filamentous fungus demonstrated its potential as a support structure for myoblasts. However, this POC relied on a model mammalian cell line combination with a single mycelium species, limiting realistic applicability to cultivated meat production. This study aims to advance the POC. We found that the species of fungi composing the carriers impacts C2C12 myoblast cell attachment-with carriers derived from Aspergillus oryzae promoting the best proliferation. C2C12 myoblasts effectively differentiated on mycelium carriers when induced in myogenic differentiation media. Mycelium carriers also supported proliferation and differentiation of bovine satellite cells. These findings demonstrate the potential of edible mycelium carrier technology to be readily adapted in product development within the cultivated meat industry.

Abstract Background Patient participation is key in person-centred care, emphasizing individual choices in treatment. Oral health, integral to overall well-being, is sometimes a neglected part of health. This intervention introduces a novel approach to strengthen person-centred care in homecare settings, employing collaborative, interprofessional teamwork and shared documentation across care organizations. This protocol outlines the design of a cluster-randomized controlled trial (RCT) in Sweden, comparing traditional oral assessments with an interorganizational, team-based oral health care planning model facilitated by a shared digital platform for documentation. The overall aim is to evaluate a person-centred interprofessional and interorganizational model for oral health care planning supported by a digital platform to enable healthy ageing. Methods/design The intervention, co-designed with older adults, academic institutions, healthcare providers in public dental care, and municipal organizations, will undergo ethical approval. The RCT will randomize older adults, dental hygienists (DHs) and nursing assistants (NAs) into two groups. The intervention group will attend a two-day workshop on a person-centred, three-step team-based model, while the control group will continue using standard procedures. Thereafter, the three-step collaborative model will be compared to standard procedures. Primary outcomes will be measured using the Revised Oral Assessment Guide (ROAG) and the General Oral Health Assessment Index (GOHAI). Secondary outcomes include health economic evaluations, participation rates and quality of care assessments. Qualitative studies from theoretical perspectives of change and learning based on interviews with key stakeholders will be conducted in both the test and control groups. Discussion Taking a co-produced approach where theory and practice shape the research iteratively, a person-centred health care planning model supported by a shared digital platform for home settings is evaluated. Anticipated outcomes include improved oral assessments and a deeper understanding of effective person-centred care practices. The co-produced approach of the intervention is also expected to further develop knowledge regarding co-production within domains of healthy ageing from an oral health perspective. As such, the intervention shapes and fosters co-produced person-centred care and healthy ageing. Trial registration ClinicalTrials.gov NCT06310798. Registered on 13 March 2024.

Abstract Triple-Negative Breast Cancer (TNBC) is the most aggressive type of breast malignancy, with chemotherapy as the only mainstay treatment. TNBC patients have the worst prognoses as a large fraction of them do not achieve complete pathological response post-treatment and develop drug-resistant residual disease. Molecular mechanisms that trigger proliferation in drug-resistant chemo-residual TNBC cells are poorly understood due to the lack of investigations using clinically relevant cellular models. In this study, we have established TNBC subtype-specific cellular models of proliferating drug-tolerant persister (PDTP) cells using different classes of chemotherapeutic agents that recapitulate clinical residual disease with molecular heterogeneity. Analysis of total phospho-tyrosine signals in TNBC PDTPs showed an enhanced phospho-tyrosine content compared to the parental cells (PC). Interestingly, using mass-spectrometry analysis, we identified a dramatic decrease in epidermal growth factor receptor (EGFR) expression in the PDTPs, while the presence of hyper-activated tyrosine phosphorylation of EGFR compared to PC. Further, we show that EGFR has enhanced lysosomal trafficking in PDTPs with a concomitant increase in N-Myc Downstream Regulated-1 (NDRG1) expression that co-localizes with EGFR to mediate receptor degradation. More surprisingly, we found that reduced protein levels of EGFR are coupled with a robust increase in Src family kinases, including Lyn and Fyn kinases, that creates a hyper-phosphorylation state of EGFR-Src tyrosine kinases axis in PDTPs and mediates downstream over-activation of STAT3, AKT and MAP kinases. Moreover, paclitaxel-derived PDTPs show increased sensitivity to EGFR TKI Gefitinib and its combination with paclitaxel selectively induced cell death in Paclitaxel-derived PDTP (PDTP-P) TNBC cells and 3D spheroids by strongly downregulating phosphorylation of EGFR-Src with concomitant downregulation of Lyn and Fyn tyrosine kinases. Collectively, this study identifies a unique hyper-phosphorylation cellular state of TNBC PDTPs established by switching of EGFR–Src family tyrosine kinases, creating a vulnerability to EGFR TKI.

Background: Severe burns induce volume shifts via capillary leaks, eventually requiring massive fluid resuscitation and promoting tissue edema. Albumin may help to mitigate the edema, thereby improving perfusion. This study shows that sublingual microcirculation measurements can quantify both tissue perfusion and edema. Methods: This prospective observational study was conducted between November 2018 and December 2019 in the intensive care unit of Maasstad Hospital Burn Center, Rotterdam, The Netherlands. Patients with severe burns affecting >15% of the total body surface area were included. Fluid management was conducted in accordance with the Parkland formula. Albumin (20%) was administered at a rate of 0.5 mL/(kg·h), starting 12 h after the burn incident. Alterations in the sublingual microcirculation, including capillary perfusion and density, were measured at admission (T0) and 4 h (T4) and 12 h (T12) after admission. Sublingual depth of focus (DOF) of the microcirculation was used to quantify the tissue edema. Results: Nine patients were recruited with a mean total body surface area of 36% ± 23%. By T12, a median of 4085 mL (interquartile range [IQR]: 3714–6756 mL) of crystalloids and 446 mL (IQR: 176–700 mL) of 20% albumin were administered. The DOF increased significantly after crystalloid administration (T4 vs. T0, mean difference [MD]=27.4 µm, 95% confidence interval [CI]: 3.4 to 50.9, P=0.040). Following albumin administration, DOF significantly decreased (T12 vs. T4, MD=−76.4 µm, 95% CI: −116.6 to −36.1, P=0.002). Total vessel density decreased significantly with crystalloid administration (T4 vs. T0, MD=−3.5 mm/mm2, 95% CI: −5.7 to −1.4, P=0.004) but increased after albumin administration (T12 vs. T4, MD=6.2 mm/mm2, 95% CI: 3.2 to 9.3, P=0.001). Conclusion: Sublingual microcirculation measurement of DOF and other parameters provide a valuable tool for the assessment of tissue perfusion and edema in patients with severe burns. Further investigation is required to evaluate the role of albumin in increasing microcirculatory convection and reducing tissue edema.

In vivo tendon and ligament research can be limited by the difficultly of obtaining tissue samples that can be biochemically analyzed. In this study, we characterize the most widely used in vitro engineered ligament model. Despite previous works suggesting multiple passages change gene expression in 2D primary tenocytes, we found no relationship between passage number and expression of classical tendon fibroblast markers across different biological donors. When engineered into 3D ligaments, there was an increase in maximal tensile load between 7 and 14 days in culture, that corresponded with an increase in collagen content. By contrast, percent collagen increased logarithmically from Day 7 to Day 14, and this was similar to the increase in the modulus of the tissue. Importantly, there was no relationship between passage number and mechanical function or collagen content in the two independent donors tested. These results suggest that the model develops quickly and is reliable across differing passage numbers. This provides the field with the ability to 1) consistently determine functional changes of interventions out to passage number 10; and 2) to time interventions to the appropriate developmental stage: developing/regenerating (Day 7) or mature (Day 14) tissue.

Abstract Background Climbing places high loads through the hands and fingers, and climbers may benefit from specific finger strength training (hangboarding) protocols. The purpose of this study was to evaluate the effect of a 10-minute low intensity hangboard finger strengthening protocol (“Abrahangs”), compared with the generally accepted Max Hangs protocol for training maximal grip strength. Methods We retrospectively evaluated the change in grip strength and Strength: Weight following Max Hangs, Abrahangs, or the two protocols performed concurrently in rock climbers who used the Crimpd app to log their training. Users who had completed two finger strength tests within a 4–16-week period were included. Climbers were grouped by the number of training sessions into: “Climbing Only”, “Abrahangs Only”, “Max Hangs Only” and “Both” Max Hangs and Abrahangs. Results Frequent low intensity finger loading was as effective at improving grip strength in climbers as training with maximal loads. Additionally, combining low intensity and maximal load training resulted in additive strength gains. Conclusions These results suggest that low-intensity long duration holds provide a promising training paradigm for training finger strength that is gentle enough to incorporate into existing training programs.

Abstract Background and aims Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy – including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. Patients and methods We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. Results 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. Conclusions Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

Tendons are dense connective tissues with relatively few cells which makes studying the molecular profile of the tissue challenging. There is not a consensus on the spatial location of various cell types within a tendon, nor the accompanying transcriptional profile. In the present study, we used two male rat patellar tendon samples for sequencing-based spatial transcriptomics to determine the gene expression profile. We integrated our data with a mouse Achilles single cell dataset to predict the cell type composition of the patellar tendon as a function of location within the tissue. The spatial location of the predicated cell types suggested that there were two populations of tendon fibroblasts, one located in the tendon midsubstance, while the other localized with red blood cells, pericytes, and immune cells to the tendon peripheral connective tissue. Of the highest expressed spatially variable genes, there were multiple genes with known function in tendon: Col1a1, Col1a2, Dcn, Fmod, Sparc, and Comp. Further, a novel spatially regulated gene (AABR07000398.1) with no known function was identified. The spatial gene expression of tendon associated genes (Scx, Thbs4, Tnmd, Can, Bgn, Lum, Adamts2, Lox, Ppib, Col2a1, Col3a1, Col6a2) was also visualized. Both patellar tendon samples had similar expression patterns for all these genes. This dataset provides new spatial insights into gene expression in a healthy tendon.

PURPOSE: Implement STEAM-DTI to model time-dependent diffusion eigenvalues using the random permeable barrier model (RPBM) to study age-related differences in the medial gastrocnemius (MG) muscle. Validate diffusion model-extracted fiber diameter for histological assessment. METHODS: Diffusion imaging at different diffusion times (Δ) was performed on seven young and six senior participants. Time-dependent diffusion eigenvalues (λ2 (t), λ3 (t), and D⊥ (t); average of λ2 (t) and λ3 (t)) were fit to the RPBM to extract tissue microstructure parameters. Biopsy of the MG tissue for histological assessment was performed on a subset of participants (four young, six senior). RESULTS: λ3 (t) was significantly higher in the senior cohort for the range of diffusion times. RPBM fits to λ2 (t) yielded fiber diameters in agreement to those from histology for both cohorts. The senior cohort had lower values of volume fraction of membranes, ζ, in fits to λ2 (t), λ3 (t), and D⊥ (t) (significant for fit to λ3 (t)). Fits of fiber diameter from RPBM to that from histology had the highest correlation for the fit to λ2 (t). CONCLUSION: The age-related patterns in λ2 (t) and λ3 (t) could tentatively be explained from RPBM fits; these patterns may potentially arise from a decrease in fiber asymmetry and an increase in permeability with age.

Introduction Human milk plays a crucial role in infants’ nutrition and immunity, with its composition being influenced by different factors. The role of maternal diet on human milk fatty acid composition, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is well studied. Higher fish intake is associated with higher DHA levels in human milk, while fewer associations have been reported for EPA. Yet, maternal diet’s impact on human milk composition for other nutrients is understudied, and variations in sampling protocols and study quality hinder definitive conclusions on its overall impact. Ethnicity may also impact milk composition, with different dietary habits intertwined with different genetic backgrounds, but also here research lacks standardised protocols. Our study aims to investigate maternal diet, ethnicity, and their association with human milk composition, along with their potential short-term associations with infant health and development, through detailed dietary assessment and by recruiting participants from diverse backgrounds. Understanding these associations could inform the development of tailored nutritional guidelines for mothers and infants, ultimately promoting optimal health and well-being for both. The study design, with its strict sampling procedure, can guide and inspire future studies.Methods and analysis We will conduct an observational study involving 120 healthy mothers from three ethnic backgrounds (Chinese, Caucasian and Turkish), exclusively breastfeeding their 2-month-old infants. We will collect human milk samples at two time points and assess maternal dietary intake over 4 days. Additionally, we will collect data on various maternal and child characteristics, including maternal stress, socioeconomic status and health, and infant feeding, sleeping, crying, gastrointestinal health and developmental status.Ethics and dissemination The study has been approved by the Medical Ethical Committee Oost-Nederland (NL79447.091.21), and all participants provided written informed consent before entering the study. Findings will be widely disseminated at international conferences and meetings including the annual Nutrition & Growth conference, ESPGHAN, and through publication in scientific peer-reviewed journals.Trial registration number ISRCTN registry (ISRCTN35735283).

Early excision and grafting are standard care for severe burns, though implementation varies globally. In the Netherlands, surgery for moderate and severe burns tends to be relatively late. This study analysed the timing of surgery in Dutch burn care by examining patient, injury and treatment characteristics, and clinical outcomes. A multicentre registry-based cohort study was conducted using data from the Dutch Burn Repository R3 (2009–2021), including adult patients who underwent surgery at a Dutch burn centre. The primary outcome was surgical timing, with patients classified into early (≤7 days) and late surgery (>7 days) groups. Multivariable logistic regression identified predictors of early surgery, while trends in timing were assessed with quantile regression. The median time to surgery was 14 days (Q1–Q3: 9.0–19.0), with 670 of 3291 patients receiving early surgery (20 %). Surgical timing increased slightly over the 13-year period. Predictors of early surgery included older age, larger total body surface area burned, psychiatric medical history, and flame, flash, and contact burns compared to scald burns. This study underscores the nuanced Dutch policy regarding surgery and the influence of burn severity on surgical timing. Further research is needed, focusing on patient-centred outcomes and international perspectives.

Following rupture, the anterior cruciate ligament (ACL) will not heal and therefore more than 400,000 surgical repairs are performed annually. Ligament engineering is one way to meet the increasing need for donor tissue to replace the native ligament; however, currently these tissues are too weak for this purpose. Treating engineered human ligaments with insulin-like growth factor-1 (IGF-1) improves the structure and function of these grafts. Since the anabolic effects of IGF-1 are largely mediated by mTORC1, we used rapamycin to determine whether mTORC1 was necessary for the improvement in collagen content and mechanics of engineered ligaments. The effect of IGF-1 and rapamycin were determined independently and interactions between the two treatments were tested. Grafts were treated for 6 days before mechanical testing and analysis of collagen content. Following 8 days of treatment, mechanical properties increased 34% with IGF-1 and decreased 24.5% with rapamycin. Similarly, collagen content increased 63% with IGF-1 and decreased 36% with rapamycin. Interestingly, there was no interaction between IGF-1 and rapamycin, suggesting that IGF-1 was working in a largely mTORC1-independent manner. Acute treatment with IGF-1 did not alter procollagen synthesis in growth media, even though rapamycin decreased procollagen 55%. IGF-1 decreased collagen degradation 15%, whereas rapamycin increased collagen degradation 10%. Once again, there was no interaction between IGF-1 and rapamycin on collagen degradation. Together, these data suggest that growth factor-dependent increases in collagen synthesis are dependent on mTORC1 activity; however, IGF-1 improves human engineered ligament mechanics and collagen content by decreasing collagen degradation in a rapamycin-independent manner.

In this work, we applied a multi-information source modeling technique to solve a multi-objective Bayesian optimization problem involving the simultaneous minimization of cost and maximization of growth for serum-free C2C12 cells using a hyper-volume improvement acquisition function. In sequential batches of custom media experiments designed using our Bayesian criteria, collected using multiple assays targeting different cellular growth dynamics, the algorithm learned to identify the trade-off relationship between long-term growth and cost. We were able to identify several media with >100% more growth of C2C12 cells than the control, as well as a medium with 23% more growth at only 62.5% of the cost of the control. These algorithmically generated media also maintained growth far past the study period, indicating the modeling approach approximates the cell growth well from an extremely limited data set.

Burn care quality indicators are used to monitor and improve quality of care and for benchmark purposes. The perspectives of burn survivors, however, are not included in current sets of quality indicators while patient-centred care gains importance. The aim of this study was to explore burn survivors’ perspectives on quality aspects of burn care, which was used to translate their perspectives into patient-centred quality of care indicators. Qualitative descriptive research was conducted in a patient panel group. First, thematic analysis was applied to the focus groups to identify overarching themes. Second, patient-centred quality indicators, informed by burn survivors’ valued aspects of care, were defined. Ten burn survivors with an average age of 54 years (SD = 11; range 38–72 years) and mean TBSA burned of 14% (SD = 11%; range 5–35%) participated in two focus groups. Four overarching themes were identified, pointing to the importance of (1) information tailored to the different phases of recovery, (2) significant others’ wellbeing and involvement, (3) a therapeutic relationship and low-threshold access to healthcare professionals and (4) to participate in decision-making. Eighteen patient-centred process quality of care indicators within nine aspects of care were formulated. The overarching themes are reflected in patient-centred quality indicators, which present a broadened and complementary view of existing clinical quality indicators for burn care. Evaluating these patient-centred quality indicators may increase quality of care and refine patient-centred care.

Commercial camera traps are widely used in global wildlife monitoring, but their effectiveness is often compromised by oversights in specifications and technical considerations. This study evaluates the performance of three camera trap models, including the Solar Powered 4K-trail, HC-801A-Pro and HC-801A, by analysing their resolution limits and lens distortion correction capabilities. To determine the resolution limits, A4-sized templates with red circles of varying diameters were placed within the cameras’ field of view at various distances, with measurements taken using a measuring tape and verified with GPS. Using the cv2.TM_CCOEFF_NORMED template matching algorithm with templates scaled from 0.01 to 2.0 and a confidence threshold of 0.6, the resolution threshold was defined as the distance at which the observed circle size deviated from the expected size. Among the models, the Solar Powered 4K Trail camera had the highest resolution threshold at 17.29 m, while the HC 801A had the lowest at 15.3 m. Lens distortion coefficients were derived by analysing checkerboard pattern images taken at different distances and angles. All three camera models exhibited lens distortion. The Solar Powered 4K-trail and HC-801A-Pro exhibited barrel distortion, while the HC-801A exhibited pincushion distortion. The calculated coefficients successfully corrected these distortions, improving image accuracy. The derived coefficients effectively corrected these distortions, improving image accuracy. This practical and reproducible calibration method, which does not require expensive optical equipment, offers significant improvements in camera trap optimisation, enabling conservationists and researchers to obtain more reliable ecological data.

Background and Objectives: The mental health system in Moldova is transitioning toward a community-based model, which requires data on population mental health. This is the first mental health survey among a representative sample of the adult population. Methods: A stratified multistage sample (n = 1826) was collected using in-person door-to-door interviewing during July and August of 2022. The main outcome measures were depression symptoms (PHQ-2), anxiety symptoms (GAD-2), loneliness (UCLA-3), and mental well-being (WHO-5). Multivariable regression models were used to compare outcomes across age, gender, ethnicity, education, employment, and household income groups. Results: Prevalence was 19.8% for depression, 25.5% for anxiety, and 16.1% for loneliness. Average well-being was 69.6 out of 100. Women reported higher prevalence of depression and anxiety symptoms, more loneliness, and lower well-being than men. Older individuals reported higher prevalence of anxiety, more loneliness, and lower well-being than younger individuals. Individuals with low household income reported higher prevalence of depression and anxiety symptoms, more loneliness, and lower well-being than those with higher income, even when adjusting for education and employment. Conclusions: The study provides new data-supported insights into the target populations most at need of mental health support in Moldova (women, older adults, and those with low income) and provides baseline data for population mental health that can inform and guide future policy and research.

Transitioning from weather forecasts and warnings to impact-based forecast and warning services represents a paradigm shift in service delivery for many national hydrological and meteorological services (NHMS). NHMS typically excel at delivering information about hazardous weather, but are less experienced at inferring measures of risk of impact of extreme weather. Severe wind storms are high-impact weather phenomena that generally have a detrimental effect on distinct socio-economic sectors. In the Netherlands, the emergency services record locations where wind damage occurred to public or private property. In this work, we take 10 years of damage locations (2013–2023) provided by two safety regions in the Dutch province of Noord-Brabant. Each of the reports is enriched with an array of weather and environmental features, intended to describe the local conditions where wind damage was recorded. We model the wind reports using an ensemble of data-driven methods (i.e., One-Class Support Vector Machine) which are capable of learning from these hyper local conditions and predict for the rest of the study area. Results show how the ensemble of data-driven models are able to skillfully map locations where wind-induced damages are likely at spatial resolutions of 1 km and 5 km under high and low wind conditions scenarios. These results are encouraging for NHMS to strengthen national multi-hazard early warning systems by providing a new range of services at the urban scales in collaboration with external partners. As a consequence, the transition of scientific knowledge towards society would accelerate, hence helping at better protecting communities and livelihoods.

Cancer-associated cachexia (CAC) is a critical contributor to pancreatic ductal adenocarcinoma (PDAC) mortality. Thus, there is an urgent need for new strategies to mitigate PDAC-associated cachexia; and the exploration of dietary interventions is a critical component. We previously observed that a ketogenic diet (KD) combined with gemcitabine enhances overall survival in the autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. In this study, we investigated the effect and cellular mechanisms of a KD in combination with gemcitabine on the maintenance of skeletal muscle mass in KPC mice. For this purpose, male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD), a KD, a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. We observed that a KD or a KG-mitigated muscle strength declined over time and presented higher gastrocnemius weights compared CD-fed mice. Mechanistically, we observed sex-dependent effects of KG treatment, including the inhibition of autophagy, and increased phosphorylation levels of eIF2α in KG-treated KPC mice when compared to CG-treated mice. Our data suggest that a KG results in preservation of skeletal muscle mass. Additional research is warranted to explore whether this diet-treatment combination can be clinically effective in combating CAC in PDAC patients.

As humans age, we lose skeletal muscle mass, even in the absence of disease (sarcopenia), increasing the risk of death. Low mitochondrial mass and activity contributes to sarcopenia. It is our hypothesis that a ketogenic diet improves skeletal muscle mitochondrial mass and function when they have declined because of aging or disease, but not in athletes where mitochondrial quality is high.

Background: Cannabidiol (CBD) is becoming increasingly popular for the treatment of clinical conditions including as an aid for muscle recovery. Previous work demonstrated that CBD exhibited mild effects on skeletal muscle, with a tendency to increase anabolic signaling and decrease inflammatory signaling. Methods: To gain mechanistic insight and extend these findings, we conducted a set of experiments using C2C12 myotubes. Results: Increasing the dose of CBD (1-5 μM) provided with insulin-like growth factor 1 (IGF-1) showed no effect on anabolic signaling through mTORC1 (S6K1 [Thr389], p=0.27; rpS6 [Ser240/244], p=0.81; or 4E-BP1 [Thr37/46], p=0.87). Similarly, inflammatory signaling through nuclear factor kappa B (NF-κB) (p105, p=0.88; p50, p=0.93; or phosphorylated p65 [Ser536], p=0.84) in response to tumor necrosis factor α (TNFα) was unaffected by CBD (2.5 μM), whereas dioscin, a natural product that blocks NF-κB signaling, reduced p105 and phosphorylated p65 (Ser536) compared with the TNFα and the TNFα + CBD condition (p

The effect of a ketogenic diet (KD) on middle aged female mice is poorly understood as most of this work have been conducted in young female mice or diseased models. We have previously shown that an isocaloric KD started at middle age in male mice results in enhanced mitochondrial mass and function after 2 months on diet and improved cognitive behavior after being on diet for 14 months when compared with their control diet (CD) fed counterparts. Here, we aimed to investigate the effect of an isocaloric 2-month KD or CD on healthy 14-month-old female mice. At 16 months of age cognitive behavior tests were performed and then serum, skeletal muscle, cortex, and hippocampal tissues were collected for biochemical analysis. Two months on a KD resulted in enhanced cognitive behavior associated with anxiety, memory, and willingness to explore. The improved neurocognitive function was associated with increased PGC1α protein in the gastrocnemius (GTN) muscle and nuclear fraction. The KD resulted in a tissue specific increase in mitochondrial mass and kynurenine aminotransferase (KAT) levels in the GTN and soleus muscles, with a corresponding decrease in kynurenine and increase in kynurenic acid levels in serum. With KAT proteins being responsible for converting kynurenine into kynurenic acid, which is unable to cross the blood brain barrier and be turned into quinolinic acid-a potent neurotoxin, this study provides a potential mechanism of crosstalk between muscle and brain in mice on a KD that may contribute to improved cognitive function in middle-aged female mice.

The growth and activity of adherent cells can be enabled or enhanced through attachment to a solid surface. For food and beverage production processes, these solid supports should be food-grade, low-cost, and biocompatible with the cell of interest. Solid supports that are edible can be a part of the final product, thus simplifying downstream operations in the production of fermented beverages and lab grown meat. We provide proof of concept that edible filamentous fungal pellets can function as a solid support by assessing the attachment and growth of two model cell types: yeast, and myoblast cells. The filamentous fungus Aspergillus oryzae was cultured to produce pellets with 0.9 mm diameter. These fugal pellets were inactivated by heat or chemical methods and characterized physicochemically. Chemically inactivated pellets had the lowest dry mass and were the most hydrophobic. Scanning electron microscope images showed that both yeast and myoblast cells naturally adhered to the fungal pellets. Over 48 h of incubation, immobilized yeast increased five-fold on active pellets and six-fold on heat-inactivated pellets. Myoblast cells proliferated best on heat-treated pellets, where viable cell activity increased almost two-fold, whereas on chemically inactivated pellets myoblasts did not increase in the cell mass. These results support the use of filamentous fungi as a novel cell immobilization biomaterial for food technology applications.

OECD reports a mismatch between field of study and job content for Humanities students, while at the same time signalling labour market shortages for skills that seem clearly linked with the Humanities, e.g. delivering information. In order to investigate which skills Humanities students associate with their university studies, we conducted a survey among 1306 European Humanities and 231 non-Humanities students. The survey asked these students whether they felt they acquired skills during their Humanities university education which were identified in a pilot phase. The students' answers were analysed quantitatively, arriving at a Humanities self-perception skills profile of 70 detailed descriptions of skills that fall under six clusters. We argue that this profile could be a crucial step to improve the employability of Humanities students, as students' perceptions of their skills greatly determine the quality of transition to the labour market.