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Aims: The Bankart and Latarjet procedures are two of the most common surgical techniques to treat anterior shoulder instability with satisfactory clinical and functional outcomes. However, the outcomes in the adolescent population remain unclear, and there is no information regarding the arthroscopic Latarjet in this population. The purpose of this study was to evaluate the outcomes of the arthroscopic Bankart and arthroscopic Latarjet procedures in the management of anterior shoulder instability in adolescents. Methods: We present a retrospective, matched-pair study of teenagers with anterior glenohumeral instability treated with an arthroscopic Bankart repair (ABR) or an arthroscopic Latarjet (AL) procedure with a minimum two-year follow-up. Preoperative demographic and clinical features, factors associated with dislocation, and complications were collected. Recurrence, defined as dislocation or subluxation, was established as the primary outcome. Clinical and functional outcomes were analyzed using objective (Rowe), and subjective (Western Ontario Shoulder Instability Index (WOSI) and Single Assessment Numeric Evaluation (SANE)) scores. Additionally, the rate of return to sport was assessed. Results: A total of 51 adolescents were included, of whom 46 (92%) were male, with 17 (33%) in the Latarjet group and 34 (66%) in the Bankart group. The mean age at time of surgery was 18 years (15 to 19). There were no intraoperative complications. At a median follow-up of nine years (IQR 2 to 18), recurrence was observed in 12 patients in the Bankart group (35.3%) and one patient in the Latarjet group (5.9%) (p = 0.023). Satisfactory postoperative outcomes were obtained, with mean Rowe, WOSI, and SANE scores noted at 95 (10 to 100), 325 (25 to 1,975), and 87.5 (10 to 100), respectively. Most patients (29 in the Bankart group (85.3%) and 16 in the Latarjet group (94.1%)) were able to return to sport (p = 0.452). Conclusion: The ABR and AL procedures both obtain satisfactory clinical and functional outcomes in the treatment of anterior glenohumeral instability in adolescents with a low complication rate. However, the ABR is associated with a significantly higher recurrence rate. Cite this article: Bone Jt Open 2024;5(11):1041–1048.

Abstract Fat accumulation, de novo lipogenesis, and glycolysis are key drivers of hepatocyte reprogramming and the consequent metabolic dysfunction-associated steatotic liver disease (MASLD). Here we report that obesity leads to dysregulated expression of hepatic protein-tyrosine phosphatases (PTPs). PTPRK was found to be increased in steatotic hepatocytes in both humans and mice, and correlates positively with PPARγ-induced lipogenic signaling. High-fat-fed PTPRK knockout male and female mice have lower weight gain and reduced hepatic fat accumulation. Phosphoproteomic analysis in primary hepatocytes and hepatic metabolomics identified fructose-1,6-bisphosphatase 1 and glycolysis as PTPRK targets in metabolic reprogramming. Mechanistically, PTPRK-induced glycolysis enhances PPARγ and lipogenesis in hepatocytes. Silencing PTPRK in liver cancer cell lines reduces colony-forming capacity and high-fat-fed PTPRK knockout mice exposed to a hepatic carcinogen develop smaller tumours. Our study defines the role of PTPRK in the regulation of hepatic glycolysis, lipid metabolism, and tumour development in obesity.

Introduction Digital platforms serve as an avenue for the tobacco industry to promote both conventional tobacco and emerging products, with a notable focus on capturing the attention of young people through sophisticated marketing campaigns. This research aims to analyze the prevalence of different advertising strategies on digital platforms and to assess the impact of exposure to these strategies on the probability of use initiation and increased consumption of conventional tobacco and new tobacco products among young Spaniards. Methods An online survey was conducted on a representative sample of 1730 young Spaniards aged 16–21 years in November 2022 using a comprehensive approach, considering all possible relevant factors and perspectives regarding the issue of the study. A descriptive analysis and two adjusted logistic regression models were employed to explore the association of exposure to digital platforms with the likelihood of conventional tobacco and new tobacco product use among this population. Results Among the participants, 83.2% reported witnessing individuals smoking, 61.6% observed identifiable logos or explicit advertisements, and 77.6% encountered indirect product placement on social media. Notably, exposure to conventional tobacco product placement (AOR=1.71; 95% CI: 1.27–2.30) emerged as the variable most significantly associated with an increased probability of tobacco use. Furthermore, exposure to advertising related to new tobacco products (AOR=2.47; 95% CI: 1.90–3.21) was linked to a heightened likelihood of subsequent use. Similarly, the direct promotion of these novel products is also associated with a higher probability of conventional tobacco use (AOR=1.58; 95% CI: 1.21–2.07). Conclusions A reciprocal impact was identified, with the promotion of vaping being associated with an elevated probability of engaging in conventional tobacco smoking. Urgent attention is warranted for formulating public policies to mitigate the adverse effects of such insidious indirect advertising practices on digital platforms.

Abstract WEMAC is a unique open multi-modal dataset that comprises physiological, speech, and self-reported emotional data records of 100 women, targeting Gender-based Violence detection. Emotions were elicited through visualizing a validated video set using an immersive virtual reality headset. The physiological signals captured during the experiment include blood volume pulse, galvanic skin response, and skin temperature. The speech was acquired right after the stimuli visualization to capture the final traces of the perceived emotion. Subjects were asked to annotate among 12 categorical emotions, several dimensional emotions with a modified version of the Self-Assessment Manikin, and liking and familiarity labels. The technical validation proves that all the targeted categorical emotions show a strong statistically significant positive correlation with their corresponding reported ones. That means that the videos elicit the desired emotions in the users in most cases. Specifically, a negative correlation is found when comparing fear and not-fear emotions, indicating that this is a well-portrayed emotional dimension, a specific, though not exclusive, purpose of WEMAC towards detecting gender violence

Aims: This study aims to describe a new method that may be used as a supplement to evaluate humeral rotational alignment during intramedullary nail (IMN) insertion using the profile of the perpendicular peak of the greater tuberosity and its relation to the transepicondylar axis. We called this angle the greater tuberosity version angle (GTVA). Methods: This study analyzed 506 cadaveric humeri of adult patients. All humeri were CT scanned using 0.625 × 0.625 × 0.625 mm cubic voxels. The images acquired were used to generate 3D surface models of the humerus. Next, 3D landmarks were automatically calculated on each 3D bone using custom-written C++ software. The anatomical landmarks analyzed were the transepicondylar axis, the humerus anatomical axis, and the peak of the perpendicular axis of the greater tuberosity. Lastly, the angle between the transepicondylar axis and the greater tuberosity axis was calculated and defined as the GTVA. Results: The value of GTVA was 20.9° (SD 4.7°) (95% CI 20.47° to 21.3°). Results of analysis of variance revealed that females had a statistically significant larger angle of 21.95° (SD 4.49°) compared to males, which were found to be 20.49° (SD 4.8°) (p = 0.001). Conclusion: This study identified a consistent relationship between palpable anatomical landmarks, enhancing IMN accuracy by utilizing 3D CT scans and replicating a 20.9° angle from the greater tuberosity to the transepicondylar axis. Using this angle as a secondary reference may help mitigate the complications associated with malrotation of the humerus following IMN. However, future trials are needed for clinical validation. Cite this article: Bone Jt Open 2024;5(10):929–936.

Abstract Background Female ticks remain attached to their host for multiple days to complete a blood meal. This prolonged feeding period is accompanied by a significant increase in the tick’s size and body weight, paralleled by noteworthy changes to the tick midgut. While the midgut is recognized for its established role in blood storage and processing, its importance extends to playing a crucial role in the acquisition, survival, and proliferation of pathogens. Despite this, our overall understanding of tick midgut biology is limited. Results Our transcriptome analysis identified 15,599 putative DNA coding sequences (CDS), which were classified into 26 functional groups. Dimensional and differential expression analyses revealed four primary transcriptional profiles corresponding to unfed, slow-feeding, transitory (from slow- to rapid-feeding), and rapid-feeding stages. Additionally, comparing the current dataset with previously deposited transcriptome from other tick species allowed the identification of commonly expressed transcripts across different feeding stages. Conclusion Our findings provide a detailed temporal resolution of numerous metabolic pathways in the midgut of A. americanum adult females throughout the feeding process, highlighting the dynamic transcriptional regulation of the tick’s midgut as feeding progresses. Furthermore, we identified conserved transcripts across three different tick species that exhibit similar expression patterns. This knowledge not only enhances our understanding of the physiological processes within the tick midgut but also opens up potential avenues for developing control methods that target multiple tick species.

Abstract Background Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and compromises the viability of transplanted human bone marrow-derived mesenchymal stromal cells (BM-MSCs). Hence, BM-MSCs were genetically-engineered to express the anti-fibrotic and renoprotective hormone, human relaxin-2 (RLX) and green fluorescent protein (BM-MSCs-eRLX + GFP), which enabled BM-MSCs-eRLX + GFP delivery via a single intravenous injection. Methods BM-MSCs were lentiviral-transduced with human relaxin-2 cDNA and GFP, under a eukaryotic translation elongation factor-1α promoter (BM-MSCs-eRLX + GFP) or GFP alone (BM-MSCs-eGFP). The ability of BM-MSCs-eRLX + GFP to differentiate, proliferate, migrate, produce RLX and cytokines was evaluated in vitro, whilst BM-MSC-eRLX + GFP vs BM-MSCs-eGFP homing to the injured kidney and renoprotective effects were evaluated in preclinical models of ischemia reperfusion injury (IRI) and high salt (HS)-induced hypertensive CKD in vivo. The long-term safety of BM-MSCs-RLX + GFP was also determined 9-months after treatment cessation in vivo. Results When cultured for 3- or 7-days in vitro, 1 × 106 BM-MSCs-eRLX + GFP produced therapeutic RLX levels, and secreted an enhanced but finely-tuned cytokine profile without compromising their proliferation or differentiation capacity compared to naïve BM-MSCs. BM-MSCs-eRLX + GFP were identified in the kidney 2-weeks post-administration and retained the therapeutic effects of RLX in vivo. 1–2 × 106 BM-MSCs-eRLX + GFP attenuated the IRI- or therapeutically abrogated the HS-induced tubular epithelial damage and interstitial fibrosis, and significantly reduced the HS-induced hypertension, glomerulosclerosis and proteinuria. This was to an equivalent extent as RLX and BM-MSCs administered separately but to a broader extent than BM-MSCs-eGFP or the angiotensin-converting enzyme inhibitor, perindopril. Additionally, these renoprotective effects of BM-MSCs-eRLX + GFP were maintained in the presence of perindopril co-treatment, highlighting their suitability as adjunct therapies to ACE inhibition. Importantly, no major long-term adverse effects of BM-MSCs-eRLX + GFP were observed. Conclusions BM-MSCs-eRLX + GFP produced greater renoprotective and therapeutic efficacy over that of BM-MSCs-eGFP or ACE inhibition, and may represent a novel and safe treatment option for acute kidney injury and hypertensive CKD.

Abstract Background The International Survey of People living with Chronic Conditions (OECD-PaRIS survey), aims to systematically gather patient-reported experiences (PREMs) and - outcomes (PROMs) and potential predictors for these outcomes for persons with chronic conditions as well as information from professionals about health care provided. In such patient surveys, the advantages of a multilevel (nested) approach in which patients are sampled ‘within providers’ need to be balanced against the potential for bias if patient populations from participating GPs significantly differ from those of non-participating GPs. The objective was to assess the effects of general practitioner (GP) non-participation on the representativeness of the Norwegian patient data of the International Survey of People living with Chronic Conditions (OECD-PaRIS survey). Methods To test all aspects of the first main PaRIS survey, it was preceded by a field trial which this paper reports on the Norwegian part of. For the Norwegian part of the field trial in 2022, we randomly sampled and surveyed 75 GPs and 125 patients 45 years and older for each GP, regardless of whether their GP were also participating in the study. GPs were sampled from a national register that included all GPs. The surveys were primarily digital, but we sent postal questionnaires to non-digital patients and non-responding digital patients. We compared GP and patient characteristics as well as patient-reported experiences and outcomes according to GP participation status in bivariate analysis, supplemented with multiple linear regressions with PREMs/PROMs as dependent variables and participation status as independent adjusting for significant patient factors. Results 17 of 75 sampled GPs participated (22.7%), of which 993 of 2,015 patients responded (49.3%). 3,347 of 7,080 patients of non-responding GPs answered (47.3%). Persons with chronic conditions from participating GPs reported significantly better patient-centred coordinated care (p = 0.017), overall experiences with the GP office the last 12 months (p = 0.004), mental well-being (p = 0.039) and mental health (p = 0.013) than patients from non-participating GPs. The raw differences between participating and non-participating GPs on patient-reported experiences and – outcomes varied from 1.5 to 2.9 points on a 0-100 scale, and from 2.2 to 3.0 after adjustment for case-mix. Conclusions The Norwegian field trial indicates that estimates based on participants in the PaRIS survey may modestly overestimate patient-reported experiences and -outcomes at the aggregated level and the need for more research within and across countries to identify and address this potential bias.

Abstract Background Current acute healthcare service metrics are not meaningful for older people living with frailty. Healthcare knowledge, situational security, and physical and psychosocial function are important outcomes typically not collected. The use of patient-reported outcome measures (PROMs) could support these assessments. Existing instruments are not comprehensive as they typically consider function, while older people with frailty also value enablement (self-determination and security in health and healthcare). This study field-tested and validated a PROM for older people with frailty receiving acute care (PROM-OPAC) to measure enablement. Methods People aged 65+ with Clinical Frailty Scale 5–8 were recruited within seventy-two hours of an emergency attendance. Iterations of the novel instrument were administered over three stages: (1) preliminary field-testing for reliability (response distribution and internal consistency) and structure (exploratory factor analysis, EFA); (2) intermediate field-testing of an improved instrument for reliability and structure; (3) final draft validation assessing reliability, structure (confirmatory factor analysis, CFA), and construct validity based on a priori hypotheses. Feasibility was appraised throughout using data completeness and response rates and times. Results 241 people participated. Three items of a preliminary seven-item measure had poor response distribution or loading and were accordingly improved. The intermediate instrument had interpretability issues and three items required further improvement. The final eight-item draft had acceptable reliability (Cronbach’s alpha: 0.71), structure (two factors for self-determination and security; RMSEA: 0.065; TLI: 0.917; CFI: 0.944), and construct validity (lower scores from respondents waiting longer and requiring admission). Feasibility was promising (response rate 39%; 98% responses complete; median completion time 11 (IQR: 12) minutes). Conclusions Administration of the PROM-OPAC appeared feasible and the instrument had acceptable psychometric properties. Further evaluation is required to assess generalisability.

Abstract Cancer staging is an essential clinical attribute informing patient prognosis and clinical trial eligibility. However, it is not routinely recorded in structured electronic health records. Here, we present BB-TEN: Big Bird – TNM staging Extracted from Notes, a generalizable method for the automated classification of TNM stage directly from pathology report text. We train a BERT-based model using publicly available pathology reports across approximately 7000 patients and 23 cancer types. We explore the use of different model types, with differing input sizes, parameters, and model architectures. Our final model goes beyond term-extraction, inferring TNM stage from context when it is not included in the report text explicitly. As external validation, we test our model on almost 8000 pathology reports from Columbia University Medical Center, finding that our trained model achieved an AU-ROC of 0.815–0.942. This suggests that our model can be applied broadly to other institutions without additional institution-specific fine-tuning.

Abstract Background Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS). Methods We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted. Results Six independent sentinel variants reached the genome-wide significance (p

Abstract Plants can survive in soils of low micromolar potassium (K+) concentrations. Root K+ intake is accomplished by the K+ channel AKT1 and KUP/HAK/KT type high-affinity K+ transporters. Arabidopsis HAK5 mutants impaired in low K+ acquisition have been identified already more than two decades ago, the molecular mechanism, however, is still a matter of debate also because of lack of direct measurements of HAK5-mediated K+ currents. When we expressed AtHAK5 in Xenopus oocytes together with CBL1/CIPK23, no inward currents were elicited in sufficient K+ media. Under low K+ and inward-directed proton motive force (PMF), the inward K+ current increased indicating that HAK5 energetically couples the uphill transport of K+ to the downhill flux of H+. At extracellular K+ concentrations above 25 μM, the initial rise in current was followed by a concentration-graded inactivation. When we replaced Tyr450 in AtHAK5 to Ala the K+ affinity strongly decreased, indicating that AtHAK5 position Y450 holds a key for K+ sensing and transport. When the soil K+ concentration drops toward the range that thermodynamically cannot be covered by AKT1, the AtHAK5 K+/H+ symporter progressively takes over K+ nutrition. Therefore, optimizing K+ use efficiency of crops, HAK5 could be key for low K+ tolerant agriculture.

Introduction: Globally, persons with disabilities (PWD) face structural and social barriers to inclusive healthcare. Medical schools, as crucibles of medical professional identity formation, have the responsibility to foster person-centredness toward all patients, including PWD, among her graduates. We co-designed with PWD a “Communications with Persons with Disabilities” workshop and evaluated its impact. Methods: The workshop enlisted PWD as patient educators, occurred within the third-year undergraduate Family Medicine posting, and was designed to positively impact communications skills and attitudes toward PWD. Students (n=135) were surveyed pre- and post- workshop following a mixed-methods approach (demographic data, Attitude Towards Disabled Persons (ATDP)-O scale, feedback questions, and post-workshop free reflections). Descriptive analysis was used for demographic and feedback questions, and thematic analysis for reflections. Paired t-test was used to evaluate change in ATDP-O scores. Results: There were 69 survey respondents (51.11%). Most students agreed that communications training with PWD could be strengthened in medical school, and that the workshop was relevant to their future medical career (n=68, 98.55%). Attitudes towards PWD significantly improved after the workshop (ATDP-O change: +9.29 points (12.7%), p

Abstract Background Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease characterized by intestinal inflammation and injury, with high mortality risk. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that propagates inflammation and tissue injury; however, the role of eCIRP in NEC remains unknown. We hypothesize that eCIRP exacerbates NEC pathogenesis and the novel eCIRP-scavenging peptide, milk fat globule-epidermal growth factor-factor VIII (MFG-E8)-derived oligopeptide 3 (MOP3), attenuates NEC severity, serving as a new therapeutic strategy to treat NEC. Methods Stool samples from premature neonates were collected prospectively and eCIRP levels were measured. Wild-type (WT) and CIRP−/− mouse pups were subjected to NEC utilizing a combination of hypoxia and hypercaloric formula orogastric gavage with lipopolysaccharide supplementation. In parallel, WT pups were treated with MOP3 or vehicle. Endpoints including NEC severity, intestinal injury, barrier dysfunction, lung injury, and overall survival were determined. Results Stool samples from NEC neonates had elevated eCIRP levels compared to healthy age-matched controls (p

Abstract Human pluripotent stem cells (hPSCs) represent an excellent cell source for regenerative medicine and tissue engineering applications. However, there remains a need for robust and scalable differentiation of stem cells into functional adult tissues. In this paper, we sought to address this challenge by developing magnetic microcapsules carrying hPSC spheroids. A co-axial flow-focusing microfluidic device was employed to encapsulate stem cells in core-shell microcapsules that also contained iron oxide magnetic nanoparticles (MNPs). These microcapsules exhibited excellent response to an external magnetic field and could be held at a specific location. As a demonstration of utility, magnetic microcapsules were used for differentiating hPSC spheroids as suspension cultures in a stirred bioreactor. Compared to standard suspension cultures, magnetic microcapsules allowed for more efficient media change and produced improved differentiation outcomes. In the future, magnetic microcapsules may enable better and more scalable differentiation of hPSCs into adult cell types and may offer benefits for cell transplantation.

Abstract Background North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. Results We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa. Conclusions We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.

Abstract Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

Abstract Background We used the Spanish national hospital discharge data from 2016 to 2022 to analyze procedures and hospital outcomes among patients aged ≥ 18 years admitted for ST-elevation myocardial infarction (STEMI) and non–ST-elevation myocardial infarction (NSTEMI) according to diabetes mellitus (DM) status (non-diabetic, type 1-DM or type 2-DM). Methods We built logistic regression models for STEMI/NSTEMI stratified by DM status to identify variables associated with in-hospital mortality (IHM). We analyzed the effect of DM on IHM. Results Spanish hospitals reported 201,950 STEMIs (72.7% non-diabetic, 0.5% type 1-DM, and 26.8% type 2-DM; 26.3% female) and 167,285 NSTEMIs (61.6% non-diabetic, 0.6% type 1-DM, and 37.8% type 2-DM; 30.9% female). In STEMI, the frequency of percutaneous coronary intervention (PCI) increased among non-diabetic people (60.4% vs. 68.6%; p

Abstract Background Pancreatic head cancer patients who undergo pancreatoduodenectomy (PD) often experience disease recurrence, frequently associated with a positive margin status (R1). Total mesopancreas excision (TMpE) has emerged as a potential approach to increase surgical radicality and minimize locoregional recurrence. However, its effectiveness and safety remain under evaluation. Methods We conducted a systematic review and meta-analysis to synthesize current evidence on TMpE outcomes. A systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases was conducted up to March 2024 to identify studies comparing TMpE with standard pancreatoduodenectomy (sPD). The risk ratio (RR) or mean difference (MD) was pooled using a random effects model. Results From 452 studies identified, 9 studies with a total of 738 patients were included, with 361 (49%) undergoing TMpE. TMpE significantly improved the R0 resection rate (RR 1.24; 95% CI 1.11–1.38; P

Abstract Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women.

Abstract The structure of helical polymers is dictated by the molecular chirality of their monomer units. Particularly, macromolecular helices with monomer sequence control have the potential to generate chiral topologies. In α-helical folded peptides, the sequential repetition of amino acids generates a chiral layer defined by the amino acid side chains projected outside the amide backbone. Despite being closely related to peptides’ structural and functional properties, to the best of our knowledge, a general exo-helical symmetry model has not been yet described for the α-helix. Here, we perform the theoretical, computational, and spectroscopic elucidation of the α-helix principal exo-helical topologies. Non-canonical labeled amino acids are employed to spectroscopically characterize the different exo-helical topologies in solution, which precisely match the theorical prediction. Backbone-to-chromophore distance also shows the expected impact in the exo-helices’ geometry and spectroscopic fingerprint. Theoretical prediction and spectroscopic validation of this exo-helical topological model provides robust experimental evidence of the chiral potential on the surface of helical peptides and outlines an entirely new structural scenario for the α-helix.

Abstract Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.

Abstract Key message The elapsed times to deplete starch concentrations and to reach a null hydraulic safety margin were related to tree seedling mortality under experimental drought. Starch concentration showed an accelerated decline across all species during the early stages of dehydration, while the concentrations of soluble sugars and total nonstructural carbohydrates remained stable. Concomitant carbohydrate depletion and hydraulic failure drive seedling mortality under drought. Context Current upsurges of drought events are provoking impacts on tree physiology, resulting in forest mortality. Hydraulic dysfunction and nonstructural carbohydrate (NSC) depletion have been posited as the main mechanisms leading to plant mortality under drought. Aims This study explores the dynamics of the two mortality-inducing processes during drought stress using an experimental approach with 12 evergreen tree species. Methods Seedlings were subjected to drought until 100% mortality was observed. Midday (ΨMD) and predawn (ΨPD) water potentials, xylem pressure leading to a 50% loss of hydraulic conductivity (Ψ50), along with NSC concentrations in different organs (leaves, stems, and roots) were measured regularly during drought. Results Total NSC concentrations and soluble sugar pools did not decline during drought. However, starch pools showed strong reductions early during drought stress as ΨPD decreased, and the time leading to starch depletion emerged as a strong mortality predictor. Ψ50 alone did not provide an accurate estimate of mortality, while the elapsed time to reach a null hydraulic safety margin (ΨMD—Ψ50 = 0) was related to seedling mortality. Conclusion Adopting a dynamic approach by estimating the times to consume both starch reserves and hydraulic safety margins is highly relevant to improve predictions of tree mortality under the current context of increasing global drought.

Abstract In 2021, the International Earth Rotation and Reference Systems Service (IERS) established a working group tasked with conducting the Second Earth Orientation Parameters Prediction Comparison Campaign (2nd EOP PCC) to assess the current accuracy of EOP forecasts. From September 2021 to December 2022, EOP predictions submitted by participants from various institutes worldwide were systematically collected and evaluated. This article summarizes the campaign's outcomes, concentrating on the forecasts of the dX, dY, and dψ, dε components of celestial pole offsets (CPO). After detailing the campaign participants and the methodologies employed, we conduct an in-depth analysis of the collected forecasts. We examine the discrepancies between observed and predicted CPO values and analyze their statistical characteristics such as mean, standard deviation, and range. To evaluate CPO forecasts, we computed the mean absolute error (MAE) using the IERS EOP 14 C04 solution as the reference dataset. We then compared the results obtained with forecasts provided by the IERS. The main goal of this study was to show the influence of different methods used on predictions accuracy. Depending on the evaluated prediction approach, the MAE values computed for day 10 of forecast were between 0.03 and 0.16 mas for dX, between 0.03 and 0.12 mas for dY, between 0.07 and 0.91 mas for dψ, and between 0.04 and 0.41 mas for dε. For day 30 of prediction, the corresponding MAE values ranged between 0.03 and 0.12 for dX, and between 0.03 and 0.14 mas for dY. This research shows that machine learning algorithms are the most promising approach in CPO forecasting and provide the highest prediction accuracy (0.06 mas for dX and 0.08 mas for dY for day 10 of prediction). Graphical abstract

Abstract Background Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. Methods ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. Conclusions This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. Trial registration EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016.

Abstract Most child-friendly court reforms are based on the assumption that the court setting is a stressful experience. Our objective was to analyze the acute stress levels of children who come to testify in a child-friendly investigative court using a person-by-environment approach. We employed a simple repeated measures design for this study, which included 42 minors of Spanish nationality who provided testimony as victims of violence in Spain’s inaugural Child-Friendly Court. Among the participants, 73.8% were girls with a mean age of 12.5 years (SD = 3.4), and 26.2% were boys with a mean age of 11.4 years (SD = 3.1). Stress levels were measured using heart rate variability, and anxiety was assessed using state-trait questionnaires. The study found that the mean percentile of anxiety remained at moderate levels, while stress remained at medium-low levels. No significant differences in anxiety or stress were found based on gender or type of crime. Repeated measures ANOVA revealed significant differences in stress levels among different court settings. Stress levels in the waiting room and Gesell room were significantly higher than those in the decompression room. In conclusion, the experience of testifying in a Gesell room about the aggressions suffered increases stress levels. However, in this sample and for this Pilot Court, the stress levels observed during testimony did not reach levels considered detrimental to children’s health. Our results lend support to the new European Judicial Policy, which includes the establishment and operation of Specialized Courts adapted to the needs of children and adolescents.

Abstract Healthcare professionals have first-hand experience with patients in clinical practice and the dynamics in the healthcare system, which can be of great value in the design, implementation, data analysis and dissemination of research study results. Primary care professionals are particularly important as they provide first contact, accessible, coordinated, comprehensive and continuous people-focused care. However, in-depth examination of the engagement of health professionals in health system research and planning activities—how professionals are engaged and how this varies across national contexts- is limited, particularly in international initiatives. There is a need to identify gaps in the planning of engagement activities to inform the design and successful implementation of future international efforts to improve the responsiveness of health systems to the changing needs of patients and professionals. The aim of this study was to explore how primary care professionals were engaged in the design and implementation plans of an international health policy study led by the Organisation for Economic Co-operation and Development (OECD). The OECD’s international PaRIS survey measures and disseminates information on patient-reported outcome and experience measures (PROMs and PREMs) of people living with chronic conditions who are managed in primary care. A documentary analysis of 17 written national implementation plans (country roadmaps) was conducted between January and June 2023. Two reviewers independently performed the screening and data abstraction and resolved disagreements by discussion. We reported the intended target primary care professionals, phase of the study, channel of engagement, level of engagement, and purpose of engagement. All 17 countries aimed to engage primary care professionals in the execution plans for the international PaRIS survey. While organisations of primary care professionals, particularly of family doctors, were the most commonly targeted group, variation was found in the timing of engagement activities during the different phases of the study and in the level of engagement, ranging from co-development (half of the countries co-developed the survey together with primary care professionals) to one-off consultations with whom. International guidance facilitated the participation of primary care professionals. Continuous collaborative efforts at the international and national levels can foster a culture of engagement with primary care organisations and individual professionals and enhance meaningful engagement of primary care professionals.

Abstract Background Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient’s evolution from multivariate sequential patterns. Methods In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient’s state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient’s clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa. Results The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying. Conclusions Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation.

Abstract Background Skin diseases can have a significant impact on the physical, psychological and social well‐being of patients. Quantification of the burden of chronic spontaneous urticaria (CSU) compared to other dermatological conditions is limited. Objectives To evaluate the comparative humanistic and economic burden of CSU, atopic dermatitis (AD), and psoriasis (PSO) in five European countries (EU5). Methods This cross‐sectional analysis compared data from adult respondents with a physician diagnosis of CSU, AD and PSO from the 2020 National Health and Wellness Survey in EU5 (France, Germany, Italy, Spain and the United Kingdom). Outcomes included Short Form (SF)‐12v2 [mental (MCS) and physical component (PCS) summary scores], SF‐6D, EQ‐5D, EQ‐Visual Analogue Scale (VAS), Dermatology Life Quality Index (DLQI), General Anxiety Disorder‐7 (GAD‐7), Patient Health Questionnaire‐9 (PHQ‐9), Work Productivity and Activity Impairment (WPAI) and healthcare resource utilization (HRU). Multivariable analyses comparing CSU to AD and PSO, respectively, were conducted for each outcome. Results This analysis included 379 CSU, 788 AD and 2,636 PSO patients. Adjusted MCS and PCS scores were lower among CSU patients than AD (MCS, p = 0.006; PCS, p

IntroductionThe cowpea weevil, Callosobruchus maculatus Fab., is the most economically important storage pest of cowpeas, causing up to 100 percent grain losses within six months of storage. To sustainably resist weevil damage, the cowpea cultivar IT86D-1010 was genetically modified via Agrobacterium-mediated transformation to produce event CSI-32, which expresses the kidney bean alpha-amylase inhibitor 1 (αAI-1) protein exclusively in the seed, providing suppression of weevil development.MethodsTrials were conducted in Ghana and Nigeria during the 2023 growing season to assess the performance in the field and in post-harvest storage of this transgenic event (CSI-32) and of four check lines: the non-transformed parental line (IT86D-1010) and three released varieties (SAMPEA 7, SAMPEA 20-T and IT13K-1070-2). Data collected from the field trials comprised plant growth parameters, pest infestations and damage, and grain yield. Harvested grain from each replicated entry was used in a storage assessment of bruchid resistance following artificial infestation with laboratory-reared cowpea weevils. Data were collected on egg oviposition, adult emergence, and grain damage as well as computation of median development period and Dobie’s susceptibility index for each entry.Results and discussionThe agronomic performance and phenotypic characteristics of event CSI-32 were very similar to its parental counterpart and the other compared varieties. However, event CSI-32 exhibited complete suppression of weevil emergence and resistance to seed damage over the four-month period of the post-harvest study.ConclusionsThis work represents the first field study of genetically modified cowpea expressing the αAI-1 protein. It demonstrates how a biotechnology solution to mitigate significant economic losses during cowpea storage, offers great potential for cowpea improvement programs.

Introduction Recurrent shoulder dislocations often cause attrition of the labrum and progressive loss of the anterior bony contour of the glenoid. Treatment options for this pathology involve either soft tissue repair or bony augmentation procedure. The optimal management for patients with shoulder instability with subcritical bone loss remains unknown and current clinical practice is highly varied.Methods and analysis The Shoulder instability Trial comparing Arthroscopic stabilisation Benefits compared with Latarjet procedure Evaluation (STABLE) is an ongoing multicentre, randomised controlled trial of 114 patients diagnosed with recurrent anterior shoulder instability and subcritical glenoid bone loss (10%–20%, measured on 3D CT using circle of best fit technique). Patients are randomised either arthroscopic capsuloligamentous repair (Bankart repair+remplissage) or open or arthroscopic coracoid transfer (Latarjet procedure). The primary outcome of this trial will be the between-group difference in the change from baseline to 24 months postintervention in Western Ontario Shoulder Instability Index scores. Secondary outcomes include: (1) rates of recurrent shoulder dislocations and symptoms of instability up to 24 months’ postsurgery; (2) clinical outcomes measured by American Shoulder and Elbow Society score, Shoulder Activity Scale, EQ-5D and Patient Satisfaction Scale; (3) physical examination (range of motion, stability); (4) return to previous level of activity/sport; (5) rate of shoulder-related complications and serious adverse events.Ethics and dissemination This protocol has been reviewed and approved by the Hamilton Integrated Research Ethics Board (HiREB; project number 15998) prior to commencement of the trial. Results from the study will be submitted for publication in a peer-reviewed journal regardless of whether there are statistically significant findings.Trial registration number NCT05705479; this study was prospectively registered on clinicaltrials.gov.

IntroductionPeriodontitis, affecting approximately 3.9 billion individuals globally, significantly impacts quality of life and has raised interest in its potential systemic effects. Sodium perborate, a common component in oral care products for biofilm control, is widely used, though concerns about its safety persist. This study aimed to evaluate the in vitro toxicity of six commercial oral care products and varying concentrations of sodium perborate, utilizing human gingival fibroblasts (HGF) and keratinocytes (HaCat) as cell models.MethodsExperiments were performed in both 2D monolayer and 3D cultures using MTT and electrical impedance assays, adhering to the manufacturer’s recommended exposure time of 30–60 s for product testing. For the reconstructed epidermis model, a prolonged exposure time of 42 min was applied, following the Organization for Economic Cooperation and Development (OECD) Test Guideline 439.ResultsResults indicated that all products and sodium perborate at 1 mg/mL were cytotoxic in monolayer cultures. However, at concentrations relevant to commercial formulations (0.06 mg/mL sodium perborate), no significant toxicity was observed. In contrast, the 3D culture models, including spheroids and reconstructed epidermis, exhibited minimal to no cytotoxic effects for the commercial products, with sodium perborate showing no significant toxicity below 0.1 mg/mL. The reconstructed epidermis model, used as surrogate for oral mucosa, further confirmed that the products were non-irritating, in compliance with OECD TG 439 standards.DiscussionThis study highlights the importance of considering exposure time, dosage, and cellular model when assessing the safety of oral care products. While 2D models are useful for preliminary screenings, 3D models provide a more physiologically relevant assessment, emphasizing the need for robust testing protocols to ensure product safety.

Abstract Chronic kidney disease (CKD) is a significant global health concern, impacting over 10% of the world population. Despite advances in home‐based treatments, CKD diagnosis and monitoring remain centralized in large laboratories. This work reports on the development of a Graphene‐based Lab‐On‐a‐Chip (G‐LOC) for the self‐testing of multiple renal function biomarkers in capillary blood. G‐LOC integrates bioelectronic sensors with a 3D‐printed microfluidic system that enables the multiplex quantification of urea, potassium, sodium, and chloride, from one drop of blood. The potentials of three graphene sensors modified with ion‐selective membranes and enzymes are simultaneously measured. The analytical performance of the test is evaluated in terms of linearity, accuracy, and coefficient of variability (CV). Accuracy values higher than 98.7%, and CV values lower than 10.8% are obtained for all the biomarkers. Correlation and Bland–Altman plots show good correlation (slopes in the range of 0.94–1.15) and high agreement of G‐LOC with a reference method. It is also demonstrated that the test can correctly differentiate biomarker levels normally obtained for healthy people, early‐stage CKD, and end‐stage CKD. Finally, user experience is studied with a group of untrained volunteers who highlight the simple usability of the test and its suitability for at‐home diagnostics.

Objective: Glucagon has long been proposed as a component of multi-agonist obesity therapeutics due to its ability to induce energy expenditure and cause weight loss. However, chronic glucagon-receptor agonism has been associated with a reduction in circulating amino acids and loss of lean mass. Importantly, it is currently not known whether the metabolic benefits of glucagon can be maintained under contexts that allow the defence of lean mass. Methods: We investigate the metabolic effects of the long-acting glucagon receptor agonist, G108, when administered to obese mice at low-doses, and with dietary protein supplementation. Results: Dietary protein supplementation can only fully defend lean mass at a low dose of G108 that is sub-anorectic and does not reduce fat mass. However, in this context, G108 is still highly effective at improving glucose tolerance and reducing liver fat in obese mice. Mechanistically, liver RNA-Seq analysis reveals that dietary protein supplementation defends anabolic processes in low-dose G108-treated mice, and its effects on treatment-relevant glucose and lipid pathways are preserved. Conclusion: Glucagon-mediated energy expenditure and weight loss may be mechanistically coupled to hypoaminocidemia and lean mass loss. However, our data suggest that glucagon can treat MAFLD at doses which allow full defence of lean mass given sufficient dietary protein intake. Therefore, proportionate glucagon therapy may be safe and effective in targeting hepatocytes and improving in glycaemia and liver fat.

Background: Contradictory findings link trait conscientiousness in mid- and late life to increased healthspan and lifespan, as well as to death by suicide. It remains unclear whether conscientiousness is associated with higher odds of attempting suicide or with more severe suicidal behavior among attempters, and whether its relationship to suicide risk varies with aging-related stressors, such as declining health. Methods: In this cross-sectional study comprising 313 depressed adults aged ≥40 years and participating in the Longitudinal Research Program in Late-Life Suicide (Pittsburgh, USA), we employed logistic and linear regression to test whether conscientiousness was associated with the presence of recent suicidal behavior (≤2 years) and with intent severity in recent attempters (n = 84). We further tested whether the above relationships varied based on mental, cognitive, and physical health status, measured as depression severity, cognitive functioning, and the presence/absence of severe physical illness. Results: Participants were 62.1 years old on average (SD = 7.6), 85% White, and 53% female. Recent attempters had a mean age of 61.8 years at their most recent attempt (SD = 8.5), had lower cognitive functioning and were more likely severely physically ill than comparisons. Conscientiousness was positively associated with a higher likelihood of recent suicidal behavior overall (adjusted OR = 1.44, 95% CI = 1.09, 1.90, p = .010), but not in case of co-occurring severe physical illness (interaction OR = 0.54, 95% CI = 0.30, 0.97, p = .039). Conscientiousness was also positively associated with suicidal intent at the most recent attempt (adjusted β = 1.60, SE = 0.62, p = .012), explaining 7% of its variance, although this association lost significance after adjusting for other personality dimensions. Conclusions: Highly conscientious middle-aged and older adults may be at increased risk of resolute suicidal behavior, although conscientiousness may not confer additional suicide risk among those severely physically ill.

Objective: to describe the norms and perceptions of a sample of Spanish parents and guardians on the use of mobile devices (smartphone and/or tablet) by their children and their association with such use. Method: a quantitative, analytical, cross-sectional, online, exploratory study was conducted with a non-probability sample of parents or guardians of children using smartphones or tablets. The virtual questionnaire consisted of 44 questions and was available at https://www.kenkolab.org/participa/ . Results: the total number of participants (parents or guardians) was 183 people. It was observed that 26.2% of parents admitted that their children had free and unrestricted access to smartphones or tablets. Associations were identified between time spent using mobile devices and parental attitudes, such as permission without time limitation and use as a reward or punishment. Approximately half of the respondents believe that their children use the mobile device longer than recommended. Conclusion: most parents exercise some control over their children’s use of devices. Acting on parental norms and perceptions is vital to success in addressing children’s time spent on mobile devices. Community nursing could be a vehicle for education in healthy screen consumption habits in early childhood.

There are many methodologies for assessing odour impact, such as dynamic olfactometry coupled with dispersion models, field inspections, Instrumental Odour Monitoring Systems and many others. However, none of these techniques can directly link this odour impact to the annoyance caused. Traditionally, odour impact assessment has been carried out using psychometry, which focuses on the theory and technique of psychological measurement used for several decades in the odour field. Nowadays, it is possible to assess odour impact using more advanced psychometric tools based on mobile applications that record an odour observation's exact time/ location. The International Environmental Association of Odour Managers (AMIGO) and other consultants, NGOs, odour-emitting activities and public administrations developed and published the first standard on mapping odour annoyance using advanced psychometry (UNE 77270) in September 2023. This standard is the first one, to our knowledge, that deals with using Citizen Science to take a snapshot of the odour reality in a community. There are several tens of projects around the world on this topic, but until now, no methodology has been developed to allow the unification of criteria when evaluating odour annoyance.

Background The benefit of patent foramen ovale closure (PFOC) ≤9 months after a cryptogenic stroke has been demonstrated in several randomised clinical trials. There is, however, insufficient data to support PFOC in non-recent cryptogenic strokes.Aims The objective of the study was to evaluate the effectiveness of PFOC in relation to the time since the patient’s most recent cryptogenic cerebrovascular event (CVE) or systemic embolism (SE).Methods We conducted a multicentre, retrospective cohort study with international participation, to assess the results of an early closure (EC,

Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Western world. Despite dramatic improvements in immunotherapies in the field of cancers, MM immunotherapy has not been promising until now. Recent clinical studies of immune checkpoint inhibitor therapy, either alone or in combination with anticancer drugs, showed excessive side effects or low efficacy, particularly in advanced MM patients. In this context, lymphocyte levels of exhaustion markers play a pivotal role in the MM tumor microenvironment (TME). Hence in the present review, the mechanisms relevant to MM of five inhibitory molecules including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and their rapidly emerging role in pathways in MM along with presenting recent clinical trials in context.

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations.

Summary: Background: Detection and management of late-life depression largely relies on primary care. Yet in Singapore, older adults are unlikely to seek help for their mental health from their primary care providers. This qualitative descriptive study explores how late-life depression manifests to general practitioners (GPs) in the Singaporean primary care setting. Methods: Twenty-eight private GPs practicing in Singapore were asked about their clinical experience with late-life depression during semi-structured group and individual discussions conducted online. Participants were purposively sampled across age, gender, and ethnicity (Chinese, Malay, Indian). Transcripts were analysed with reflexive thematic analysis. Findings: To GPs, depression in older patients often manifests through somatic symptoms or subtle behavioural changes, only detectable through follow-ups or collateral history. GPs reported that older patients attribute depressive symptoms to normal ageing or do not mention them, particularly within an Asian culture encouraging stoic endurance. GPs perceived late-life depression as reactions to ageing-related stressors, with male, low-income, or institutionalised patients being at particular risk of insidious, severe depression. GPs noted ethnic differences regarding families’ involvement in care, which they described as helpful, but sometimes stress-provoking for patients. Fear of burdensomeness or loss of autonomy/social role could prompt rejection of diagnosis and treatment in patients. GPs considered good patient-doctor rapport as a facilitator at every step of the care process, noting more favourable prognosis in care-concordant patients. Interpretation: Depression in older adults in Singapore can be covert, with favourable outcomes relying on GPs’ ability to pick up on subtle changes, assess patients holistically, and build rapport with patients and families. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project “Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients’ Voice in Primary Care” [NUHSRO/2022/049/NUSMed/DFM].

Pulsed light (PL), a relatively new non-thermal technology can be used as a possible substitute to the conventional (thermal and chemical) technology for disinfecting a wide variety of fruits and vegetables. The short-duration light pulses, ranging from 1 to 20 flashes per second with an energy density of about 0.01–50 Jcm−2, ensure the killing of several disease-causing microorganisms by causing minimal impact on the quality parameters in fruits and vegetables. This technology enhances safety and extends shelf-life period of fruits and vegetables. Furthermore, PL decreases or inhibits the harmful effect of conventional techniques on nutritional components. The review discusses recent research on PL's influence on nutritional and physicochemical parameters and its potential applications for extending the shelf life of fruits and vegetables. This PL technology can be successfully employed alone or in combination with other techniques for enhancing fresh produce life. PL is considered a safe, eco-friendly and non-thermal technique for shelf-life extension. For this review article, keywords such as pulsed light, fruits and vegetables, microbial safety and shelf life were selected and most relevant papers were cited. Thus, the present review article, supported by 70 references, highlights the novel potential of PL treatment and its diverse applications in the fruit and vegetable sector.

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic remains an international health problem caused by the recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of May 2024, SARS-CoV-2 has caused more than 775 million cases and over 7 million deaths globally. Despite current vaccination programs, infections are still rapidly increasing, mainly due to the appearance and spread of new variants, variations in immunization rates, and limitations of current vaccines in preventing transmission. This underscores the need for pan-variant antivirals and treatments. The interferon (IFN) system is a critical element of the innate immune response and serves as a frontline defense against viruses. It induces a generalized antiviral state by transiently upregulating hundreds of IFN-stimulated genes (ISGs). To gain a deeper comprehension of the innate immune response to SARS-CoV-2, its connection to COVID-19 pathogenesis, and the potential therapeutic implications, this review provides a detailed overview of fundamental aspects of the diverse ISGs identified for their antiviral properties against SARS-CoV-2. It emphasizes the importance of these proteins in controlling viral replication and spread. Furthermore, we explore methodological approaches for the identification of ISGs and conduct a comparative analysis with other viruses. Deciphering the roles of ISGs and their interactions with viral pathogens can help identify novel targets for antiviral therapies and enhance our preparedness to confront current and future viral threats.

Purpose This research proposes an adapted version of Business Model Canvas (BMC) as a potential strategic tool for the design of the business model of Higher Education Institutions (HEIs). In the context of fifth-generation universities, the University-Model Canvas (Unicanvas) offers a solution to some limitations of traditional strategic tools. Unicanvas aims to be a critical visual and dynamic tool to address the new challenges faced by universities such as internationalization, digitalization, sustainability, and corporate social responsibility. Research methods/Approach We adapt the strategic building blocks, in which some of the BMC blocks have been renamed and an achievement block has been added. We reflect theoretically on the peculiarities of each block in the context of universities to explain the versatility of the tool for designing university business models tailored to different value propositions and for various beneficiaries. Findings and implications Unicanvas offers universities the flexibility and dynamism to adapt their different business models to various forms of value creation that arise from their growing number of beneficiaries, missions, and the new trends and challenges they face.. We conclude that using this participatory,, dynamic, intuitive, and flexible strategic tool will facilitate the holistic design of the business model of these institutions.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Summary: The tumor microenvironment (TME) is characterized by a network of cancer cells, recruited immune cells, and extracellular matrix (ECM). However, the specific role of neutrophils during tumor development, and their interactions with other immune cells is still not well understood. Here, we use both standard well plate culture and an under oil microfluidic (UOM) assay with an integrated ECM bridge to elucidate how naive primary neutrophils respond to tumor cells. Our data demonstrated that tumor cells trigger cluster formation in neutrophils accompanied with the generation of reactive oxygen species (ROS) and neutrophil extracellular trap (NET) release. Using label-free optical metabolic imaging (OMI), we observed changes in the metabolic activities of primary neutrophils during the different clustering phases when challenged with tumor cells. Finally, our data demonstrates that neutrophils in direct contact, or in close proximity, with tumor cells exhibit greater metabolic activities compared to non-contact neutrophils.