Central nervous system multiple myeloma: A real-world multi-institutional study of the Greek Myeloma Study Group.

Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM between 2000 and 2022. A matched-control group of MM patients without CNS-MM was used for comparisons. Median age was 63 years. Median time to CNS-MM was 28 months; 6/54 experienced CNS-MM at MM diagnosis. Abnormal lactate dehydrogenase (LDH), high-risk cytogenetics, and extramedullary involvement (EMI), that is, soft tissue plasmacytomas and/or plasma cell leukemia (PCL), were more frequent in CNS-MM versus controls (p < .05); 13/54 had PCL at CNS-MM. The majority had leptomeningeal infiltration (LMI) (66%); 26% had CNS-MM without systemic myeloma; EMI was the strongest predictor for CNS-MM (OR: 6.3). Median overall survival (OS) of CNS-MM patients versus controls was 43 months (95% CI: 32-54) versus 60 months (95% CI: 38-82) (p < .001); treatment of CNS-MM included mainly bortezomib/thalidomide/chemotherapy whereas 20% received novel drugs/immunotherapy combinations; 28 patients underwent cerebrospinal fluid infusions; EMI was the strongest negative predictor for post CNS-MM OS (p = .005; HR: 2.9). Treatment after 2016 predicted significantly for OS (p = .002; HR: 0.27). Median post CNS-MM OS was 4 months (95% CI: 2.6-5.4); in patients treated after 2016 median OS was 12 months. In conclusion, we have demonstrated in this large real-world series that survival of CNS-MM remains poor; however, there is a positive impact of treatment after 2016, related to the efficacy of modern anti-myeloma therapy; EMI significantly increases the probability to develop CNS-MM and the risk of post CNS-MM death, indicating a potential need for CNS prophylaxis for those patients.

Implications of right aortic arch prenatal diagnosis: the multicentric nationwide ARCADE cohort.

OBJECTIVES: This study aims to describe the various presentations of the prenatally diagnosed isolated right aortic arch (RAA), that is, without associated congenital heart defect and to evaluate the impact of prenatal diagnosis of isolated RAA in terms of postnatal outcome. METHOD: In this multicentric retrospective study, from 2010 to 2019, all live births with a prenatal ultrasound diagnosis of isolated RAA were included, with a 1-year postnatal follow-up. The concordance between the different diagnostic steps (prenatal ultrasound, postnatal ultrasound and postnatal CT scan) was evaluated using Gwet's AC1 coefficient. RESULTS: A total of 309 cases of prenatally diagnosed RAA were analysed, most of which had a left ductus arteriosus (83%). The concordance between prenatal and postnatal ultrasound diagnosis was excellent regarding the RAA type (AC1=0.97, 95% CI=(0.94 to 0.99)). The rare discrepancies mainly involved non-diagnosed or misdiagnosed double aortic arch (2%). CT scan was performed in 108 neonates (35%) and the concordance between prenatal ultrasound and postnatal CT scan was good regarding the RAA diagnosis (AC1=0.80, 95% CI=(0.69 to 0.90)) but poor regarding the distribution of brachiocephalic vessels (AC1=0.21, 95% CI=(0.06 to 0.36)). An associated genetic anomaly was sought for in half of the cases and identified in 4% of the cohort. During the first year of life, 50 (18%) infants presented with vascular ring symptoms and 24 (8%) underwent aortic arch surgery. CONCLUSION: This multicentric nationwide cohort of 309 prenatally diagnosed isolated RAA demonstrated the reliability of prenatal screening, highlighted the rare cases of discrepancies between prenatal and postnatal diagnosis and underlined the value of CT scan to improve the postnatal follow-up. TRIAL REGISTRATION NUMBER: NCT04029064.

Prospective, International, Multisite Comparison of Platelet Isolation Techniques for Genome-Wide Transcriptomics: Communication from the SSC of the ISTH.

Genome-wide platelet transcriptomics is increasingly used to uncover new aspects of platelet biology and as a diagnostic and prognostic tool. Nevertheless, platelet isolation methods for transcriptomic studies are not standardized, introducing challenges for cross-study comparisons, data integration, and replication. In this prospective multicenter study, called "Standardizing Platelet Transcriptomics for Discovery, Diagnostics, and Therapeutics in the Thrombosis and Hemostasis Community (STRIDE)" by the ISTH SSCs, we assessed how three of the most commonly used platelet isolation protocols influence metrics from next-generation bulk RNA sequencing and functional assays. Compared with washing alone, more stringent removal of leukocytes by anti-CD45 beads or PALLTM filters resulted in a sufficient quantity of RNA for next-generation sequencing and similar quality of RNA sequencing metrics. Importantly, stringent removal of leukocytes resulted in the lower relative expression of known leukocyte-specific genes and the higher relative expression of known platelet-specific genes. The results were consistent across enrolling sites, suggesting the techniques are transferrable and reproducible. Moreover, all three isolation techniques did not influence basal platelet reactivity, but agonist-induced integrin αIIbß3 activation is reduced by anti-CD45 bead isolation compared to washing alone. In conclusion, the isolation technique chosen influences genome-wide transcriptional and functional assays in platelets. These results should help the research community make informed choices about platelet isolation techniques in their own platelet studies.

A Comparative Study of Human Leptospirosis between Mayotte and Reunion Islands Highlights Distinct Clinical and Microbial Features Arising from Distinct Inter-Island Bacterial Ecology.

Leptospirosis is a neglected zoonosis for which investigations assessing host-pathogen interaction are scarce. The aim of this study was to compare the severity and bacterial species involved in human cases of leptospirosis on Reunion and Mayotte islands, territories located in the southwest Indian Ocean that have recorded high human leptospirosis incidence but display fairly distinct epidemiological situations. A retrospective multicentric study including all patients over 18 years of age from Mayotte or Reunion with proven leptospirosis was conducted from January 2018 to April 2020. This study collected demographic, geographical, clinical, and biological data. Overall, 490 patients were included, 222 on Mayotte and 268 on Reunion. More patients were hospitalized on Reunion (n = 215, 80%) compared with Mayotte (n = 102, 46%). Severe disease was more common on Reunion (n = 75, 28%) than on Mayotte (n = 22, 10%). The dominant Leptospira species on Reunion was Leptospira interrogans (79%) followed by Leptospira borgpetersenii (21%), contrasting with the epidemiological situation on Mayotte where L. interrogans was found in only a minority of patients (10%). The high frequency of severe cases on Reunion could be explained not only by higher comorbidities but also by the higher occurrence of L. interrogans infections compared with Mayotte. Finally, the distribution of cases linked to L. borgpetersenii was found almost exclusively on the west coast of Reunion, raising the potential role of a ruminant reservoir.

Improving laboratory animal genetic reporting: LAG-R guidelines.

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals' genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. METHODS: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. RESULTS: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. DISCUSSION: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Pre-graft vaccination or infection do not decrease COVID-19 infections in recipients of allogeneic stem cell transplantation vaccinated and/or protected by immunotherapy after transplant.

The impact of pre-graft COVID-19 vaccinations in donor or recipient as well as pre-graft infection has been studied in 157 adults having received allogeneic stem cell transplantation (Allo-SCT) for various hematological diseases during the delta/omicron waves. We showed here that pre-Allo-SCT COVID-19 vaccination and/or infection do not provide more protection in patients receiving vaccine, immunotherapy or both after transplant. COVID-19 vaccination is and remains of crucial importance after Allo-SCT, reinforcing the recommendation to start COVID-19 vaccination as soon as the third month following the transplant.

Impact of a bundle of care (intravenous iron, erythropoietin and transfusion metabolic adjustment) on post-operative transfusion incidence in cardiac surgery: a single-centre, randomised, open-label, parallel-group controlled pilot trial.

Background: Red blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions. Methods: In this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20 mg/kg intravenous ferric carboxymaltose if Hb < 13 g/dL the day before surgery or at ICU admission, and RBC transfusion if Hb ≤ 8 g/dL and ScvO2 ≤ 65%, or additional EPO dose if 8 < Hb < 13 g/dL) or to the control group (RBC transfusion if Hb ≤ 8 g/dL, or, if 8 < Hb < 13 g/dL, intravenous iron sucrose 200 mg or 300 mg according to weight). Primary outcome was the incidence of postoperative RBC transfusion up to hospital discharge or postoperative day 28. The trial is registered with ClinicalTrials.gov, NCT04141631. Findings: Between Jan 20, 2020, and Sept 6, 2022, among 128 patients enrolled, 123 (male, 54.4%, 67/123) were included in the full analysis set: 62 in the STOP group and 61 in the control group. Nine patients (14.5%, 9/62) in the STOP group required RBC transfusion vs 19 (31.2%, 19/61) in the control group (odds ratio 0.37 [95% CI: 0.15-0.91], p = 0.03). The median length of follow up to transfusion was 2.6 days (1.5; 4.6) and 3.3 (1.6; 4.2) in control and STOP groups respectively (p = 0.61). Interpretation: The bundle of care may reduce postoperative RBC transfusion. The findings should be taken with caution due to the unblinded and exploratory nature of the study. Funding: University of Montpellier Hospital and Vifor Pharma.

Beneficial Effects of Synbiotics on the Gut Microbiome in Individuals with Low Fiber Intake: Secondary Analysis of a Double-Blind, Randomized Controlled Trial.

Insufficient dietary fiber intake can negatively affect the intestinal microbiome and, over time, may result in gut dysbiosis, thus potentially harming overall health. This randomized controlled trial aimed to improve the gut microbiome of individuals with low dietary fiber intake (<25 g/day) during a 7-week synbiotic intervention. The metabolically healthy male participants (n = 117, 32 ± 10 y, BMI 25.66 ± 3.1 kg/m2) were divided into two groups: one receiving a synbiotic supplement (Biotic Junior, MensSana AG, Forchtenberg, Germany) and the other a placebo, without altering their dietary habits or physical activity. These groups were further stratified by their dietary fiber intake into a low fiber group (LFG) and a high fiber group (HFG). Stool samples for microbiome analysis were collected before and after intervention. Statistical analysis was performed using linear mixed effects and partial least squares models. At baseline, the microbiomes of the LFG and HFG were partially separated. After seven weeks of intervention, the abundance of SCFA-producing microbes significantly increased in the LFG, which is known to improve gut health; however, this effect was less pronounced in the HFG. Beneficial effects on the gut microbiome in participants with low fiber intake may be achieved using synbiotics, demonstrating the importance of personalized synbiotics.

The body interior in anorexia nervosa: from interoception to conceptual representation of body interior.

Background: Body image disorders are well documented in anorexia nervosa (AN); however, knowledge of interoceptive awareness (IA) in this population remains poor. This descriptive study investigated whether and how the representation of the interior of the body may have an impact on IA. Methods: The representations and knowledge of the body interior were evaluated with a drawing task in 34 women with AN and 34 healthy controls (HCs). A lexicometric analysis was performed on the vocabulary used to describe the drawn body parts in a structured interview. It was assumed that the conceptual representation of the body interior could be affected by or influence IA. Thus, the relationship between IA, measured with the heartbeat task and the ischemia-induction test, and the drawings was explored. Other scales, such as those of body shape, awareness or satisfaction, were used to assess affective representations of the body. Results: The drawing, lexicometric and IA results were similar in the two groups. No correlations were found among IA, body representation scores and representation level of body interior. Only the representation of bones by the AN group was significantly different. Discussion: Increased visual attention to the skeleton or greater awareness of bone health could explain the stronger representation of bones in the AN group. The psychophysical therapy received by some AN participants (73%) did not seem to have influenced IA. Our results do not support a relationship between IA and the representation of the body interior.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03988218.

Diagnosis and management of children and adult craniopharyngiomas: a French Endocrine Society/French Society for Paediatric Endocrinology & Diabetes Consensus Statement.

Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.

A national survey of children's experiences and needs when attending Canadian pediatric emergency departments.

BACKGROUND: Optimizing a child's emergency department (ED) experience positively impacts their memories and future healthcare interactions. Our objectives were to describe children's perspectives of their needs and experiences during their ED visit and relate this to their understanding of their condition. METHODS: 514 children, aged 7-17 years, and their caregivers presenting to 10 Canadian pediatric EDs completed a descriptive cross-sectional survey from 2018-2020. RESULTS: Median child age was 12.0 years (IQR 9.0-14.0); 56.5% (290/513) were female. 78.8% (398/505) reported adequate privacy during healthcare conversations and 78.3% (395/504) during examination. 69.5% (348/501) understood their diagnosis, 89.4% (355/397) the rationale for performed tests, and 67.2% (338/503) their treatment plan. Children felt well taken care of by nurses (90.9%, 457/503) and doctors (90.8%, 444/489). Overall, 94.8% (475/501) of children were happy with their ED visit. Predictors of a child better understanding their diagnosis included doctors talking directly to them (OR 2.21 [1.15, 4.28]), having someone answer questions and worries (OR 2.51 [1.26, 5.01]), and older age (OR 1.08 [1.01, 1.16]). Direct communication with a doctor (OR 2.08 [1.09, 3.99]) was associated with children better understanding their treatment, while greater fear/ 'being scared' at baseline (OR 0.59 [0.39, 0.89]) or at discharge (OR 0.46 [0.22, 0.96]) had the opposite effect. INTERPRETATION: While almost all children felt well taken care of and were happy with their visit, close to 1/3 did not understand their diagnosis or its management. Children's reported satisfaction in the ED should not be equated with understanding of their medical condition. Further, caution should be employed in using caregiver satisfaction as a proxy for children's satisfaction with their ED visit, as caregiver satisfaction is highly linked to having their own needs being met.

Two-year prognosis and cardiovascular disease prevention after acute coronary syndrome; the role of cardiac rehabilitation: a French nationwide study.

AIMS: To evaluate the impact of cardiac rehabilitation (CR) on optimization of secondary prevention treatments for acute coronary syndrome (ACS), medication persistence, medical follow-up, rehospitalisation, and all-cause mortality. METHODS: The national health insurance database was used to identify all patients hospitalised for ACS in France in 2019 and those among them who received CR. Patients' characteristics and outcomes were described and compared between CR and non-CR patients. Poisson regression models were used to identify the impact of CR after adjusting for confounders. A Cox model was fitted to identify the variables related to mortality after adjustment for medication persistence and cardiologic follow-up. RESULTS: In 2019, 22% of 134,846 patients hospitalised for ACS in France received CR within six months of their discharge. After one year, only 60% of patients who did not receive CR were still taking BASI drugs (combination of Beta blockers, Antiplatelets agents, Statins and RAAS Inhibitors). This rate and the medical follow-up rate were higher in patients who received CR. Two years after the ACS event, patients who received CR had better medical follow-up and lower mortality risk, after adjusting for cofounding variables (adjusted HR all-cause mortality = 0.65 [0.61-0.69]). After adjustment for the dispensing of cardiovascular drugs and cardiologic follow-up, the independent effect of CR was not as strong but remained significant (HR = 0.90 [95%CI: 0.84-0.95]). CONCLUSION: Patients who received CR after hospitalisation for ACS had a better prognosis. Optimization of efficient secondary prevention strategies, improved medication persistence, and enhanced cardiologic follow-up seemed to play a major role.

In our nationwide study of all patients hospitalized for acute coronary syndrome in 2019 (n = 134,846), 22% were admitted in cardiac rehabilitation after their hospitalisation. The admission in cardiac rehabilitation unit increased patients medication persistence, increased the chance to initiate a tobacco replacement therapy in smokers, reduced rehospitalisation risk and the recurrence of acute coronary syndrome. In addition the risk of death was reduced in the two years following the hospitalization. Health benefits associated with an admission in cardiac rehabilitation following an acute coronary syndrome are significant focusing recurrence and mortality. The correction of cardiovascular risk factors, the improvement of medication persistence and a more frequent cardiologic follow-up play a major role in these health benefits.These results should help to encourage increased referral for and patient participation in cardiac rehabilitation programs, whose rate is still very low in many countries, including France. Finally, decreasing hospital capacity means that new rehabilitation modalities need to be considered, including supervised home-based CR and tele-rehabilitation.

Hypertriglyceridemia Results From an Impaired Catabolism of Triglyceride-Rich Lipoproteins in PLIN1-Related Lipodystrophy.

BACKGROUND: Pathogenic variants in PLIN1-encoding PLIN1 (perilipin-1) are responsible for an autosomal dominant form of familial partial lipodystrophy (FPL) associated with severe insulin resistance, hepatic steatosis, and important hypertriglyceridemia. This study aims to decipher the mechanisms of hypertriglyceridemia associated with PLIN1-related FPL. METHODS: We performed an in vivo lipoprotein kinetic study in 6 affected patients compared with 13 healthy controls and 8 patients with type 2 diabetes. Glucose and lipid parameters, including plasma LPL (lipoprotein lipase) mass, were measured. LPL mRNA and protein expression were evaluated in abdominal subcutaneous adipose tissue from patients with 5 PLIN1-mutated FPL and 3 controls. RESULTS: Patients with PLIN1-mutated FPL presented with decreased fat mass, insulin resistance, and diabetes (glycated hemoglobin A1c, 6.68±0.70% versus 7.48±1.63% in patients with type 2 diabetes; mean±SD; P=0.27). Their plasma triglycerides were higher (5.96±3.08 mmol/L) than in controls (0.76±0.27 mmol/L; P<0.0001) and patients with type 2 diabetes (2.94±1.46 mmol/L, P=0.006). Compared with controls, patients with PLIN1-related FPL had a significant reduction of the indirect fractional catabolic rate of VLDL (very-low-density lipoprotein)-apoB100 toward IDL (intermediate-density lipoprotein)/LDL (low-density lipoprotein; 1.79±1.38 versus 5.34±2.45 pool/d; P=0.003) and the indirect fractional catabolic rate of IDL-apoB100 toward LDL (2.14±1.44 versus 7.51±4.07 pool/d; P=0.005). VLDL-apoB100 production was not different between patients with PLIN1-related FPL and controls. Compared with patients with type 2 diabetes, patients with PLIN1-related FPL also showed a significant reduction of the catabolism of both VLDL-apoB100 (P=0.031) and IDL-apoB100 (P=0.031). Plasma LPL mass was significantly lower in patients with PLIN1-related FPL than in controls (21.03±10.08 versus 55.76±13.10 ng/mL; P<0.0001), although the LPL protein expression in adipose tissue was similar. VLDL-apoB100 and IDL-apoB100 indirect fractional catabolic rates were negatively correlated with plasma triglycerides and positively correlated with LPL mass. CONCLUSIONS: We show that hypertriglyceridemia associated with PLIN1-related FPL results from a marked decrease in the catabolism of triglyceride-rich lipoproteins (VLDL and IDL). This could be due to a pronounced reduction in LPL availability, related to the decreased adipose tissue mass.

Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.

INTRODUCTION: Many patients referred for suspicion of myelodysplastic neoplasm (MDS) are subjected to unnecessary discomfort from bone marrow aspiration, due to the low disease prevalence in this population. Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression could rule out MDS with sensitivity and negative predictive value estimates close to 100%, ultimately obviating the need for bone marrow aspiration in up to 35% of patients. However, the generalisability of these findings is uncertain due to the limited sample size, the enrolment of patients at a single study site, and the reliability issues associated with laboratory-developed tests and varying levels of operator experience. This study aims to validate the accuracy attributes of peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis in an independent multicentre sample. METHODS AND ANALYSIS: The MPO-MDS-Valid project is a cross-sectional diagnostic accuracy study comparing an index test to a reference standard. Consecutive adult patients referred for suspicion of MDS are being recruited at seven university hospitals and one cancer centre in France. At each site, flow cytometric analysis of peripheral blood samples is performed by operators who are blinded to the reference diagnosis. A central adjudication committee whose members are unaware of the index test results will determine the reference diagnosis of MDS, based on cytomorphological evaluation of bone marrow performed in duplicate by experienced hematopathologists. The target sample size is 400 patients and the anticipated study recruitment completion date is 31 December 2025. ETHICS AND DISSEMINATION: An institutional review board (Comité de Protection des Personnes Nord-Ouest III, Caen, France) approved the protocol, prior to the start of the study. Participants are recruited using an opt-out approach. Efforts will be made to publish the primary results within 6 months after study completion. TRIAL REGISTRATION NUMBER: NCT05175469.

Core-Double-Shell TiO2@Fe3O4@C Microspheres with Enhanced Cycling Performance as Anode Materials for Lithium-Ion Batteries.

Due to the volume expansion effect during charge and discharge processes, the application of transition metal oxide anode materials in lithium-ion batteries is limited. Composite materials and carbon coating are often considered feasible improvement methods. In this study, three types of TiO2@Fe3O4@C microspheres with a core-double-shell structure, namely TFCS (TiO2@Fe3O4@C with 0.0119 g PVP), TFCM (TiO2@Fe3O4@C with 0.0238 g PVP), and TFCL (TiO2@Fe3O4@C with 0.0476 g PVP), were prepared using PVP (polyvinylpyrrolidone) as the carbon source through homogeneous precipitation and high-temperature carbonization methods. After 500 cycles at a current density of 2 C, the specific capacities of these three microspheres are all higher than that of TiO2@Fe2O3 with significantly improved cycling stability. Among them, TFCM exhibits the highest specific capacity of 328.3 mAh·g-1, which was attributed to the amorphous carbon layer effectively mitigating the capacity decay caused by the volume expansion of iron oxide during charge and discharge processes. Additionally, the carbon coating layer enhances the electrical conductivity of the TiO2@Fe3O4@C materials, thereby improving their rate performance. Within the range of 100 to 1600 mA·g-1, the capacity retention rates for TiO2@Fe2O3, TFCS, TFCM, and TFCL are 27.2%, 35.2%, 35.9%, and 36.9%, respectively. This study provides insights into the development of new lithium-ion battery anode materials based on Ti and Fe oxides with the abundance and environmental friendliness of iron, titanium, and carbon resources in TiO2@Fe3O4@C microsphere anode materials, making this strategy potentially applicable.

Silanization Strategies for Tailoring Peptide Functionalization on Silicon Surfaces: Implications for Enhancing Stem Cell Adhesion.

Biomaterial surface engineering and the integration of cell-adhesive ligands are crucial in biological research and biotechnological applications. The interplay between cells and their microenvironment, influenced by chemical and physical cues, impacts cellular behavior. Surface modification of biomaterials profoundly affects cellular responses, especially at the cell-surface interface. This work focuses on enhancing cellular activities through material manipulation, emphasizing silanization for further functionalization with bioactive molecules such as RGD peptides to improve cell adhesion. The grafting of three distinct silanes onto silicon wafers using both spin coating and immersion methods was investigated. This study sheds light on the effects of different alkyl chain lengths and protecting groups on cellular behavior, providing valuable insights into optimizing silane-based self-assembled monolayers (SAMs) before peptide or protein grafting for the first time. Specifically, it challenges the common use of APTES molecules in this context. These findings advance our understanding of surface modification strategies, paving the way for tailoring biomaterial surfaces to modulate the cellular behavior for diverse biotechnological applications.

Maintain the light, long-term seasonal monitoring of luminous capabilities in the brittle star Amphiura filiformis.

The European brittle star Amphiura filiformis emits blue light, via a Renilla-like luciferase, which depends on the dietary acquisition of coelenterazine. Questions remain regarding luciferin availability across seasons and the persistence of luminous capabilities after a single boost of coelenterazine. To date, no study has explored the seasonal, long-term monitoring of these luminous capabilities or the tracking of luciferase expression in photogenic tissues. Through multidisciplinary analysis, we demonstrate that luminous capabilities evolve according to the exogenous acquisition of coelenterazine throughout adult life. Moreover, no coelenterazine storage forms are detected within the arms tissues. Luciferase expression persists throughout the seasons, and coelenterazine's presence in the brittle star diet is the only limiting factor for the bioluminescent reaction. No seasonal variation is observed, involving a continuous presence of prey containing coelenterazine. The ultrastructure description provides a morphological context to investigate the green autofluorescence signal attributed to coelenterazine during luciferin acquisition. Finally, histological analyses support the hypothesis of a pigmented sheath leading light to the tip of the spine. These insights improve our understanding of the bioluminescence phenomenon in this burrowing brittle star.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.