Multiscale and multimodal evaluation of autosomal dominant polycystic kidney disease development.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent kidney genetic disorder, producing structural abnormalities and impaired function. This research investigates its evolution on mouse models, utilizing a combination of histology imaging, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate its progression thoroughly. ADPKD has been induced in mice via PKD2 gene knockout, followed by image acquisition at different stages. Histology data provides two-dimensional details, like the cystic area ratio, whereas CT and MRI facilitate three-dimensional temporal monitoring. Our approach allows to quantify the affected tissue at different disease stages through multiple quantitative metrics. A pivotal point is shown at approximately ten weeks after induction, marked by a swift acceleration in disease advancement, and leading to a notable increase in cyst formation. This multimodal strategy augments our comprehension of ADPKD dynamics and suggests the possibility of employing higher-resolution imaging in the future for more accurate volumetric analyses.

Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine.

This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

Liposomal formulation of a gold(III) metalloantibiotic: a promising strategy against antimicrobial resistance.

A novel lipoformulation was developed by encapsulating cationic (S^C)-cyclometallated gold(III) complex [Au(dppta)(N2Py-PZ-dtc)]+ (AuPyPZ) in liposomes. The liposomal form of compound AuPyPZ has a bactericidal action similar to that of the free drug without any appreciable effect on the viability of mammalian cells. Furthermore, the nanoformulation reduces metalloantibiotic-induced inhibition of hERG and the inhibition of cytochromes, significantly decreasing the potential liabilities of the metallodrug. The obtained metalloantibiotic liposomal formulation shows high stability and suitable properties for drug delivery, representing an effective strategy to fight against drug-resistant bacteria.

Psychedelic public health: State of the field and implications for equity.

BACKGROUND: Psychedelic Public Health is an emerging discipline uniting the practices of public health with the potential benefits of psychedelics to reduce harm and promote health, wellness, and equity at community and population levels. Little is known regarding the current state of psychedelic public health despite rising psychedelic usage, evidence of its health efficacy, opening policy environments, and concerns regarding equity and potential harms. METHODS: To characterize the current state of psychedelic public health, this survey reviewed relevant webpages from 228 universities housing accredited Schools and Programs in Public Health (SPPHs) and 59 Psychedelic Research Centers (PRCs) in the US and globally. The scan corresponded to the Prisma 2020 checklist, identifying URLs through keyword searches by Beautiful Soup python package and Google search engine web application. Measures were coded through webpage text analysis. FINDINGS: Fewer than 10% (9.6%) of SPPHs engaged with psychedelics (2.6% substantially), while half (52.6%) of universities engaged (28.1% substantially). Among PRCs, only 10% indicated a collaboration with SPPHs, and fewer than 3% of PRC personnel held public health degrees. PRCs were preponderantly affiliated with medical schools. Although Indigeneity significantly contributes to Western therapeutic psychedelic protocols, only approximately one-quarter of active universities, SPPHs, or PRCs visibly addressed Indigeneity and only one PRC included Indigenous leadership. 92% of PRCs were led or co-led by people characterized as White-European and 88% by men. Only 20-43% of SPPHs, universities, and PRCs visibly addressed social determinants of health. CONCLUSIONS: Public health schools, which train, study, and advise the future of public health, showed limited involvement in the growing psychedelic field, signifying a gap in psychedelic science and practice. The absence of public health's population-level approaches signifies a missed opportunity to maximize benefits and protect against potential harms of psychedelics at community and population levels.

Incidence and long-term outcomes of upper limb deep vein thrombosis associated with intracardiac devices: analysis of bleeding, recurrence, and sequelae.

Pacemakers (PM) and implantable cardioverter-defibrillators are vital devices in contemporary clinical practice, but their growing adoption poses challenges. Complications, including lead migration, infections, and post-implantation venous thrombosis, underscore the importance of comprehensive investigation. This retrospective observational study enrolled patients diagnosed with upper limb deep vein thrombosis (DVT) secondary to intracardiac devices at a tertiary hospital from 2015 to 2022. The aim of the study was to determine the incidence and long-term outcomes (bleeding, DVT recurrence and sequelae) in these patients. Across the study period, 2681 intracardiac devices were implanted, with 12 cases of upper limb DVT documented. The majority of patients were male (91.7%), with a mean age of 63.92 years. DVT occurred in patients with PM (50%), implantable cardioverter-defibrillators (25%) and implantable cardioverter-defibrillators with Cardiac Resynchronization Therapy (25%). Treatment encompassed low-molecular-weight heparin (91.7%) during the acute episode and long-term anticoagulation with direct oral anticoagulants (75%) or vitamin K antagonists (25%). Over a mean follow-up period of 33.17 months, half of the patients exhibited long-term sequelae, notably collateral circulation (66.7%). Remarkably, no thrombosis recurrences were observed during follow-up. However, one patient (8.3%) experienced a major bleeding event during treatment, and one patient (8.3%) required device removal (PM) due to persistent symptoms. This study revealed upper limb DVT occurred in 0.45% of patients after intracardiac device implantation. Rate of thrombosis recurrence was low during follow-up. Although half of the patients developed long-term sequelae, the need for prolonged anticoagulant therapy in these cases remains uncertain.

First report of Fusarium oxysporum f. sp. fragariae race 1 causing Fusarium wilt of strawberry (Fragaria × ananassa) in the Alentejo region of Portugal.

In the summer of 2023, within the Alentejo region (Portugal), a new occurrence of a plant disease of strawberry (Fragaria × ananassa) cv. 'Monterey' was observed in a Spring commercial planting. Symptoms consisted of foliar wilting, drying of older leaves, deformed and highly chlorotic leaflets, crown discoloration, plant stunting, and in some cases death. Several outbreak foci, covering nearly half a hectare, were observed within the affected farm, with almost 80% of the plants showing symptoms. Four samples,of 6 plants, were collected from 4 locations within the field. Petiole sections (1 cm) were rinsed with 0.1% Tween 20, submersed in 70% EtOH for 20 s followed by 60 s in 1% NaOCL, and then placed on Komada's medium (Komada, 1975). After incubation at room temperature in the dark for a week, white-colored fluffy mycelia grew profusely from the petioles of all samples. Colony morphology and non-septate, ellipsoidal microconidia (5.7-12.4×2.5-4.3 µm) borne on monophialides, exhibited a resemblance to Fusarium oxysporum (Leslie and Summerell, 2006). Ten single strains were obtained from different plants by single hyphal tip isolation. For molecular confirmation, a portion of the translation elongation factor 1-alpha (EF1α) was amplified by PCR using EF1/EF2 primers (O'Donnell et al., 1998). Additionally, the RNA polymerase subunit RPB2 was amplified as two contiguous fragments via primers and protocols described by O'Donnell et al., 2021. Amplicons were sequenced (GenBank Accession Nos. PP426617 - 426626, PQ058494 - 058513). Using Fusarium-ID and Fusarioid-ID databases, EF1α and RPB2 sequences were found to be more than 99% identical to published F. oxysporum type isolates and Fusarium sp. isolates in the F. oxysporum species complex (Crous et al., 2021; Wang et al., 2022). A specific F. oxysporum f. sp. fragariae (Fof) qPCR assay (Burkhardt et al., 2019) was used to determine if these isolates could be Fof race 1. A Fof race 1 isolate (MAFF305558), negative controls, and water controls were included. All ten isolates and the Fof race 1 control were positive (Ct < 30), while other Fusarium spp. used as negative controls and the water controls did not amplify. Two isolates (F.200 and F.202) and MAFF305558 (positive control) were included in a pathogenicity test on two strawberry cultivars, 'Monterey' (susceptible to race 1) and 'Fronteras' (resistant to race 1) (Dilla-Ermita et al., 2023). Each isolate was included in two independent trials. In each trial, 5 plants per cultivar were inoculated by dipping roots for 10 min in 5 × 106 conidia/mL of 0.1% water agar (WA) or in sterile 0.1% WA for the negative control plants. Each plant was then planted in a pot filled with peat. Pots were placed randomly in random positions in a growth chamber at 28/20°C and 12h photoperiod. After 8 - 10 weeks, the control plants and 'Fronteras' plants remained healthy, while the inoculated plants cv. 'Monterey' were severely wilted and/or dead. Fusarium oxysporum was re-isolated from all symptomatic plants. Recovered isolates were confirmed to be the same as the inoculated ones using the Fof-qPCR, including the same controls as above. This is the first report of Fof race 1 in the Iberian Peninsula. Given that the land was not previously used for strawberry, it is highly probable that the pathogen was introduced with the planting material originated from a Spanish nursery. In conclusion, it is imperative to implement more severe control measures in nurseries to avoid the spread of this race.

Transitional discharge interventions for people with schizophrenia.

BACKGROUND: Schizophrenia is a chronic mental illness characterized by delusions, hallucinations, and important functional and social disability. Interventions labeled as 'transitional' add to care plans made during the hospital stay in preparation for discharge. They also include interventions developed after discharge to support people with serious mental illness as they make the transition from the hospital to the community. Transitional discharge interventions may anticipate the future needs of the patient after discharge by co-ordinating the different levels of the health system that can effectively guarantee continuity of care in the community. This occurs through the provision of therapeutic relationships which give a safety net throughout the discharge and community reintegration processes to improve the general condition of users, level of functioning, use of health resources, and satisfaction with care. OBJECTIVES: To assess the effects of transitional discharge interventions for people with schizophrenia. SEARCH METHODS: On 7 December 2022, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, PubMed, CINAHL, ClinicalTrials.gov, ISRCTN, PsycINFO, and WHO ICTRP. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating the effects of transitional discharge interventions in people with schizophrenia and schizophrenia-related disorders. Eligible interventions included three key elements: predischarge planning, co-ordination of care and follow-up, and postdischarge support. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes of this review included global state (relapse), service use (hospitalization), general functioning, satisfaction with care, adverse effects/events, quality of life, and direct costs. For binary outcomes, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes, we calculated the mean difference (MD) or standardized mean difference (SMD) and their 95% CIs. We used GRADE to assess certainty of evidence. MAIN RESULTS: We found 12 studies with 1748 participants comparing transitional discharge interventions to usual care. All were parallel-group RCTs. No studies assessed global state (relapse) or reported data about adverse events/effects. All studies had a high risk of bias, mainly due to serious concerns about allocation concealment, deviations from intended interventions, measurement of the outcomes, and missing outcome data. Transitional discharge interventions may make little to no difference in service use (hospitalization) at short- and long-term follow-ups, but the evidence is very uncertain (RR 1.18, 95% CI 0.55 to 2.50; I2 = 54%; 4 studies, 462 participants; very low-certainty evidence). Transitional discharge intervention may increase the levels of functioning after discharge (clinically important change in general functioning) (SMD 0.95, 95% CI -0.06 to 1.97; I² = 95%; 4 studies, 437 participants; very low-certainty evidence) and may increase the proportion of participants who are satisfied with the intervention (clinically important change in satisfaction) (RR 1.96, 95% CI 1.37 to 2.80; 1 study, 76 participants; very low-certainty evidence), but for both outcomes the evidence is very uncertain. Transitional discharge intervention may make little to no difference in quality of life compared to treatment as usual (SMD 0.24, 95% CI -0.30 to 0.78; I² = 90%; 4 studies, 748 participants; very low-certainty evidence), but we are very uncertain. For direct costs, one study with 124 participants did not report full details and thus the results were inconclusive. AUTHORS' CONCLUSIONS: There is currently no clear evidence for or against implementing transitional discharge interventions for people with schizophrenia. Transitional discharge interventions may improve patient satisfaction and functionality, but this evidence is also very uncertain. For future research, it is important to improve the quality of the conduct and reporting of these trials, including using validated tools for measuring their outcomes.

Acidovorax bellezanensis sp. nov., a novel bacterium from uranium mill tailings repository sites with selenium bioremediation capabilities.

A Gram-stain-negative bacterial strain designated Be4T, belonging to the genus Acidovorax, was isolated from mining porewaters sampled in uranium mill tailings repository sites, located in Bellezane, near Bessines-sur-Gartempe (Limousin, France). Cells were facultative anaerobic, rod-shaped, non-endospore-forming and motile with flagella. The mean cell size was 1.25-1.31 µm long and 0.70-0.73 µm wide. Colonies were light yellow, opaque, circular, convex with smooth margins, and 1-2 mm in diameter. Growth occurs at 4-37 °C and between pH 5.5-9.0. It differed from its phylogenetically related strains by phenotypic and physiological characteristics such as growth at 4 °C, presence of acid phosphatase, naphthol-AS-BI-phosphohydrolase and ß-glucosidase enzymatic activities, and fermentation of l-xylose and esculin. The major fatty acids were C16:0, C16:1 ω7c/C16:1 ω6c, C17:0 cyclo and C18:1 ω7c. Phylogenetic analysis based on 16S rRNA and 938 core genes, confirmed its placement within the genus Acidovorax as a novel species. Strain Be4T showed highest 16S rRNA sequence similarity to Acidovorax antarcticus (98.2 %), Acidovorax radicis (97.9 %), Acidovorax temperans (97.8 %) and Acidovorax facilis (97.7 %). The genome of strain Be4T is 5,041,667 bp size with a DNA G + C content of 65.15 %. By automatic annotation numerous sequences involved in the interaction with metals/metalloids including some genes related to Se uptake and selenite resistance were detected in its genome. The average nucleotide identity (ANI) values calculated from whole genome sequences between strain Be4T and the most closely related strains A. radicis and A. facilis were below the threshold value of 95 %. Thus, the data from the phylogenetic, physiological, biochemical, and genomic analyses clearly indicates that strain Be4T represents a novel species with the suggested name Acidovorax bellezanensis sp. nov. The type strain is Acidovorax bellezanensis Be4T (=DSM116209T = CECT30865T). This novel species, due to its unique isolation source, genomic analysis, and preliminary laboratory tests where it was able to reduce toxic Se(IV) to less harmful Se(0) in the form of nanoparticles, holds great potential for further investigation in bioremediation, particularly concerning Se.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Prognosis recovery score of apical surgery Guided Bone Regeneration using cone beam computed tomography and digital bioinformatics.

Objective: Guided Bone Regeneration (GBR) is a dental surgical procedure that uses barrier membranes to prevent soft tissue invasion and conduct new bone growth. This study aimed to define a Prognosis Recovery score (PR score) to objectively classify post-surgery responders from non-responder patients who underwent GBR using Cone Beam Computed Tomography (CBCT). Methods: This prospective-observational-longitudinal-cohort study recruited 250 individuals who were assigned to: Conventional-Apical-Surgery (CAS, n = 39), Apical-Surgery using human fascia lata Membrane placement (ASM, n = 42), and Apical-Surgery using human fascia lata Membrane placement and lyophilized allograft Bone powder (ASMB, n = 39); and Apical-Surgery using collagen membrane Porcine origin and Bovine Bone-matrix (ASPBB, n = 130), an independent external validation cohort. Surgery was performed, and evolution was monitored by CBCTs at 0, 6-, 12-, 18-, and 24 months post-surgery. Results: Normalized lesion volumes were calculated, and non-linear time evolution morphology curves were characterized. The three-time evolution bone growth patterns were: a linear tendency (PR0), "S'' shaped log-logistic (PR1), and "C" cellular growth (PR2). The treatment success rates were PR2-46 %, PR2-88 %, and PR2-95 %/PR1-5% for CAS, ASM, and ASMB groups. The xenograft ASPBB counterpart achieved PR2-92 % and PR1-8%. The score PR had a sensitivity, specificity, and accuracy of 100 %. Conclusions: Patients' treatment success can be quantitatively, objectively, and precisely predicted with the Prognosis Recovery score (using only two CBCTs), according to their biological response to allograft or xenograft materials (time-evolution bone growth curves), reducing cost and radiation exposure. Clinical significance: Through digital imaging and bioinformatic analysis of bone regeneration observed in CBCTs, we defined a Prognosis Recovery (PR) score using only two CBCT volume assessments (0 and 6 months). The PR score allowed us to define three time-evolution curves depending on the biomaterials used and to classify patients in a quantitative, objective, and accurate way.

Soluble urokinase type plasminogen activator receptor (suPAR) and mortality in acute pulmonary embolism.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated. MATERIAL AND METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality. RESULTS: Fifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48-0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63-61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69-40.99; p<0.01). CONCLUSION: suPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE.

The Potential Role of CA-125 as a Biomarker for Short-Term Mortality Risk in Patients with Acute Symptomatic Pulmonary Embolism.

Background: Antigen carbohydrate 125 (CA-125) is a complex glycoprotein extensively studied as a prognostic biomarker in heart failure, yet its potential role in the short-term prognosis of an acute pulmonary embolism (PE) remains unexplored. Methods: In this observational, prospective, single-center study, consecutive patients aged 18 and older with a confirmed acute symptomatic PE and no history of prior anticoagulant therapy were enrolled. Primary and secondary objectives aimed to assess the prognostic capacity of CA-125 at PE diagnosis for 30-day mortality and major bleeding, respectively. Results: A total of 164 patients were included (mean age 69.8 years, SD 17), with 56.1% being male. Within 30 days, 17 patients (10.4%) died and 9 patients (5.5%) suffered major bleeding. ROC curve analysis for 30-day mortality yielded an area under the curve of 0.69 (95% CI 0.53-0.85) with an optimal CA-125 cut-off point of 20 U/mL and a negative predictive value of 96%. Multivariate analysis revealed a significant association between CA-125 levels exceeding 20 U/mL and 30-day mortality (adjusted odds ratio 4.95; 95% CI 1.61-15.2) after adjusting for age, cancer, NT-proBNP > 600 ng/mL, and the simplified pulmonary embolism severity index score. Survival analysis for 30-day mortality exhibited a hazard ratio of 5.47 (95% CI 1.78-16.8). No association between CA-125 levels and 30-day major bleeding was found. Conclusions: CA-125 emerges as a promising surrogate biomarker for short-term mortality prediction in an acute symptomatic PE. Future investigations should explore the integration of CA-125 into PE mortality prediction scores to enhance the prognostic accuracy in this patient population.

Micro-CT evaluation of the presence of voids in endodontic obturation.

Identifying the presence, size, type and location of voids in an endodontic obturation is of great clinical importance because it enables evaluation of the three-dimensionality of the sealing techniques, which can be related to the success of the endodontic treatment. AIM: To analyze by micro-CT the presence of voids in lower single-rooted premolar root canal obturations prepared using the single cone and ultrasound vibration technique. MATERIALS AND METHODS: Twenty extracted single-rooted lower premolars were selected, and the root canal prepared surgically and chemically. In GROUP 1 - Without Vibration, the canal was obturated with a single cone and bioceramic, without applying vibration. In GROUP 2 - With Vibration, the gutta-percha cone inside the root canal was held with a cotton plier to which ultrasound vibration was applied for 3 periods of 3 seconds each. A micro-CT scanner was used to acquire and reconstruct images for analysis. RESULTS: No significant difference was found between obturation techniques, though there were differences between thirds, with the cervical third having a higher percentage of voids than the middle and apical thirds. CONCLUSIONS: The results suggest that the volume of closed, open and total voids does not differ between treatments with and without ultrasound vibration. In the cervical third, the highest volume of voids was related to oval geometry in the teeth evaluated.

La presencia de vacíos en la obturación endodóntica, su tamaño y el tipo y localización tiene gran importancia clínica ya que permite evaluar la tridimensionalidad de las técnicas de sellado y relacionarlas con el éxito del tratamiento endodóntico. OBJETIVO: analizar mediante microtomografía la presencia de vacíos en la obturación del conducto radicular de premolares inferiores unirradiculares, utilizando la técnica de cono único y vibración con ultrasonido. MATERIALES Y MÉTODOS: se seleccionaron 20 premolares inferiores unirradiculares a los que se les realizó la preparación quirúrgica y química del conducto radicular. Se realizó la obturación con cono único y biocerámico GRUPO 1- sin vibración. En el GRUPO 2 - con vibración se aplicó vibración por ultrasonido, se tomó del cono de gutapercha colocado en el interior del conducto con pinza de algodón que fue vibrada durante 3 períodos de 3 segundos cada uno. Las mismas fueron adquiridas y reconstruidas en un microtomógrafo para posterior análisis de las imágenes obtenidas. RESULTADOS: No se evidenciaron diferencias significativas entre ambas técnicas de obturación comparadas, pero si entre los tercios analizados, siendo el cervical el que mayor porcentaje de vacíos presenta en comparación a los cortes correspondientes al tercio medio y apical. CONCLUSIONES: Los resultados sugieren que el volumen de vacíos cerrados, abiertos y total no varía en los tratamientos donde se aplica vibración por ultrasonido. En el tercio cervical, el mayor volumen de vacíos se relaciona con la geometría oval que presentaron las piezas dentarias evaluadas en este estudio.

Effect of early initiation of noninvasive ventilation in patients transported by emergency medical service for acute heart failure.

BACKGROUND: While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course, the benefit of early initiation before patient arrival to the emergency department (ED) remains unknown. OBJECTIVE: This study aimed to assess the impact of early initiation of NIV during emergency medical service (EMS) transportation on outcomes in patients with AHF. DESIGN: A secondary retrospective analysis of the EAHFE (Epidemiology of AHF in EDs) registry. SETTING: Fifty-three Spanish EDs. PARTICIPANTS: Patients with AHF transported by EMS physician-staffed ambulances who were treated with NIV at any time during of their emergency care were included and categorized into two groups based on the place of NIV initiation: prehospital (EMS group) or ED (ED group). OUTCOME MEASURES: Primary outcome was the composite of in-hospital mortality and 30-day postdischarge death, readmission to hospital or return visit to the ED due to AHF. Secondary outcomes included 30-day all-cause mortality after the index event (ED admission) and the different component of the composite primary endpoint considered individually. Multivariate logistic regressions were employed for analysis. RESULTS: Out of 2406 patients transported by EMS, 487 received NIV (EMS group: 31%; EMS group: 69%). Mean age was 79 years, 48% were women. The EMS group, characterized by younger age, more coronary artery disease, and less atrial fibrillation, received more prehospital treatments. The adjusted odds ratio (aOR) for composite endpoint was 0.66 (95% CI: 0.42-1.05). The aOR for secondary endpoints were 0.74 (95% CI: 0.38-1.45) for in-hospital mortality, 0.74 (95% CI: 0.40-1.37) for 30-day mortality, 0.70 (95% CI: 0.41-1.21) for 30-day postdischarge ED reconsultation, 0.80 (95% CI: 0.44-1.44) for 30-day postdischarge rehospitalization, and 0.72 (95% CI: 0.25-2.04) for 30-day postdischarge death. CONCLUSION: In this ancillary analysis, prehospital initiation of NIV in patients with AHF was not associated with a significant reduction in short-term outcomes. The large confidence intervals, however, may preclude significant conclusion, and all point estimates consistently pointed toward a potential benefit from early NIV initiation.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study.

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

Automatic classification of normal and abnormal cell division using deep learning.

In recent years, there has been a surge in the development of methods for cell segmentation and tracking, with initiatives like the Cell Tracking Challenge driving progress in the field. Most studies focus on regular cell population videos in which cells are segmented and followed, and parental relationships annotated. However, DNA damage induced by genotoxic drugs or ionizing radiation produces additional abnormal events since it leads to behaviors like abnormal cell divisions (resulting in a number of daughters different from two) and cell death. With this in mind, we developed an automatic mitosis classifier to categorize small mitosis image sequences centered around one cell as "Normal" or "Abnormal." These mitosis sequences were extracted from videos of cell populations exposed to varying levels of radiation that affect the cell cycle's development. We explored several deep-learning architectures and found that a network with a ResNet50 backbone and including a Long Short-Term Memory (LSTM) layer produced the best results (mean F1-score: 0.93 ± 0.06). In the future, we plan to integrate this classifier with cell segmentation and tracking to build phylogenetic trees of the population after genomic stress.

Rashba-like Spin Textures in Graphene Promoted by Ferromagnet-Mediated Electronic Hybridization with a Heavy Metal.

Epitaxial graphene/ferromagnetic metal (Gr/FM) heterostructures deposited onto heavy metals have been proposed for the realization of spintronic devices because of their perpendicular magnetic anisotropy and sizable Dzyaloshinskii-Moriya interaction (DMI), allowing for both enhanced thermal stability and stabilization of chiral spin textures. However, establishing routes toward this goal requires the fundamental understanding of the microscopic origin of their unusual properties. Here, we elucidate the nature of the induced spin-orbit coupling (SOC) at Gr/Co interfaces on Ir. Through spin- and angle-resolved photoemission spectroscopy along with density functional theory, we show that the interaction of the heavy metals with the Gr layer via hybridization with the FM is the source of strong SOC in the Gr layer. Furthermore, our studies on ultrathin Co films underneath Gr reveal an energy splitting of ∼100 meV for in-plane and negligible for out-of-plane spin polarized Gr π-bands, consistent with a Rashba-SOC at the Gr/Co interface, which is either the fingerprint or the origin of the DMI. This mechanism vanishes at large Co thicknesses, where neither in-plane nor out-of-plane spin-orbit splitting is observed, indicating that Gr π-states are electronically decoupled from the heavy metal. The present findings are important for future applications of Gr-based heterostructures in spintronic devices.

Plasma Exchange in Anti-Signal Recognition Particle Myopathy: A Systematic Review and Combined Analysis of Patient Individual Data.

Anti-signal recognition particle myopathy (anti-SRP myopathy) is a rare subtype of immune-mediated inflammatory myopathy characterized by muscle weakness and anti-SRP autoantibodies. Although plasma exchange (PE) is used in severe cases, its role remains unclear. A systematic review was conducted following PRISMA guidelines, identifying 23 patients with anti-SRP myopathy treated with PE. Data on demographics, clinical features, laboratory findings, treatments, and outcomes were analyzed combining individual patient data if available. Sixteen (69.6%) patients were male, with muscle weakness as the predominant symptom in 100% of cases. After PE, most patients showed improvement in symptoms, and the proportion of patients with muscle weakness was reduced (p = 0.001). Relapse occurred in 17.4% of the cases. The incidence of adverse events was low (8.7%). Despite limitations, including a small sample size and heterogeneous data, our systematic review suggests that PE may be effective in inducing remission and controlling symptoms in anti-SRP myopathy, particularly in severe cases. Since evidence on PE in anti-SRP myopathy is limited, further research, including prospective multicenter studies, is warranted to understand better its efficacy and safety and establish its role in treatment algorithms.

Plasma-Based Scaffold Containing Bone-Marrow Mononuclear Cells Promotes Wound Healing in a Mouse Model of Pressure Injury.

Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography-computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism.

BACKGROUND: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. OBJECTIVES: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. METHODS: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. RESULTS: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. CONCLUSION: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.