Epidemiology of Neuro-Behçet's Disease in Northern Spain 1999-2019: A Population-Based Study.

Background/Objectives: Neuro-Behçet's disease (NBD) is one of the most severe complications of Behçet's disease (BD). The incidence of NBD varies widely worldwide. This study aimed to estimate its current incidence in Northern Spain. Methods: This was a retrospective population-based cohort study of 120 patients in Northern Spain diagnosed with BD according to the 2013 International Criteria for BD (ICBD) between 1 January 1999 and 31 December 2019. NBD diagnoses were made according to International Consensus Recommendation (ICR) criteria. Overall, 96 patients were included, and their demographic and clinical data were collected. The incidence of NBD was estimated by age, gender, and year of diagnosis between 1999-2019. Results: NBD was diagnosed in 23 of 96 (24%) patients (15 women/8 men) (mean age: 44 ± 13.9 years). HLA-B51 was positive in 5 of 13 (38.4%) cases tested. A total of 10 (43.5%) patients had parenchymatous NBD, 10 (43.5%) had non-parenchymatous NBD, and 3 (13%) had mixed NBD. Incidence during the study period was 0.13 (95% CI, 0.11-0.26) per 100,000 people-years. There were no significant differences in gender in the incidence rate stratified by age (p > 0.05). Furthermore, there was a linear relationship with a mild decrease in age at diagnosis over time. Conclusions: Epidemiological characteristics of NBD in Northern Spain are similar to those of neighboring countries, except female gender predominance.

Preparation and Characterization of Zein-Metformin/Gelatin Nanofibers by Coaxial Electrospinning.

Metformin is a drug commonly used for the treatment of type 2 diabetes. However, it has been associated with damaging side effects when used over a long period of time. A potential solution to this problem is the implementation of a prolonged-release system for metformin, which would enhance the efficiency of the doses administered to patients. To achieve this, it is necessary to use materials compatible with humans. Electrospinning is an efficient technique that can be employed for this purpose, utilizing solvents that are safe for human use. Therefore, the objective of this study was to prepare and characterize a system for the prolonged release of metformin from zein and gelatin through coaxial electrospinning as well as to investigate its in vitro release. Metformin-loaded zein/gelatin coaxial nanofibers were prepared using the coaxial electrospinning technique and then characterized by morphological, structural, and thermal analysis. Morphologically, metformin-loaded zein/gelatin coaxial nanofibers were obtained with an average diameter of 322.6 ± 44.5 nm and a smooth surface. Fourier transform infrared spectroscopy (FTIR) analysis showed band shifts at a higher wavenumber due to drug-protein interactions by hydrogen bonding between N-H and C=O groups. Thermal gravimetric analysis (TGA) results suggested a possible interaction between materials due to an increase in the degradation temperatures of zein and gelatin when metformin was included. The transition of the crystallinity of metformin to the amorphous form was also confirmed by differential scanning calorimetry (DSC). Coaxial nanofibers exhibited an encapsulation efficiency of 66% and a profile release that showed an initial release of metformin (40%) in the first hour, followed by a gradual release until it reached equilibrium at 60 h and a cumulative release of 97% of metformin. It was concluded that using the coaxial electrospinning technique, it is possible to obtain nanofibers from polymeric solutions of zein and gelatin to encapsulate metformin, with a potential application as a prolonged-release system.

Reprint: The Importance of Natural Acidified Systems in the Study of Ocean Acidification: What Have We Learned?

Human activity is generating an excess of atmospheric CO2, resulting in what we know as ocean acidification, which produces changes in marine ecosystems. Until recently, most of the research in this area had been done under small-scale, laboratory conditions, using few variables, few species and few life cycle stages. These limitations raise questions about the reproducibility of the environment and about the importance of indirect effects and synergies in the final results of these experiments. One way to address these experimental problems is by conducting studies in situ, in natural areas where expected future pH conditions already occur, such as CO2 vent systems. In the present work, we compile and discuss the latest research carried out in these natural laboratories, with the objective to summarize their advantages and disadvantages for research to improve these investigations so they can better help us understand how the oceans of the future will change.

Natural acidified marine systems: Lessons and predictions.

Natural acidified marine systems (ASs) are environments with relatively low pH levels due to natural causes such as volcanic activity, geochemical reactions, and biological processes. These systems act as natural laboratories for the study of the effects of ocean acidification, allowing for the observation of long-term ecological and evolutionary responses. Understanding these systems is crucial for predicting the effects of anthropogenic ocean acidification (OA) on marine ecosystems. There are 23 ASs in which scientific research has shown significant parallelisms in their results worldwide, such as the disappearance of calcareous organisms and the loss of species with key ecological functions under OA conditions. Future research should emphasize continuous collaboration among teams, as well as public access to oceanographic and biological data along with the monitoring of environmental variables at each AS. To preserve these areas, it is imperative to employ non-destructive methods and protect them as human heritage sites.

Howler Monkey Die-Off in Southern Mexico.

In May and June 2024, a die-off of Mexican mantled howler monkeys (Alouatta palliata mexicana) occurred in southern Mexico. This commentary documents the event, attributing it to extreme heatwaves, drought, wildfires, and habitat impoverishment. Despite their reported resilience to habitat disturbances, mantled howler monkey mortality rate in some areas reached 31%. Key evidence points to heatstroke as the primary cause of death, exacerbated by limited hydration and reduced dietary diversity in disturbed habitats. Immediate responses included community-led rescues (e.g., hydrating the monkeys), coordination of rescue activities by nongovernmental organizations (NGOs) (e.g., managing donations), involvement of scientists (e.g., monitoring of primate populations), and assistance from government officials (e.g., providing legal support for animal management). This event underscores the urgency of developing action plans to prevent and attend future crises. Among other actions, we highlight (i) establishing primate care infrastructure with medical and rehabilitation centers; (ii) developing protocols and training programs to ensure rapid crisis response; (iii) fostering collaboration among government, NGOs, and academic institutions for effective crisis management; and (iv) developing targeted research on climate change impacts, predictive models, and long-term health monitoring. We emphasize the critical need for coordinated conservation efforts to protect wild primates and maintain natural ecosystem resilience in the face of escalating climate challenges.

Development of mixed linear models to analyze and describe the impact of malathion on the larval growth of Megaselia scalaris (Diptera: Phoridae) under various feeding media and environmental conditions.

Forensic entomology plays a crucial role in estimating the minimum postmortem interval through the study of insect larvae found at crime scenes. The precision of this estimation relies on various biotic and abiotic elements that simultaneously influence insect growth and development, encompassing factors such as temperature, humidity, photoperiod, diet, and the existence of xenobiotics in decomposing tissues. Despite numerous studies on the influence of these factors, including the impact of xenobiotics, there are currently no robust tools available for making corrections to this estimation considering concurrently all variables. In an attempt to propose an exploratory and descriptive statistical model to analyze the simultaneous effect and interaction of different variables on larval growth, this study aimed to compare the effect of malathion on the growth of Megaselia scalaris (Loew, 1866) (Diptera: Phoridae) raised in malathion-spiked porcine muscle, under controlled and uncontrolled temperature and humidity conditions (environmental conditions). Larvae were also reared using various growth media. A split-plot design that combined crossed and nested factors was employed; 2 linear mixed models were developed to assess the relationships between the variables. The model provides valuable insights into the complex interactions among xenobiotics, growth media, and environmental conditions in the size and development of M. scalaris.

5q14.3 Microdeletion Syndrome With Simultaneous Involvement of MEF2C and RASA1. Clinical Case and Review of the Literature.

5q14.3 microdeletion syndrome is a rare condition involving multiple genes such as MEF2C and RASA1 and is potentially classified as a neurocutaneous syndrome. Deletion of the MEF2C gene accounts for the majority of clinical manifestations, including global developmental delay, intellectual disability, seizures, and behavioral disorders. RASA1 deletion is linked to capillary malformations with arteriovenous malformations (CM-AVM). Until now, only 17 cases have been described with deletions of both genes. We present the first case described in Spain with the microdeletion in the 5q14.3 cytoband simultaneously affecting both MEF2C and RASA1, exhibiting the typical manifestations of this entity, and review the published cases to date.

Percutaneous recanalization of non-cirrhotic extrahepatic portal vein obstruction in children: technical considerations in a preliminary cohort.

OBJECTIVES: Portal hypertension resulting from non-cirrhotic extrahepatic portal vein obstruction (EHPVO) in children has been primarily managed with the Meso-Rex bypass, but only a few patients have a viable Rex recessus, required by surgery. This study reports a preliminary series of patients who underwent interventional radiology attempts at portal vein recanalization (PVR), with a focus on technical aspects and safety. METHODS: A retrospective review of consecutive patients with severe portal hypertension due to non-cirrhotic EHPVO at a single institution from 2022, who underwent percutaneous attempts at PVR, was performed. Technical and clinical data including fluoroscopy time, radiation exposure, technical and clinical success, complications and follow-up were recorded. RESULTS: Eleven patients (6 males and 5 females; median age 7 years, range 1-14) underwent 15 percutaneous transhepatic (n = 1), transplenic (n = 11), or simultaneous transhepatic/transplenic (n = 3) procedures. Rex recessus was patent in 4/11 (36%). Fluoroscopy resulted in a high median total dose area product (DAP) of 123 Gycm2 (range 17-788 Gycm2) per procedure. PVR was achieved in 5/11 patients (45%), 3/5 with obliterated Rex recessus. Two adverse events of grade 2 and grade 3 occurred without sequelae. After angioplasty, 4/5 patients required stenting to obtain sustained patency, as demonstrated by colour-Doppler ultrasound in all PVR after a median follow-up of 6 months (range 6-14). CONCLUSION: Our preliminary experience suggests that 45% of children with non-cirrhotic EHPVO can restore portal flow even with obliterated Rex recessus. In non-cirrhotic EHPVO, PVR may be an option, if a Meso-Rex bypass is not feasible, although the radiation exposure deserves attention. CLINICAL RELEVANCE STATEMENT: Innovative percutaneous procedures may have the potential to be an alternative option to the traditional surgical approach in the management of non-cirrhotic EHPVO and its complications in children not eligible for Meso-Rex bypass surgery. KEY POINTS: Non-cirrhotic portal hypertension in children has been traditionally managed by surgery with Meso-Rex bypass creation. Percutaneous PVR may restore the patency of the native portal system even when the Rex recessus is obliterated and surgery has been excluded. Interventional radiological techniques may offer a minimally invasive solution in complex cases of EHPVO in children when Meso-Rex bypass is not feasible.

Fuchs' Endothelial Corneal Dystrophy evaluation using a high-resolution wavefront sensor.

This study aims to evaluate the applicability of the high-resolution WaveFront Phase Imaging Sensor (WFPI) in eyes with Fuchs' Endothelial Corneal Dystrophy (FECD) through qualitative and quantitative analysis using a custom-designed Automatic Guttae Detection Method (AGDM). The ocular phase was measured using the t · eyede aberrometer and then was processed to obtain its High-Pass Filter Map (HPFM). The subjects were pathological and healthy patients from the Fundación Jiménez-Díaz Hospital (Madrid, Spain). The AGDM was developed and applied in pupils with 3 and 5 mm of diameter. A set of metrics were extracted and evaluated like the Root-Mean-Square error (RMS), Number of guttae, Guttae Area, and Area of Delaunay Triangulation (DT). Finally, a Support Vector Machine (SVM) model was trained to classify between pathological and healthy eyes. Quantitatively, the HPFM reveals a dark spots pattern according to the ophthalmologist's description of the slit-lamp examination of guttae distribution. There were significant statistical differences in all the metrics when FECD and Healthy groups were compared using the same pupil size; but comparing both pupil sizes for the same group there were significant differences in most of the variables. This sensor is a value tool to objectively diagnose and monitor this pathology through wavefront phase changes.

Strategies to improve cardiovascular health and treatment of dyslipidemia in Spain. Expert Insights Project. / Estrategias de mejora en la salud cardiovascular y el tratamiento de la dislipidemia en España. Proyecto Expert Insights.

OBJECTIVES: To gather opinions, recommendations, and proposals for improvement from Spanish clinicians on cardiovascular (CV) health, with particular focus on dyslipidemia management. METHODS: The Expert Insights project involved 8face-to-face sessions held throughout Spain, attended by 138 CV health experts. Clinicians answered to 25 questions survey related to CV health and dyslipidemia control. Each session included an analysis and a discussion on the perceived realities and areas for improvement. RESULTS: 72% of centers have a standardized process for monitoring patients after a CV episode at discharge, but only 37% during their clinical follow-up. Patient care and management are dependent on the physician, with a lack of coordination between hospital specialties and primary care (PC). 95% of clinicians believe it is necessary to standarize treatment optimization. 65% of centers prescribe combined lipid-lowering treatment after a CV episode. Updating cLDL levels in the Therapeutic Positioning Report and standardizing and globalizing the prescription document would reduce iPCSK9 prescription barriers and lead to more equitable access. CONCLUSIONS: In Spain, there are significant deficiencies in the management of dyslipidemia, with a great need for a consensus on standardizing management processes and optimizing patient treatment. The opinions, recommendations, and improvement proposals from Spanish clinicians on CV health are an important starting point to improve the situation.

Antibiotic resistant Escherichia coli strains in healthy pets from Tamaulipas, Mexico.

Antibiotic resistance constitutes a significant public health challenge, with diverse reservoirs of resistant bacteria playing pivotal roles in their dissemination. Among these reservoirs, pets are carrying antibiotic-resistant strains. The objective of this study was to assess the resistance profiles of Escherichia coli, and the prevalence of extended-spectrum ß-lactamase (ESBL) producing E. coli strains in dogs and cats from Tamaulipas, Mexico. A total of 300 stool samples (150 dogs and 150 cats) from healthy pets were subjected to analysis. Antibiotic susceptibility testing and the identification of ESBLs were carried out by disc diffusion method. The presence of resistance genes, class 1, 2, and 3 integrons (intI1, intI2, and intI3) and phylogroups was determined by PCR analysis. The findings reveal that 42.6% (128/300) of the strains exhibited resistance to at least one of the eight antibiotics assessed, and 18.6% (56/300) demonstrated multidrug resistance (MDR), that distributed across 69 distinct resistance patterns. Altogether 2.6% of E. coli strains (8/300) were confirmed as TEM and CTX-M type ESBL producers. These outcomes underscore the roles of dogs and cats in Tamaulipas as reservoirs for the dissemination of MDR and/or ESBL strains. The results underscore the necessity for conducting prevalence studies on ESBL-producing E. coli, forming a foundation for comprehending the present scenario and formulating strategies for the control and mitigation of this issue.

Anticipated prehospital decision delay in response to different symptom clusters in acute coronary syndrome: Results from the Spanish Cardiobarometer study.

BACKGROUND AND OBJECTIVE: Reducing patient decision delay - the time elapsed between symptom onset and the moment the patient decides to seek medical attention - can help improve acute coronary syndrome survival. Patient decision delay is typically investigated in retrospective studies of acute coronary syndrome survivors that are prone to several biases. To offer an alternative approach, the goal of this research was to investigate anticipated patient decision delay in the general population in response to different symptom clusters. METHODS: We developed scenarios representing four commonly experienced symptom clusters: classic (chest symptoms only), heavy (a large number of very intense symptoms including chest pain), diffuse (mild symptoms including chest pain), and weary (mild symptoms without clear chest involvement). The scenarios were administered in random order in a representative survey of 1002 adults ≥55 years old from the non-institutionalized general population in Spain. We measured help-seeking intentions, anticipated patient decision delay (waiting >30 min to seek help), and symptom attribution. RESULTS: Patient decision delay was most common in the diffuse scenario (55%), followed by the weary (34%), classic (22%), and heavy (11%) scenarios. Attributing the symptoms to a cardiovascular cause and intentions to call emergency services were least frequent in the weary and diffuse scenarios. Women were less likely to intend to seek help than men in the classic (OR = 0.48, [0.27, 0.85], diffuse (OR = 0.67, [0.48, 0.92]), and weary (OR = 0.66, [0.44, 0.98]) scenarios, despite being more likely to attribute symptoms to cardiovascular causes. Participants with traditional cardiovascular risk factors (e.g., diabetes, hypercholesterolemia, hypertension) reported faster help-seeking, whereas participants with obesity and history of depression were more likely to delay. DISCUSSION: The diverse manifestations of acute coronary syndrome generate fundamentally different appraisals. Anticipated patient decision delay varies as a function of socio-demographic characteristics and medical history, supporting findings from studies with patients who experienced ACS. Measuring anticipated patient decision delay in the general population can help reveal potential barriers to help-seeking and capture effects of population interventions.

Thrombocytopenia after transcatheter aortic valve implantation.

INTRODUCTION AND OBJECTIVES: Thrombocytopenia frequently occurs after transcatheter aortic valve implantation (TAVI) but its impact is poorly understood. We aimed to analyze the incidence, clinical impact, and predictors of acquired thrombocytopenia after TAVI. METHODS: This retrospective multicenter registry included 3913 patients undergoing TAVI with a baseline platelet count of ≥ 100 *109/L. Acquired thrombocytopenia was defined as a decrease in baseline platelet count of ≥ 50% (early nadir ≤ 3 days and late nadir ≥ 4 days) post-TAVI. The primary endpoint was 30-day all-cause mortality and secondary endpoints were procedural safety and 2-year all-cause mortality. RESULTS: The incidence of acquired thrombocytopenia was 14.8% (early nadir: 61.5%, late nadir: 38.5%). Thirty-day mortality occurred in 112 (3.0%) patients and was significantly higher in those with thrombocytopenia (8.5% vs 2.0%, adjusted OR, 2.3; 95%CI, 1.3-4.2). Procedural safety was lower and 2-year mortality was higher in patients with thrombocytopenia vs those without (52.1 vs 77.0%; P <.001, and 30.2% vs 16.8%; HR, 2.2, 95%IC, 1.3-2.7) and especially in those with late nadir thrombocytopenia (45.8% vs 54.5%; P=.056, and 38.6% vs 23.8%, HR, 2.1; 95%CI, 1.5-2.9). Independent predictors of thrombocytopenia comprised baseline and procedural factors such as body surface area, absence of diabetes, poorer renal function, peripheral vascular disease, nontransfemoral access, vascular complications, type of transcatheter heart valve, and earlier TAVI procedures. CONCLUSIONS: Acquired thrombocytopenia was common (15%) after TAVI and was associated with increased short- and mid-term mortality and decreased procedural safety. Moreover, late thrombocytopenia compared with early thrombocytopenia was associated with significantly worse clinical outcomes. Further investigations are needed to elucidate the etiologic mechanisms behind these findings.

Identifying genetic variants that influence the abundance of cell states in single-cell data.

Disease risk alleles influence the composition of cells present in the body, but modeling genetic effects on the cell states revealed by single-cell profiling is difficult because variant-associated states may reflect diverse combinations of the profiled cell features that are challenging to predefine. We introduce Genotype-Neighborhood Associations (GeNA), a statistical tool to identify cell-state abundance quantitative trait loci (csaQTLs) in high-dimensional single-cell datasets. Instead of testing associations to predefined cell states, GeNA flexibly identifies the cell states whose abundance is most associated with genetic variants. In a genome-wide survey of single-cell RNA sequencing peripheral blood profiling from 969 individuals, GeNA identifies five independent loci associated with shifts in the relative abundance of immune cell states. For example, rs3003-T (P = 1.96 × 10-11) associates with increased abundance of natural killer cells expressing tumor necrosis factor response programs. This csaQTL colocalizes with increased risk for psoriasis, an autoimmune disease that responds to anti-tumor necrosis factor treatments. Flexibly characterizing csaQTLs for granular cell states may help illuminate how genetic background alters cellular composition to confer disease risk.

Striated duct adenoma: The cytological description of a rare entity.

INTRODUCTION: Striated duct adenoma is a benign salivary gland tumour recently recognized by the World Health Organization. To date, no report has described the cytological features of this entity. MATERIALS AND METHODS: We report the case of a 60-year-old woman with a tumour in the right parotid gland with a diameter greater than 2.4 cm confirmed by imaging tests. RESULTS: Two fine-needle aspiration cytologies (FNAC) were performed with inconclusive results, reporting epithelioid and spindle-shaped cellularity, with little stroma, and nuclei with abundant pseudoinclusions. Myoepithelioma and Schwannoma were proposed as differential diagnoses. An immunocytochemical panel was performed, showing positivity for S-100, SOX10, CK7 and vimentin, and negativity for both myoepithelial (p63 and calponin) and thyroid markers. In the absence of a conclusive diagnosis, the patient accepted surgery. The biopsy results confirmed diagnosis of striated duct adenoma, with immunohistochemical features superimposable to cytology. CONCLUSION: Little information is available in the literature, both on biopsy and, more strikingly, on cytology of this neoplasm. The aim of this work is to provide cytological characteristics that allow diagnosis of this entity with FNAC and thus avoid unnecessary surgeries.

Population genomic structure of the sea urchin Diadema africanum, a relevant species in the rocky reef systems across the Macaronesian archipelagos.

The sea urchin Diadema africanum is a macro-herbivore found in the rocky reef systems of the West African region and Macaronesian archipelagos. Over several decades, high densities of this species have generated marine barrens in certain areas at the Canary Islands. In contrast, more recently, during the last few years, the species has suffered mass mortality events that continue to the present day. In this study, we used 9,109 Single Nucleotide Polymorphisms (SNPs) and a fragment of a mitochondrial gene to evaluate the species' population structure, effects of mass mortalities on its diversity, and potential local adaptation across the Canary Islands and Cabo Verde. Our research provides compelling evidence of low genomic diversity and homogeneity across the studied area for neutral markers, along with recent demographic fluctuations. The high connectivity among distant areas likely allows a rapid recovering of the populations from local mortality events. Interestingly, we also observed genomic sub-structure from 405 SNPs identified as candidate loci under selection for seawater temperature. The lack of divergence among distant sites and the low diversity found can be attributed to the species' divergence from a small ancestral genomic pool, followed by a contemporary demographic expansion, and ongoinggene flow.

Evaluating ecological risks and metal bioavailability in post-dredging sediments of a wetland affected by artisanal gold mining.

The evaluation of metal contamination, ecological risk, bioavailability, and the environmental dredging depth in sediments of two Colombian riverine systems impacted by artisanal and small-scale gold mining (ASGM) and agricultural activities, was conducted following dredging processes. Results indicated significant contamination by Cd and Pb before dredging, based on the contamination factor (CF) and the geoaccumulation index (Igeo). Additionally, Cu and Hg were found to cause adverse biological effects according to sediment quality guidelines. Post-dredging, surface sediments exhibited a moderate ecological risk index (RI, 150-300), primarily due to increased contamination by Hg, Pb, and Cd. To mitigate this ecological risk (RI < 150), the environmental dredging depth needed to exceed 20 cm for all metals. On average, the bioavailable fraction increased 2.3 times within two months after dredging. However, the low environmental risk (%F1 = 1-10) calculated using risk assessment codes (RAC) indicates a potential risk due to metals entering the water column and bioaccumulating in organisms. These findings provide insights into the dynamics of metals and the impact of dredging activities on sediments in the Colombian Caribbean coast affected by various anthropogenic activities. The research underscores the importance of integrating sustainable practices in mining and agriculture to protect the ecological integrity of these riverine systems.

Predictive and dynamic signature for anti-angiogenics in combination with PD-1 inhibitor in soft-tissue sarcoma: correlative studies linked to the IMMUNOSARC trial.

PURPOSE: IMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (nivolumab) in advanced sarcomas. Here we present the first correlative studies of the STS cohort enrolled in this trial. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) and peripheral blood samples were collected at baseline and week 13. FFPE were used for transcriptomics and multiplex immunofluorescence, while peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients. RESULTS: The density of intratumoral CD8+ T cells, measured by multiplexed immuno-phenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in gene expression of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1, and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at W13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated two groups with distinct progression-free survival (PFS): 4.1 months (95% CI 3.5-NR) vs 17 months (95% CI 12.0 - NR), p=0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples. CONCLUSIONS: Treatment with sunitinib and nivolumab inflamed the sarcoma microenvironment, increasing CD8+ T cell density and the expression of several genes/ proteins with relevance in the response to PD-1 inhibitors. A molecular signature identified two groups of patients with distinct PFS for the combination of anti-angiogenics plus PD-1 inhibitor.

Chitosan-coated manganese ferrite nanoparticles enhanced Rhodotorula toruloides carotenoid production.

The present study aims to analyze the interaction between Rhodotorula toruloides and magnetic nanoparticles and evaluate their effect on carotenoid production. The manganese ferrite nanoparticles were synthesized without chitosan (MnFe2O4) and chitosan coating (MnFe2O4-CS) by the co-precipitation method assisted by hydrothermal treatment. XRD (X-ray diffraction), Magnetometry, Dynamic Light Scattering (DLS) and FTIR (Fourier-Transform Infrared Spectroscopy), are used to characterize the magnetic nanoparticles. The crystallite size of MnFe2O4 was 16 nm for MnFe2O4 and 20 nm for MnFe2O4-CS. The magnetic saturation of MnFe2O4-CS was lower (39.6 ± 0.6 emu/g) than the same MnFe2O4 nanoparticles (42.7 ± 0.3 emu/g), which was attributed to the chitosan fraction presence. The MnFe2O4-CS FTIR spectra revealed the presence of the characteristic chitosan bands. DLS demonstrated that the average hydrodynamic diameters were 344 nm for MnFe2O4 and 167 nm for MnFe2O4-CS. A kinetic study of cell immobilization performed with their precipitation with a magnet demonstrated that interaction between magnetic nanoparticles and R. toruloides was characterized by an equilibrium time of 2 h. The adsorption isotherm models (Langmuir and Freundlich) were fitted to the experimental values. The trypan blue assay was used for cell viability assessment. The carotenoid production increased to 256.2 ± 6.1 µg/g dry mass at 2.0 mg/mL MnFe2O4-CS. The use of MnFe2O4-CS to stimulate carotenoid yeast production and the magnetic separation of biomass are promising nanobiotechnological alternatives. Magnetic cell immobilization is a perspective technique for obtaining cell metabolites.