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Significant efforts have been devoted to investigating the oxidation of MXenes in various environments. However, the underlying mechanism of MXene oxidation and its dependence on the electrode potential remain poorly understood. Here we show the oxidation behavior of MXenes under the working conditions of electrochemical processes in terms of kinetics and thermodynamics by using constant-potential ab initio simulations. The theoretical results indicate that the potential effects can be attributed to the nucleophilic attack of water molecules on metal atoms, similar to that taking place in the Oxygen Evolution Reaction. Building upon these findings, we deduced the oxidation potential of the common MXenes, and proposed antioxidant strategies for MXene. Finally, we demonstrated that MBenes, the boron analogs of MXenes, may undergo a similar nucleophilic attack in water and inferred that molecule-induced Walden inversion is widely present in material reconstructions. This work contributes to a fundamental understanding MXene stability at the atomic level, and promotes the transition in materials discovery from trial-and-error synthesis to rational design. more...

Snjezana Zeba,1 Maja Surbatovic,2 Ivo Udovicic,1 Ivan Stanojevic,3 Danilo Vojvodic,3 Goran Rondovic,1 Katarina Mladenovic,1 Tanja Abazovic,2 Almina Hasanovic,4 Aleksandra N Ilic,5 Dzihan Abazovic,6 Wasim Khan,7 Dragan Djordjevic1 1Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia; 2Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Belgrade, Serbia; 3Institute for Medical Research, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia; 4Nephrology Clinic, Military Medical Academy, Belgrade, Serbia; 5Faculty of Medicine, University of Pristina, Kosovska Mitrovica, Serbia; 6Atlas Hospital, Belgrade, Serbia, Aba Medica Healthcare Centre, Ulcinj, Montenegro; 7Division of Trauma & Orthopaedic Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UKCorrespondence: Maja Surbatovic, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, 17 Crnotravska Street, Belgrade, 11000, Serbia, Tel +381 11 2665 125, Email maja.surbatovic@gmail.comPurpose: The aim of the retrospective, single-center study was to assess the prognostic value of immune cell-based and albumin-based ratios regarding lethal outcome in critically ill COVID-19 patients.Patients and Methods: We analyzed 612 adult critically ill COVID-19 patients admitted to the intensive care unit (ICU) between April 2020 and November 2022. Blood measurement on admission to the ICU encompassed complete blood count (CBC), IL-6, C-reactive protein (CRP), albumin, lactate, lactate dehydrogenase (LDH), serum bicarbonate, arterial base deficit/excess (BD/E), and D-dimer. All the measured and calculated parameters were compared between survivors and nonsurvivors, with the outcome measure being hospital mortality.Results: Immune cell-based ratios [NLR - Neutrophil-to-Lymphocyte Ratio, MLR - Monocyte-to-Lymphocyte Ratio, PLR - Platelet-to-Lymphocyte Ratio, MPV - Mean Platelet Volume, MPV/PC - Mean Platelet Volume-to-Platelet Count Ratio, Derived (d-)NLR ratio - neutrophil count divided by the result of white blood cell (WBC) count – neutrophil count), N/LP - Neutrophil count x 100/Lymphocyte count x Platelet count, CLR – C-reactive protein (CRP)-to-Lymphocyte Ratio, CPR - CRP-to-Platelet Ratio, LLR - Lactate dehydrogenase (LDH)-to-Lymphocyte Ratio, Systemic Immune Inflammation Index (SII) - platelet x neutrophil/lymphocyte count, Systemic Inflammation Response Index (SIRI) - neutrophil x monocyte/lymphocyte count] were investigated. White blood cell and neutrophil counts were significantly higher, while lymphocyte and platelet counts were significantly lower in nonsurvivors. MPV, MPV/PC, NLR, d-NLR, MLR, N/LP, CRP, LDH, CPR, CLR, LLR, SII, and SIRI values were significantly higher in nonsurvivors. Monocyte count and PLR values did not differ significantly between groups. Albumin-based ratios included CRP-to-Albumin Ratio (CAR), Lactate-to-Albumin Ratio (LAR) and LDH-to-Albumin Ratio (LDH/ALB). All values were significantly higher in nonsurvivors.Conclusion: The only independent predictor of lethal outcomes at ICU admission is the albumin-based LDH/ALB ratio. Most of the other parameters were moderate, although highly significant predictors of mortality in critically ill COVID-19 patients.Keywords: LDH/albumin ratio, critically ill, COVID-19, mortality more...

Abstract Objective Cortical atrophy close to medial temporal structures has been described consistently in patients with temporal lobe epilepsy (TLE). Successful TLE surgery may have a neuroprotective effect preventing further atrophy of temporal and extratemporal cortex. However, the effects of epilepsy surgery on subcortical structures demand additional enlightenment. This work aimed to determine how epilepsy surgery affects volumes of subcortical structures in medically refractory temporal lobe epilepsy patients. Methods We compared MRI volumes of subcortical structures in 62 patients with TLE (36 left, 26 right) before and after anterior temporal lobectomy with 38 TLE patients (20 left, 18 right) who were considered to be good surgical candidates and had at least two brain MRIs. Results There were no volume differences in subcortical structures on preoperative and initial MRIs of non‐operated TLE patients. At baseline, the ipsilateral thalamus and putamen in TLE patients were marginally smaller than contralateral structures. Operated patients showed a significant postoperative volume reduction in ipsilateral thalamus, putamen, and globus pallidus. In contrast, there were no significant volumetric reductions in non‐operated patients longitudinally. There were no volumetric changes associated with different surgical outcomes or different postoperative cognitive outcomes. Significance Our study demonstrated postoperative volume loss of thalamus, putamen and globus pallidus ipsilaterally to the side of resection. Our findings suggest surgery‐related changes, likely Wallerian degeneration within subcortical networks not related to seizure or cognitive outcome. Plain Language Summary We studied 100 patients with epilepsy, comparing those who had surgery to those who did not. After surgery, the thalamus, putamen and globus pallidus on the same side as the surgery shrank significantly, but not in non‐surgery patients. This suggests surgery‐related changes in deeper brain structures, unrelated to seizure freedom or cognitive outcomes. This research sheds additional light on the response of the subcortical structure to epilepsy surgery, highlighting potential areas for further study. more...

Abstract Significant efforts have been devoted to investigating the oxidation of MXenes in various environments. However, the underlying mechanism of MXene oxidation and its dependence on the electrode potential remain poorly understood. Here we show the oxidation behavior of MXenes under the working conditions of electrochemical processes in terms of kinetics and thermodynamics by using constant-potential ab initio simulations. The theoretical results indicate that the potential effects can be attributed to the nucleophilic attack of water molecules on metal atoms, similar to that taking place in the Oxygen Evolution Reaction. Building upon these findings, we deduced the oxidation potential of the common MXenes, and proposed antioxidant strategies for MXene. Finally, we demonstrated that MBenes, the boron analogs of MXenes, may undergo a similar nucleophilic attack in water and inferred that molecule-induced Walden inversion is widely present in material reconstructions. This work contributes to a fundamental understanding MXene stability at the atomic level, and promotes the transition in materials discovery from trial-and-error synthesis to rational design. more...

Introduction Cancer and its treatments can lead to a wide range of side-effects that can persist long after treatments have ended. Across Europe, survivorship care is traditionally hospital-based specialist-led follow-up, leading to gaps in supportive care. Improved screening, diagnosis and treatment increase survival rates. With more individuals living with, through and beyond cancer, the predominance of the hospital-based specialist model is unsustainable, costly and resource-intensive. An understanding of what alternative Models of Care are available and the barriers and facilitators to their implementation is a first step towards enhancing supportive care across the cancer journey. The aim of this scoping review is to source and synthesise information from studies evaluating patient-oriented models of cancer survivorship supportive care for adults in Europe.Methods and analysis The scoping review will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses—Scoping Review Extension guidelines and will be guided by a six-stage methodological framework. A search strategy has been developed according to the Population, Concept and Context structure and will be applied to seven databases. A targeted search of grey literature will be completed. All identified records will be screened using predefined eligibility criteria by at least two researchers and undergo full-text review for inclusion. Data pertaining to the conceptualisation, evaluation and implementation of sourced Models of Care will be extracted.Ethics and dissemination As there is no primary data, ethical approval is not required. This review will be conducted as part of the EU COST Action CA21152—Implementation Network Europe for Cancer Survivorship Care. The protocol and subsequent scoping review will be published in a peer-reviewed journal. The Action involves representatives from most countries across Europe which will assist with the dissemination of the work to key stakeholders. more...

La cirugía basada en la evidencia (CBE) se sustenta en la investigación clínica y en el positivismo. Ambas están siendo cuestionadas en razón a las características propias de la práctica quirúrgica donde predomina la técnica y el arte. Consecuencia de ello no existe un número importante de evidencias publicadas. Esto constituye una limitacion en la aplicación de la CBE. El proposito de este artículo es discutir las amenazas, debilidades y limitaciones de la CBE. more...

La pandemia de la COVID-19 obligó a los programas educativos a adaptarse al entorno virtual debido a la cuarentena y al distanciamiento social, así como a las limitaciones de los centros hospitalarios para la práctica clínica. Las escuelas y facultades de Medicina, en su mayoría, no estaban preparadas para enfrentar este desafío en el pregrado. Gran parte de los profesores, salvo los que trabajaban en posgrado y con medios virtuales, carecían de experiencia en el uso de estrategias didácticas virtuales, los procesos educativos institucionales no estaban hechos para desarrollarse en este medio y los estudiantes también tuvieron dificultades para adaptarse a estos cambios repentinos (1). more...

AimsCONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.Methods and resultsPatients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups.ConclusionsThis is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients. more...

La investigación se erige como un pilar fundamental que distingue a la universidad como una entidad de relevancia institucional y social. Esta afirmación es particularmente verídica en el ámbito de las ciencias de la salud, donde no solo se espera que las instituciones educativas generen conocimiento en beneficio de la sociedad, sino que también moldeen individuos capacitados para sumergirse en la investigación y fortalecer esta premisa vital. En este contexto, emergen conceptos intrincados que delinean la naturaleza y el propósito de la investigación en el ámbito académico. La investigación científica, por un lado, se alza como el motor principal que impulsa el avance del conocimiento, y pone énfasis en el método riguroso y sistemático para desentrañar los misterios de la realidad. Por otro lado, la formación para la investigación se erige como un vehículo educativo primordial para cultivar mentes analíticas y curiosas, que dota a los futuros profesionales con las herramientas necesarias para indagar y contribuir al progreso científico. Asimismo, la investigación formativa, si bien menos conocida, desempeña un rol crucial al integrar la investigación en la experiencia de aprendizaje, lo cual fomenta habilidades de pensamiento crítico y resolución de problemas desde etapas tempranas. En esta travesía educativa e investigativa, diversos actores y componentes adquieren protagonismo. Los institutos de investigación se presentan como pilares fundamentales, ya que proporcionan el ambiente propicio para la colaboración interdisciplinaria y el florecimiento de ideas innovadoras. Los docentes, por su parte, ejercen un rol de guías y mentores, transmitiendo su experiencia y conocimientos a las nuevas generaciones de profesionales. Además, las actividades extracurriculares o extraprogramáticas en el área de la investigación surgen como terrenos fértiles para la expansión de horizontes intelectuales, que ofrecen espacios para la exploración creativa y la aplicación práctica de los conocimientos adquiridos por los alumnos. No obstante, estos conceptos y componentes no están exentos de desafíos y controversias en su integración dentro de los programas académicos. La implementación de estos enfoques en los niveles de pregrado y posgrado requiere un análisis profundo de sus objetivos y metas específicas. Las discusiones en torno a la ponderación del tiempo y los recursos dedicados a la investigación frente a otros aspectos curriculares son una constante. La presente revisión se propone delinear y definir de manera precisa los conceptos de investigación científica, formación para la investigación e investigación formativa, así como subrayar el papel cardinal que desempeñan los institutos de investigación, los docentes y las actividades extracurriculares en la configuración de programas académicos en el ámbito de las ciencias de la salud. more...

BackgroundAnthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.ObjectivesSENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.MethodsCancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers.ResultsA total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group.ConclusionsIn this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC. more...

Numerous redox transformations that are essential to life are catalyzed by metalloenzymes that feature Earth-abundant metals. In contrast, platinum-group metals have been the cornerstone of many industrial catalytic reactions for decades, providing high activity, thermal stability, and tolerance to chemical poisons. We assert that nature's blueprint provides the fundamental principles for vastly expanding the use of abundant metals in catalysis. We highlight the key physical properties of abundant metals that distinguish them from precious metals, and we look to nature to understand how the inherent attributes of abundant metals can be embraced to produce highly efficient catalysts for reactions crucial to the sustainable production and transformation of fuels and chemicals. more...

En el ámbito de la educación médica existen muchas y diferentes definiciones de profesionalismo médico (1). Sin embargo, se acepta de una manera general que “es cumplir con excelencia y responsabilidad con los deberes y atributos del profesional” (2). Una definición que nos acerca más al detalle es la presentada por Swick: “El profesionalismo médico consiste en aquellas conductas mediante las cuales nosotros como médicos demostramos que somos dignos de la confianza que nos otorgan nuestros pacientes y el público, porque estamos trabajando por el bien de los pacientes y del público. Si no demostramos que merecemos esa confianza, se perderá y, por lo tanto, se perderá el estatus de la medicina como profesión” (3). more...

Abstract Micro RNAs (miRNAs) have a key role in gene expression regulation in cancer. The aim of the current study is to evaluate the prognostic value of miR-34b/c promoter hypermethylation, gene expression, and polymorphism in HPV-negative oral squamous cell carcinomas (OSCC). MiR-34b/c promoter hypermethylation and pre-miR-34b/c polymorphism rs4938723 were evaluated in tumor tissues of 148 patients, and miR-34b expression in 123 HPV-negative OSCC. For risk assessment, the control group was comprised of 175 healthy individuals. MiR-34b/c promoter hypermethylation was determined by methylation-specific PCR. Gene expression, genotyping and HPV screening was assessed by Q-PCR. The data from our hospital cohort indicated that miR-34b/c DNA methylation was associated with nodal status (p = 0.048), and predicted the shorter overall survival of HPV-negative OSCC patients (p = 0.008). Down-regulated miR-34b/c expression was associated with smoking (p = 0.047), alcohol use (p = 0.009), stage (p = 0.025), recurrences (p = 0.000), and a poor survival (p = 0.00029). Median values of miR-34b expression were significantly lower in advanced stages III/IV as opposed to stage I/II, p = 0.006, and in nodal positive vs negative patients (p = 0.045). TCGA data also indicated that tumors with stage I–III expressed significantly higher levels of miR-34b, compared to tumors with stage IV (p = 0.035), Low miR-34b/c expression was associated with poor survival in smokers (p = 0.001) and patients with tongue carcinomas (p = 0.00003), and TCGA analysis confirmed these findings although miR-34b expression and miR-34b/c methylation were not associated with survival outcome in the whole TCGA cohort. A significant negative miR-34b/c expression–methylation correlation was observed in our hospital cohort (p = 0.017) and in TCGA cohort. Pre-miR-34b/c polymorphism was not associated with oral cancer risk. Our findings indicate that miR-34b/c hypermethylation and low miR-34b expression could promote the progression and predict the poor prognosis for HPV-negative OSCC, which suggests miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future. more...

Intensive care units (ICUs) are expert hospital areas that provide treatment and 24 h care for people who are very sick. Sepsis represents a serious, severe condition and it can lead to septic shock and multiple organ dysfunction syndromes and is one of the most common reasons for patients’ hospitalization in ICUs. We wanted to explore the prognostic values of interleukin (IL) 33, soluble suppression of tumorigenicity 2 (sST2), IL 27, and galectin 3 in critically-ill patients. We assumed that these parameters in combination or alone could predict mortality in ICU patients. This research represents a clinical non-randomized prospective study, performed at the Medical Military Academy, a tertiary care hospital in Belgrade, Serbia. The patients were divided in four groups: patients with sepsis (peritonitis, pancreatitis, trauma) and patients without sepsis (trauma). Total number of patients enrolled in the study was 151 and average years of patients were 56.48. The values greater than the cut-off were the predictors of mortality. The IL-33, IL-27 as well as galectin-3 can successfully predict the outcome of critically-ill patients in ICUs. The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs. more...

Elastic strain is being increasingly employed to enhance the catalytic properties of mixed ion-electron conducting oxides. However, its effect on oxygen storage capacity is not well established. Here, we fabricate ultrathin, coherently strained films of CeO2-δ between 5.6% biaxial compression and 2.1% tension. In situ ambient pressure X-ray photoelectron spectroscopy reveals up to a fourfold enhancement in equilibrium oxygen storage capacity under both compression and tension. This non-monotonic variation with strain departs from the conventional wisdom based on a chemical expansion dominated behaviour. Through depth profiling, film thickness variations and a coupled photoemission-thermodynamic analysis of space-charge effects, we show that the enhanced reducibility is not dominated by interfacial effects. On the basis of ab initio calculations of oxygen vacancy formation incorporating defect interactions and vibrational contributions, we suggest that the non-monotonicity arises from the tetragonal distortion under large biaxial strain. These results may guide the rational engineering of multilayer and core-shell oxide nanomaterials. more...

Background: The management of patients with massive burns remains a challenge. Early burn wound excision followed by timely coverage are key factors of successful surgical treatment. As donor sites are extremely limited, timely coverage requires intermediate wound coverage and expansion of grafts. Although high expansions rates of 1:6 to 1:9 are feasible, they are commonly known to result in poor graft stability and subpar aesthetic outcome.This report aims to illustrate how the availability of three different large-scale laboratory grown autologous tissues used in combination with NovoSorb® BTM allowed not only complete timely coverage, but also provided for a highly favourable outcome in a patient surviving a 95% total body surface area burn (TBSA). Case presentation: We present the case of a 14-year-old who sustained deep flame burns involving 95% TBSA. Only his feet and an area on his scalp were spared, yielding 630 cm2 of available donor site surface area. A sterile 40 cm2 split thickness biopsy was taken from the patient‘s left foot on the day of injury. The biopsy was divided and used for the simultaneous production of cultured epithelial autografts (CEAs) and cultured dermo-epidermal autografts (CDEAs) in Lausanne, as well as Zurich Skin/denovoSkin (dS), a complex autologous cultured dermo-epidermal skin substitute, in Zurich. Over a course of 5 months, 49 surgical procedures were performed. 60% of the patient‘s TBSA was covered with NovoSorb® BTM while the remaining area received fresh frozen allografts. For definitive coverage, autologous split thickness skin grafts (30% TBSA), CEAs/CDEAs (53% TBSA), and Zurich Skin/dS (12% TBSA) were applied, translating to expansion ratios of 1:8, of 1:383, and of 1:131, respectively. Graft take was excellent for all coverage types with no relevant infectious complications. Conclusions: Sophisticated treatment strategies and innovative surgical methods led to an overall excellent result in this massively burned teenager. The challenge of timely large-scale wound coverage was mastered by applying allografts and NovoSorb® BTM. This is the first report showing successful expansion rates of up to 1:383 in the sequential use of three variants of autologous cultured skin substitutes. This novel approach is highly promising for the management of patients with massive burns. more...

β-N-methylamino-L-alanine (BMAA) and its isomers, 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)-glycine (AEG), along with microcystins (MCs)-RR, -LR, and -YR (the major MC congeners), are cyanotoxins that can cause detrimental health and environmental impacts during toxic blooms. Currently, there are no reverse-phase (RP) LC-MS/MS methods for the simultaneous detection and quantification of BMAA, its isomers, and the major MCs in a single analysis; therefore, multiple analyses are required to assess the toxic load of a sample. Here, we present a newly developed and validated method for the detection and quantification of BMAA, 2,4-DAB, AEG, MC-LR, MC-RR, and MC-YR using RP LC-MS/MS. Method validation was performed, assessing linearity (r2 > 0.996), accuracy (>90% recovery for spiked samples), precision (7% relative standard deviation), and limits of detection (LODs) and quantification (LOQs) (ranging from 0.13 to 1.38 ng mL−1). The application of this combined cyanotoxin analysis on a culture of Microcystis aeruginosa resulted in the simultaneous detection of 2,4-DAB (0.249 ng mg−1 dry weight (DW)) and MC-YR (4828 ng mg−1 DW). This study provides a unified method for the quantitative analysis of BMAA, its isomers, and three MC congeners in natural environmental samples. more...