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Abstract Background Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone. Method Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs. Results Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an ‘off-disc’ stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds. Conclusion The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Traditional methodologies often fall short in addressing the complexity of biological systems. In this regard, system biology omics have brought invaluable tools for conducting comprehensive analysis. Current sequencing capabilities have revolutionized genetics and genomics studies, as well as the characterization of transcriptional profiling and dynamics of several species and sample types. Biological systems experience complex biochemical processes involving thousands of molecules. These processes occur at different levels that can be studied using mass spectrometry-based (MS-based) analysis, enabling high-throughput proteomics, glycoproteomics, glycomics, metabolomics, and lipidomics analysis. Here, we present the most up-to-date techniques utilized in the completion of omics analysis. Additionally, we include some interesting examples of the applicability of multi omics to a variety of biological systems.

Agrostis is one of the most diverse genera of the Poaceae, including ca. 198 species, principally distributed in cold and temperate regions of the world, but also found in the high mountains of the tropics. We present a revision based on morphoanatomical evidence, for the biogeographic region known as Megamexico 3 (i.e., Mexico including the desert areas of southern USA and the Central America territory, to northern Nicaragua). We include taxonomic descriptions and an identification key for the found taxa, maps with the known geographical distribution of the species, and figures with the morphoanatomical characteristics, elevation and phenology. Agrostis is represented in the study zone by 20 species, of which four are endemic and three are introduced. Most records of the genus are distributed in the mountains, above 1500 m a.s.l., in open areas of temperate forests, with conifers and Quercus. Specimens with spikelets occur year round, but most records occur during the wet season, in the months of July to October. We propose a preliminary conservation assessment for each species in the study zone, according to the International Union for Conservation of Nature categories: one with Deficient Data (DD), six as Endangered (EN), two as Vulnerable (VU), and 11 as Least Concern (LC).

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson’s disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients’ quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. Methods: This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. Results: No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. Conclusions: These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.

Cholangiocarcinoma encompasses a heterogeneous group of highly aggressive malignancies, arising from the biliary tract, that are often associated with poor survival rates [...]

We report a disjunct population of Dicrodon guttulatum Duméril & Bibron, 1839 on the eastern slope of the Cordillera Occidental in the inter-Andean Seasonally Dry Forests of the Marañón River, in the Departments of Cajamarca and Piura in northwestern Peru. We include an updated range distribution map using records from museum specimens, the Global Biodiversity Information Facility, and available photographic records on iNaturalist. In addition, we identify widespread cultivation of rice crops as the main threat to D. guttulatum in the inter-Andean Seasonally Dry Forests of the Marañón.

Abstract Mitochondrial dysfunction plays a key role in doxorubicin-induced cardiotoxicity (DIC). In this proof-of-principle study, we investigated whether PET mapping of cardiac membrane potential, an indicator of mitochondrial function, could detect an acute cardiotoxic effect of doxorubicin (DOX) in a large animal model. Eight Yucatan pigs were imaged dynamically with [18F](4-Fluorophenyl)triphenylphosphonium ([18F]FTPP+) PET/CT. Our experimental protocol included a control saline infusion into the left anterior descending coronary artery (LAD) followed by a DOX test infusion of either 1 mg/kg or 2 mg/kg during PET. We measured the change in total cardiac membrane potential (ΔΨT), a proxy for the mitochondrial membrane potential, ΔΨm, after the saline and DOX infusions. We observed a partial depolarization of the mitochondria following the DOX infusions, which occurred only in myocardial areas distal to the intracoronary catheter, thereby demonstrating a direct association between the exposure of the mitochondria to DOX and a change in ΔΨT. Furthermore, doubling the DOX dose caused a more severe depolarization of myocardium in the LAD territory distal to the infusion catheter. In conclusion, [18F]FTPP+ PET-based ΔΨT mapping can measure partial depolarization of myocardial mitochondria following intracoronary DOX infusion in a large animal model.

Abstract The homogeneous Yang-Baxter deformation is part of a larger web of integrable deformations and dualities that recently have been studied with motivations in integrable σ-models, solution-generating techniques in supergravity and Double Field Theory, and possible generalisations of the AdS/CFT correspondence. The σ-models obtained by the homogeneous Yang-Baxter deformation with periodic boundary conditions on the worldsheet are on-shell equivalent to undeformed models, yet with twisted boundary conditions. While this has been known for some time, the expression provided so far for the twist features non-localities (in terms of the degrees of freedom of the deformed model) that prevent practical calculations, and in particular the construction of the classical spectral curve. We solve this problem by rewriting the equation defining the twist in terms of the degrees of freedom of the undeformed yet twisted model, and we show that we are able to solve it in full generality. Remarkably, this solution is a local expression. We discuss the consequences of the twist at the level of the monodromy matrix and of the classical spectral curve, analysing in particular the concrete examples of abelian, almost abelian and Jordanian deformations of the Yang-Baxter class.

The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.

PURPOSE: Spain is leader in the world ranking of surface vineyards of ecological production, with almost 27% of world production. Consumers are demanding for more information about these sustainable practices and the official certificates can be a good option to help them. In the case of natural wines, four certifications can be used in the packaging of wines to inform consumers that they are acquiring natural wine: i) certified organic winery by the EU; ii) certified biodynamic winery by Demeter; iii) certified organic (EU) and biodynamic (Demeter) winery; iv) certified by the National Institute of Origins and Quality (INAO) as ‘vin méthode nature’ (natural method wine) with two logos (natural method without added sulphites and natural method with less than 30 mg/l added sulphites). To obtain the results we have conducted a pilot study with a sample of 358 Spanish consumers of wine divided by experts and non-experts. RESULTS: The results have confirmed there is a tendency in foodrelated on labelling in recent years to be focused on sustainability labelling and certification. CONCLUSIONS AND IMPLICATIONS: The research has given us an idea about the importance of sustainability for consumers of natural wine and if an official certificate is a necessary question for them in the decision-making process. Thus, labelling certifications may increase the information for the consumers and could also be an opportunity to generate an increased level of credibility in natural wines, "the great unknown".

Analgesic consumption increased significantly during the COVID-19 pandemic. A high concentration of this kind of drug is discarded in the urine, reaching the effluents of rivers, lakes, and seas. These medicines have brought serious problems for the flora and, especially, the ecosystems’ fauna. This paper presents the results of removing diclofenac, ibuprofen, and paracetamol in an aqueous solution, using Sargassum spp. from the Caribbean coast. The study consisted of mixing each drug in an aqueous solution with functionalized Sargassum spp in a container under constant agitation. Therefore, this work represents an alternative to solve two of the biggest problems in recent years; first, the reduction of the overpopulation of sargassum through its use for the remediation of the environment. Second is the removal of drug waste used excessively during the COVID-19 pandemic. Liquid samples of the solution were taken at intervals of 10 min and analyzed by fluorescence to determine the concentration of the drug.The sorption capacity for diclofenac, ibuprofen, and paracetamol was 2.46, 2.08, and 1.41 μg/g, corresponding to 98 %, 84 %, and 54 % of removal, respectively. The removal of the three drugs was notably favored by increasing the temperature to 30 and 40 °C, reaching efficiencies close to 100 %. Moreover, the system maintains its effectiveness at various pH values. In addition, the Sargassum used can be reused for up to three cycles without reducing its removal capacity. The wide diversity of organic compounds favors the biosorption of drugs, removing them through various kinetic mechanisms. On the other hand, the Sargassum used in the drugs removal was analyzed by X-ray diffraction, FTIR spectroscopy, TGA analysis, and scanning electron microscopy before and after removal. The results showed an evident modification in the structure and morphology of the algae and demonstrated the presence of the biosorbed drugs. Therefore, this system is sustainable, simple, economical, environmentally friendly, highly efficient, and scalable at a domestic and industrial level that can be used for aquatic remediation environments.

Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy to spread and can cause difficult-to-treat infections. Here, we summarize the available evidence on the impact of the COVID-19 pandemic on infections caused by ESBL-PE. Using specific criteria and keywords, we searched PubMed, MEDLINE, and EMBASE for articles published up to 30 March 2023 on potential changes in the epidemiology of ESBL-E since the beginning of the COVID-19 pandemic. We identified eight studies that documented the impact of COVID-19 on ESBL-E. Five studies were focused on assessing the frequency of ESBL-PE in patient-derived specimens, and three studies investigated the epidemiological aspects of ESBL-PE infections in the context of the COVID-19 pandemic. Some of the studies that were focused on patient specimens reported a decrease in ESBL-PE positivity during the pandemic, whereas the three studies that involved patient data (1829 patients in total) reported a higher incidence of ESBL-PE infections in patients hospitalized for COVID-19 compared with those with other conditions. There are limited data on the real impact of the COVID-19 pandemic on the epidemiology of ESBL-PE infections; however, patient-derived data suggest that the pandemic has exacerbated the spread of these pathogens.

Background The onset and mechanisms of endothelial‐to‐mesenchymal transition (EndMT) in mitral valve (MV) leaflets following myocardial infarction (MI) are unknown, yet these events are closely linked to stiffening of leaflets and development of ischemic mitral regurgitation. We investigated whether circulating molecules present in plasma within days after MI incite EndMT in MV leaflets. Methods and Results We examined the onset of EndMT in MV leaflets from 9 sheep with inferior MI, 8 with sham surgery, and 6 naïve controls. Ovine MVs 8 to 10 days after inferior MI displayed EndMT, shown by increased vascular endothelial cadherin/α‐smooth muscle actin–positive cells. The effect of plasma on EndMT in MV endothelial cells (VECs) was assessed by quantitative polymerase chain reaction, migration assays, and immunofluorescence. In vitro, post‐MI plasma induced EndMT marker expression and enhanced migration of mitral VECs; sham plasma did not. Analysis of sham versus post‐MI plasma revealed a significant drop in the Wnt signaling antagonist sFRP3 (secreted frizzled‐related protein 3) in post‐MI plasma. Addition of recombinant sFRP3 to post‐MI plasma reversed its EndMT‐inducing effect on mitral VECs. RNA‐sequencing analysis of mitral VECs exposed to post‐MI plasma showed upregulated FOXM1 (forkhead box M1). Blocking FOXM1 reduced EndMT transcripts in mitral VECs treated with post‐MI plasma. Finally, FOXM1 induced by post‐MI plasma was downregulated by sFRP3. Conclusions Reduced sFRP3 in post‐MI plasma facilitates EndMT in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels or inhibiting FOXM1 soon after MI may provide a novel strategy to modulate EndMT in the MV to prevent ischemic mitral regurgitation and heart failure.

Background: Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment. Methods: Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array. Results: Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6–41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15–3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response. Conclusion: Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data. Trial registration: EudraCT 2009-018171-13

Scientific societies serve as communities of practice in which scientists develop many of the skills and connections required for the progression of their careers. For example, scientific societies offer their members opportunities to attend career development programs, gain experience in communicating science, and receive recognition for achievements within their discipline. Programming for undergraduate student members has recently been increasing, both in prevalence and in its range of offerings. The Alliance to Catalyze Change for Equity in STEM Success, ACCESS, a meta-organization seeking equity and inclusivity in life sciences fields, has examined programs and opportunities focused on undergraduates across its member scientific societies to identify common themes, promising practices and challenges. In this article, we share and discuss our findings.

Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to carbapenems, a group of antibiotics considered as the last-resource for the treatment of infections caused by multidrug-resistant bacteria. CRE constitutes a major threat to health care systems because infections caused by these pathogens are difficult to treat and are commonly associated with high mortality due to the limited availability of effective antibiotics. While infection prevention and timely detection are of vital importance to control CRE infections, developing new and effective anti-CRE therapies is also crucial. Accumulating evidence indicates that gut microbiota alteration (dysbiosis) is associated with an increased intestinal colonization with CRE and consequently with higher risk of developing CRE infections. Importantly, therapeutic interventions aimed to modify the gut microbiota composition via fecal microbiota transplantation (FMT) have been explored in various clinical settings with some of them showing promising results, although larger clinical trials are needed to confirm the efficacy of this strategy. Here, we highlight the challenges associated with the emergence of CRE infections.

Receptor tyrosine kinase mutations are frequent and associated with poor prognosis in acute myeloid leukemia (AML). Here the authors show that the antipsychotic drug chlorpromazine reduces AML cells viability by perturbing the intracellular localization of FLT3-ITD and KIT-D816V.

Abstract Background Reliable information about the spatial distribution of aboveground biomass (AGB) in tropical forests is fundamental for climate change mitigation and for maintaining carbon stocks. Recent AGB maps at continental and national scales have shown large uncertainties, particularly in tropical areas with high AGB values. Errors in AGB maps are linked to the quality of plot data used to calibrate remote sensing products, and the ability of radar data to map high AGB forest. Here we suggest an approach to improve the accuracy of AGB maps and test this approach with a case study of the tropical forests of the Yucatan peninsula, where the accuracy of AGB mapping is lower than other forest types in Mexico. To reduce the errors in field data, National Forest Inventory (NFI) plots were corrected to consider small trees. Temporal differences between NFI plots and imagery acquisition were addressed by considering biomass changes over time. To overcome issues related to saturation of radar backscatter, we incorporate radar texture metrics and climate data to improve the accuracy of AGB maps. Finally, we increased the number of sampling plots using biomass estimates derived from LiDAR data to assess if increasing sample size could improve the accuracy of AGB estimates. Results Correcting NFI plot data for both small trees and temporal differences between field and remotely sensed measurements reduced the relative error of biomass estimates by 12.2%. Using a machine learning algorithm, Random Forest, with corrected field plot data, backscatter and surface texture from the L-band synthetic aperture radar (PALSAR) installed on the on the Advanced Land Observing Satellite-1 (ALOS), and climatic water deficit data improved the accuracy of the maps obtained in this study as compared to previous studies (R2 = 0.44 vs R2 = 0.32). However, using sample plots derived from LiDAR data to increase sample size did not improve accuracy of AGB maps (R2 = 0.26). Conclusions This study reveals that the suggested approach has the potential to improve AGB maps of tropical dry forests and shows predictors of AGB that should be considered in future studies. Our results highlight the importance of using ecological knowledge to correct errors associated with both the plot-level biomass estimates and the mismatch between field and remotely sensed data.

Abstract The classical spectral curve for the worldsheet theory of the AdS5 ×S 5 lambda superstring is constructed. The lambda string is interpreted as a regularized, non-abelian T-dual of the AdS5 ×S 5 superstring with respect to the full PSU(2, 2|4) symmetry. The form of the curve is identified as the semi-classical limit of a set of Bethe ansatz equations for an XXZ type spin chain for the supergroup PSU(2, 2|4) in contrast to the string in AdS5 ×S 5 which is XXX type.

Tactics to increase the number of underrepresented (UR) students in biomedical research PhD training programs have not yet translated to UR faculty numbers that reflect the diversity of the United States. Continued interventions are required to build skills beyond those that result in placement into a PhD program. We hypothesize that successful interventions must build skills that give UR students foundations for confident self-efficacy in leadership. We seek interventions that allow UR students to envision themselves as successful faculty. We posit that development of such skills is difficult in the classroom or laboratory alone. Therefore, novel interventions are required. As part of the NIH-funded Post-baccalaureate Research Education Program (PREP) and Initiative for Maximizing Student Development (IMSD) at the Mayo Clinic Graduate School of Biomedical Sciences, we designed and implemented a unique intervention to support development of student leadership skills: a biannual student-organized and student-led national research conference titled “Scientific Innovation Through Diverse Perspectives” (SITDP). This initiative is based on the concept that students who actively live out realistic roles as scientific leaders will be encouraged to persist to scientific leadership as faculty. Here we describe the motivation for, design of, and outcomes from, the first three pilot conferences of this series. We further discuss approaches needed to rigorously evaluate the effectiveness of such interventions in the future.

Las universidades son agentes culturales territoriales en el sentido de que ejercen una influencia clara en la vida cultural de las ciudades en las que tienen su sede. El caso de la Universidad de Cádiz (UCA) es peculiar en tanto quedicha institución tiene cuatro campus diferentes en la provincia de Cádiz (Algeciras, Cádiz, Jerez y Puerto Real). Este hecho hace que su influencia sea la de un agente provincial que alcanza como mínimo al 60% de la población de dicho territorio. En los últimos años, la UCA ha ejercido una clara influencia en las políticas culturales locales con un reparto equilibrado de sus recursos entre los cuatro municipios e incluso en algunos otros que no poseen campus. Sin duda, el ecosistema cultural de la provincia de Cádiz no estaría completo sin considerar a la UCA parte esencial del mismo. Palabras clave: políticas culturales; territorio; municipios; campus universitarios. Cultural policies in cities with campus of the province of Cádiz and the experience of the extension University of the UCA. Cádiz, Puerto Real, Jerez and Algeciras Abstract: Universities are territorial cultural agents in the sense that they exert a clear influence on the cultural life of the cities in which they are based. The case of the University of Cádiz (UCA) is peculiar insofar as said institution has four different campuses in the province of Cádiz (Algeciras, Cádiz, Jerez and Puerto Real). This fact it makes its influence that of a provincial agent that reaches at least 60% of the population of that territory. In recent years, the UCA has had a clear influence on local cultural policies with a balanced distribution of its resources among the four municipalities and even in some others that do not have a campus. Without a doubt, the cultural ecosystem of the province of Cádiz would not be complete without considering the UCA an essential part of it. Keywords: cultural policies; territory; municipalities; university campus. Artículo recibido: 28/10/2021. Revisado: 02/11/2021. Aceptado: 02/11/2021

Fast Scan Cyclic Voltammetry (FSCV) has been used for decades as a neurochemical tool for in vivo detection of phasic changes in electroactive neurotransmitters in animal models. Recently, multiple research groups have initiated human neurochemical studies using FSCV or demonstrated interest in bringing FSCV into clinical use. However, there remain technical challenges that limit clinical implementation of FSCV by creating barriers to appropriate scientific rigor and patient safety. In order to progress with clinical FSCV, these limitations must be first addressed through (1) appropriate pre-clinical studies to ensure accurate measurement of neurotransmitters and (2) the application of a risk management framework to assess patient safety. The intent of this work is to bring awareness of the current issues associated with FSCV to the scientific, engineering, and clinical communities and encourage them to seek solutions or alternatives that ensure data accuracy, rigor and reproducibility, and patient safety.

Singlet fission is a promising carrier multiplication process, where a singlet exciton is split in two triplet states. Here the authors propose an oxygen-assisted two-step mechanism for singlet fission accounting for ~ 40% triplet quantum yield in dilute solutions where the single-step mechanism is inactive.

Abstract Sarcoidosis is a rare inflammatory disease characterized by the development of granulomas in various organs, especially in the lungs and lymph nodes. Clinics of the disease largely depends on the organ involved and may range from mild symptoms to life threatening manifestations. Over the last two decades, significant advances in the diagnosis, clinical assessment and treatment of sarcoidosis have been achieved, however, the precise etiology of this disease remains unknown. Current evidence suggests that, in genetically predisposed individuals, an excessive immune response to unknown antigen/s is crucial for the development of sarcoidosis. Epidemiological and microbiological studies suggest that, at least in a fraction of patients, microbes or their products may trigger the immune response leading to sarcoid granuloma formation. In this article, we discuss the scientific evidence on the interaction of microbes with immune cells that may be implicated in the immunopathogenesis of sarcoidosis, and highlight recent studies exploring potential implications of human microbiota in the pathogenesis and the clinical course of sarcoidosis.

Paulownia tomentosa (P. tomentosa) is a hardwood tree that has economic and scientific relevance but has no use as food. For that reason, we selected it to conduct a study on the synthesis of silver nanoparticles (AgNPs) using hydroalcoholic extracts from its leaves. Phytochemical sources had been widely used as reducing agents for synthesis of nanoparticles. Our work is the first approach for studying the correlation between the composition of the extracts and the AgNPs synthesis features. Isopropyl alcohol, ethanol, and water were proposed as extraction solvents. Nanoparticles were characterized by UV–vis, FTIR, and Scanning Electron Microscopy/Energy Dispersive X-ray spectroscopy (SEM/EDX) and the Antimicrobial activity was evaluated. Our findings suggest that the composition of the extracts varies with the selection of the extraction solvent. This is relevant because solvents with similar characteristics and polarity (isopropyl alcohol and ethanol) produced different AgNPs features such as ζ potential that was −20.5 ± 0.41, −25 ± 0.12 and 31 ± 0.79 mV for samples extracted with isopropyl alcohol, ethanol, and water, respectively. Samples obtained with isopropyl alcohol produced nanoparticles with the highest antioxidant activity and stability. Also, we found that size, shape, reaction kinetics, and bactericidal properties have a strong correlation with the composition of the plant extract. Our results justify the use of a wide range of extraction solvents to obtain detail implications on size and shape of nanoparticles, and the use of chromatographic techniques to determine each fraction composition. Our investigation is the first step in a coherent path to propose reaction mechanisms on nanoparticles synthesis using complex mixtures from Paulownia tomentosa extracts. Keywords: Biosynthesis, Silver nanoparticles (AgNPs), Paulownia tomentosa, Electrochemical-CUPRAC, Trolox Equivalent Antioxidant Capacity, Flavonoid oxidation

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is an important public health issue worldwide, not only due to the potential of these pathogens for widespread dissemination, but also due to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. As with other multidrug-resistant organisms (MDROs), active surveillance via timely testing, early diagnosis, and contact isolation is an important strategy to control the occurrence and spread of CRE bacteria. Here we summarize the epidemiology of CRE infections in Japan from 2015 to 2019. Data were extracted from a public dataset collected by the nationwide surveillance system via the National Institute of Infectious Diseases (NIID) of Japan. The annual number of reported CRE infections has remained relatively stable, with a tendency to increase in the last two years (1671 cases reported in 2015 and 2333 cases reported in 2019). The majority of patients who presented CRE infections over this five year period were older than 65 years (~80%, mean age 75), 60% of them were men, and mortality rates were around 3.5%. Importantly, about 60% of infections are caused by both Enterobacter cloacae and Klebsiella aerogenes (previously known as Enterobacter aerogenes), the former being the most common pathogen in 2015 and 2016 (~30%), and the latter the leading pathogen since 2017 (~40%). The most common carbapenemase isolated was the IMP carbapenemase type. Further studies are needed to determine the prevalence of CRE colonization, especially in the healthcare setting, and to elucidate the mechanisms behind the local predominance of Klebsiella aerogenes and Enterobacter cloacae.

Acute myeloid leukemia (AML) is a heterogeneous disease often associated with poor prognosis. We previously showed that the localization of KIT-D816V at endolysosomes is critical to activate aberrant Akt signaling and Chlorpromazine (CPZ) perturbs the intracellular localization, leading to cell death in AML cells with KIT-D816V. We report that daily administration of CPZ, prescribed for controlling anxiety disorder in patient with AML harboring KIT-D816V, led to a dramatic reduction in AML cells. In vitro and in vivo experiments showed that CPZ inhibited the growth and survival of the patient-derived AML cells, implying potent efficacy of CPZ in AML with KIT-D816V.

The potential sub-shell closures N=32 and N=34 are analyzed at high spins in the titanium isotopes within the generalized beyond mean field theory considering triaxial deformations and the angular frequency as generator coordinates together with the particle number and the angular momentum conservation. A good description of bulk properties, high angular momenta spectra and transition probabilities is obtained. The outcome at high spin in these nuclei is consistent with the magic number character of N=32 but not of N=34. Keywords: Titanium isotopes, New magic numbers, N=32, 34 sub-shell closures, GCM, Beyond mean field theories

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article “A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate” by Asp et. al.

Introduction: A clean and functional microscope is necessary for accurate diagnosis of infectious diseases. In tropical climates, high humidity levels and improper storage conditions allow for the accumulation of debris and fungus on the optical components of diagnostic equipment, such as microscopes. Objective: Our objective was to develop and implement a low-cost, sustainable, easy to manage, low-maintenance, passive humidity control chamber to both reduce debris accumulation and microbial growth onto the optical components of microscopes. Methods: Constructed from easily-sourced and locally available materials, the cost of each humidity control chamber is approximately $2.35 USD. Relative humidity levels were recorded every 30 minutes over a period of 10 weeks from two chambers deployed at the Belize Vector and Ecology Center and the University of Belize. Results: The humidity control chamber deployed at the University of Belize maintained internal relative humidity at an average of 35.3% (SD = 4.2%) over 10 weeks, while the average external relative humidity was 86.4% (SD = 12.4%). The humidity control chamber deployed at the Belize Vector and Ecology Center effectively maintained internal relative humidity to an average of 54.5% (SD = 9.4%) over 10 weeks, while the average external relative humidity was 86.9% (SD = 12.9%). Conclusions: Control of relative humidity is paramount for the sustainability of medical equipment in tropical climates. The humidity control chambers reduced relative humidity to levels that were not conducive for fungal growth while reducing microscope contamination from external sources. This will likely extend the service life of the microscopes while taking advantage of low-cost, locally sourced components.

We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD. Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT.

Abstract Here, the concept of a new and interesting Riemann–Liouville type fractional derivative operator is exploited. Treatment of a fractional derivative operator has been made associated with the extended Appell hypergeometric functions of two variables and Lauricella hypergeometric function of three variables. With a view on analytic properties and application of new Riemann–Liouville type fractional derivative operator, we have obtained new fractional derivative formulas for some familiar functions and for Mellin transformation formulas. For the sake of justification of our new operator, we have established some presumably new generating functions for an extended hypergeometric function using the new definition of fractional derivative operator.

Abstract: Hematopoietic stem cells (HSCs) that lack HLA-class I alleles as a result of copy-number neutral loss of heterozygosity of the short arm of chromosome 6 (6pLOH) or HLA allelic mutations often constitute hematopoiesis in patients with acquired aplastic anemia (AA), but the precise mechanisms underlying clonal hematopoiesis induced by these HLA-lacking (HLA−) HSCs remain unknown. To address this issue, we generated induced pluripotent stem cells (iPSCs) from an AA patient who possessed HLA-B4002–lacking (B4002−) leukocytes. Three different iPSC clones (wild-type [WT], 6pLOH+, and B*40:02-mutant) were established from the patient's monocytes. Three-week cultures of the iPSCs in the presence of various growth factors produced hematopoietic cells that make up 50% to 70% of the CD34+ cells of each phenotype. When 106 iPSC-derived CD34+ (iCD34+) cells with the 3 different genotypes were injected into the femoral bone of C57BL/6.Rag2 mice, 2.1% to 7.3% human multilineage CD45+ cells of each HLA phenotype were detected in the bone marrow, spleen, and peripheral blood of the mice at 9 to 12 weeks after the injection, with no significant difference in the human:mouse chimerism ratio among the 3 groups. Stimulation of the patient's CD8+ T cells with the WT iCD34+ cells generated a cytotoxic T lymphocyte (CTL) line capable of killing WT iCD34+ cells but not B4002− iCD34+ cells. These data suggest that B4002− iCD34+ cells show a repopulating ability similar to that of WT iCD34+ cells when autologous T cells are absent and CTL precursors capable of selectively killing WT HSCs are present in the patient's peripheral blood.

Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers.

Sargassum species-based extracts were used to carry out the synthesis of homogeneous gold nanoparticles. Various techniques were used to determine the characteristics and composition of the nanoparticles. The UV-Vis results showed that the 50% water/ethanol extract had the most reducing agents and stabilizers. Therefore, this type of extract was used to synthesize nanoparticles and for their subsequent characterization. Crystallinity and crystal size were evaluated using X-ray diffraction. Size and morphology were analyzed using scanning electron microscopy, showing that the gold nanoparticles were mostly spherical, with a size range of 15–30 nm. The catalytic activity of the gold nanoparticles was evaluated through the degradation of organic dyes: methylene blue, methyl orange, and methyl red. The degradation rates were different, depending on the nature of each dye, the simplest to degrade was methylene blue and methyl red was the most difficult to degrade. The results indicated that the use of Sargassum spp. for the synthesis of gold nanoparticles has potential in the remediation of water that is contaminated with organic dyes. Moreover, given the recent serious environmental and economic problems caused by the overpopulation of Sargassum spp. in the Mexican Caribbean, the findings hold promise for their practical and sustainable use in the synthesis of nanomaterials.

Summary The massive production of urban and agricultural wastes has promoted a clear need for alternative processes of disposal and waste management. The potential use of municipal solid wastes (MSW) as feedstock for the production of polyhydroxyalkanoates (PHA) by a process known as syngas fermentation is considered herein as an attractive bio‐economic strategy to reduce these wastes. In this work, we have evaluated the potential of Rhodospirillum rubrum as microbial cell factory for the synthesis of PHA from syngas produced by microwave pyrolysis of the MSW organic fraction from a European city (Seville). Growth rate, uptake rate, biomass yield and PHA production from syngas in R. rubrum have been analysed. The results revealed the strong robustness of this syngas fermentation where the purity of the syngas is not a critical constraint for PHA production. Microwave‐induced pyrolysis is a tangible alternative to standard pyrolysis, because it can reduce cost in terms of energy and time as well as increase syngas production, providing a satisfactory PHA yield.

Abstract The analogues of giant magnon configurations are studied on the string world sheet in the lambda background. This is a discrete deformation of the AdS5×S 5 background that preserves the integrability of the world sheet theory. Giant magnon solutions are generated using the dressing method and their dispersion relation is found. This reduces to the usual dyonic giant magnon dispersion relation in the appropriate limit and becomes relativistic in another limit where the lambda model becomes the generalized sine-Gordon theory of the Pohlmeyer reduction. The scattering of giant magnons is then shown in the semi-classical limit to be described by the quantum S-matrix that is a quantum group deformation of the conventional giant magnon S-matrix. It is further shown that in the small g limit, a sector of the S-matrix is related to the XXZ spin chain whose spectrum matches the spectrum of magnon bound states.

We present a self-consistent theory for odd nuclei with exact blocking and particle number and angular momentum projection. The demanding treatment of the pairing correlations in a variation-after-projection approach as well as the explicit consideration of the triaxial deformation parameters in a projection after variation method, together with the use of the finite-range density-dependent Gogny force, provides an excellent tool for the description of odd–even and even–even nuclei. We apply the theory to the Magnesium isotopic chain and obtain an outstanding description of the ground-state properties, in particular binding energies, odd–even mass differences, mass radii and electromagnetic moments among others.

El núcleo de la carpeta de aprendizaje es el proceso metacognitivo que promueve en los estudiantes. Este aspecto junto con la comprensión de la dimensión colectiva del conocimiento y del aprendizaje son factores determinantes en la construcción de la identidad profesional. Se presenta una propuesta de carpeta de aprendizaje centrada en competencias transversales, elaborada en grupo y asociada con un entorno de Aprendizaje Basado en Problemas que se implantó en dos asignaturas obligatorias de la titulación de Bellas Artes. El estudio empírico analizó las puntuaciones que dos profesores asignaron a los 307 estudiantes universitarios que elaboraron la carpeta con el fin de determinar la validez y la fiabilidad de las inferencias sobre su aprendizaje. La valoración de la coherencia de las puntuaciones obtenidas en las actividades que constituyeron la carpeta y de su consistencia interna, así como de la adecuación de la carpeta al contexto educativo demostró una validez y fiabilidad aceptables, de manera que puede concluirse el buen funcionamiento del recurso en el contexto en que se aplicó.

En este trabajo se abordan las estrategias que permitan la introducción de modelos diseñados por ordenador como sustitutos de los modelos de cera utilizados tradicionalmente en la fundición artística. Estos modelos digitales, se fabrican mediante impresión 3D en ácido poliláctico (PLA), material que por sus propiedades se presenta como un sustituto viable a la cera, dentro de los procesos de fundición artística mediante cascarilla cerámica (Ceramic Shell casting). Para comprobar la viabilidad se han diseñado dos modelos complejos y difícilmente realizables con técnicas tradicionales. En concreto, un busto figurativo hueco y una síntesis figurativa de formas vegetales con una solución estructural de gradiente. Además se hizo un estudio con diferentes técnicas para unificar la textura de capas que presentan los objetos fabricados mediante impresión 3D. Se comprueba que es viable introducir los modelos de PLA en el proceso de fundición a menor coste y menor tiempo que con técnicas tradicionales. Además se pueden fundir formas en metal que no son posibles de crear con técnicas manuales.

Achieving human-like locomotion with humanoid platforms often requires the use of variable stiffness actuators (VSAs) in multi-degree-of-freedom robotic joints. VSAs possess 2 motors for the control of both stiffness and equilibrium position. Hence, they add mass and mechanical complexity to the design of humanoids. Mass distribution of the legs is an important design parameter, because it can have detrimental effects on the cost of transport. This work presents a novel VSA module, designed to be implemented in a bio-inspired humanoid robot, Binocchio, that houses all components on the same side of the actuated joint. This feature allowed to place the actuator's mass to more proximal locations with respect to the actuated joint instead of concentrating it at the joint level, creating a more favorable mass distribution in the humanoid. Besides, it also facilitated it's usage in joints with centralized multi-degree of freedom (DoF) joints instead of cascading single DoF modules. The design of the VSA module is presented, including it's integration in the multi-DoFs joints of Binocchio. Experiments validated the static characteristics of the VSA module to accurately estimate the output torque and stiffness. The dynamic responses of the driving and stiffening mechanisms are shown. Finally, experiments show the ability of the actuation system to replicate the envisioned human-like kinematic, torque and stiffness profiles for Binocchio.

Myelodysplastic syndromes (MDS) are a heterogeneous group clonal disorders of hematopoietic stem cells (HSC) characterized by ineffective hematopoiesis that lead to variable grades of impaired blood cell production. Chromosomal aberrations are often detected in MDS patients and thus cytogenetic analysis is useful for the diagnosis of these disorders. Common recurring chromosomal defects, such as the −5/5q- and −7/7q- are relatively well characterized cytogenetic abnormalities in MDS, however, the biological significance of uncommon cytogenetic alterations is unknown. We report here, two cases of peripheral blood and bone marrow hypereosinophilia in patients with MDS harboring the unbalanced translocation der(1;7)(q10;p10), a poorly characterized cytogenetic abnormality that is found in certain myeloid malignancies, including MDS. The patients reported here presented hypereosinophilia that was refractory to steroids and cytotoxic therapy, leading to severe target tissue damage that ultimately resulted in fatal end-organ failure. Potential roles of the der(1;7)(q10;p10) aberrations in the pathogenesis of aggressive eosinophilia and disease prognosis are discussed here.