The Immunogenomic Landscape of Peripheral High-Dose IL-2 Pharmacodynamics in Patients with Metastatic Renal Cell Carcinoma: A Benchmark for Next-Generation IL-2-Based Immunotherapies.

High-dose (HD) IL-2 was the first immuno-oncology agent approved for treating advanced renal cell carcinoma and metastatic melanoma, but its use was limited because of substantial toxicities. Multiple next-generation IL-2 agents are being developed to improve tolerability. However, a knowledge gap still exists for the genomic markers that define the target pharmacology for HD IL-2 itself. In this retrospective observational study, we collected PBMC samples from 23 patients with metastatic renal cell carcinoma who were treated with HD IL-2 between 2009 and 2015. We previously reported the results of flow cytometry analyses. In this study, we report the results of our RNA-sequencing immunogenomic survey, which was performed on bulk PBMC samples from immediately before (day 1), during (day 3), and after treatment (day 5) in cycle 1 and/or cycle 2 of the first course of HD IL-2. As part of a detailed analysis of immunogenomic response to HD IL-2 treatment, we analyzed the changes in individual genes and immune gene signatures. By day 3, most lymphoid cell types had transiently decreased, whereas myeloid transcripts increased. Although most genes and/or signatures generally returned to pretreatment expression levels by day 5, certain ones representative of B cell, NK cell, and T cell proliferation and effector functions continued to increase, along with B cell (but not T cell) oligoclonal expansion. Regulatory T cells progressively expanded during and after treatment. They showed strong negative correlation with myeloid effector cells. This detailed RNA-sequencing immunogenomic survey of IL-2 pharmacology complements results of prior flow cytometry analyses. These data provide valuable pharmacological context for assessing PBMC gene expression data from patients dosed with IL-2-related compounds that are currently in development.

Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia.

Long non-coding RNA (lncRNA) genes represent a large class of transcripts that are widely expressed across species. As most human lncRNAs are non-conserved, we recently employed a unique humanized liver mouse model to study lncRNAs expressed in human livers. We identified a human hepatocyte-specific lncRNA, hLMR1 (human lncRNA metabolic regulator 1), which is induced by feeding and promotes hepatic cholesterol synthesis. Recent genome-wide association studies (GWAS) found that several single-nucleotide polymorphisms (SNPs) from the hLMR1 gene locus are associated with blood lipids and markers of liver damage. These results suggest that dietary and genetic factors may regulate hLMR1 to affect disease progression. In this study, we first screened for nutritional/hormonal factors and found that hLMR1 was robustly induced by insulin/glucose in cultured human hepatocytes, and this induction is dependent on the transcription factor SREBP1. We then tested if GWAS SNPs genetically linked to hLMR1 could regulate hLMR1 expression. We found that DNA sequences flanking rs9653945, a SNP from the last exon of the hLMR1 gene, functions as an enhancer that can be robustly activated by SREBP1c depending on the presence of rs9653945 major allele (G). We further performed CRISPR base editing in human HepG2 cells and found that rs9653945 major (G) to minor (A) allele modification resulted in blunted insulin/glucose-induced expression of hLMR1. Finally, we performed genotyping and gene expression analyses using a published human NAFLD RNA-seq dataset and found that individuals homozygous for rs9653945-G have a higher expression of hLMR1 and risk of NAFLD. Taken together, our data support a model that rs9653945-G predisposes individuals to insulin/glucose-induced hLMR1, contributing to the development of hyperlipidemia and NAFLD.

Relaxed minds for healthier food choice at school: A field experiment in southern Mexico.

Stress leads to unhealthy food choices since the school-age stage. Yet, there is limited evidence particularly in low- and middle-income countries regarding the impact of stress-reduction strategies on school-age children's food choices. Such aspects were crucial during the recent COVID-19 pandemic, which exacerbated psychological distress and unhealthier food choices among children. Two years after the pandemic began, we conducted a field experiment in southern Mexico to assess the impact of stress-reduction strategies on the food choices of over 1400 children aged 9-12. Half of the school-classes in the sample were randomly assigned to a stress reduction strategy namely meditation, which comprised six audios with basic relaxation techniques and intuitive messages to guide food choices. Additionally, all participants received information signalling that an amaranth snack was nutritious (i.e., the healthy snack), which was paired with a chocolate bar (i.e., the unhealthy snack) as part of a snack choice experiment. Students that practiced meditation were slightly more likely to choose the healthy snack than those in the control group, but the effect was not statistically significant. Upon collecting their snack, students had the chance to exchange their original choice for the other snack. Students that meditated were more likely to exchange their originally chosen "unhealthy snack" towards the healthy snack than students in the control group. The meditation program effectively reduced chronic stress among treated children. The effect was larger among students attending schools in lower-income areas. Our study sheds some light on the challenges to translate an improved psychological well-being into healthier food choices at school.

Early diverting stoma closure is feasible and safe: results from a before-and-after study on the implementation of an early closure protocol at a tertiary referral center.

BACKGROUND: Evidence on early closure (EC) of defunctioning stoma (DS) after colorectal surgery shows a favorable effect when patients are carefully selected. Therefore, a clinical pathway adapted to the implementation of an EC strategy was developed in our center. The aim of this study was to carry out a comparative analysis of time until DS closure and DS-related morbidity before and after the implementation of an EC protocol (ECP). METHODS: This study is a before-and-after comparative analysis. Patients were divided into two cohorts according to the observational period: patients from the period before the ECP implementation (January 2015-December 2019) [Period 1] and those from the period after that (January 2020-December 2022) [Period 2]. All consecutive patients subjected to elective DS closure within both periods were eligible. Early closure was defined as the reversal within 30 days from DS creation. Patients excluded from EC or those not closed within 30 days since primary surgery were analyzed as late closure (LC). Baseline characteristics and DS-related morbidity were recorded. RESULTS: A total of 145 patients were analyzed. Median time with DS was shorter in patients after ECP implementation [42 (21-193) days versus 233 (137-382) days, p < 0.001]. This reduction in time to closure did not impact the DS closure morbidity and resulted in less DS morbidity (68.8% versus 49.2%, p = 0.017) and fewer stoma nurse visits (p = 0.029). CONCLUSIONS: The ECP was able to significantly reduce intervals to restoration of bowel continuity in patients with DS, which in turn resulted in a direct impact on the reduction of DS morbidity without negatively affecting DS closure morbidity.

Autonomous Sensor System for Low-Capacity Wind Turbine Blade Vibration Measurement.

This paper presents the design, implementation, and validation of an on-blade sensor system for remote vibration measurement for low-capacity wind turbines. The autonomous sensor system was deployed on three wind turbines, with one of them operating in harsh weather conditions in the far south of Chile. The system recorded the acceleration response of the blades in the flapwise and edgewise directions, data that could be used for extracting the dynamic characteristics of the blades, information useful for damage diagnosis and prognosis. The proposed sensor system demonstrated reliable data acquisition and transmission from wind turbines in remote locations, proving the ability to create a fully autonomous system capable of recording data for monitoring and evaluating the state of health of wind turbine blades for extended periods without human intervention. The data collected by the sensor system presented in this study can serve as a foundation for developing vibration-based strategies for real-time structural health monitoring.

Integrating genome-wide association study and pathway analysis reveals physiological aspects affecting heifer early calving defined at different ages in Nelore cattle.

Heifer early calving (HC) plays a key role in beef cattle herds' economic sustainability and profitability by reducing production costs and generation intervals. However, the genetic basis of HC in Nelore heifers at different ages remains to be well understood. In this study, we aimed to perform a multi-trait weighted single-step genome-wide association (MT w-ssGWAS) to uncover the genetic mechanism involved in HC at 24 (HC24), 26 (HC26), 28 (HC28), and 30 (HC30) months of age in Nelore heifers. The MT w-ssGWAS pointed out four shared windows regions for HC24, HC26, HC28, and HC30 on BTA 5, 6, 14, and 16, explaining a larger proportion of genetic variation from 9.2% for HC30 to 10.6% for HC28. The shared regions harbored candidate genes related with the major gatekeeper for early puberty onset by controlling metabolic aspects related to homeostasis, reproductive, and growth (IGF1, PARPBP, PMCH, GNRHR, LYN, TMEM68, PLAG1, CHCHD7, KISS1, GOLT1A, and PPP1R15B). The MT w-ssGWAS and pathway analysis highlighted differences in physiological processes that support complex interactions between the gonadotropic axes, growth aspects, and sexual precocity in Nelore heifers, providing useful information for genetic improvement and management strategies.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

The Dorsolateral Prefrontal Cortex Presents Structural Variations Associated with Empathy and Emotion Regulation in Psychotherapists.

Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.

Patterns of Eating Associated with Sleep Characteristics: A Pilot Study among Individuals of Mexican Descent at the US-Mexico Border.

Introduction: Previous studies have linked sleep to risk of diabetes and obesity, at least partially via alterations in food intake. Diabetes and obesity are common among Hispanics/Latinos, and studies are needed to better clarify the role of sleep in health among this group. Utilizing the revised TFEQ-R-18, this study will examine whether eating behaviors such as cognitive restraint, emotional eating and uncontrolled eating are related to self-reported sleep experiences. Specifically, we hypothesized that poor eating habits would be associated with (1) more insomnia symptoms, (2) overall worse sleep quality, (3) increased daytime sleepiness, and (4) shorter sleep duration.Methods: Data were collected from N = 100 adults (age 18-60, 47% female) of Mexican descent in the city of Nogales, AZ (34% not born in the US). Surveys were presented in English or Spanish. Eating Patterns were assessed with the Three-Factor Eating Questionnaire (TFEQ), which resulted in a total score and subscales for "cognitive restraint," "uncontrolled eating," and "emotional eating." Insomnia was assessed with the use of the Insomnia Severity Index (ISI), Sleepiness with the use of the Epworth Sleepiness Scale (ESS), Sleep quality with the use of the Pittsburgh Sleep Quality Index (PSQI), and weekday and weekend sleep duration with the use of the Sleep Timing Questionnaire (STQ). Covariates included age, sex, Body Mass Index (BMI), education and immigrant status.Results: Overall TFEQ score (problematic eating) was positively associated with greater insomnia, poorer sleep quality, more sleepiness, and less weekend (but not weekday) sleep. Mean TFEQ score in the sample was 18.7 (range 0-51). In adjusted analyses, every point on the TFEQ was associated with 0.6 ISI points, 0.8 PSQI points, 0.5 ESS points, and 1.1 minutes of less weekend sleep duration. Regarding subscale scores, relationships were generally seenbetween sleep and emotional eating and unrestricted eating, and not cognitive restraint.Conclusions: Greater insomnia, poorer sleep quality, increased daytime sleepiness and decreased weekend sleep duration were associated with eating patterns at the US-Mexico border, particularly in the area of unrestricted eating and emotional eating. This suggests possible mechanisms linking sleep and obesity in Hispanic/Latinos.

Diagnostic Accuracy of Clinical Tests and Imaging Exams for Femoroacetabular Impingement: An Umbrella Review of Systematic Reviews.

OBJECTIVE: To synthesize available evidence about diagnostic accuracy of clinical tests and imaging examinations for femoroacetabular impingement (FAI) syndrome. DESIGN: Umbrella review. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Systematic reviews (SR) indexed in Embase, LIVIVO, PubMed, SCOPUS, the Cochrane Library, and Web of Science were searched in a 2-phase process. SR assessing diagnostic accuracy were considered eligible. RESULTS: From 1520 studies, 6 SR were included, which evaluated 24 primary studies related to FAI syndrome. Of these, 5 SR assessed clinical tests, and a substantial heterogeneity was found concerning reference standards adopted across primary studies, which included arthroscopy, clinical examination (associated or not with imaging exams), intra-articular injections, and open surgery. Most clinical tests presented higher values of sensitivity compared with specificity, although evidence was considered limited because the same primary studies were often included across SR. Nonetheless, evidence around the flexion adduction internal rotation (FADIR) test was considered stronger and its use as a screening tool was consistently supported. Only one SR assessed the accuracy of imaging examinations, which adopted open surgery as the sole reference standard. Most imaging exams presented considerably high values of sensitivity, although specificity values were notably lower. CONCLUSIONS: No robust recommendations can be provided for most clinical tests, although the FADIR test, in particular, was consistently supported as a screening tool. Moreover, although imaging examinations showed considerably high sensitivity values, evidence was considered sparse and further research is strongly recommended to validate its use as reference standards for diagnostic accuracy data.

Prioritizing nurturing care at the municipal and district level with the Brazilian Early Childhood Friendly Municipal Index (IMAPI).

The Brazilian Early Childhood Friendly Municipal Index (IMAPI) is a population-based approach to monitor the nurturing care environment for early childhood development (ECD) using routine information system data. It is unknown whether IMAPI can be applied to document metropolitan urban territorial differences in nurturing care environments. We used Brasilia, Brazil's capital with a large metropolitan population of 2,881,854 inhabitants divided into 31 districts, as a case study to examine whether disaggregation of nurturing care data can inform a more equitable prioritization for ECD in metropolitan areas. IMAPI scores were estimated at the municipal level (IMAPI-M, 31 indicators) and at the district level (IMAPI-D, 29 indicators). We developed a quantitative prioritization process for indicators in each IMAPI analysis, and those selected were jointly mapped in the socioecological model for the role of indicators in relation to the enabling environment for nurturing care. Out of 28 common nurturing care indicators across IMAPI analysis, only four were prioritized in both analyses: one from the Adequate nutrition, two from the Opportunities for early learning, and one from the Responsive caregiving domains. These four indicators were mapped as enabling policies, supportive services, and caregivers' capabilities (socioecological model) and Effort, Coverage, and Quality (indicator's role). In conclusion, the different levels of nurturing care data disaggregation in the IMAPI can better inform decision-making than each one individually, especially in metropolitan areas where municipalities and districts within metropolitan areas have relative decision-making autonomy.

Extending the integrate-and-fire model to account for metabolic dependencies.

It is widely accepted that the brain, like any other physical system, is subjected to physical constraints that restrict its operation. The brain's metabolic demands are particularly critical for proper neuronal function, but the impact of these constraints continues to remain poorly understood. Detailed single-neuron models are recently integrating metabolic constraints, but these models' computational resources make it challenging to explore the dynamics of extended neural networks, which are governed by such constraints. Thus, there is a need for a simplified neuron model that incorporates metabolic activity and allows us to explore the dynamics of neural networks. This work introduces an energy-dependent leaky integrate-and-fire (EDLIF) neuronal model extension to account for the effects of metabolic constraints on the single-neuron behavior. This simple, energy-dependent model could describe the relationship between the average firing rate and the Adenosine triphosphate (ATP) cost as well as replicate a neuron's behavior under a clinical setting such as amyotrophic lateral sclerosis (ALS). Additionally, EDLIF model showed better performance in predicting real spike trains - in the sense of spike coincidence measure - than the classical leaky integrate-and-fire (LIF) model. The simplicity of the energy-dependent model presented here makes it computationally efficient and, thus, suitable for studying the dynamics of large neural networks.

Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.

RATIONALE: Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors. OBJECTIVE: Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist. METHODS AND RESULTS: In recombinant cells, a mouse alpha-1A-AR with a 6-residue substitution in the third intracellular loop does not couple to Gq signaling. Here we studied a knockin mouse with this alpha-1A-AR mutation. Heart alpha-1A receptor levels and antagonist affinity in the knockin were identical to wild-type. In wild-type cardiac myocytes, the selective alpha-1A agonist A61603-stimulated phosphoinositide-phospholipase C and myocyte contraction. In myocytes with the alpha-1A knockin, both A61603 effects were absent, indicating that Gq coupling was absent. Surprisingly, A61603 activation of cardioprotective ERK (extracellular signal-regulated kinase) was markedly impaired in the KI mutant myocytes, and A61603 did not protect mutant myocytes from doxorubicin toxicity in vitro. Similarly, mice with the α1A KI mutation had increased mortality after transverse aortic constriction, and A61603 did not rescue cardiac function in mice with the Gq coupling-defective alpha-1A receptor. CONCLUSIONS: Gq coupling is required for cardioprotection by an alpha-1A-AR agonist. Gq signaling can be adaptive.

Perisynaptic astrocytes as a potential target for novel antidepressant drugs.

Emerging evidence suggests that dysfunctions in glutamatergic signaling are associated with the pathophysiology of depression. Several molecules that act on glutamate binding sites, so-called glutamatergic modulators, are rapid-acting antidepressants that stimulate synaptogenesis. Their antidepressant response involves the elevation of both extracellular glutamate and brain-derived neurotrophic factor (BDNF) levels, as well as the postsynaptic activation of the mammalian target of rapamycin complex 1. The mechanisms involved in the antidepressant outcomes of glutamatergic modulators, including ketamine, suggest that astrocytes must be considered a cellular target for developing rapid-acting antidepressants. It is well known that extracellular glutamate levels and glutamate intrasynaptic time-coursing are maintained by perisynaptic astrocytes, where inwardly rectifying potassium channels 4.1 (Kir4.1 channels) regulate both potassium and glutamate uptake. In addition, ketamine reduces membrane expression of Kir4.1 channels, which raises extracellular potassium and glutamate levels, increasing postsynaptic neural activities. Furthermore, inhibition of Kir4.1 channels stimulates BDNF expression in astrocytes, which may enhance synaptic connectivity. In this review, we discuss glutamatergic modulators' actions in regulating extracellular glutamate and BDNF levels, and reinforce the importance of perisynaptic astrocytes for the development of novel antidepressant drugs.

Morphoanatomical aspects of the starting material for the improvement of pineapple cryopreservation by the droplet-vitrification technique.

Cryopreservation of pineapple shoot tips has been established from various protocols, including droplet vitrification. Thus, this work aimed to evaluate the morphoanatomical conditions of the starting material over different times (30, 45 and 60 days) of culture before freezing and its correlation with the survival percentage of the cryopreserved shoot tips. Four accessions, Ananas comosus var. comosus (BGA-009); var. bracteatus (BGA-119); var. parguazensis (BGA-376), var. erectifolius (BGA-750) from the Pineapple Active Germplasm Bank (BGA Pineapple) and two hybrids from the Embrapa Genetic Breeding Program, FIB-ROX1 (var. bracteatus X var. erectifolius) and FIB-ROX2 ( var. erectifolius X var. bracteatus), recently introduced in the field from in vitro storage, were used. Histological sections before freezing and the percentages of survival after freezing were obtained taking into account the different times of cultivation of the donor plants. The results showed a significative interaction between genotypes (accessions and hybrids) and the culture period. The accessions BGA-009 and BGA-119 showed the highest survival rates, with 95% and 90% respectively for the 30-day culture time. Different results were obtained for each genotype, showing the need for improvements in the standardization of starting material, which would allow better repeatability of the protocol.

Reassessing the Use of Undecanoic Acid as a Therapeutic Strategy for Treating Fungal Infections.

Treating fungal infections is challenging and frequently requires long-term courses of antifungal drugs. Considering the limited number of existing antifungal drugs, it is crucial to evaluate the possibility of repositioning drugs with antifungal properties and to revisit older antifungals for applications in combined therapy, which could widen the range of therapeutic possibilities. Undecanoic acid is a saturated medium-chain fatty acid with known antifungal effects; however, its antifungal properties have not been extensively explored. Recent advances indicate that the toxic effect of undecanoic acid involves modulation of fungal metabolism through its effects on the expression of fungal genes that are critical for virulence. Additionally, undecanoic acid is suitable for chemical modification and might be useful in synergic therapies. This review highlights the use of undecanoic acid in antifungal treatments, reinforcing its known activity against dermatophytes. Specifically, in Trichophyton rubrum, against which the activity of undecanoic acid has been most widely studied, undecanoic acid elicits profound effects on pivotal processes in the cell wall, membrane assembly, lipid metabolism, pathogenesis, and even mRNA processing. Considering the known antifungal activities and associated mechanisms of undecanoic acid, its potential use in combination therapy, and the ability to modify the parent compound structure, undecanoic acid shows promise as a novel therapeutic against fungal infections.

Leishmania infantum in US-Born Dog.

Leishmaniasis is a vectorborne disease that can infect humans, dogs, and other mammals. We identified one of its causative agents, Leishmania infantum, in a dog born in California, USA, demonstrating potential for autochthonous infections in this country. Our finding bolsters the need for improved leishmaniasis screening practices in the United States.

The utility of pulmonary function testing in the preoperative risk stratification of patients undergoing transcatheter aortic valve replacement.

BACKGROUND: The role of pulmonary function testing (PFT) as a predictor of clinically relevant endpoints in transcatheter aortic valve replacement (TAVR) is unclear. OBJECTIVE: To determine the utility of PFT in the preoperative risk stratification of patients undergoing TAVR. METHODS: An evaluation of PFT (i.e., FEV1), arterial blood gases (i.e., PO2), the diagnosis of chronic obstructive lung disease (COPD) by the Global Initiative for COPD (GOLD), and the diagnosis of chronic lung disease (CLD) by the Society of Thoracic Surgeons (STS) was performed to determine whether a relationship exists among these parameters and clinically relevant outcomes, including all-cause 30-day and 1-year mortality. RESULTS: A total of 513 patients underwent TAVR between March 2013 and December 2016. Per STS criteria, 269/513 (52%) had CLD with a mean FEV1 of 55.4 ± 12%. Per GOLD criteria, 158/513 (30%) of patients had COPD with a mean FEV1/forced vital capacity of 61.8 ± 8.2%. The severity of CLD was affected by changes in ejection fraction, albumin, creatinine, and B-type natriuretic peptide levels (p = .009, p < .001, p < .001, and p < .001, respectively), whereas the severity of COPD was not affected by these same variables, (p = .302, .079, .137, and .102, respectively). An increased A-a gradient (p = .035), increased PCO2 (p = .016), and decreased PO2 (p = <.001) demonstrated increased risk of 30-day mortality. Neither classification (COPD or CLD), nor PFT changes, showed association with 30-day and 1-year mortality (p = NS). CONCLUSION: This study suggests that isolated abnormalities in spirometry are a poor indicator of clinically relevant outcomes in TAVR. When classified correctly, COPD does not predict clinically relevant postoperative outcomes.

Simultaneous Detection and Photocatalysis Performed on a 3D Graphene/ZnO Hybrid Platform.

The synergy between graphene foam (Gf) and ZnO nanoparticles (NPs) allows the detection of analytes at low conentrations, which can be subsequently photocatalyzed on the hybrid surface as well as in the liquid phase upon illumination with low-power UV-vis light-emitting diode (LED) lamps. Detection of methylene blue (MB) and bisphenol A (BPA) is monitored either by graphene-enhanced Raman scattering (GERS) or molecular doping/sensing upon analyte adsorption. Using GERS, we were able to detect concentrations as low as 0.3 ppm of MB, which remained adsorbed on the graphene surface after a photocatalytic conversion of 88% (total conversion). The photocatalysis performances of BPA and MB performed in the liquid phase were lower and corresponded to 73 and 33% as indicated by gas chromatography-mass spectrometry (GC/MS) and UV-vis, respectively. The kinetics of photocatalysis was fitted with a quasi-first-order reaction, and the apparent rate constant (kapp) was calculated according to the Langmuir-Hinshelwood model. The fastest kinetics was achieved with the hybrid platform named "Gf-ZnO400", which was thermally treated at high temperatures and with most of the Ni etched away. This is consistent with the excellent electronic interaction between ZnO and graphene foam as indicated by photoelectrochemistry analysis. We mainly employed Raman scattering and UV-vis spectroscopy analyses for detection and photocatalysis applications; however, we also used other complementary techniques such as focused ion-beam scanning electron microscopy (FIB-SEM), X-ray photoelectron spectroscopy (XPS), diffuse reflectance, GC/MS, and photoelectrochemistry to explore the synergetic behavior of these two nanomaterials. This work brings about new insights into the detection of analyte molecules followed by photocatalysis performed in the solid and liquid states.

Best match graphs and reconciliation of gene trees with species trees.

A wide variety of problems in computational biology, most notably the assessment of orthology, are solved with the help of reciprocal best matches. Using an evolutionary definition of best matches that captures the intuition behind the concept we clarify rigorously the relationships between reciprocal best matches, orthology, and evolutionary events under the assumption of duplication/loss scenarios. We show that the orthology graph is a subgraph of the reciprocal best match graph (RBMG). We furthermore give conditions under which an RBMG that is a cograph identifies the correct orthlogy relation. Using computer simulations we find that most false positive orthology assignments can be identified as so-called good quartets-and thus corrected-in the absence of horizontal transfer. Horizontal transfer, however, may introduce also false-negative orthology assignments.