How and why do species break a developmental trade-off? Elucidating the association of trichomes and stomata across species.

PREMISE: Previous studies have suggested a trade-off between trichome density (Dt) and stomatal density (Ds) due to shared cell precursors. We clarified how, when, and why this developmental trade-off may be overcome across species. METHODS: We derived equations to determine the developmental basis for Dt and Ds in trichome and stomatal indices (it and is) and the sizes of epidermal pavement cells (e), trichome bases (t), and stomata (s) and quantified the importance of these determinants of Dt and Ds for 78 California species. We compiled 17 previous studies of Dt-Ds relationships to determine the commonness of Dt-Ds associations. We modeled the consequences of different Dt-Ds associations for plant carbon balance. RESULTS: Our analyses showed that higher Dt was determined by higher it and lower e, and higher Ds by higher is and lower e. Across California species, positive Dt-Ds coordination arose due to it-is coordination and impacts of the variation in e. A Dt-Ds trade-off was found in only 30% of studies. Heuristic modeling showed that species sets would have the highest carbon balance with a positive or negative relationship or decoupling of Dt and Ds, depending on environmental conditions. CONCLUSIONS: Shared precursor cells of trichomes and stomata do not limit higher numbers of both cell types or drive a general Dt-Ds trade-off across species. This developmental flexibility across diverse species enables different Dt-Ds associations according to environmental pressures. Developmental trait analysis can clarify how contrasting trait associations would arise within and across species.

Automated Detection and Grading of Extraprostatic Extension of Prostate Cancer at MRI via Cascaded Deep Learning and Random Forest Classification.

RATIONALE AND OBJECTIVES: Extraprostatic extension (EPE) is well established as a significant predictor of prostate cancer aggression and recurrence. Accurate EPE assessment prior to radical prostatectomy can impact surgical approach. We aimed to utilize a deep learning-based AI workflow for automated EPE grading from prostate T2W MRI, ADC map, and High B DWI. MATERIAL AND METHODS: An expert genitourinary radiologist conducted prospective clinical assessments of MRI scans for 634 patients and assigned risk for EPE using a grading technique. The training set and held-out independent test set consisted of 507 patients and 127 patients, respectively. Existing deep-learning AI models for prostate organ and lesion segmentation were leveraged to extract area and distance features for random forest classification models. Model performance was evaluated using balanced accuracy, ROC AUCs for each EPE grade, as well as sensitivity, specificity, and accuracy compared to EPE on histopathology. RESULTS: A balanced accuracy score of .390 ± 0.078 was achieved using a lesion detection probability threshold of 0.45 and distance features. Using the test set, ROC AUCs for AI-assigned EPE grades 0-3 were 0.70, 0.65, 0.68, and 0.55 respectively. When using EPE≥ 1 as the threshold for positive EPE, the model achieved a sensitivity of 0.67, specificity of 0.73, and accuracy of 0.72 compared to radiologist sensitivity of 0.81, specificity of 0.62, and accuracy of 0.66 using histopathology as the ground truth. CONCLUSION: Our AI workflow for assigning imaging-based EPE grades achieves an accuracy for predicting histologic EPE approaching that of physicians. This automated workflow has the potential to enhance physician decision-making for assessing the risk of EPE in patients undergoing treatment for prostate cancer due to its consistency and automation.

Nurses Step Up to Address Climate Change and Health.

Opportunities exist to mitigate impacts.

Deep Learning-Based Detection and Classification of Bone Lesions on Staging Computed Tomography in Prostate Cancer: A Development Study.

RATIONALE AND OBJECTIVES: Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs. metastatic lesion classification on staging CTs and to compare its performance with radiologists. MATERIALS AND METHODS: This retrospective study developed two AI models using 297 staging CT scans (81 metastatic) with 4601 benign and 1911 metastatic lesions in PCa patients. Metastases were validated by follow-up scans, bone biopsy, or PET/CT. Segmentation AI (3DAISeg) was developed using the lesion contours delineated by a radiologist. 3DAISeg performance was evaluated with the Dice similarity coefficient, and classification AI (3DAIClass) performance on AI and radiologist contours was assessed with F1-score and accuracy. Training/validation/testing data partitions of 70:15:15 were used. A multi-reader study was performed with two junior and two senior radiologists within a subset of the testing dataset (n = 36). RESULTS: In 45 unseen staging CT scans (12 metastatic PCa) with 669 benign and 364 metastatic lesions, 3DAISeg detected 73.1% of metastatic (266/364) and 72.4% of benign lesions (484/669). Each scan averaged 12 extra segmentations (range: 1-31). All metastatic scans had at least one detected metastatic lesion, achieving a 100% patient-level detection. The mean Dice score for 3DAISeg was 0.53 (median: 0.59, range: 0-0.87). The F1 for 3DAIClass was 94.8% (radiologist contours) and 92.4% (3DAISeg contours), with a median false positive of 0 (range: 0-3). Using radiologist contours, 3DAIClass had PPV and NPV rates comparable to junior and senior radiologists: PPV (semi-automated approach AI 40.0% vs. Juniors 32.0% vs. Seniors 50.0%) and NPV (AI 96.2% vs. Juniors 95.7% vs. Seniors 91.9%). When using 3DAISeg, 3DAIClass mimicked junior radiologists in PPV (pure-AI 20.0% vs. Juniors 32.0% vs. Seniors 50.0%) but surpassed seniors in NPV (pure-AI 93.8% vs. Juniors 95.7% vs. Seniors 91.9%). CONCLUSION: Our lesion detection and classification AI model performs on par with junior and senior radiologists in discerning benign and metastatic lesions on staging CTs obtained for PCa.

Supporting Biomedical Research Training for Historically Underrepresented Undergraduates Using Interprofessional, Nonformal Education Structures.

Research experience provides critical training for new biomedical research scientists. Students from underrepresented populations studying science, technology, engineering, and mathematics (STEM) are increasingly recruited into research pathways to diversify STEM fields. However, support structures outside of research settings designed to help these students navigate biomedical research pathways are not always available; nor are program support components outside the context of laboratory technical skills training and formal mentorship well understood. This study leveraged a multi-institutional research training program, Enhancing Cross-Disciplinary Infrastructure and Training at Oregon (EXITO), to explore how nine institutions designed a new curricular structure (Enrichment) to meet a common goal of enhancing undergraduate research training and student success. EXITO undergraduates participated in a comprehensive, 3-year research training program with the Enrichment component offered across nine sites: three universities and six community colleges, highly diverse in size, demographics, and location. Sites' approaches to supporting students in the training program were studied over a 30-month period. All sites independently created their own nonformal curricular structures, implemented interprofessionally via facilitated peer groups. Site data describing design and implementation were thematically coded to identify essential programmatic components across sites, with student feedback used to triangulate findings. Enrichment offered students time to critically reflect on their interests, experiences, and identities in research; network with peers and professionals; and support negotiation of hidden and implicit curricula. Students reported the low-pressure setting and student-centered curriculum balanced the high demands associated with academics and research. Core curricular themes described Enrichment as fostering a sense of community among students, exposing students to career paths and skills, and supporting development of students' professional identities. The non-formal, interprofessional curricula enabled students to model diverse biomedical identities and pathways for each other while informing institutional structures to improve diverse undergraduate students' success in academia and research.

Genetic and morphological diversity of mouse lemurs (Microcebus spp.) in northern Madagascar: The discovery of a putative new species?

Tropical forests harbor extremely high levels of biological diversity and are quickly disappearing. Despite the increasingly recognized high rate of habitat loss, it is expected that new species will be discovered as more effort is put to document tropical biodiversity. Exploring under-studied regions is particularly urgent if we consider the rapid changes in habitat due to anthropogenic activities. Madagascar is known for its extraordinary biological diversity and endemicity. It is also threatened by habitat loss and fragmentation. It holds more than 100 endemic primate species (lemurs). Among these, Microcebus (mouse lemurs) is one of the more diverse genera. We sampled mouse lemurs from several sites across northern Madagascar, including forests never sampled before. We obtained morphological data from 99 Microcebus individuals; we extracted DNA from tissue samples of 42 individuals and amplified two mitochondrial loci (cytb and cox2) commonly used for species identification. Our findings update the distribution of three species (Microcebus tavaratra, Microcebus arnholdi, and Microcebus mamiratra), including a major increase in the distribution area of M. arnholdi. We also report the discovery of a new Microcebus lineage genetically related to M. arnholdi. Several complementary approaches suggest that the newly identified Microcebus lineage might correspond to a new putative species, to be confirmed or rejected with additional data. In addition, morphological analyses showed (a) clear phenotypic differences between M. tavaratra and M. arnholdi, but no clear differences between the new Microcebus lineage and the sister species M. arnholdi; and (b) a significant correlation between climatic variables and morphology, suggesting a possible relationship between species identity, morphology, and environment. By integrating morphological, climatic, genetic, and spatial data of two northern Microcebus species, we show that the spatial distribution of forest-dwelling species may be used as a proxy to reconstruct the past spatial changes in forest cover and vegetation type.

Identifying Charge Transfer Mechanisms across Semiconductor Heterostructures via Surface Dipole Modulation and Multiscale Modeling.

The design and fabrication of stable and efficient photoelectrochemical devices requires the use of multifunctional structures with complex heterojunctions composed of semiconducting, protecting, and catalytic layers. Understanding charge transport across such devices is challenging due to the interplay of bulk and interfacial properties. In this work, we analyze hole transfer across n-Si(111)- R|TiO2 photoanodes where - R is a series of mixed aryl/methyl monolayers containing an increasing number of methoxy units (mono, di, and tri). In the dimethoxy case, triethylene glycol units were also appended to substantially enhance the dipolar character of the surface. We find that hole transport is limited at the n-Si(111)- R|TiO2 interface and occurs by two processes- thermionic emission and/or intraband tunneling-where the interplay between them is regulated by the interfacial molecular dipole. This was determined by characterizing the photoanode experimentally (X-ray photoelectron spectroscopy, voltammetry, impedance) with increasingly thick TiO2 films and complementing the characterization with a multiscale computational approach (first-principles density functional theory (DFT) and finite-element device modeling). The tested theoretical model that successfully distinguished thermionic emission and intraband tunneling was then used to predict the effect of solution potential on charge transport. This prediction was then experimentally validated using a series of nonaqueous redox couples (ferrocence derivatives spanning 800 mV). As a result, this work provides a fundamental understanding of charge transport across TiO2-protected electrodes, a widely used semiconductor passivation scheme, and demonstrates the predictive capability of the combined DFT/device-modeling approach.

La psicopatía: una revisión bibliográfica y bibliométrica / A psicopatia: uma revisão bibliográfica e bibliométrica / Psychopathy: a bibliographic and bibliometric review

La psicopatía es un trastorno de personalidad caracterizado tanto por la falta de afecto, remordimientos y empatía como por seducción, manipulación y utilización del otro. Nuestro objetivo es realizar una revisión bibliométrica sobre los artículos de revistas científicas recogidos en la plataforma de datos PsycINFO, hasta febrero del 2013, en base a los descriptores "Psychopathy" y "Antisocial Personality Disorder". Los resultados ofrecen información sobre: la evolución y tratamiento de ambos términos, la productividad anual, lugar de publicación, revistas científicas, autores más prolíficos, conceptos clave más utilizados, así como se concretizan los esfuerzos en muestras penitenciarias, mediante la realización de un análisis del contenido de los principales autores y la intervención en la psicopatía, lo que nos permite observar la necesidad de aumentar los criterios de diagnóstico de la psicopatía, aludiendo a la perspectiva de género, al contexto social, y a las características de personalidad.

A psicopatía é um transtorno de personalidade caracterizado tanto por falta de afeto, remorsos e empatía como sedução, manipulação e uso do outro. Nosso objetivo é realizar uma revisão bibliométrica de artigos em revistas científicas recolhidas no banco de dados PsycINFO até fevereiro de 2013, a partir dos descritores "Psicopatia" e "Transtorno da Personalidade Anti-Social". Os resultados fornecem informações sobre: o desenvolvimento e tratamento de ambos os termos, a produtividade anual, local de publicação, revistas científicas, autores mais produtivos, conceitos-chave mais utilizados, assim como os esforços em amostras penitenciárias realizando uma análise de conteúdo dos principais autores e a intervenção em psicopatia, permitindo mostrar a necessidade de incrementar os critérios de diagnóstico de psicopatia, em referência ao gênero, ao contexto social e à caracteristicas de personalidade.

Psychopathy is a personality disorder characterized both by a lack of affection, remorse and empathy, as by the ability to seduce, manipulate and use other people. Our goal is to perform a bibliometric review of articles published in scientific journals listed in the PsycINFO database by February 2013, using the keywords "Psychopathy" and "Antisocial Personality Disorder". The results provide information on the evolution and treatment of both terms; annual productivity; place of publication; recurrent scientific journals; most prolific authors; most popular keywords; as well as efforts undertaken in prison samples. Content analysis of the main authors show the need to increase diagnostic criteria for psychopathy according to gender, social context and personality traits.

La psicopatía: Una revisión bibliográfica y bibliométrica / A psicopatia: uma revisão bibliográfica e bibliométrica / Psychopathy: a Bibliographic and Bibliometric Review

La psicopatía es un trastorno de personalidad caracterizado tanto por la falta de afecto, remordimientos y empatía como por seducción, manipulación y utilización del otro. Nuestro objetivo es realizar una revisión bibliométrica sobre los artículos de revistas científicas recogidos en la plataforma de datos PsycINFO, hasta febrero del 2013, en base a los descriptores "Psychopathy" y "Antisocial Personality Disorder". Los resultados ofrecen información sobre: la evolución y tratamiento de ambos términos, la productividad anual, lugar de publicación, revistas científicas, autores más prolíficos, conceptos clave más utilizados, así como se concretizan los esfuerzos en muestras penitenciarias, mediante la realización de un análisis del contenido de los principales autores y la intervención en la psicopatía, lo que nos permite observar la necesidad de aumentar los criterios de diagnóstico de la psicopatía, aludiendo a la perspectiva de género, al contexto social, y a las características de personalidad(AU)

A psicopatía é um transtorno de personalidade caracterizado tanto por falta de afeto, remorsos e empatía como sedução, manipulação e uso do outro. Nosso objetivo é realizar uma revisão bibliométrica de artigos em revistas científicas recolhidas no banco de dados PsycINFO até fevereiro de 2013, a partir dos descritores "Psicopatia" e "Transtorno da Personalidade Anti-Social". Os resultados fornecem informações sobre: o desenvolvimento e tratamento de ambos os termos, a produtividade anual, local de publicação, revistas científicas, autores mais produtivos, conceitos-chave mais utilizados, assim como os esforços em amostras penitenciárias realizando uma análise de conteúdo dos principais autores e a intervenção em psicopatia, permitindo mostrar a necessidade de incrementar os critérios de diagnóstico de psicopatia, em referência ao gênero, ao contexto social e à caracteristicas de personalidade(AU)

Psychopathy is a personality disorder characterized both by a lack of affection, remorse and empathy, as by the ability to seduce, manipulate and use other people. Our goal is to perform a bibliometric review of articles published in scientific journals listed in the PsycINFO database by February 2013, using the keywords "Psychopathy" and "Antisocial Personality Disorder". The results provide information on the evolution and treatment of both terms; annual productivity; place of publication; recurrent scientific journals; most prolific authors; most popular keywords; as well as efforts undertaken in prison samples. Content analysis of the main authors show the need to increase diagnostic criteria for psychopathy according to gender, social context and personality traits(AU)

Towards the determination of Mytilus edulis food preferences using the dynamic energy budget (DEB) theory.

The blue mussel, Mytilus edulis, is a commercially important species, with production based on both fisheries and aquaculture. Dynamic Energy Budget (DEB) models have been extensively applied to study its energetics but such applications require a deep understanding of its nutrition, from filtration to assimilation. Being filter feeders, mussels show multiple responses to temporal fluctuations in their food and environment, raising questions that can be investigated by modeling. To provide a better insight into mussel-environment interactions, an experiment was conducted in one of the main French growing zones (Utah Beach, Normandy). Mussel growth was monitored monthly for 18 months, with a large number of environmental descriptors measured in parallel. Food proxies such as chlorophyll a, particulate organic carbon and phytoplankton were also sampled, in addition to non-nutritious particles. High-frequency physical data recording (e.g., water temperature, immersion duration) completed the habitat description. Measures revealed an increase in dry flesh mass during the first year, followed by a high mass loss, which could not be completely explained by the DEB model using raw external signals. We propose two methods that reconstruct food from shell length and dry flesh mass variations. The former depends on the inversion of the growth equation while the latter is based on iterative simulations. Assemblages of food proxies are then related to reconstructed food input, with a special focus on plankton species. A characteristic contribution is attributed to these sources to estimate nutritional values for mussels. M. edulis shows no preference between most plankton life history traits. Selection is based on the size of the ingested particles, which is modified by the volume and social behavior of plankton species. This finding reveals the importance of diet diversity and both passive and active selections, and confirms the need to adjust DEB models to different populations and sites.

Monitoring mindfulness practice quality: an important consideration in mindfulness practice.

Mindfulness-Based Stress Reduction (MBSR) is an experientially based group intervention empirically supported to reduce psychological symptomology. Although MBSR has shown to be an effective intervention, little is known about which facets of the intervention are important in producing positive outcomes. This study tested several aspects of mindfulness practice (total practice duration, practice frequency and practice quality) with the primary focus being on validating (i.e., predictive and convergent validity) a new measure of mindfulness practice quality (PQ-M). The PQ-M fit a two-factor solution via a Maximum Likelihood Exploratory Factor Analysis (n=99). Using longitudinal multilevel modeling on a smaller subsample (n=19), preliminary support was found for changes in practice quality over the course of the MBSR intervention. Further, change in practice quality was associated with improvements in psychological symptoms. While this study was exploratory, these findings suggest that practice quality is a relevant factor to promote positive outcomes and may guide mindfulness instructors in providing highly tailored interventions.

A vector-based minigene vaccine approach results in strong induction of T-cell responses specific of hepatitis C virus.

Multiepitope-based vaccines against hepatitis C virus (HCV) were designed in the form of three minigenes encompassing four domains of the NS3, NS4 and NS5B proteins that contain multiple class I/II restricted epitopes. The polyEp-WT minigene encodes all four domains in fusion, the polyEp-C minigene encodes the same fusion but optimised for mammalian translation and the polyEp-E3 minigene has an additional endoplasmic reticulum targeting sequence. Whereas the minigenes vectorised by DNA were poorly immunogenic, adenovirus vectorisation induced strong and broader IFNgamma-ELISpot and CTL responses in HLA-A2 transgenic mice. In addition, polyEp-WT and polyEp-E3 responses were found cross-reactive in a recombinant Listeria-NS3-based surrogate challenge. This study illustrates the potency of vectorised minigenes in the field of HCV vaccine development.

Plasmid DNA delivery by D-alanine-deficient Listeria monocytogenes.

Optimal DNA vaccine efficacy requires circumventing several obstacles, including low immunogenicity, a need for adjuvant, and the costs of purifying injection grade plasmid DNA. Bacterial delivery of plasmid DNA may provide an efficient and low-cost alternative to plasmid purification and injection. Also, the bacterial vector may exhibit potential as an immune adjuvant in vivo. Thus, we elected to examine the use of cell-wall-deficient Listeria monocytogenes as a DNA delivery vehicle in vitro. First, the D-alanine-deficient (Deltadal-dat) L. monocytogenes strain DP-L3506, which undergoes autolysis inside eukaryotic host cells in the absence of D-alanine, was transformed with a plasmid encoding green fluorescent protein (GFP) under control of the CMV promoter (pAM-EGFP). Then COS-7 and MC57G cell lines were infected with the transformed DP-L3506 at various multiplicities of infection (MOI) in the presence or absence of D-alanine. Subsequent GFP expression was observed in both cell lines by 24 h post-infection with DP-L3506(pAM-EGFP). Notably, no GFP positive cells were observed when D-alanine was omitted. Although transfection efficiency initially increased as a result of D-alanine supplementation, high concentration or long-term supplementation led to sustained bacterial growth that killed the infected host cells, resulting in fewer GFP-expressing cells. Thus, efficient DNA delivery by transformed bacteria must balance bacterial invasion and survival with target cell health and survival.

DNA vaccination protects mice against challenge with Listeria monocytogenes expressing the hepatitis C virus NS3 protein.

The goal of this study was to develop a new surrogate challenge model for use in evaluating protective cell-mediated immune responses against hepatitis C virus (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which express HCV antigens provides novel tools with which to assay such in vivo protection, as expression of immunity against this hepatotropic bacterial pathogen is dependent on antigen-specific CD8(+) T lymphocytes. A plasmid DNA vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T cells following vaccination of BALB/c mice. These immunized mice also exhibited specific in vivo protection against subsequent challenge with a recombinant L. monocytogenes strain (TC-LNS3) expressing the NS3 protein. Notably, sublethal infection of naive mice with strain TC-LNS3 induced similar NS3-specific T-cell responses. These findings suggest that recombinant strains of L. monocytogenes expressing HCV antigens should prove useful for evaluating, or even inducing, protective immune responses against HCV antigens.

Gene transfer to fish cells by attenuated invasive Escherichia coli.

Genetic immunization has proved effective in a number of applications including vaccination of rainbow trout (Oncorhynchus mykiss) against the fish pathogen infectious hematopoietic necrosis virus. However, injection vaccines, especially in aquaculture, are not as desirable as oral or immersion dosing schemes. In this report we present evidence that attenuated invasive Escherichia coli can infect and deliver plasmid DNA to salmonid fish cells.