Understanding social situations: study protocol for a randomized controlled trial evaluating a novel social cognitive training versus modified problem-solving training for people with psychosis.

Background: Psychotic spectrum disorders (PSD) are associated with poor social function. In this study, we investigate which of two different types of 2-month long training courses is more effective in improving day-to-day interactions and quality of life. Methods/design: Participants with psychotic spectrum disorders will be randomly assigned to one of two training courses. Social functioning, everyday activities, social cognition and symptoms will be assessed at multiple timepoints, including baseline, treatment midpoint, end of treatment and 2-month follow-up. One training focuses on how to make good judgments about what other people may be thinking or feeling in social situations, and why people might act in certain ways in different situations. The other training focuses on different strategies for handling everyday problems and stressors. Both trainings are done in one-on-one sessions with a research staff member. There will be 16-20 training sessions, each about 45-60 minutes long. The investigators will ask participants to attend 2 training sessions per week, so the total training time should be about 2 months. Clinical Trials Registration: PROSPERO, identifier NCT04557124.

Determining the legality of newly described CITES-listed species in the horticulture trade of tropical pitcher plants (Nepenthes).

Due diligence is a fundamental component of ensuring a sustainable and legal wildlife trade that is also supportive of the livelihoods and businesses that depend on the trade. This is particularly true with species listed on the Convention on International Trade in Endangered Species (CITES) that are considered threatened or may become threatened by trade. Undertaking due diligence exercises requires access to information on which to base such decisions; however, the extent to which information is available is unclear. We used the trade in tropical pitcher plants (Nepenthes) for horticultural purposes as a case study to determine the extent to which information is available. A systematic survey of online trade was conducted for species described from 1996 to 2016. For the species found in trade, these were cross-referenced with the CITES trade database, and inquiries were made to the relevant CITES Management Authorities and National Focal Points Access and Benefit Sharing (ABS). Of 83 newly described species, 61% were offered for sale online in 2018. Despite all Nepenthes species being listed on CITES, only 23% (n = 19) of the species being sold online were reported in trade on the CITES Trade Database, and only 3 were from the countries of origin. Thirty-two of these species had no international trade recorded according to the database. Management authorities of CITES for the countries of origin confirmed trade had been permitted for 5 of 32 species. Lack of CITES records may be explained by trade under "Nepenthes spp." or as exempt parts and derivatives. However, permits to collect and commercialize are likely to be required as part of the Nagoya Protocol on ABS from the Convention on Biological Diversity. The ABS National Focal Points were contacted to determine whether collection or commercialization permits had been issued for the remaining species. Only 2 of 7 focal points replied, and both stated no permits had been issued. Lack of traceability information or response related to the issuance of collection and commercialization permits is concerning and hinders the due diligence of businesses and consumers wanting to ensure their trade is legal, sustainable, and ethical.

Definición de la legalidad de especies recién catalogadas en CITES en la horticultura comercial de plantas de jarra tropicales (Nepenthes) Resumen La diligencia debida es un componente fundamental para garantizar un comercio de vida silvestre legal y sostenible que también apoye los medios de subsistencia y las empresas que dependen del comercio. Esto es especialmente cierto en el caso de las especies incluidas en la Convención sobre el Comercio Internacional de Especies Amenazadas de Fauna y Flora Silvestres (CITES) que se consideran amenazadas o pueden verse amenazadas por el comercio. La realización de ejercicios de diligencia debida requiere acceso a información con la cual fundamentar tales decisiones; sin embargo, no está claro hasta qué punto se dispone de información. Usamos como estudio de caso el comercio de plantas de jarra tropicales (Nepenthes) con fines hortícolas para determinar cuánta información hay disponible. Realizamos un estudio sistemático del comercio en línea de las especies descritas entre 1996 y 2016. Para las especies encontradas en el comercio, hicimos referencias cruzadas con la base de datos de comercio CITES y consultamos a las Autoridades Administrativas CITES pertinentes y a los Puntos Focales Nacionales de Acceso y Distribución de Beneficios. De las 83 especies con descripción reciente, el 61% se pusieron a la venta en línea en 2018. A pesar de que todas las especies de Nepenthes están catalogadas en CITES, sólo el 23% (n = 19) de las especies que se vendían en línea figuraban en la base de datos sobre comercio CITES, y sólo tres procedían de los países de origen. Treinta y dos de estas especies no tenían comercio internacional registrado según la base de datos. Las autoridades de gestión de CITES de los países de origen confirmaron que se permitió el comercio de 5 de las 32 especies. La falta de registros CITES puede explicarse por el comercio de «Nepenthes spp¼ o como partes y derivados exentos. Sin embargo, es probable que se exijan permisos de recolección y comercialización en el marco del Protocolo de Nagoya sobre Acceso y Participación en los Beneficios (APB) del Convenio sobre la Diversidad Biológica. Contactamos a los Puntos Focales Nacionales de APB para determinar si se habían expedido permisos de recolección o comercialización para las especies restantes. Sólo dos de los siete puntos focales respondieron y ambos afirmaron que no se había expedido ningún permiso. La falta de información de rastreo o de respuesta en relación con la expedición de permisos de recolección y comercialización es preocupante y obstaculiza la diligencia debida de las empresas y los consumidores que desean asegurarse de que su comercio es legal, sostenible y ético.

Navigating ethical challenges in online wildlife trade research.

The surge in internet accessibility has transformed wildlife trade by facilitating the acquisition of wildlife through online platforms. This scenario presents unique ethical challenges for researchers, as traditional ethical frameworks for in-person research cannot be readily applied to the online realm. Currently, there is a lack of clearly defined guidelines for appropriate ethical procedures when conducting online wildlife trade (OWT) research. In response to this, we consulted the scientific literature on ethical considerations in online research and examined existing guidelines established by professional societies and ethical boards. Based on these documents, we present a set of recommendations that can inform the development of ethically responsible OWT research. Key ethical challenges in designing and executing OWT research include the violation of privacy rights, defining subjects and illegality, and the risk of misinterpretation or posing risks to participants when sharing data. Potential solutions include considering participants' expectations of privacy, defining when participants are authors versus subjects, understanding the legal and cultural context, minimizing data collection, ensuring anonymization, and removing metadata. Best practices also involve being culturally sensitive when analyzing and reporting findings. Adhering to these guidelines can help mitigate potential pitfalls and provides valuable insights to editors, researchers, and ethical review boards, enabling them to conduct scientifically rigorous and ethically responsible OWT research to advance this growing field.

Los retos éticos de la investigación del mercado virtual de fauna Resumen El incremento en el acceso al internet ha transformado el mercado de fauna ya que facilita la adquisición de ejemplares a través de plataformas virtuales. Este escenario representa un reto ético único para los investigadores, pues los marcos éticos tradicionales para la investigación en persona no pueden aplicarse fácilmente en línea. Actualmente no hay lineamientos claros para el procedimiento ético apropiado cuando se investiga el mercado virtual de fauna (MVF). Como respuesta, consultamos la literatura científica sobre las consideraciones éticas en la investigación en línea y analizamos los lineamientos existentes establecidos por las sociedades profesionales y los comités éticos. Con base en estos documentos, presentamos un conjunto de recomendaciones que pueden guiar el desarrollo de la investigación sobre el MVF con responsabilidad ética. Los retos más importantes para el diseño y ejecución de la investigación sobre el MVF incluyen la violación del derecho a la privacidad, la definición de los sujetos y la ilegalidad y el riesgo de malinterpretar o presentar riesgos para los participantes cuando se comparten datos. Las soluciones potenciales incluyen considerar las expectativas de privacidad de los participantes, definir cuándo los participantes son autores y cuándo sujetos, entender el contexto legal y cultural, minimizar la recolección de datos, asegurar el anonimato y eliminar los metadatos. Las mejores prácticas también involucran la sensibilidad cultural cuando se analizan y reportan los resultados. La adhesión a estos lineamientos puede mitigar los posibles retos y proporcionar información valiosa para los editores, investigadores y comités de ética, permitiéndoles realizar una investigación con rigor científico y responsabilidad ética sobre el MVF para avanzar en este campo creciente de investigación.

Successful Extracorporeal Cardiopulmonary Resuscitation Despite Aortic Occlusion.

We present the case of a 62-year-old man with severe coronary artery disease who presented to the hospital in refractory ventricular fibrillation cardiac arrest. He showed signs of life despite prolonged resuscitation. We thus decided to initiate extracorporeal cardiopulmonary resuscitation (ECPR). The patient had a known total occlusion of his infrarenal aorta that had been surgically bypassed with a bifemoral-axillary graft. We successfully initiated ECPR via the surgical graft, establishing blood flow to the central circulation through the axillary artery in a peripheral configuration while ensuring blood flow to the left leg via the femoral-femoral graft. The patient was extubated neurologically intact the following day and subsequently underwent coronary artery bypass graft surgery while on extracorporeal membrane oxygenation (ECMO) support. He was subsequently weaned off inotropic support and decannulated from ECMO. He was discharged home neurologically intact and independent in his activities of daily living. This case demonstrates that cannulation for ECPR via a surgical vascular graft is possible and that a total occlusion of the infrarenal aorta in the presence of a surgical bypass is not an absolute contraindication to ECMO.

The UT Health Living Room: Expanding the Psychiatric Crisis Continuum of Care.

Traditional forms of psychiatric crisis treatment increasingly are being buttressed by services along the Psychiatric Crisis Continuum of Care, such as short-term crisis stabilization services and peer crisis services. The UT Health Living Room (LR) is an outpatient crisis counseling service that adds three promising elements to the Continuum: (1) it integrates outpatient treatment plans into crisis counseling, (2) provides care in a space and with staff who are familiar to patients, and (3) provides training in evidence-based crisis intervention. We examined two-year LR feasibility and outcome data. Mixed-method analyses used longitudinal clinic data and patient self-report measures. Results provide initial support for the feasibility, cost effectiveness and clinical effectiveness of the LR. Limitations include non-blinded ratings, limited experimental control, and simple cost-effectiveness methodology. The UT Living Room is feasible and offers novel elements to help patients in community clinics address emotional crises.

Automated Image Analysis for Detection of Coccidia in Poultry.

Coccidiosis, caused by the protozoan Eimeria sp., is one of the most common and costly diseases impacting the poultry industry. To establish effective control measures, it is essential to identify these protozoa. Typical methods for identifying and determining the severity of the protozoal infection include intestinal lesion scoring or enumeration of the protozoal oocysts in fecal samples. Standard analysis methods require highly skilled technicians or veterinarians to manually identify and manually enumerate these protozoal parasites. This process is labor intensive, time-consuming, and susceptible to human error. None of the current methods available, including molecular flow cytometry or even digital image analysis, can determine if an oocyst is sporulated or not. Oocysts are not infectious until they sporulate. The goal of this study was to design an automated model using Artificial Intelligence (AI) to expedite the process of enumeration, improve the efficiency and accuracy of the species identification, and determine the ability of the oocysts to infect. To this end, we trained and evaluated computer vision models based on the Mask RCNN neural network architecture. A model was trained to detect and differentiate three species and to determine sporulation for each (totaling six detection groups). This model achieved a mean relative percentage difference (RPD) of 5.64%, representing a slight overcount compared to manual counts, averaging across all groups. The mean RPD for each group individually fell within a range from -33.37% to 52.72%. These results demonstrate that these models were speedy and had high agreement with manual counts, with minimal processing of field-quality samples. These models also could differentiate the sporulation status of the oocysts, providing critical diagnostic information for potential field applications.

A missense SNP in the tumor suppressor SETD2 reduces H3K36me3 and mitotic spindle integrity in Drosophila.

Mutations in SETD2 are among the most prevalent drivers of renal cell carcinoma (RCC). We identified a novel single nucleotide polymorphism (SNP) in SETD2, E902Q, within a subset of RCC patients, which manifests as both an inherited or tumor-associated somatic mutation. To determine if the SNP is biologically functional, we used CRISPR-based genome editing to generate the orthologous mutation within the Drosophila melanogaster Set2 gene. In Drosophila, the homologous amino acid substitution, E741Q, reduces H3K36me3 levels comparable to Set2 knockdown, and this loss is rescued by reintroduction of a wild-type Set2 transgene. We similarly uncovered significant defects in spindle morphogenesis, consistent with the established role of SETD2 in methylating α-Tubulin during mitosis to regulate microtubule dynamics and maintain genome stability. These data indicate the Set2 E741Q SNP affects both histone methylation and spindle integrity. Moreover, this work further suggests the SETD2 E902Q SNP may hold clinical relevance.

Understanding and tackling the reproducibility crisis - Why we need to study scientists' trust in data.

In the life sciences, there is an ongoing discussion about a perceived 'reproducibility crisis'. However, it remains unclear to which extent the perceived lack of reproducibility is the consequence of issues that can be tackled and to which extent it may be the consequence of unrealistic expectations of the technical level of reproducibility. Large-scale, multi-institutional experimental replication studies are very cost- and time-intensive. This Perspective suggests an alternative, complementary approach: meta-research using sociological and philosophical methodologies to examine researcher trust in data. An improved understanding of the criteria used by researchers to judge data reliability will provide crucial, initial evidence on the actual scale of the reproducibility crisis and on measures to tackle it.

Efficacy of social cognition and interaction training in outpatients with schizophrenia spectrum disorders: randomized controlled trial.

Given the relationship between social cognition and functional outcome in schizophrenia, a number of social cognitive interventions have been developed, including Social Cognition Interaction Training (SCIT), a group-based, comprehensive, manualized intervention. In the current trial, we examined SCIT efficacy as well as potential moderators of treatment effects. Fifty-one outpatients were randomized to SCIT or a wait-list-control (WLC), with assessments of social cognition, neurocognition, self-report, symptoms, and functioning conducted at baseline and end of the active phase. Relative to WLC, we did not find significant improvements for SCIT on neurocognition, social cognition, self-report, or symptoms, though there was a trend-level, medium effect favoring the SCIT condition on interpersonal and instrumental role function. Post-hoc analyses indicated that baseline neurocognition did not impact degree of social cognitive or functional change. Shorter duration of illness was significantly associated with better post-training neurocognition and self-esteem and, at trend-level with better symptoms and social functioning. We discuss the importance of outcome measure selection and the need for continued evaluation of potential treatment moderators in order to better match people to existing treatments. Clinical trial registration: Clinicaltrials.gov, Identifier NCT00587561.

A randomized controlled trial of social cognition and interaction training for persons with first episode psychosis in Hong Kong.

Social cognitive impairment is a core limiting factor of functional recovery among persons with first episode psychosis (FEP). Social Cognition and Interaction Training (SCIT) is a group-based, manualized training with demonstrated evidence in improving social cognitive performance among people with schizophrenia. However, there are few studies on the effect of SCIT for people with FEP and for people in non-Western societies. This study evaluated the feasibility, acceptability and initial effectiveness of the locally-adapted SCIT in improving social cognitive functioning in Chinese people with FEP. The SCIT was delivered two sessions per week over a 10-weeks period, each session lasted for 60-90 min. A total of 72 subjects with FEP were recruited from an outpatient clinic and randomized to conventional rehabilitation ("Rehab") and experimental ("SCIT and Rehab") groups. Primary outcome measures included four social cognitive domains including emotion perception, theory-of-mind, attributional bias and jumping-to-conclusion, and secondary measures included neurocognition, social competence and quality of life. Participants were assessed at baseline, post-treatment, and 3-months post-treatment. Repeated measures ANCOVAs, with baseline scores as covariates, were used to compare the group differences in various outcomes across time. The results showed that the SCIT was well-accepted, with a satisfactory completion rate and subjective ratings of relevance in the experimental group. Moreover, treatment completers (n = 28) showed evidence of an advantage, over conventional group (n = 31), in reduced attributional bias and jumping-to-conclusions at treatment completion, lending initial support for the SCIT in Chinese people with FEP. Future research should address the limitations of this study, using more refined outcome measurements and higher treatment intensity of the SCIT.

Understanding the drivers of expert opinion when classifying species as extinct.

The criteria as laid out by the International Union for the Conservation of Nature (IUCN) Red List are the gold standard by which the extinction risk of a species is assessed and where appropriate biological extinctions are declared. However, unlike all other categories, the category of extinct lacks a quantitative framework for assigning this category. Given its subjective nature, we surveyed expert assessors working on a diversity of taxa to explore the attributes they used to declare a species extinct. Using a choice experiment approach, we surveyed 674 experts from the IUCN Species Survival Commission specialist groups and taskforces. Data availability, time from the last sighting, detectability, habitat availability, and population decline were all important attributes favored by assessors when inferring extinction. Respondents with red-listing experience assigned more importance to the attributes data availability, time from the last sighting, and detectability when considering a species extinction, whereas those respondents working with well-known taxa gave more importance to the time from the last sighting. Respondents with no red-listing experience and those working with more well-known taxa (i.e., mammals and birds) were overall less likely to consider species extinct. Our findings on the importance assessors place on attributes used to declare a species extinct provide a basis for informing the development of specific criteria for more accurately assessing species extinctions.

Los criterios establecidos por la Unión Internacional para la Conservación de la Naturaleza (UICN) son la regla de oro con la cual se evalúa el riesgo de extinción de una especie y en donde se declaran las extinciones biológicas. Sin embargo, como con todas las demás categorías, la categoría "extinto" carece de un marco de trabajo cuantitativo para asignar esta categoría. Dada su naturaleza subjetiva, pedimos a los asesores expertos que trabajan con la diversidad de taxones que exploraran los atributos que usan para declarar extinta a una especie. Mediante un experimento de elección, sondeamos a 674 expertos de los grupos especialistas y de trabajo de la Comisión de Supervivencia de Especies de la UICN. La disponibilidad de datos, el tiempo desde la última detección, la detectabilidad, la disponibilidad del hábitat y la declinación poblacional fueron atributos importantes que los asesores favorecieron al inferir las extinciones. Los respondientes con experiencia con la lista roja les asignaron mayor importancia a los atributos de disponibilidad de datos, tiempo desde la última detección y detectabilidad cuando consideraron la extinción de una especie, mientras que los respondientes que trabajan con taxones conocidos le dieron más importancia al tiempo desde la última detección. En general fue menos probable que los respondientes sin experiencia con la lista roja y aquellos que trabajan con los taxones más conocidos (es decir, mamíferos y aves) consideraran extinta a una especie. Nuestros descubrimientos sobre la importancia que los asesores colocan sobre los atributos utilizados para declarar extinta a una especie proporcionan una base para orientar el desarrollo de criterios específicos para evaluar de manera más acertada las extinciones de las especies.

Preliminary Evaluation of a System with On-Body and Aerial Sensors for Monitoring Working Dogs.

This paper presents a system for behavioral, environmental, and physiological monitoring of working dogs using on-body and aerial sensors. The proof of concept study presented here includes two trained dogs performing nine scent detection tasks in an uncontrolled environment encompassing approximately two acres. The dogs were outfitted with a custom designed wearable harness to monitor their heart rate, activity levels and skin temperature. We utilized a commercially available micro-air vehicle to perform aerial sensing by tracking the terrain and movement of the dog in the outdoor space. The dogs were free to explore the space working at maximal speeds to complete a scent-based search-and-retrieval task. Throughout the experiment, the harness data was transferred to a base station via Wi-Fi in real-time. In this work, we also focused on testing the performance of a custom 3D electrode with application specific ergonomic improvements and adaptive filter processing techniques to recover as much electrocardiography data as possible during high intensity motion activity. We were able to recover and use 84% of the collected data where we observed a trend of heart rate generally increasing immediately after successful target localization. For tracking the dogs in the aerial video footage, we applied a state-of-the-art deep learning algorithm designed for online object tracking. Both qualitative and quantitative tracking results are very promising. This study presents an initial effort towards deployment of on-body and aerial sensors to monitor the working dogs and their environments during scent detection and search and rescue tasks in order to ensure their welfare, enable novel dog-machine interfaces, and allow for higher success rate of remote and automated task performance.

Hormetic association between perceived stress and human epigenetic aging based on resilience capacity.

Chronic stress is associated with deleterious health outcomes and mortality risk. A potential mechanism by which stress affects healthspan and lifespan is acceleration of cellular aging. Biologic age prediction models, termed epigenetic clocks, have been developed to estimate biologic age differences among people with the same chronologic age. This study evaluates the simultaneous impact of perceived chronic stress and resilience on Grim Age acceleration. The perceived stress score (PSS) and Connor-Davidson Resilience Scale (CD-RISC) were used to measure chronic stress and resilience, respectively. DNA was extracted from whole blood and analyzed using the MethylationEPIC BeadChip. GrimAge estimates were calculated using the methylation age calculator. Forty-seven business executives were categorized by levels of high or low stress and resilience scores. Compared to participants with low stress and high resilience, those with low stress and low resilience demonstrated the strongest association with Grim Age acceleration (p = 0.044), after controlling for age and estimated cellular proportions. Interestingly, among participants with low resilience, those with high perceived stress had a weaker association with Grim Age acceleration than participants with low perceived stress. However, among participants with high resilience, low perceived stress had a weaker association with Grim Age acceleration than high perceived stress. Our findings suggest that the impact of perceived stress on epigenetic age acceleration may differ based on resilience capacity, with a potential paradoxical beneficial effect among those with low resilience.

Societal extinction of species.

The ongoing global biodiversity crisis not only involves biological extinctions, but also the loss of experience and the gradual fading of cultural knowledge and collective memory of species. We refer to this phenomenon as 'societal extinction of species' and apply it to both extinct and extant taxa. We describe the underlying concepts as well as the mechanisms and factors that affect this process, discuss its main implications, and identify mitigation measures. Societal extinction is cognitively intractable, but it is tied to biological extinction and thus has important consequences for conservation policy and management. It affects societal perceptions of the severity of anthropogenic impacts and of true extinction rates, erodes societal support for conservation efforts, and causes the loss of cultural heritage.

Suicidal Ideation Across Three Timepoints in Patients Discharged from Psychiatric Hospitalization.

This article describes the rate of suicidal ideation (SI) across three timepoints among treatment-seeking patients recently discharged from psychiatric hospitalization-a group that is at ultrahigh-risk for suicide. Retrospective chart review was used to quantify the rate of SI in 252 consecutive patients discharged to a post-hospital mental health clinic. Data include patients' lifetime history of SI, SI at the time of hospital intake, and SI at post-hospital outpatient clinic intake, as well as demographics and diagnosis. Overall, 67% of the sample reported a lifetime history of SI, 49% reported SI during hospital intake, and 6% reported SI at post-hospital clinic intake. Age was the only variable associated with history of SI (p = .04), with younger patients more likely (OR = 1.85) to report a history of SI. These results may help inform the development of interventions for the population of ultrahigh-risk patients being discharged from hospital after psychiatric care.

Hair cortisol, perceived stress, and resilience as predictors of coronary arterial disease.

The widespread prevalence of cardiovascular disease underscores the continuing need for identifying modifiable risk factors and novel targets for therapeutic intervention. Hair cortisol concentration (HCC) is a promising biomarker for evaluating the contribution of chronic stress to the pathogenesis and prognosis of coronary arterial disease (CAD). In this cross-sectional study of 24 participants, we assessed the risk of CAD associated with HCC and with perceived chronic stress (Perceived Stress Score), controlling for the established risk factors of age, diabetes, hypertension, dyslipidemia, and obesity. In fully adjusted Poisson regression models, we additionally evaluated CAD risk with the simultaneous inclusion of psychological and physiologic resilience measures (CD-RISC, DHEA-S). Our results show that HCC, but not PSS, is significantly associated with CAD (incident rate ratio 0.99, confidence interval 0.98-1.00, p = 0.01), but the magnitude of the association is weak and inverse, and less than with dyslipidemia and age. The association remained significant after inclusion of the sum of resilience measures via a combined resiliency score. Resilience was not independently significantly associated with CAD. Our findings indicate the contribution of HCC to CAD risk is small in an average-risk population and remains after adjustment for multisystem resilience.

Correction: Biogeographical patterns and speciation of the genus Pinguicula (Lentibulariaceae) inferred by phylogenetic analyses.

[This corrects the article DOI: 10.1371/journal.pone.0252581.].

Urine-Based Metabolomics and Machine Learning Reveals Metabolites Associated with Renal Cell Carcinoma Stage.

Urine metabolomics profiling has potential for non-invasive RCC staging, in addition to providing metabolic insights into disease progression. In this study, we utilized liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of urine metabolites associated with RCC progression. Two machine learning questions were posed in the study: Binary classification into early RCC (stage I and II) and advanced RCC stages (stage III and IV), and RCC tumor size estimation through regression analysis. A total of 82 RCC patients with known tumor size and metabolomic measurements were used for the regression task, and 70 RCC patients with complete tumor-nodes-metastasis (TNM) staging information were used for the classification tasks under ten-fold cross-validation conditions. A voting ensemble regression model consisting of elastic net, ridge, and support vector regressor predicted RCC tumor size with a R2 value of 0.58. A voting classifier model consisting of random forest, support vector machines, logistic regression, and adaptive boosting yielded an AUC of 0.96 and an accuracy of 87%. Some identified metabolites associated with renal cell carcinoma progression included 4-guanidinobutanoic acid, 7-aminomethyl-7-carbaguanine, 3-hydroxyanthranilic acid, lysyl-glycine, glycine, citrate, and pyruvate. Overall, we identified a urine metabolic phenotype associated with renal cell carcinoma stage, exploring the promise of a urine-based metabolomic assay for staging this disease.

Biogeographical patterns and speciation of the genus Pinguicula (Lentibulariaceae) inferred by phylogenetic analyses.

Earlier phylogenetic studies in the genus Pinguicua (Lentibulariaceae) suggested that the species within a geographical region was rather monophyletic, although the sampling was limited or was restricted to specific regions. Those results conflicted with the floral morphology-based classification, which has been widely accepted to date. In the current study, one nuclear ribosomal DNA (internal transcribed spacer; ITS) and two regions of chloroplast DNA (matK and rpl32-trnL), from up to ca. 80% of the taxa in the genus Pinguicula, covering all three subgenera, were sequenced to demonstrate the inconsistency and explore a possible evolutionary history of the genus. Some incongruence was observed between nuclear and chloroplast topologies and the results from each of the three DNA analyses conflicted with the morphology-based subgeneric divisions. Both the ITS tree and network, however, corresponded with the biogeographical patterns of the genus supported by life-forms (winter rosette or hibernaculum formation) and basic chromosome numbers (haploidy). The dormant strategy evolved in a specific geographical region is a phylogenetic constraint and a synapomorphic characteristic within a lineage. Therefore, the results denied the idea that the Mexican group, morphologically divided into the three subgenera, independently acquired winter rosette formations. Topological incongruence among the trees or reticulations, indicated by parallel edges in phylogenetic networks, implied that some taxa originated by introgressive hybridisation. Although there are exceptions, species within the same geographical region arose from a common ancestor. Therefore, the classification by the floral characteristics is rather unreliable. The results obtained from this study suggest that evolution within the genus Pinguicula has involved; 1) ancient expansions to geographical regions with gene flow and subsequent vicariance with genetic drift, 2) acquirement of a common dormant strategy within a specific lineage to adapt a local climate (i.e., synapomorphic characteristic), 3) recent speciation in a short time span linked to introgressive hybridisation or multiplying the ploidy level (i.e., divergence), and 4) parallel evolution in floral traits among lineages found in different geographical regions (i.e., convergence). As such, the floral morphology masks and obscures the phylogenetic relationships among species in the genus.

Machine Learning-Enabled Renal Cell Carcinoma Status Prediction Using Multiplatform Urine-Based Metabolomics.

Renal cell carcinoma (RCC) is diagnosed through expensive cross-sectional imaging, frequently followed by renal mass biopsy, which is not only invasive but also prone to sampling errors. Hence, there is a critical need for a noninvasive diagnostic assay. RCC exhibits altered cellular metabolism combined with the close proximity of the tumor(s) to the urine in the kidney, suggesting that urine metabolomic profiling is an excellent choice for assay development. Here, we acquired liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) data followed by the use of machine learning (ML) to discover candidate metabolomic panels for RCC. The study cohort consisted of 105 RCC patients and 179 controls separated into two subcohorts: the model cohort and the test cohort. Univariate, wrapper, and embedded methods were used to select discriminatory features using the model cohort. Three ML techniques, each with different induction biases, were used for training and hyperparameter tuning. Assessment of RCC status prediction was evaluated using the test cohort with the selected biomarkers and the optimally tuned ML algorithms. A seven-metabolite panel predicted RCC in the test cohort with 88% accuracy, 94% sensitivity, 85% specificity, and 0.98 AUC. Metabolomics Workbench Study IDs are ST001705 and ST001706.