The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

Cobertura de MRS e indicación de terapia hormonal en Pedro Aguirre Cerda, septiembre de 2019

Introducción: El envejecimiento de la población en todo el mundo es un fenómeno progresivo y Chile no se queda atrás frente a esto. Actualmente existe un subprograma de climaterio mujeres entre los 45 a 64 años, que presenta diversas acciones y propósitos. Objetivo: Describir la cobertura de la aplicación de la Menopause Rating Scale (MRS) e indicación de terapia de reemplazo hormonal en mujeres inscritas en los CESFAM de la comuna de Pedro Aguirre Cerda. Método: Descriptivo transversal. Resultados: La cobertura de aplicación de MRS en mujeres entre 45-64 años fue de un 62,6%. Un 34,3% de mujeres presentaron un puntaje MRS alterado, indicándose terapia hormonal en un 37,8% de los casos, en las indicaciones un 21,8% eran usuarias candidatas acorde a criterios médicos y un 78,2% no lo eran. Conclusiones: Se debe aumentar la cobertura de MRS y recursos para exámenes de laboratorio, de imágenes y capacitaciones, esto para mejorar la entrega de las prestaciones en el subprograma climaterio.

Introduction: The aging of the population worldwide is a progressive phenomenon and Chile is not lagging behind in this. Currently, there is a climacteric subprogram for women between 45 and 64 years of age, which has various actions and purposes. Objective: To describe the coverage of the application of the Menopause Rating Scale (MRS) and indication of hormone replacement therapy in women enrolled in the CESFAM of the commune of Pedro Aguirre Cerda. Method: Cross-sectional descriptive study. Results: The coverage of the MRS application in women between 45-64 years old was 62.6%. A 34.3% of women presented an altered MRS score, indicating hormone therapy in 37.8% of the cases, 21.8% of the indications were candidates according to medical criteria and 78.2% were not. Conclusions: There is a lack of labs and images tests in the climacteric controls, resulting in a mayor number of women no candidates to the hormonal therapy according to medical criteria.

Efficient computational modeling of electronic stopping power of organic polymers for proton therapy optimization.

This comprehensive study delves into the intricate interplay between protons and organic polymers, offering insights into proton therapy in cancer treatment. Focusing on the influence of the spatial electron density distribution on stopping power estimates, we employed real-time time-dependent density functional theory coupled with the Penn method. Surprisingly, the assumption of electron density homogeneity in polymers is fundamentally flawed, resulting in an overestimation of stopping power values at energies below 2 MeV. Moreover, the Bragg rule application in specific compounds exhibited significant deviations from experimental data around the stopping maximum, challenging established norms.

Effects of Vape Use on Oral Health: A Review of the Literature.

Background and Objectives: The widespread use of tobacco has evolved with the popularity of vapes, especially among young people, despite the lack of clarity in warnings about their risks. Studies indicate the need for more effective communication about the oral risks of vaping. In addition to systemic, respiratory, and cardiovascular effects, vaping is associated with an increased risk of gingivitis and periodontal disease as well as reduced antioxidant capacity of saliva. The objectives of this narrative review are to summarize the existing information in the literature on the effects of vaping at the oral level and to bring together knowledge about the mechanism of action of vaping in oral tissues. Materials and Methods: In the present study, articles were searched in PubMed, Elsevier Scopus, and Web of Science using the keywords "oral health", "vaping", and "vape". Studies published in the last 6 years that addressed the effects of oral vaping were selected, including comparisons among vape users, smokers, and non-smokers. Repeated articles, prior to 2017 and in languages other than English, were excluded. Two review authors (A.M.I and M.F.E.M) independently selected the papers based on titles and abstracts and conducted a full review of the remaining papers. In cases of disagreement, a third reviewer was used. Results: A total of 113 results were obtained, distributed as 16 from PubMed, 35 from Web of Science, and 62 from Elsevier Scopus. After removing duplicates, 67 articles were filtered by reviewing titles and abstracts, and finally, 22 articles were selected for comprehensive reading. Subsequently, eight of these articles were chosen for qualitative synthesis and are presented in standardized tables. The sample size of all included studies was composed of 31,647 participants, (14,477 male and 17,170 female) with a mean of 35.016 ± 7.57 years of age. Conclusions: This review indicates that the use of vapes is associated with an increased risk of periodontitis and caries. Although users experience more oral problems than non-smokers, these are less severe than those of traditional smokers. The widespread prevalence, especially among young people, highlights the urgency of awareness campaigns to warn of risks and understand potential harm.

Efecto del farmacéutico clínico en las reconsultas a los 30 días posalta del servicio de urgencias: ensayo clínico controlado / Effect of a clinical pharmacist on 30-day revisits following discharge from an emergency department: a randomized controlled clinical trial

Objetivos. Determinar el efecto de la inclusión del farmacéutico clínico en el servicio de urgencias (SU) en las reconsultas durante 30 días posalta y la satisfacción de los pacientes. Métodos. Ensayo clínico controlado, aleatorizado, paralelo y pragmático, realizado en el SU de un hospital universitario. Los pacientes reclutados fueron asignados aleatoriamente al grupo control (GC) que recibió la atención habitual o al grupo intervenido (GI) que recibió además la atención de un farmacéutico clínico, el cual se integró al equipo clínico para optimizar la selección, evaluación y educación farmacoterapéutica en el SU y al alta. El desenlace primario fue reconsultas no programadas 30 días posaltarelacionadas con la atención inicial al SU. Las diferencias entre grupos se analizaron por curvas de supervivencia de Kaplan-Meier y prueba de log-rank. La asociación entre intervención y tiempo al evento fue analizada mediante regresión multivariada de riesgos proporcionales de Cox y se expresó como hazard ratio ajustada (HRa). Resultados. Un total de 1.001 pacientes ingresaron al estudio (GI=500 y GC=501). Ambos grupos eran similares, predominaron las mujeres (61,5%), edad 51 años (RIC: 33-65). La intervención redujo significativamente las reconsultas a cualquier centro durante 30 días posalta comparado con GC [25 (6,3%) vs 66 (16,7%); HRa: 0,29 (IC 95%: 0,17-0,50)] y para el mismo centro [15 (3,0%) vs 32 (6,5%); HRa: 0,46 (IC 95%: 0,24-0,87)]. La satisfacción del usuario fue mayor en el GI que GC (87,2% vs 83,2%; p<0,05). Conclusiones. La inclusión del farmacéutico clínico en un SU reduce sustancialmente las reconsultas durante 30 días posalta y mejora la satisfacción de los usuarios. (AU)

Objectives. To evaluate a clinical pharmacist’s inclusion in emergency department (ED) care in terms of the effect on on 30-day revisits after discharge from the ED and patient satisfaction. Methods. Randomized, controlled parallel-group pragmatic trial in a university hospital ED. Recruited patients were randomly assigned to a control group for standard care only or an intervention group to receive standard care plus the attention of a clinical pharmacist integrated into the care team to optimize the selection and evaluation of medications and provide pharmacotherapeutic education on the patient’s discharge. The primary outcome was unplanned revisits within 30 days after discharge because of the same complaint that led to the initial ED visit. Between-group differences were analyzed with Kaplan-Meier survival curves and log-rank tests. The association between the intervention and time to the outcome event was explored with multivariate Cox proportional hazard regression analysis. Results. A total of 1001 patients were enrolled (intervention, 500; control, 501). Patients in both groups were similar. A majority were women (61.5%), and the median age (interquartile range) was 51 years (33-65 years). The pharmacist’s intervention significantly reduced the number of 30-day revisits to any ED: 25 (6.3%) revisited vs 66 (16.7%) in the control group. The adjusted hazard ratio (aHR) was 0.29 (95% CI, 0.17-0.50). Fifteen patients (3.0%) from the intervention group revisited the same ED vs 32 (6.5%) from the control group (aHR, 0.46 [95% CI, 0.24-0.87]). More patients expressed satisfaction in the intervention group (87.2%) than in the control group ( 83.2%) (P<.05). Conclusions. Including a clinical pharmacist in ED care substantially reduces the number of 30-day revisits and increases patient satisfaction. (AU)

Efecto del farmacéutico clínico en las reconsultas a los 30 días posalta del servicio de urgencias: ensayo clínico controlado / Effect of a clinical pharmacist on 30-day revisits following discharge from an emergency department: a randomized controlled clinical trial

Objetivos. Determinar el efecto de la inclusión del farmacéutico clínico en el servicio de urgencias (SU) en las reconsultas durante 30 días posalta y la satisfacción de los pacientes. Métodos. Ensayo clínico controlado, aleatorizado, paralelo y pragmático, realizado en el SU de un hospital universitario. Los pacientes reclutados fueron asignados aleatoriamente al grupo control (GC) que recibió la atención habitual o al grupo intervenido (GI) que recibió además la atención de un farmacéutico clínico, el cual se integró al equipo clínico para optimizar la selección, evaluación y educación farmacoterapéutica en el SU y al alta. El desenlace primario fue reconsultas no programadas 30 días posaltarelacionadas con la atención inicial al SU. Las diferencias entre grupos se analizaron por curvas de supervivencia de Kaplan-Meier y prueba de log-rank. La asociación entre intervención y tiempo al evento fue analizada mediante regresión multivariada de riesgos proporcionales de Cox y se expresó como hazard ratio ajustada (HRa). Resultados. Un total de 1.001 pacientes ingresaron al estudio (GI=500 y GC=501). Ambos grupos eran similares, predominaron las mujeres (61,5%), edad 51 años (RIC: 33-65). La intervención redujo significativamente las reconsultas a cualquier centro durante 30 días posalta comparado con GC [25 (6,3%) vs 66 (16,7%); HRa: 0,29 (IC 95%: 0,17-0,50)] y para el mismo centro [15 (3,0%) vs 32 (6,5%); HRa: 0,46 (IC 95%: 0,24-0,87)]. La satisfacción del usuario fue mayor en el GI que GC (87,2% vs 83,2%; p<0,05). Conclusiones. La inclusión del farmacéutico clínico en un SU reduce sustancialmente las reconsultas durante 30 días posalta y mejora la satisfacción de los usuarios. (AU)

Objectives. To evaluate a clinical pharmacist’s inclusion in emergency department (ED) care in terms of the effect on on 30-day revisits after discharge from the ED and patient satisfaction. Methods. Randomized, controlled parallel-group pragmatic trial in a university hospital ED. Recruited patients were randomly assigned to a control group for standard care only or an intervention group to receive standard care plus the attention of a clinical pharmacist integrated into the care team to optimize the selection and evaluation of medications and provide pharmacotherapeutic education on the patient’s discharge. The primary outcome was unplanned revisits within 30 days after discharge because of the same complaint that led to the initial ED visit. Between-group differences were analyzed with Kaplan-Meier survival curves and log-rank tests. The association between the intervention and time to the outcome event was explored with multivariate Cox proportional hazard regression analysis. Results. A total of 1001 patients were enrolled (intervention, 500; control, 501). Patients in both groups were similar. A majority were women (61.5%), and the median age (interquartile range) was 51 years (33-65 years). The pharmacist’s intervention significantly reduced the number of 30-day revisits to any ED: 25 (6.3%) revisited vs 66 (16.7%) in the control group. The adjusted hazard ratio (aHR) was 0.29 (95% CI, 0.17-0.50). Fifteen patients (3.0%) from the intervention group revisited the same ED vs 32 (6.5%) from the control group (aHR, 0.46 [95% CI, 0.24-0.87]). More patients expressed satisfaction in the intervention group (87.2%) than in the control group ( 83.2%) (P<.05). Conclusions. Including a clinical pharmacist in ED care substantially reduces the number of 30-day revisits and increases patient satisfaction. (AU)

Effect of a clinical pharmacist on 30-day revisits following discharge from an emergency department: a randomized controlled clinical trial. / Efecto del farmacéutico clínico en las reconsultas a los 30 días posalta del servicio de urgencias: ensayo clínico controlado.

OBJECTIVES: To evaluate a clinical pharmacist's inclusion in emergency department (ED) care in terms of the effect on on 30-day revisits after discharge from the ED and patient satisfaction. MATERIAL AND METHODS: Randomized, controlled parallel-group pragmatic trial in a university hospital ED. Recruited patients were randomly assigned to a control group for standard care only or an intervention group to receive standard care plus the attention of a clinical pharmacist integrated into the care team to optimize the selection and evaluation of medications and provide pharmacotherapeutic education on the patient's discharge. The primary outcome was unplanned revisits within 30 days after discharge because of the same complaint that led to the initial ED visit. Between-group differences were analyzed with Kaplan-Meier survival curves and log-rank tests. The association between the intervention and time to the outcome event was explored with multivariate Cox proportional hazard regression analysis. RESULTS: A total of 1001 patients were enrolled (intervention, 500; control, 501). Patients in both groups were similar. A majority were women (61.5%), and the median age (interquartile range) was 51 years (33-65 years). The pharmacist's intervention significantly reduced the number of 30-day revisits to any ED: 25 (6.3%) revisited vs 66 (16.7%) in the control group. The adjusted hazard ratio (aHR) was 0.29 (95% CI, 0.17-0.50). Fifteen patients (3.0%) from the intervention group revisited the same ED vs 32 (6.5%) from the control group (aHR, 0.46 [95% CI, 0.24-0.87]). More patients expressed satisfaction in the intervention group (87.2%) than in the control group ( 83.2%) (P .05). CONCLUSION: Including a clinical pharmacist in ED care substantially reduces the number of 30-day revisits and increases patient satisfaction.

OBJETIVO: Determinar el efecto de la inclusión del farmacéutico clínico en el servicio de urgencias (SU) en las reconsultas durante 30 días posalta y la satisfacción de los pacientes. METODO: Ensayo clínico controlado, aleatorizado, paralelo y pragmático, realizado en el SU de un hospital universitario. Los pacientes reclutados fueron asignados aleatoriamente al grupo control (GC) que recibió la atención habitual o al grupo intervenido (GI) que recibió además la atención de un farmacéutico clínico, el cual se integró al equipo clínico para optimizar la selección, evaluación y educación farmacoterapéutica en el SU y al alta. El desenlace primario fue reconsultas no programadas 30 días posaltarelacionadas con la atención inicial al SU. Las diferencias entre grupos se analizaron por curvas de supervivencia de Kaplan-Meier y prueba de log-rank. La asociación entre intervención y tiempo al evento fue analizada mediante regresión multivariada de riesgos proporcionales de Cox y se expresó como hazard ratio ajustada (HRa). RESULTADOS: Un total de 1.001 pacientes ingresaron al estudio (GI = 500 y GC = 501). Ambos grupos eran similares, predominaron las mujeres (61,5%), edad 51 años (RIC: 33-65). La intervención redujo significativamente las reconsultas a cualquier centro durante 30 días posalta comparado con GC [25 (6,3%) vs 66 (16,7%); HRa: 0,29 (IC 95%: 0,17-0,50)] y para el mismo centro [15 (3,0%) vs 32 (6,5%); HRa: 0,46 (IC 95%: 0,24-0,87)]. La satisfacción del usuario fue mayor en el GI que GC (87,2% vs 83,2%; p 0,05). CONCLUSIONES: La inclusión del farmacéutico clínico en un SU reduce sustancialmente las reconsultas durante 30 días posalta y mejora la satisfacción de los usuarios.

Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model.

Molecular characterization of antibody immunity and human antibody discovery is mainly carried out using peripheral memory B cells, and occasionally plasmablasts, that express B cell receptors (BCRs) on their cell surface. Despite the importance of plasma cells (PCs) as the dominant source of circulating antibodies in serum, PCs are rarely utilized because they do not express surface BCRs and cannot be analyzed using antigen-based fluorescence-activated cell sorting. Here, we studied the antibodies encoded by the entire mature B cell populations, including PCs, and compared the antibody repertoires of bone marrow and spleen compartments elicited by immunization in a human immunoglobulin transgenic mouse strain. To circumvent prior technical limitations for analysis of plasma cells, we applied single-cell antibody heavy and light chain gene capture from the entire mature B cell repertoires followed by yeast display functional analysis using a cytokine as a model immunogen. We performed affinity-based sorting of antibody yeast display libraries and large-scale next-generation sequencing analyses to follow antibody lineage performance, with experimental validation of 76 monoclonal antibodies against the cytokine antigen that identified three antibodies with exquisite double-digit picomolar binding affinity. We observed that spleen B cell populations generated higher affinity antibodies compared to bone marrow PCs and that antigen-specific splenic B cells had higher average levels of somatic hypermutation. A degree of clonal overlap was also observed between bone marrow and spleen antibody repertoires, indicating common origins of certain clones across lymphoid compartments. These data demonstrate a new capacity to functionally analyze antigen-specific B cell populations of different lymphoid organs, including PCs, for high-affinity antibody discovery and detailed fundamental studies of antibody immunity.

Augmentation of the RSNA Pulmonary Embolism CT Dataset with Bounding Box Annotations and Anatomic Localization of Pulmonary Emboli.

Supplemental material is available for this article. Keywords: CT, Pulmonary Arteries, Embolism/Thrombosis, Feature Detection © RSNA, 2023.

Cell activation-based screening of natively paired human T cell receptor repertoires.

Adoptive immune therapies based on the transfer of antigen-specific T cells have been used successfully to treat various cancers and viral infections, but improved techniques are needed to identify optimally protective human T cell receptors (TCRs). Here we present a high-throughput approach to the identification of natively paired human TCRα and TCRß (TCRα:ß) genes encoding heterodimeric TCRs that recognize specific peptide antigens bound to major histocompatibility complex molecules (pMHCs). We first captured and cloned TCRα:ß genes from individual cells, ensuring fidelity using a suppression PCR. We then screened TCRα:ß libraries expressed in an immortalized cell line using peptide-pulsed antigen-presenting cells and sequenced activated clones to identify the cognate TCRs. Our results validated an experimental pipeline that allows large-scale repertoire datasets to be annotated with functional specificity information, facilitating the discovery of therapeutically relevant TCRs.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Heritability estimates and predictive ability for pig meat quality traits using identity-by-state and identity-by-descent relationships in an F2 population.

Genomic relationships can be computed with dense genome-wide genotypes through different methods, either based on identity-by-state (IBS) or identity-by-descent (IBD). The latter has been shown to increase the accuracy of both estimated relationships and predicted breeding values. However, it is not clear whether an IBD approach would achieve greater heritability ( h 2 ) and predictive ability ( r ̂ y , y ̂ ) than its IBS counterpart for data with low-depth pedigrees. Here, we compare both approaches in terms of the estimated of h 2 and r ̂ y , y ̂ , using data on meat quality and carcass traits recorded in experimental crossbred pigs, with a pedigree constrained to only three generations. Three animal models were fitted which differed on the relationship matrix: an IBS model ( G IBS ), an IBD (defined within the known pedigree) model ( G IBD ), and a pedigree model ( A 22 ). In 9 of 20 traits, the range of increase for the estimates of σ u 2 and h 2 was 1.2-2.9 times greater with G IBS and G IBD models than with A 22 . Whereas for all traits, both parameters were similar between genomic models. The r ̂ y , y ̂ of the genomic models was higher compared to A 22 . A scarce increment in r ̂ y , y ̂ was found with G IBS when compared to G IBD , most likely due to the former recovering sizeable relationships among founder F0 animals.

The receptor kinase SRF3 coordinates iron-level and flagellin dependent defense and growth responses in plants.

Iron is critical for host-pathogen interactions. While pathogens seek to scavenge iron to spread, the host aims at decreasing iron availability to reduce pathogen virulence. Thus, iron sensing and homeostasis are of particular importance to prevent host infection and part of nutritional immunity. While the link between iron homeostasis and immunity pathways is well established in plants, how iron levels are sensed and integrated with immune response pathways remains unknown. Here we report a receptor kinase SRF3, with a role in coordinating root growth, iron homeostasis and immunity pathways via regulation of callose synthases. These processes are modulated by iron levels and rely on SRF3 extracellular and kinase domains which tune its accumulation and partitioning at the cell surface. Mimicking bacterial elicitation with the flagellin peptide flg22 phenocopies SRF3 regulation upon low iron levels and subsequent SRF3-dependent responses. We propose that SRF3 is part of nutritional immunity responses involved in sensing external iron levels.

Atypical Clinical Presentation of Monkeypox Complicated by Myopericarditis.

We present a case of monkeypox infection in a man presenting with genital and labial ulcers, followed by submandibular lymphadenopathy, fever, and constitutional symptoms. His course was complicated by myopericarditis and an ongoing pleomorphic skin eruption. Viral deoxyribonucleic acid was detected by polymerase chain reaction in skin swabs, nasopharyngeal swab, saliva, and semen.

Detection of Clinically Significant Index Prostate Cancer Using Micro-ultrasound: Correlation With Radical Prostatectomy.

OBJECTIVE: To determine the detection of clinically significant prostate cancer (csPCa) index lesion using high resolution transrectal micro-ultrasound (MicroUS) applying PRI-MUS (Prostate Risk Identification using Micro Ultrasound) score v1.0. METHODS: Men who underwent radical prostatectomy following biopsy and MicroUS assessment were included. MicroUS dynamic cine loops of these patients were retrospectively reviewed by an experienced radiologist. The radiologist was aware that patients had undergone radical prostatectomy but was blinded to pathological data. Suspicious sites were assigned a PRI-MUS score. Radical prostatectomy specimens were examined with the quarter mount technique. Detection rate of csPCa index lesion [Grade Group (GG) ≥2] by MicroUS was assessed at a patient level. RESULTS: Twenty-five participants were included in the analysis. The median age was 65.5 years (range 56-74). Median PSA was 6.45 ng/dL (range 2-31.72). Two of 25 patients did not have csPCa (GG1 disease) on radical prostatectomy. MicroUS visualized 20/23 (87%) of the csPCa index lesions [median length 9 mm (range 1.5- 28.5)]. All identified lesions were categorized PRIMUS score 4 or 5. The 3 missed index lesions were in the transition zone [median length 10.5 mm (range 4.5-22.5)]. MicroUS missed 11 non index csPCa in 9 participants [median length 1.5 mm (range 1.5-10.5)]. Of these, 8 were GG2, 2 GG3 and 1 GG5. MicroUS identified the csPCa index lesion in all 9 of these men. CONCLUSION: MicroUS showed the high sensitivity (87%) in detecting index lesions in the prostate gland and identified 100% of index lesions in the peripheral zone.

Anterior Cruciate Ligament Rupture in Skeletally Immature Patients.

In the past 20 years, sports injuries in pediatric and adolescent athletes have increased dramatically, with anterior cruciate ligament (ACL) injuries accounting for more than 25% of all knee injuries at this age. Diagnosis is based on detailed clinical history, physical examination, and imaging assessment, where magnetic resonance imaging plays a central role. The growing immature skeleton presents specific characteristics, which require unique methods for surgical reconstruction, ideally avoiding the physes or minimizing the risk of damaging them. Specific rehabilitation protocols are needed, and these patients face a higher risk of recurrent and contralateral ACL injury. Nonsurgical treatment or delayed reconstruction has been associated with persistent instability, activity modifications, worst functional outcomes, and increased risk of irreparable injuries to menisci and articular cartilage. Consequently, surgical stabilization is the preferred treatment for most patients, despite the eventual risk of angular deformities or limb-length discrepancies due to iatrogenic physeal injury. A variety of surgical techniques have been described, depending on the skeletal maturity and growth remaining. Targeted prevention programs play a key role in reducing the risk of ACL injury, are easy to implement, and require no additional equipment. High-quality evidence supports its use in all pediatric athletes.

Immortalization and functional screening of natively paired human T cell receptor repertoires.

Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:ß amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs.

Comparing Genomic Prediction Models by Means of Cross Validation.

In the two decades of continuous development of genomic selection, a great variety of models have been proposed to make predictions from the information available in dense marker panels. Besides deciding which particular model to use, practitioners also need to make many minor choices for those parameters in the model which are not typically estimated by the data (so called "hyper-parameters"). When the focus is placed on predictions, most of these decisions are made in a direction sought to optimize predictive accuracy. Here we discuss and illustrate using publicly available crop datasets the use of cross validation to make many such decisions. In particular, we emphasize the importance of paired comparisons to achieve high power in the comparison between candidate models, as well as the need to define notions of relevance in the difference between their performances. Regarding the latter, we borrow the idea of equivalence margins from clinical research and introduce new statistical tests. We conclude that most hyper-parameters can be learnt from the data by either minimizing REML or by using weakly-informative priors, with good predictive results. In particular, the default options in a popular software are generally competitive with the optimal values. With regard to the performance assessments themselves, we conclude that the paired k-fold cross validation is a generally applicable and statistically powerful methodology to assess differences in model accuracies. Coupled with the definition of equivalence margins based on expected genetic gain, it becomes a useful tool for breeders.

Regulatory Approved Monoclonal Antibodies Contain Framework Mutations Predicted From Human Antibody Repertoires.

Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences. Our analysis shows that human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from baseline human antibody sequence data. We find that mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in baseline human antibody repertoires. In addition, high frequency mutations in baseline human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that baseline human antibody repertoires may be useful as predictive tools to guide mAb development in the future.