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BackgroundMachine learning models require large datasets that may be siloed across different health care institutions. Machine learning studies that focus on COVID-19 have been limited to single-hospital data, which limits model generalizability. ObjectiveWe aimed to use federated learning, a machine learning technique that avoids locally aggregating raw clinical data across multiple institutions, to predict mortality in hospitalized patients with COVID-19 within 7 days. MethodsPatient data were collected from the electronic health records of 5 hospitals within the Mount Sinai Health System. Logistic regression with L1 regularization/least absolute shrinkage and selection operator (LASSO) and multilayer perceptron (MLP) models were trained by using local data at each site. We developed a pooled model with combined data from all 5 sites, and a federated model that only shared parameters with a central aggregator. ResultsThe LASSOfederated model outperformed the LASSOlocal model at 3 hospitals, and the MLPfederated model performed better than the MLPlocal model at all 5 hospitals, as determined by the area under the receiver operating characteristic curve. The LASSOpooled model outperformed the LASSOfederated model at all hospitals, and the MLPfederated model outperformed the MLPpooled model at 2 hospitals. ConclusionsThe federated learning of COVID-19 electronic health record data shows promise in developing robust predictive models without compromising patient privacy.

In the late 1800s, observations that bacterial infections could lead to tumor regression and that the immune system could recognize and eliminate precancerous cells, later proved by the identification of [...]

AbstractWe are entering a new era in genomics–that of large-scale, place-based, highly contextualized genomic research. Here we review this emerging paradigm shift and suggest that sites of utmost scientific importance be expanded into ‘Genomic Observatories’ (GOs). Investment in GOs should focus on the digital characterization of whole ecosystems, from all-taxa biotic inventories to time-series ’omics studies. The foundational layer of biodiversity–genetic variation–would thus be mainstreamed into Earth Observation systems enabling predictive modelling of biodiversity dynamics and resultant impacts on ecosystem services.

Abstract Background A steep drop in the cost of next-generation sequencing during recent years has made the technology affordable to the majority of researchers, but downstream bioinformatic analysis still poses a resource bottleneck for smaller laboratories and institutes that do not have access to substantial computational resources. Sequencing instruments are typically bundled with only the minimal processing and storage capacity required for data capture during sequencing runs. Given the scale of sequence datasets, scientific value cannot be obtained from acquiring a sequencer unless it is accompanied by an equal investment in informatics infrastructure. Results Cloud BioLinux is a publicly accessible Virtual Machine (VM) that enables scientists to quickly provision on-demand infrastructures for high-performance bioinformatics computing using cloud platforms. Users have instant access to a range of pre-configured command line and graphical software applications, including a full-featured desktop interface, documentation and over 135 bioinformatics packages for applications including sequence alignment, clustering, assembly, display, editing, and phylogeny. Each tool's functionality is fully described in the documentation directly accessible from the graphical interface of the VM. Besides the Amazon EC2 cloud, we have started instances of Cloud BioLinux on a private Eucalyptus cloud installed at the J. Craig Venter Institute, and demonstrated access to the bioinformatic tools interface through a remote connection to EC2 instances from a local desktop computer. Documentation for using Cloud BioLinux on EC2 is available from our project website, while a Eucalyptus cloud image and VirtualBox Appliance is also publicly available for download and use by researchers with access to private clouds. Conclusions Cloud BioLinux provides a platform for developing bioinformatics infrastructures on the cloud. An automated and configurable process builds Virtual Machines, allowing the development of highly customized versions from a shared code base. This shared community toolkit enables application specific analysis platforms on the cloud by minimizing the effort required to prepare and maintain them.

Background: Modulation of physical exercise (PE) represents an intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie beneficial effects of PE involves the apparent stimulation of adult hippocampal neurogenesis (AHNG). BCI‐838 is a pro‐drug whose metabolite BCI‐632 is one of the most active proneurogenic agents known and is an antagonist at group II metabotropic receptors (mGluR2/3). The drug stimulates AHNG while enhancing learning behavior and exerting anxiolytic and antidepressant properties. We previously demonstrated that the administration of BCI‐838 to a mouse model of cerebral and cerebrovascular accumulation of oligomeric AbE22Q (APPE693Q = "Dutch") reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Thy1.1‐Dutch APP mice (Kim et al., Mol Psych 2014). Herein, we sought to determine whether BCI‐838 might substitute for PE, and/or whether treatment with a BCI‐838+PE combination might demonstrate synergistic effects in a mouse model of amyloidosis (APPKM670/671NL/PSEN1Δexon9 = APP/PS1). Method: 3‐month‐old APP/PS1 mice were treated with either BCI‐838, PE (running wheels), or a combination of BCI‐838+PE for 1 month. We performed learning behavior tests (novel object recognition and Barnes maze), biochemical, and transcriptomic analyses on the hippocampal dentate gyrus (DG) of APP/PS1 mice. We performed gene set enrichment analysis, drug repurposing, and chemogenomic enrichment analyses to reveal molecular pathways of interest and investigated compounds with transcriptomically similar profiles as well as drug targets and side effects. Result: We report that: (i) BCI‐838, PE, or BCI‐838+PE combination enhanced AHNG, (ii) BCI‐838 alone or associated with PE led to improvement in both spatial and recognition learning behaviors, (iii) BCI‐838 treatment increased mRNA levels of BDNF, metabotropic glutamate receptors, and PIK3C2A of the PI3K‐MTOR pathway, and decreased EIF5A of ketamine‐modulating mTOR activity in the hippocampal DG. qPCR results validated the statistical significance of the association between BCI‐838 treatment and increased levels of BDNF. Conclusion: Our study points to BCI‐838 as a safe and orally active compound capable of mimicking the beneficial effect of exercise on AHNG, learning behavior, and anxiety in the APP/PS1 mouse model. [ABSTRACT FROM AUTHOR]

• BCI-838 is an mGluR2/3 receptor antagonist pro-drug. • BCI-838 rescued deficits in object recognition memory in PS19 tauopathy mice. • Treatment was effective whether begun at 3 or 7 months of age. • mGluR2/3 dependent mechanisms underlie the behavioral deficits in PS19 mice. Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer's disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APPE693Q) transgenic mice, a model of the pathological accumulation of Aβ oligomers found in AD. Herein, we investigated effects of BCI-838 on PS19 male mice that express the tauopathy mutation MAPTP301S associated with human frontotemporal lobar degeneration (FTLD). These mice develop an aging-related tauopathy without amyloid accumulation. Mice were divided into three experimental groups: (1) non-transgenic wild type mice treated with vehicle, (2) PS19 mice treated with vehicle and (3) PS19 mice treated with 5 mg/kg BCI-838. Groups of 10–13 mice were utilized. Vehicle or BCI-838 was administered by oral gavage for 4 weeks. Behavioral testing consisting of a novel object recognition task was conducted after drug administration. Two studies were performed beginning treatment of mice at 3 or 7 months of age. One month of BCI-838 treatment rescued deficits in recognition memory in PS19 mice whether treatment was begun at 3 or 7 months of age. These studies extend the potential utility of BCI-838 to neurodegenerative conditions that have tauopathy as their underlying basis. They also suggest an mGluR2/3 dependent mechanism as a basis for the behavioral deficits in PS19 mice. [ABSTRACT FROM AUTHOR]

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits. [ABSTRACT FROM AUTHOR]

This report summarizes the proceedings of the 14 workshop of the Genomic Standards Consortium (GSC) held at the University of Oxford in September 2012. The primary goal of the workshop was to work towards the launch of the Genomic Observatories (GOs) Network under the GSC. For the first time, it brought together potential GOs sites, GSC members, and a range of interested partner organizations. It thus represented the first meeting of the GOs Network (GOs1). Key outcomes include the formation of a core group of 'champions' ready to take the GOs Network forward, as well as the formation of working groups. The workshop also served as the first meeting of a wide range of participants in the Ocean Sampling Day (OSD) initiative, a first GOs action. Three projects with complementary interests - COST Action ES1103, MG4U and Micro B3 - organized joint sessions at the workshop. A two-day GSC Hackathon followed the main three days of meetings. [ABSTRACT FROM AUTHOR]

Abstract Background Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. Objective To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. Design, setting, and participants Blood samples from 11 506 men in Sweden were collected during 1991–1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. Outcome measurements and statistical analysis A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 × 10−6 was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. Results and limitations We found 12 SNPs at seven independent loci associated with prostate-cancer-specific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 × 10−8) and replicated in an independent cohort: rs73055188 (p = 5.27 × 10−9, per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72–2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p < 1 × 10−6) and replicated in an independent cohort: rs2702185 (p = 7.1 × 10−7, per-allele HR = 2.55, 95% CI = 1.76–3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. Conclusions The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. Patient summary We identify two genetic markers that are associated with prostate-cancer-specific survival time. Take Home Message We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence. [ABSTRACT FROM AUTHOR]

Background: Modulation of physical activity represents an important intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie the beneficial effect of physical exercise (PE) involves the apparent stimulation of adult hippocampal neurogenesis (AHN). BCI-838 is a pro-drug whose active metabolite BCI-632 is a negative allosteric modulator at group II metabotropic glutamate receptors (mGluR2/3). We previously demonstrated that administration of BCI-838 to a mouse model of brain accumulation of oligomeric Aβ E22Q ( APP E 693 Q = " Dutch APP ") reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Dutch APP mice., Methods: 3-month-old mice were administered BCI-838 and/or physical exercise for 1 month and then tested in novel object recognition, neurogenesis, and RNAseq., Results: Here we show that (i) administration of BCI-838 and a combination of BCI-838 and PE enhanced AHN in a 4-month old mouse model of AD amyloid pathology ( APP KM 670/671 NL /PSEN1 Δ exon 9 = APP/PS1), (ii) administration of BCI-838 alone or with PE led to stimulation of AHN and improvement in recognition memory, (iii) the hippocampal dentate gyrus transcriptome of APP/PS1 mice following BCI-838 treatment showed up-regulation of brain-derived neurotrophic factor (BDNF), PIK3C2A of the PI3K-mTOR pathway, and metabotropic glutamate receptors, and down-regulation of EIF5A involved in modulation of mTOR activity by ketamine, and (iv) validation by qPCR of an association between increased BDNF levels and BCI-838 treatment., Conclusion: Our study points to BCI-838 as a safe and orally active compound capable of mimicking the beneficial effect of PE on AHN and recognition memory in a mouse model of AD amyloid pathology., Competing Interests: JB was employed by Generable, Inc. CB was employed by E-Scape Bio. MS has served as a consultant for Bayer Schering Pharma, Bristol-Meyers Squibb, Elan Corporation, Genentech, Medivation, Medpace, Pfizer, Janssen, Takeda Pharmaceutical Company Limited, and United Biosource Corporation. She receives research support from the NIH. FHG was a founder and member of the SAB for BCI, but he no longer serves as a consultant or has stock because BCI no longer exists as a company. He has received funding from NIA, HIH, and NIMH on projects related to adult neurogenesis but not related to this or related compounds. CB is a former employee of BrainCells, Inc. BrainCells, Inc. provided drug and advice. JD has served as a consultant for Janssen and is an equity holder in Thorne HealthTech. BG is a consultant for Anthem AI and a scientific advisor and consultant for Prometheus Biosciences. He has received consulting fees from GLG Research and honoraria from Virtual EP Connect. ME receives research support from the NIH, the XDP Foundation, and the Cure Alzheimer's Fund. SG is a co-founder of Recuerdo Pharmaceuticals. He has served as a consultant in the past for J&J, Diagenic, and Pfizer, and he currently consults for Cognito Therapeutics, GLG Group, SVB Securities, Guidepoint, Third Bridge, Leerink, MEDACORP, Altpep, Vigil Neurosciences, and Eisai. He has received research support from Warner-Lambert, Pfizer, Baxter Healthcare, Amicus, Avid, and ADDF. He served on the DSMB for an amyloid vaccine trial by Elan Pharmaceuticals. He receives research support from the VA, NIH, and the Cure Alzheimer's Fund. SG and ME have received compensation for chart review in the areas of cognitive neurology and pediatric neurology, respectively. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) SG, BG, FHG, MG, and J-VH-M declare that they were editors board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Perez Garcia, Bicak, Buros, Haure-Mirande, Perez, Otero-Pagan, Gama Sosa, De Gasperi, Sano, Gage, Barlow, Dudley, Glicksberg, Wang, Readhead, Ehrlich, Elder and Gandy.)

Noninvasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer therapies. AR is a critical driver and mediator of resistance of prostate cancer but currently available noninvasive prostate cancer biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of prostate cancer, and DNA damage induced by EBRT upregulates AR pathway activity to promote therapeutic resistance. [89Zr]11B6-PET is a novel modality targeting prostate-specific protein human kallikrein 2 (hK2), which is a surrogate biomarker for AR activity. Here, we studied whether [89Zr]11B6-PET can accurately assess EBRT-induced AR activity.Genetic and human prostate cancer mouse models received EBRT (2-50 Gy) and treatment response was monitored by [89Zr]11B6-PET/CT. Radiotracer uptake and expression of AR and AR target genes was quantified in resected tissue.EBRT increased AR pathway activity and [89Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [89Zr]11B6 uptake in prostate cancer-bearing mice (Hi-Myc x Pb&#95;KLK2) with no significant changes in uptake in healthy (Pb&#95;KLK2) mice, and this correlated with hK2 protein levels., Implications: hK2 expression in prostate cancer tissue is a proxy of EBRT-induced AR activity that can noninvasively be detected using [89Zr]11B6-PET; further clinical evaluation of hK2-PET for monitoring response and development of resistance to EBRT in real time is warranted., (©2023 American Association for Cancer Research.)

Contextual data collected concurrently with molecular samples are critical to the use of metagenomics in the fields of marine biodiversity, bioinformatics and biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and Biotechnology (M2B3) standards for "Reporting" and "Serving" data. The M2B3 Reporting Standard (1) describes minimal mandatory and recommended contextual information for a marine microbial sample obtained in the epipelagic zone, (2) includes meaningful information for researchers in the oceanographic, biodiversity and molecular disciplines, and (3) can easily be adopted by any marine laboratory with minimum sampling resources. The M2B3 Service Standard defines a software interface through which these data can be discovered and explored in data repositories. The M2B3 Standards were developed by the European project Micro B3, funded under 7(th) Framework Programme "Ocean of Tomorrow", and were first used with the Ocean Sampling Day initiative. We believe that these standards have value in broader marine science.