Managed Geo-Distributed Feature Store: Architecture and System Design

Companies are using machine learning to solve real-world problems and are developing hundreds to thousands of features in the process. They are building feature engineering pipelines as part of MLOps life cycle to transform data from various data sources and materialize the same for future consumption. Without feature stores, different teams across various business groups would maintain the above process independently, which can lead to conflicting and duplicated features in the system. Data scientists find it hard to search for and reuse existing features and it is painful to maintain version control. Furthermore, feature correctness violations related to online (inferencing) - offline (training) skews and data leakage are common. Although the machine learning community has extensively discussed the need for feature stores and their purpose, this paper aims to capture the core architectural components that make up a managed feature store and to share the design learning in building such a system.Comment: All the authors are from the AzureML Feature Store product group and are listed in alphabetical order. Bhala Ranganathan: System architect and tech lead of AzureML Feature Store. Feng Pan, Qianjun Xu: Engineering managers. Sethu Raman: Product Manager of AzureML Feature Store who structured and organized the product vision and specification

Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity

<p>Abstract</p> <p>Background</p> <p>The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells <it>in vivo</it>.</p> <p>Methods</p> <p>We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed <it>in vitro </it>and <it>in vivo </it>tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference.</p> <p>Results</p> <p>Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts <it>in vivo</it>. However, Pim1 expression enhanced the <it>in vitro </it>and <it>in vivo </it>tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes.</p> <p>Conclusion</p> <p>Our results suggest an <it>in vivo </it>role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities depending on the disease stage of the cell line. Pim1 promotes tumorigenicity at least in part by enhancing c-MYC transcriptional activity. We also made the novel discovery that treatment of cells with the c-MYC inhibitor 10058-F4 leads to a reduction in Pim1 protein levels.</p

A Pilot Randomized Trial of Levator Injections Versus Physical Therapy for Treatment of Pelvic Floor Myalgia and Sexual Pain

Introduction and hypothesis Our aim was to determine the effects of pelvic floor physical therapy (PT) and levator-directed trigger-point injections (LTPI) on sexual function and levator-related pelvic pain. Study design A randomized trial among women with pelvic floor myalgia (PFM) was performed wherein participants received either PT or LTPI. Pain was assessed and 1 month posttreatment completion. Levator-based pain was assessed using a numeric rating scale (NRS) and the Patient Global Impression of Improvement (PGI-I) scale. Sexual function was assessed using the Female Sexual Function Index (FSFI). Results Twenty-nine women completed the study (17 had PT, 12 had LTPI). Both groups reported reduction in vaginal pain: mean NRS change from baseline of 4.47 [standard deviation (SD) 2.12) for PT and 4.67 (SD 1.72) for LTPI (p = 0.8)]. A \u3e50 % improvement in NRS was documented among 59 % of women receiving PT and 58 % receiving LTPI (p = 1.0). Consistent with NRS scores, mean PGI-I score was 2.50 (SD 1.17) for PT and 2.17 (SD 1.01) for LTPI (p = 0.5). Mean change in FSFI favored PT [PT +8.87 (SD 5.60), LTPI +4.00 (SD 5.24), p = 0.04], reflecting improvement in the sexual pain domain favoring PT (p = 0.02). However, the time in weeks to effect improvement favored LTPI if controlling for the degree of change in NRS (p = 0.01) and FSFI (p = 0.01). Conclusions Vaginal myalgia and sex-related pain improved with pelvic floor PT and LTPI. Time-to-effect improvement and significance of therapy are dependent on treatment type

A Pilot Randomized Trial of Levator Injections Versus Physical Therapy for Treatment of Pelvic Floor Myalgia and Sexual Pain

Introduction and hypothesis Our aim was to determine the effects of pelvic floor physical therapy (PT) and levator-directed trigger-point injections (LTPI) on sexual function and levator-related pelvic pain. Study design A randomized trial among women with pelvic floor myalgia (PFM) was performed wherein participants received either PT or LTPI. Pain was assessed and 1 month posttreatment completion. Levator-based pain was assessed using a numeric rating scale (NRS) and the Patient Global Impression of Improvement (PGI-I) scale. Sexual function was assessed using the Female Sexual Function Index (FSFI). Results Twenty-nine women completed the study (17 had PT, 12 had LTPI). Both groups reported reduction in vaginal pain: mean NRS change from baseline of 4.47 [standard deviation (SD) 2.12) for PT and 4.67 (SD 1.72) for LTPI (p = 0.8)]. A \u3e50 % improvement in NRS was documented among 59 % of women receiving PT and 58 % receiving LTPI (p = 1.0). Consistent with NRS scores, mean PGI-I score was 2.50 (SD 1.17) for PT and 2.17 (SD 1.01) for LTPI (p = 0.5). Mean change in FSFI favored PT [PT +8.87 (SD 5.60), LTPI +4.00 (SD 5.24), p = 0.04], reflecting improvement in the sexual pain domain favoring PT (p = 0.02). However, the time in weeks to effect improvement favored LTPI if controlling for the degree of change in NRS (p = 0.01) and FSFI (p = 0.01). Conclusions Vaginal myalgia and sex-related pain improved with pelvic floor PT and LTPI. Time-to-effect improvement and significance of therapy are dependent on treatment type

Improving the prevention and management of chronic disease in low-income and middle-income countries: a priority for primary health care.

The burden of chronic diseases, such as heart disease, cancer, diabetes, and mental disorders is high in low-income and middle-income countries and is predicted to increase with the ageing of populations, urbanisation, and globalisation of risk factors. Furthermore, HIV/AIDS is increasingly becoming a chronic disorder. An integrated approach to the management of chronic diseases, irrespective of cause, is needed in primary health care. Management of chronic diseases is fundamentally different from acute care, relying on several features: opportunistic case finding for assessment of risk factors, detection of early disease, and identification of high risk status; a combination of pharmacological and psychosocial interventions, often in a stepped-care fashion; and long-term follow-up with regular monitoring and promotion of adherence to treatment. To meet the challenge of chronic diseases, primary health care will have to be strengthened substantially. In the many countries with shortages of primary-care doctors, non-physician clinicians will have a leading role in preventing and managing chronic diseases, and these personnel need appropriate training and continuous quality assurance mechanisms. More evidence is needed about the cost-effectiveness of prevention and treatment strategies in primary health care. Research on scaling-up should be embedded in large-scale delivery programmes for chronic diseases with a strong emphasis on assessment

Biocompatible Flavone-Based Fluorogenic Probes for Quick Wash-Free Mitochondrial Imaging in Living Cells

Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, <b>MC-Mito1</b> and <b>MC-Mito2</b>, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of <b>MC-Mito2</b> encourages a broader range of biological applications for understanding the cell degeneration and apoptosis mechanism