SignificanceThis work describes the most extensive discovery and functional characterization of small regulatory RNAs (sRNAs) in Mycobacterium tuberculosis to date. We comprehensively define the sRNAs expressed in M. tuberculosis under five host-like stress conditions. This reference dataset comprehensively defines the expression patterns and boundaries of mycobacterial sRNAs. We perform in-depth characterization of one sRNA, mycobacterial regulatory sRNA in iron (MrsI), which is induced in M. tuberculosis in multiple stress conditions. MrsI is critical for the iron-sparing response in mycobacteria by binding directly to mRNAs encoding nonessential iron-containing proteins to repress their expression. Interestingly, MrsI acts in an anticipatory manner, in which its induction by a variety of stresses primes M. tuberculosis to enter an iron-sparing state more rapidly upon iron deprivation.

Background: Despite efforts to address gender disparities in medicine, female representation in orthopaedics lags behind that of other fields, and little work has evaluated gender disparities within the subspecialty of arthroplasty surgery. The objective of this study was to analyze female authorship trends in arthroplasty research from 2002 to 2019. Methods: Articles published from 2002 to 2019 in 12 clinical orthopaedic and arthroplasty journals were extracted from PubMed. Articles that provided the full name of the first author and contained the terms “arthroplasty,” “hip replacement,” “knee replacement,” or “joint replacement” in the title and/or as keywords were analyzed. The gender of the author was determined with the validated Genderize algorithm, and publication trends were analyzed over time. Descriptive and comparative statistics were computed, and logistic regression was used to evaluate gender trends. Results: From 2002 to 2019, 14,692 articles met the inclusion criteria, and the gender of 63,628 authors was identified. There were 23,626 unique authors; 4,003 (16.9%) were women and 19,623 (83.1%) were men. Female involvement in arthroplasty publications increased from 11.1% in 2002 to 12.6% in 2019 (p < 0.001), and the percentage of female first authors increased from 5.0% in 2002 to 11.3% in 2019 (p < 0.001). Critically, however, the proportion of women as senior authors significantly declined from 8.5% in 2002 to 6.2% in 2019 (p < 0.001). From our analysis of U.S. publications with physician senior authors, the proportion of female senior authors remained relatively stable from 1.7% in 2002 to 2.4% in 2019 without a significantly increasing trend (p = 0.88). Overall, on average, women published a mean (and 95% confidence interval) of 1.9 ± 0.1 publications, while men published 2.9 ± 0.1 publications (p < 0.001). The proportion of female senior authors in arthroplasty publications (6.6%) was lower than that of other orthopaedic subspecialties such as sports medicine (9.2%), spine (13.6%), and foot and ankle (13.1%). Conclusions: While overall female representation and first authorship in arthroplasty literature have increased over time, the paucity of women in senior author roles remains troubling. Future studies should examine why the proportion of women publishing in arthroplasty remains lower than that in most other orthopaedic subspecialties.

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Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized-and precision medicine applications.

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Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity to fit a specific purpose via a flexible mix-and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human- based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

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