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Background:. Acute respiratory failure occurs frequently in hospitalized patients and often begins outside the ICU, associated with increased length of stay, cost, and mortality. Delays in decompensation recognition are associated with worse outcomes. Objectives:. The objective of this study is to predict acute respiratory failure requiring any advanced respiratory support (including noninvasive ventilation). With the advent of the coronavirus disease pandemic, concern regarding acute respiratory failure has increased. Derivation Cohort:. All admission encounters from January 2014 to June 2017 from three hospitals in the Emory Healthcare network (82,699). Validation Cohort:. External validation cohort: all admission encounters from January 2014 to June 2017 from a fourth hospital in the Emory Healthcare network (40,143). Temporal validation cohort: all admission encounters from February to April 2020 from four hospitals in the Emory Healthcare network coronavirus disease tested (2,564) and coronavirus disease positive (389). Prediction Model:. All admission encounters had vital signs, laboratory, and demographic data extracted. Exclusion criteria included invasive mechanical ventilation started within the operating room or advanced respiratory support within the first 8 hours of admission. Encounters were discretized into hour intervals from 8 hours after admission to discharge or advanced respiratory support initiation and binary labeled for advanced respiratory support. Prediction of Acute Respiratory Failure requiring advanced respiratory support in Advance of Interventions and Treatment, our eXtreme Gradient Boosting-based algorithm, was compared against Modified Early Warning Score. Results:. Prediction of Acute Respiratory Failure requiring advanced respiratory support in Advance of Interventions and Treatment had significantly better discrimination than Modified Early Warning Score (area under the receiver operating characteristic curve 0.85 vs 0.57 [test], 0.84 vs 0.61 [external validation]). Prediction of Acute Respiratory Failure requiring advanced respiratory support in Advance of Interventions and Treatment maintained a positive predictive value (0.31–0.21) similar to that of Modified Early Warning Score greater than 4 (0.29–0.25) while identifying 6.62 (validation) to 9.58 (test) times more true positives. Furthermore, Prediction of Acute Respiratory Failure requiring advanced respiratory support in Advance of Interventions and Treatment performed more effectively in temporal validation (area under the receiver operating characteristic curve 0.86 [coronavirus disease tested], 0.93 [coronavirus disease positive]), while achieving identifying 4.25–4.51× more true positives. Conclusions:. Prediction of Acute Respiratory Failure requiring advanced respiratory support in Advance of Interventions and Treatment is more effective than Modified Early Warning Score in predicting respiratory failure requiring advanced respiratory support at external validation and in coronavirus disease 2019 patients. Silent prospective validation necessary before local deployment.

Unilateral proptosis secondary to ectopic lacrimal gland tissue is rare. The most common site of ectopic lacrimal gland tissue is at the bulbar conjunctiva and limbal area. Although uncommon, intraorbital ectopic lacrimal gland tissue may mimic other ominous symptoms of intraorbital neoplasm in childhood. We present a rare case of intraconal ectopic lacrimal gland tissue in a 14-year-old girl with intermittent proptosis since childhood associated with subconjunctival hemorrhage and excruciating pain. She underwent lateral orbitotomy with orbital mass excision that resulted in good outcomes and no recurrence was seen at 6 months after the surgery. [ABSTRACT FROM AUTHOR]

In the past decade, high-dimensional single-cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation, which are computationally intense and difficult to evaluate and optimize. Here, we present Cytometry Clustering Optimization and Evaluation (Cyclone), an analysis pipeline integrating dimensionality reduction, clustering, evaluation, and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full-spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification but also enables the unsupervised identification of lymphocytes and mononuclear phagocyte subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on a variety of cytometry datasets, which will further power immunology research and provide a scaffold for biological discovery.

Background: eHealth interventions have proven to be valuable resources for users with diverse mental and behavioral health concerns. As these technologies continue to proliferate, both academic researchers and commercial app creators are leveraging the use of features that foster a sense of social connection on these digital platforms. Yet, the literature often insufficiently represents the functionality of these key social features, resulting in a lack of understanding of how they are being implemented., Objective: This study aimed to conduct a methodical review of commercially available eHealth apps to establish the SoCAP (social communication, affiliation, and presence) taxonomy of social features in eHealth apps. Our goal was to examine what types of social features are being used in eHealth apps and how they are implemented., Methods: A scoping review of commercially available eHealth apps was conducted to develop a taxonomy of social features. First, a shortlist of the 20 highest-rated eHealth apps was derived from One Mind PsyberGuide, a nonprofit organization with trained researchers who rate apps based on their (1) credibility, (2) user experience, and (3) transparency. Next, both mobile- and web-based versions of each app were double-coded by 2 trained raters to derive a list of social features. Subsequently, the social features were organized by category and tested on other apps to ensure their completeness., Results: Four main categories of social features emerged: (1) communication features (videoconferencing, discussion boards, etc), (2) social presence features (chatbots, reminders, etc), (3) affiliation and identity features (avatars, profiles, etc), and (4) other social integrations (social network and other app integrations). Our review shows that eHealth apps frequently use resource-intensive interactions (eg, videoconferencing with a clinician and phone calls from a facilitator), which may be helpful for participants with high support needs. Furthermore, among commercially available eHealth apps, there is a strong reliance on automated features (eg, avatars, personalized multimedia, and tailored content) that enhance a sense of social presence without requiring a high level of input from a clinician or staff member., Conclusions: The SoCAP taxonomy includes a comprehensive list of social features and brief descriptions of how these features work. This classification system will provide academic and commercial eHealth app creators with an understanding of the various social features that are commonly implemented, which will allow them to apply these features to enhance their own apps. Future research may include comparing the synergistic effects of various combinations of these social features., (©Ian Kwok, Melanie Freedman, Lisa Kamsickas, Emily G Lattie, Dershung Yang, Judith Tedlie Moskowitz. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.09.2024.)

Background: Alzheimer disease is a degenerative neurological condition that requires long-term care. The cost of these responsibilities is often borne by informal caregivers, who experience an elevated risk of negative physical and psychological outcomes. Previously, we designed a positive emotion regulation intervention that was shown to improve well-being among dementia caregivers when delivered through one-on-one videoconferencing lessons with a trained facilitator. However, the format required significant resources in terms of logistics and facilitator time. To broaden the reach of the intervention, we aimed to develop the Social Augmentation of Self-Guided Electronic Delivery of the Life Enhancing Activities for Family Caregivers (SAGE LEAF) program, an iteration of the intervention in a self-guided, web-based format with enhanced opportunities for social connection., Objective: The aim of this study was to gather feedback to inform the design of social features for the SAGE LEAF intervention. In the absence of a facilitator, our goal with the self-guided SAGE LEAF intervention was to integrate various social features (eg, discussion board, automated support, and profiles) to maximize engagement among participants., Methods: Qualitative data were collected from 26 individuals through (1) interviews with participants who completed a previous version of the intervention via videoconferencing with a facilitator, (2) focus groups with dementia caregivers who had not previously experienced the intervention, and (3) focus groups with Alzheimer disease clinical care providers. We conducted a qualitative thematic analysis to identify which social features would be the most helpful and how they could be implemented in a way that would be best received by caregivers., Results: Interview and focus group feedback indicated that participants generally liked the potential features suggested, including the discussion boards, multimedia content, and informational support. They had valuable suggestions for optimal implementation. For example, participants liked the idea of a buddy system where they would be matched up with another caregiver for the duration of the study. However, they expressed concern about differing expectations among caregivers and the possibility of matched caregivers not getting along. Participants also expressed interest in giving caregivers access to a podcast on the skills, which would allow them to review additional content when they wished., Conclusions: Taken together, the discussions with caregivers and providers offered unique insights into the types of social features that may be integrated into the SAGE LEAF intervention, as well as implementation suggestions to improve the acceptability of the features among caregivers. These insights will allow us to design social features for the intervention that are optimally engaging and helpful for caregivers., (©Ian Kwok, Emily Gardiner Lattie, Dershung Yang, Amanda Summers, Paul Cotten, Caroline Alina Leong, Judith Tedlie Moskowitz. Originally published in JMIR Formative Research (https://formative.jmir.org), 25.04.2024.)

Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec + cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpβ transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPε P27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis., (© 2024. The Author(s).)

Background: The responsibilities of being a primary caregiver for a loved one with dementia can produce significant stress for the caregiver, leading to deleterious outcomes for the caregiver's physical and psychological health. Hence, researchers are developing eHealth interventions to provide support for caregivers. Members of our research team previously developed and tested a positive emotion regulation intervention that we delivered through videoconferencing, in which caregiver participants would meet one-on-one with a trained facilitator. Although proven effective, such delivery methods have limited scalability because they require significant resources in terms of cost and direct contact hours., Objective: This study aimed to conduct a pilot test of a socially enhanced, self-guided version of the positive emotion regulation intervention, Social Augmentation of Self-Guided Electronic Delivery of the Life Enhancing Activities for Family Caregivers (SAGE LEAF). Studies have shown that social presence or the perception of others in a virtual space is associated with enhanced learning and user satisfaction. Hence, the intervention leverages various social features (eg, discussion boards, podcasts, videos, user profiles, and social notifications) to foster a sense of social presence among participants and study team members., Methods: Usability, usefulness, feasibility, and acceptability data were collected from a pilot test in which participants (N=15) were given full access to the SAGE LEAF intervention over 6 weeks and completed preintervention and postintervention assessments (10/15, 67%). Preliminary outcome measures were also collected, with an understanding that no conclusions about efficacy could be made, because our pilot study did not have a control group and was not sufficiently powered., Results: The results suggest that SAGE LEAF is feasible, with participants viewing an average of 72% (SD 42%) of the total available intervention web pages. In addition, acceptability was found to be good, as demonstrated by participants' willingness to recommend the SAGE LEAF program to a friend or other caregiver. Applying Pearson correlational analyses, we found moderate, positive correlation between social presence scores and participants' willingness to recommend the program to others (r 9 =0.672; P=.03). We also found positive correlation between social presence scores and participants' perceptions about the overall usefulness of the intervention (r 9 =0.773; P=.009). This suggests that participants' sense of social presence may be important for the feasibility and acceptability of the program., Conclusions: In this pilot study, the SAGE LEAF intervention demonstrates potential for broad dissemination for dementia caregivers. We aim to incorporate participant feedback about how the social features may be improved in future iterations to enhance usability and to further bolster a sense of social connection among participants and study staff members. Next steps include partnering with dementia clinics and other caregiver-serving organizations across the United States to conduct a randomized controlled trial to evaluate the effectiveness of the intervention., (©Ian Kwok, Emily Gardiner Lattie, Dershung Yang, Amanda Summers, Veronika Grote, Paul Cotten, Judith Tedlie Moskowitz. Originally published in JMIR Aging (https://aging.jmir.org), 06.09.2023.)

Conventional dendritic cells (cDCs) are professional antigen-presenting cells that control the adaptive immune response. Their subsets and developmental origins have been intensively investigated but are still not fully understood as their phenotypes, especially in the DC2 lineage and the recently described human DC3s, overlap with monocytes. Here, using LEGENDScreen to profile DC vs. monocyte lineages, we found sustained expression of FLT3 and CD45RB through the whole DC lineage, allowing DCs and their precursors to be distinguished from monocytes. Using fate mapping models, single-cell RNA sequencing and adoptive transfer, we identified a lineage of murine CD16/32 + CD172a + DC3, distinct from DC2, arising from Ly6C + monocyte-DC progenitors (MDPs) through Lyz2 + Ly6C + CD11c - pro-DC3s, whereas DC2s develop from common DC progenitors (CDPs) through CD7 + Ly6C + CD11c + pre-DC2s. Corresponding DC subsets, developmental stages, and lineages exist in humans. These findings reveal DC3 as a DC lineage phenotypically related to but developmentally different from monocytes and DC2s., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In the past decade, high-dimensional single cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation which are computationally intense and difficult to evaluate and optimize. Here we present Cyclone, an analysis pipeline integrating dimensionality reduction, clustering, evaluation and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification, but also enables the unsupervised identification of lymphocytes and mononuclear phagocytes subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on variety of cytometry datasets which will further power immunology research and provide a scaffold for biological discovery.

Microbial enzymes catalyze various reactions inside and outside living cells. Among the widely studied enzymes, fungal enzymes have been used for some of the most diverse purposes, especially in bioremediation, biosynthesis, and many nature-inspired commercial applications. To improve their stability and catalytic ability, fungal enzymes are often immobilized on assorted materials, conventional as well as nanoscale. Recent advances in fungal enzyme immobilization provide effective and sustainable approaches to achieve improved environmental and commercial outcomes. This review aims to provide a comprehensive overview of commonly studied fungal enzymes and immobilization technologies. It also summarizes recent advances involving immobilized fungal enzymes for the degradation or assembly of compounds used in the manufacture of products, such as detergents, food additives, and fossil fuel alternatives. Furthermore, challenges and future directions are highlighted to offer new perspectives on improving existing technologies and addressing unexplored fields of applications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neutrophils play significant roles in immune homeostasis and as neutralizers of microbial infections. Recent evidence further suggests heterogeneity of neutrophil developmental and activation states that exert specialized effector functions during inflammatory disease conditions. Neutrophils can play multiple roles during viral infections, secreting inflammatory mediators and cytokines that contribute significantly to host defense and pathogenicity. However, their roles in viral immunity are not well understood. In this review, we present an overview of neutrophil heterogeneity and its impact on the course and severity of viral respiratory infectious diseases. We focus on the evidence demonstrating the crucial roles neutrophils play in the immune response toward respiratory infections, using influenza as a model. We further extend the understanding of neutrophil function with the studies pertaining to COVID-19 disease and its neutrophil-associated pathologies. Finally, we discuss the relevance of these results for future therapeutic options through targeting and regulating neutrophil-specific responses., (©2022 Society for Leukocyte Biology.)

Circulating Ly6C hi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6C hi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.

Background: Adherence to self-guided interventions tends to be very low, especially in people with depression. Prior studies have demonstrated that enhancements may increase adherence, but little is known about the efficacy of various enhancements in comparison to, or in combination with, one another., Objective: The aim of our study is to test whether 3 enhancements-facilitator contact (FC), an online discussion board, and virtual badges (VB)-alone, or in combination, improve adherence to a self-guided, web-based intervention for depression. We also examined whether age, gender, race, ethnicity, comfort with technology, or baseline depression predicted adherence or moderated the effects that each enhancement had on adherence., Methods: Participants were recruited through web-based sources and, after completing at least 4 out of 7 daily emotion reports, were sequentially assigned to 1 of 9 conditions-the intervention alone; the intervention plus 1, 2, or all 3 enhancements; or an emotion reporting control condition. The intervention was a positive psychological program consisting of 8 skills that specifically targeted positive emotions, and it was delivered over 5 weeks in a self-guided, web-based format. We operationalized adherence as the number of skills accessed., Results: A total of 602 participants were enrolled in this study. Participants accessed, on average, 5.61 (SD 2.76) of 8 skills. The total number of enhancements participants received (0-3) did not predict the number of skills accessed. Participants who were assigned to the VB+FC condition accessed significantly more skills than those in the intervention only conditions. Furthermore, participants in arms that received the combination of both the VB and FC enhancements (VB+FC and VB+FC+online discussion board) accessed a greater number of skills relative to the number of skills accessed by participants who received either VB or FC without the other. Moderation analyses revealed that the receipt of VB (vs no VB) predicted higher adherence among participants with moderately severe depression at baseline., Conclusions: The results suggested that the VB+FC combination significantly increased the number of skills accessed in a self-guided, web-based intervention for elevated depression. We have provided suggestions for refinements to these enhancements, which may further improve adherence., Trial Registration: ClinicalTrials.gov NCT02861755; http://clinicaltrials.gov/ct2/show/NCT02861755., (©Judith Tedlie Moskowitz, Elizabeth L Addington, Eva Shiu, Sarah M Bassett, Stephanie Schuette, Ian Kwok, Melanie E Freedman, Yan Leykin, Laura R Saslow, Michael A Cohn, Elaine O Cheung. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.09.2021.)

The Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms., (© 2021. The Author(s).)

Background: Mental health tends to worsen over the course of medical school, with steep declines in well-being in students' clerkship year (M3). Positive emotion promotes adaptive coping to stress and may help preserve medical student well-being., Objective: This study describes the development of LAVENDER (Leveraging Affect and Valuing Empathy for Nurturing Doctors' Emotional Resilience), a program aimed at increasing positive emotion to preserve well-being in medical students., Methods: We conducted a single-arm pilot of LAVENDER, a positive psychology intervention developed for medical students delivered in an interactive classroom format to a cohort of 157 third-year medical students at the Albert Einstein College of Medicine. Our primary outcome was the acceptability of LAVENDER. We also examined preliminary efficacy using measures of emotion, stress and burnout collected at each intervention session., Results: LAVENDER showed good acceptability: 76% of participants agreed that the LAVENDER skills were useful and 72% agreed that they would recommend the LAVENDER program to others. Qualitative feedback suggested that medical students enjoyed the program and found the skills to be useful for coping with stress, but also reported the following barriers to engagement: lack of time to practice the skills, resistance to the mandatory nature of the wellness sessions, and difficulty integrating the skills in daily life. We did not find support for the preliminary efficacy of LAVENDER for improving medical student well-being in students' clerkship year. Participants showed decreases in positive emotion and increases in symptoms of burnout over the intervention period ( p s < .01)., Conclusion: The current paper describes the development and a single-arm pilot test of LAVENDER, a positive psychology program tailored for medical students. Although we found preliminary evidence for the acceptability of LAVENDER, we did not find support for the preliminary efficacy. Lessons learned and next steps for the program are discussed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues. Through analysis of the receptor, transcriptional, and chromatin accessibility landscapes, we identify varying neutrophil states and assign non-canonical functions, including vascular repair and hematopoietic homeostasis. Accordingly, depletion of neutrophils compromised angiogenesis during early age, genotoxic injury, and viral infection, and impaired hematopoietic recovery after irradiation. Neutrophils acquired these properties in target tissues, a process that, in the lungs, occurred in CXCL12-rich areas and relied on CXCR4. Our results reveal that tissues co-opt neutrophils en route for elimination to induce programs that support their physiological demands., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Unilateral proptosis secondary to ectopic lacrimal gland tissue is rare. The most common site of ectopic lacrimal gland tissue is at the bulbar conjunctiva and limbal area. Although uncommon, intraorbital ectopic lacrimal gland tissue may mimic other ominous symptoms of intraorbital neoplasm in childhood. We present a rare case of intraconal ectopic lacrimal gland tissue in a 14-year-old girl with intermittent proptosis since childhood associated with subconjunctival hemorrhage and excruciating pain. She underwent lateral orbitotomy with orbital mass excision that resulted in good outcomes and no recurrence was seen at 6 months after the surgery., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2020 Taiwan J Ophthalmol.)

Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1. Our dissection of the GMP hierarchy led us to further identify a previously unknown intermediate proNeu2 population. Similar populations could be detected in human samples. proNeu1s, but not proNeu2s, selectively expanded during the early phase of sepsis at the expense of monocytes. Collectively, our findings help shape the neutrophil maturation trajectory roadmap and challenge the current definition of GMPs., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Diabetes is a leading cause of years of life lost and accounts for approximately one-fourth of health care dollars spent in the United States. Many of these costs are related to poor medication adherence and lack of self-care behaviors and are thus preventable. Depression, which is more prevalent among people with diabetes than in the general population, predicts poorer management of one's diabetes, whereas positive affect predicts engaging in more positive health behaviors. Consequently, interventions that improve depression and positive affect may also improve diabetes-related outcomes among people with diabetes. Although preliminary research on the impact of such interventions among people with diabetes is promising, these studies focused primarily on in-person interventions, have had small samples, and lack long-term follow-up., Objective: This study aims to examine the short- and long-term effects of a digital therapeutic platform focused on mental health among adults with poorly managed type 2 diabetes and elevated levels of depression., Methods: This is a randomized controlled trial in which adults with a type 2 diabetes diagnosis, elevated hemoglobin A 1c (HbA 1c ) levels (≧7), and moderate to severe depressive symptoms will be randomly assigned to a positive emotion regulation skills intervention group or a sham digital intervention with only psychoeducational content. The study will take place over 14 months, including the 8-week intervention (or control) delivered via a digital therapeutic platform (Happify Health) and follow-up assessments at 3, 6, and 12 months postintervention. Throughout the intervention and for 1 week at each postintervention follow-up, participants will complete daily assessments of diabetes-related distress, diabetes regimen adherence, and mood. Our primary outcome, HbA 1c , will be self-reported every 3 months throughout the study. Secondary and exploratory outcomes will be assessed at baseline; at 8 weeks; and at 3, 6, and 12 months postintervention., Results: Recruitment is expected to begin in June 2020. Participants will begin the study as they are recruited and will finish in waves. The final wave of data collection from the 8-week intervention is expected for winter 2020, with the completion of the 12-month follow-up in winter 2021., Conclusions: Although previous research suggests that in-person psychological interventions have promising effects on both psychological and physical outcomes among adults with diabetes, digital interventions can be advantageous because they are easily scalable and reduce many barriers that prevent people from seeking treatment. This trial will provide important information about the effects of a digital mental health intervention among adults with type 2 diabetes, assessing both short- and long-term effects of this intervention on HbA1c, depressive symptoms, and other diabetes-specific outcomes. If successful, this may introduce a scalable intervention that would help reduce some of the preventable costs associated with diabetes., Trial Registration: ClinicalTrials.gov NCT04068805; https://clinicaltrials.gov/ct2/show/NCT04068805., International Registered Report Identifier (irrid): PRR1-10.2196/18578., (©Eliane Boucher, Judith T Moskowitz, Gina M Kackloudis, Julia L Stafford, Ian Kwok, Acacia C Parks. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.08.2020.)

Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3 TdT reporter, Ms4a3 Cre , and Ms4a3 CreERT2 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To undertake a systematic review of the evidence base for the effectiveness of surgical fixation of lateral compression (LC-1) fragility fractures of the pelvis compared with non-surgical approaches., Searches: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and two international trials registers were searched up to January 2017 (MEDLINE to February 2019) for studies of internal or external fixation of fragility fractures of the pelvis., Participants: Patients with lateral compression pelvic fractures, sustained as the result of a low-energy mechanism, defined as a fall from standing height or less., Interventions: Surgery using either external or internal fixation devices. Conservative non-surgical treatment was the defined comparator., Outcome Measures: Outcomes of interest were patient mobility and function, pain, quality of life, fracture union, mortality, hospital length of stay and complications (additional operative procedures, number and type of adverse events and serious adverse events)., Quality Assessment and Synthesis: The Joanna Briggs Institute Checklist for Case Series was used to assess the included studies. Results were presented in a narrative synthesis., Results: Of 3421 records identified, four retrospective case series met the inclusion criteria. Fixation types were not consistent between studies or within studies and most patients had more than one type of pelvic fixation. Where reported, mobility and function improved post-surgery, and a reduction in pain was recorded. Length of hospital stay ranged from 4 days to 54 days for surgical fixation of any type. Reported complications and adverse outcomes included: infections, implant loosening, pneumonia and thrombosis. Use of analgesia was not reported., Conclusions: There is insufficient evidence to support guidance on the most effective treatment for patients who fail to mobilise after sustaining an LC-1 fragility fracture., Trial Registration Number: CRD42017055872., Competing Interests: Competing interests: HMAI, MN, EC, MH, IK, CH declare they have no conflicts of interest. Since starting this review, AB, JK, PB and CM have received funding for a trial of surgical fixation compared to non-surgical treatment in a LC1 FFP population., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)