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Abstract The relative prevalence of endemic and cosmopolitan biogeographic ranges in marine microbes, and the factors that shape these patterns, are not well known. Using prokaryotic and eukaryotic amplicon sequence data spanning 445 near-surface samples in the Southern California Current region from 2014 to 2020, we quantified the proportion of taxa exhibiting endemic, cosmopolitan, and generalist distributions in this region. Using in-situ data on temperature, salinity, and nitrogen, we categorized oceanic habitats that were internally consistent but whose location varied over time. In this context, we defined cosmopolitan taxa as those that appeared in all regional habitats and endemics as taxa that only appeared in one habitat. Generalists were defined as taxa occupying more than one but not all habitats. We also quantified each taxon’s habitat affinity, defined as habitats where taxa were significantly more abundant than expected. Approximately 20% of taxa exhibited endemic ranges, while around 30% exhibited cosmopolitan ranges. Most microbial taxa (50.3%) were generalists. Many of these taxa had no habitat affinity (> 70%) and were relatively rare. Our results for this region show that, like terrestrial systems and for metazoans, cosmopolitan and endemic biogeographies are common, but with the addition of a large number of taxa that are rare and randomly distributed.

Background:. Microsurgical technique is still not readily available in many low- and middle-income countries. Few works in the scholarly literature describe the establishment of microsurgical practice on the African continent, and there are virtually no descriptions of the financial aspects of free flap performance by locally staffed teams in sub-Saharan Africa. The Kapsowar Hospital is a hospital in rural Kenya with 2 plastic and reconstructive surgeons certified by the American Board of Plastic Surgery and has recently expanded clinical practice to include microsurgical procedures. Methods:. A retrospective chart review was conducted on patients who received a free flap at the Kapsowar Hospital in 2022–2023. Captured parameters included age, sex, relevant medical history, etiology of wound, flap performed, intraoperative time, complications, surgical revisions, and length of stay. Billing information for all domestic patients who received free flaps were audited, and disability-adjusted life years was calculated. Results:. Nineteen free flaps were performed on 17 patients. The most common flap performed was the anterolateral thigh flap (n = 11). Flap survival rate was 94.7%. The surgical cost associated with performing an anterolateral thigh flap was $548 ± $35. The total cost associated with other free flap performances was $863 ± $269. The cost per disability-adjusted life years averted was $121, indicating that the procedure was very cost-effective. Conclusions:. Despite obstacles, microsurgical practices can be safely established in limited-resource African settings. Free flaps can be performed with greater cost-efficiency when performed by local teams. Surgical mission trips should emphasize educational components and ultimately transition care to local surgeons.

Purpose:. Both governmental and nongovernmental training programs are expanding efforts to train the next generation of plastic surgeons who will work in low- and middle-income countries (LMICs). Sufficient training is dependent on acquiring the appropriate skillset for these contexts. Few studies have characterized the spectrum of practice of plastic surgeons in LMICs and their relative disparity. Methods:. We performed a retrospective review on all patients who received plastic surgery at a single institution in rural western Kenya from 2021 to 2023. Data such as diagnoses, procedures, and home village/town of residence were collected. Patient home location was geomapped using an open-access distance matrix application programming interface to estimate travel time based on terrain and road quality, assuming patient access to a private vehicle and ideal traveling conditions. Descriptive statistics were performed. Results:. A total of 296 patients received surgery. Common procedures included treatment of cleft lip/palate (CLP), burn reconstruction, and reconstruction for benign tumors of the head and neck. The average distance to treatment was 159.2 minutes. Increased travel time was not associated with time to CLP repair (P > 0.05). Increased travel time was associated with delayed treatment for burns (P = 0.005), maxillofacial trauma (P = 0.032), and hand trauma (P = 0.016). Conclusions:. Training programs for plastic surgeons in LMICs should ensure competency in CLP, flaps, burn reconstruction, and head and neck reconstruction. Our novel use of an application programming interface indicates that international partnerships have been more successful in decreasing treatment delays for CLP patients, but not other reconstructive procedure patients. Expanded commitment from international partners to address these reconstructive burdens in LMICs is warranted.

Abstract The nuclear lamina serves important functions in the nucleus, providing structural support to the nuclear envelope and contributing to chromatin organization. The primary proteins that constitute the lamina are nuclear lamins whose functions are impacted by post-translational modifications, including phosphorylation by protein kinase C (PKC). While PKC-mediated lamin phosphorylation is important for nuclear envelope breakdown during mitosis, less is known about interphase roles for PKC in regulating nuclear structure. Here we show that overexpression of PKC ß, but not PKC α, increases the Lamin A/C mobile fraction in the nuclear envelope in HeLa cells without changing the overall structure of Lamin A/C and Lamin B1 within the nuclear lamina. Conversely, knockdown of PKC ß, but not PKC α, reduces the Lamin A/C mobile fraction. Thus, we demonstrate an isoform-specific role for PKC in regulating interphase Lamin A/C dynamics outside of mitosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is a chronic inflammatory disease. Although typically associated with inflammation of the lungs and other peripheral tissues, increasing evidence has uncovered neurological consequences attributable to Mtb infection. These include deficits in memory and cognition, increased risk for neurodegenerative disease, and progressive neuropathology. Although the neurological effects of the disease, without CNS infection, have been characterized, the mechanism of neurotoxicity is unknown. We hypothesized that alterations to the blood-brain barrier (BBB) allows peripheral immune cells to enter the brain, initiating a neuroinflammatory response. To test this hypothesis, guinea pigs were exposed by aerosol to a laboratory and a clinical Mtb strain for 15 days. Following Mtb infection, proteins critical to BBB function, including claudin V and collagen IV, are modulated without evidence of bacterial dissemination to the brain. This is correlated with increased contact of astrocytic processes to vessels in the brain, as well as increased expression of the water channel protein aquaporin 4 (AQP4) on endfeet. Upon further investigation, we discovered the potential role of glial reactivity, which is increased following infection with both bacterial strains, in the progression of BBB changes and, ultimately, the permeability of peripheral immune cells into the brain. Through these data, we have obtained a preliminary understanding of the mechanisms of cellular stress in the brain following pulmonary Mtb infection which should be further investigated in future studies.

Coastal upwelling sustains some of the most productive ocean regions. Here, the authors find that spatial patterns and temporal changes in nutrient supply explain marine microbial community structure and diversity in the Southern California Current region.

Abstract It is difficult to make skillful predictions about the future dynamics of marine phytoplankton populations. Here, we use a 22‐year time series of monthly average abundances for 198 phytoplankton taxa from Station L4 in the Western English Channel (1992–2014) to test whether and how aggregating phytoplankton into multi‐species assemblages can improve predictability of their temporal dynamics. Using a non‐parametric framework to assess predictability, we demonstrate that the prediction skill is significantly affected by how species data are grouped into assemblages, the presence of noise, and stochastic behavior within species. Overall, we find that predictability one month into the future increases when species are aggregated together into assemblages with more species, compared with the predictability of individual taxa. However, predictability within dinoflagellates and larger phytoplankton (>12 μm cell radius) is low overall and does not increase by aggregating similar species together. High variability in the data, due to observational error (noise) or stochasticity in population growth rates, reduces the predictability of individual species more than the predictability of assemblages. These findings show that there is greater potential for univariate prediction of species assemblages or whole‐community metrics, such as total chlorophyll or biomass, than for the individual dynamics of phytoplankton species.

Collin Chase,1 Amr Elsawy,2 Taher Eleiwa,3 Eyup Ozcan,4 Mohamed Tolba,2 Mohamed Abou Shousha2 1Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 2Cornea Department, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA; 3Department of Ophthalmology, Faculty of Medicine, Benha University, Benha, Egypt; 4Department of Ophthalmology, Net Eye Medical Center, Gaziantep, TurkeyCorrespondence: Mohamed Abou ShoushaCornea Department, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, 900 NW 17th Street, Miami, FL, 33136, USATel +1 305-326-6000Email Mshousha@med.miami.eduObjective: To evaluate a deep learning-based method to autonomously detect dry eye disease (DED) in anterior segment optical coherence tomography (AS-OCT) images compared to common clinical dry eye tests.Methods: In this study, 27,180 AS-OCT images were prospectively collected from 151 eyes of 91 patients. Images were used to train and test the deep learning model. Masked cornea specialist ophthalmologist diagnoses were used as the gold standard. Clinical dry eye tests were performed on patients in the DED group to compare the results of the model. The dry eye tests performed were tear break-up time (TBUT), Schirmer’s test, corneal staining, conjunctival staining, and Ocular Surface Disease Index (OSDI).Results: Our deep learning model achieved an accuracy of 84.62%, sensitivity of 86.36%, and specificity of 82.35% in the diagnosis of DED. The positive likelihood ratio was 4.89, and the negative likelihood ratio was 0.17. The mean DED probability score was 0.81 ± 0.23 in the DED group and 0.20 ± 0.27 in the healthy group (P < 0.01). The deep learning model accuracy in the diagnosis of DED was significantly better than that of corneal staining, conjunctival staining, and Schirmer’s test (P < 0.05). There was no significant difference between the deep learning diagnostic accuracy and that of the OSDI and TBUT.Conclusion: Based on preliminary results, reliable autonomous diagnosis of DED with our deep learning model was achieved, when compared with standard dry eye clinical tests that correlated significantly more or similarly to diagnoses made by cornea specialist ophthalmologists.Keywords: dry eye disease, artificial intelligence, optical coherence tomography

Interactions between phytoplankton and ultraviolet radiation (UVR: 280 – 400 nm) are undergoing changes dictated by variability in ocean temperature, the depth of mixed layers, nutrient availability, and the thickness of the ozone layer. There are a variety of mechanisms for phytoplankton to cope with UVR stress, one of the most prevalent being the presence of mycosporine-like amino acids (MAAs). Despite the importance of these molecules to phytoplankton fitness under UVR stress, knowledge of the diversity and distribution of these molecules in the world’s oceans is relatively limited. Here, the composition and distribution of MAAs in phytoplankton were examined in a transect across the Southern Ocean, crossing multiple fronts, from eastern New Zealand to the West Antarctic Peninsula in March and April of 2018. The highest concentration of MAAs (> 0.2 μg/L) was found between 50 and 60°S, as well as along a longitudinal gradient between 137.47 and 144.78°W. A strong correlation was found between a model of the preceding month’s UVR dosage experienced in the mixed layer and the ratio of MAAs to chlorophyll-a across the transect, indicating a relationship between the integrated history of light exposure and phytoplankton physiology. Haptophytes accounted for the majority of biomass north of the polar front (PF) and were strongly correlated with a diversity of MAAs. South of the PF a transition to a community dominated by diatoms was observed, with community composition changes strongly correlated to porphyra-334 concentrations. The data presented here provide a baseline for MAA abundance and association with specific phytoplankton taxa across the Southern Ocean amid a changing climate.

We have performed the first systematic search of the full Galaxy Evolution Explorer (GALEX) data archive for astrophysical variability on timescales of seconds to minutes by rebinning data across the whole mission to 30 s time resolution. The result is the GALEX Flare Catalog (GFCAT), which describes 1426 ultraviolet variable sources, including stellar flares, eclipsing binaries, δ Scuti and RR Lyrae variables, and active galactic nuclei. Many of these sources have never previously been identified as variable. We have also assembled a table of observations of ultraviolet flares and accompanying statistics and measurements, including energies, and of candidate eclipsing stars. This effort was enabled by a significantly enhanced version of the gPhoton software for analyzing time-domain GALEX data; this “gPhoton2” package is available to support follow-on efforts.

In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that coexpression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have colimited the diatom population along with low Si. Iron limitation represents an overlooked driver of both toxin production and ecological success of the low-iron-adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.

Impairments in choosing optimally between immediate and delayed rewards are associated with numerous psychiatric disorders. Such ‘intertemporal’ choice is influenced by genetic and experiential factors; however, the contributions of biological sex are understudied and data to date are largely inconclusive. Rats were used to determine how sex and gonadal hormones influence choices between small, immediate and large, delayed rewards. Females showed markedly greater preference than males for small, immediate over large, delayed rewards (greater impulsive choice). This difference was neither due to differences in food motivation or reward magnitude perception, nor was it affected by estrous cycle. Ovariectomies did not affect choice in females, whereas orchiectomies increased impulsive choice in males. These data show that male rats exhibit less impulsive choice than females and that this difference is at least partly maintained by testicular hormones. These differences in impulsive choice could be linked to gender differences across multiple neuropsychiatric conditions.

Host-pathogen relationships are an important subset of interspecies interactions that are capable of influencing population dynamics, community structure, and biogeochemical cycles. Relationships between hosts and pathogens are expected to shift in response to global climate change. Atmospheric and oceanic warming is already affecting many ecosystems, perhaps most markedly those in marine environments. Case studies illustrate some impacts ocean warming is having on marine host-pathogen dynamics, including: (1) increased host stress, (2) increased pathogen virulence, (3) pathogen range expansion, and (4) host range changes. Output from global climate models was used to calculate the number of additional months each year that various coastal regions around the globe may reach temperatures above a given threshold 50 and 100 years from now; for the Arctic region, we characterize changes in sea ice cover. Complex interactions between multiple ocean conditions that could also affect host-pathogen relationships, such as rising sea surface temperature, anoxia, ocean acidification, and stratification, should also be investigated.

Summary: Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells. Our model produces endogenous activated transforming growth factor β (TGF-β) and contains activated fibroblastic aggregates that progressively increase in size and stiffness with activation of known fibrotic molecular and cellular changes. We used this model as a phenotypic drug discovery platform for modulators of fibrosis. We validated this platform by identifying a compound that promotes resolution of fibrosis in in vivo and ex vivo models of ocular and lung fibrosis. : Vijayaraj et al. describe the generation and characterization of an in vitro progressive fibrosis model that is broadly applicable to progressive organ fibrosis. They use it to identify a promising anti-fibrotic therapy that acts by activating normal tissue repair. Keywords: disease modeling, induced pluripotent stem cells, progressive fibrosis, drug discovery, phenotypic drug screening, organ fibrosis, high content screening

Across species, aging is associated with an increased ability to choose delayed over immediate gratification. These experiments used young and aged rats to test the role of the basolateral amygdala (BLA) in intertemporal decision making. An optogenetic approach was used to inactivate the BLA in young and aged rats at discrete time points during choices between levers that yielded a small, immediate vs. a large, delayed food reward. BLA inactivation just prior to decisions attenuated impulsive choice in both young and aged rats. In contrast, inactivation during receipt of the small, immediate reward increased impulsive choice in young rats but had no effect in aged rats. BLA inactivation during the delay or intertrial interval had no effect at either age. These data demonstrate that the BLA plays multiple, temporally distinct roles during intertemporal choice, and show that the contribution of BLA to choice behavior changes across the lifespan.

The inability to scalably and precisely measure the activity of developmental cis-regulatory elements (CREs) in multicellular systems is a bottleneck in genomics. Here we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays. The resulting measurement of reporter expression is accurate over multiple orders of magnitude, with a precision approaching the limit set by Poisson counting noise. Together with RNA barcode stabilization via circularization, these scalable single-cell quantitative expression reporters provide high-contrast readouts, analogous to classic in situ assays but entirely from sequencing. Screening >200 regions of accessible chromatin in a multicellular in vitro model of early mammalian development, we identify 13 (8 previously uncharacterized) autonomous and cell-type-specific developmental CREs. We further demonstrate that chimeric CRE pairs generate cognate two-cell-type activity profiles and assess gain- and loss-of-function multicellular expression phenotypes from CRE variants with perturbed transcription factor binding sites. Single-cell quantitative expression reporters can be applied in developmental and multicellular systems to quantitatively characterize native, perturbed and synthetic CREs at scale, with high sensitivity and at single-cell resolution.

The relative prevalence of endemic and cosmopolitan biogeographic ranges in marine microbes, and the factors that shape these patterns, are not well known. Using prokaryotic and eukaryotic amplicon sequence data spanning 445 near-surface samples in the Southern California Current region from 2014 to 2020, we quantified the proportion of taxa exhibiting endemic, cosmopolitan, and generalist distributions in this region. Using in-situ data on temperature, salinity, and nitrogen, we categorized oceanic habitats that were internally consistent but whose location varied over time. In this context, we defined cosmopolitan taxa as those that appeared in all regional habitats and endemics as taxa that only appeared in one habitat. Generalists were defined as taxa occupying more than one but not all habitats. We also quantified each taxon's habitat affinity, defined as habitats where taxa were significantly more abundant than expected. Approximately 20% of taxa exhibited endemic ranges, while around 30% exhibited cosmopolitan ranges. Most microbial taxa (50.3%) were generalists. Many of these taxa had no habitat affinity (> 70%) and were relatively rare. Our results for this region show that, like terrestrial systems and for metazoans, cosmopolitan and endemic biogeographies are common, but with the addition of a large number of taxa that are rare and randomly distributed.

Nutrition has evolved into an integral part of modern critical care for both medical and surgical patients. Multiple international societies now issue evidence-based guidelines to help clinician optimize their patients’ Nutrition. However, adherence to these guidelines throughout the country is poor, and education in nutrition is still lagging in medical school. The authors also highlight four key areas where evidence-based recommendations exist – timing of initiation of enteral feeding, calculating and meeting total daily requirements, use of gastric residual volumes to guide delivery, and interuption of feeding for procedures – but are currently often not followed. Reasons for this lack of adherence are explored, and potential solutions discussed.

It was observed within the Bentley University Fall 2023 Semester Introductory Finance curriculum that applying ChatGPT-4 in a tutoring environment coincided with significantly worse student outcomes compared to no tutoring, finance tutoring, and general non-finance tutoring. This study leveraged a population of 408 freshman and sophomore undergraduates who opted-in via an IRB-approved informed consent process. The results demonstrate statistical significance under standard testing metrics and confirm several well-established principles related to the effects of tutoring and the importance of instructors for learning outcomes. A causal channel of AI interfering with learning as a "cognitive prosthesis" is proposed for further investigation.