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Tom C Woods,4 Michael J Carroll,1 Atiba A Nelson,2 Kristie D More,2 Randa Berdusco,1 Stephen Sohmer,3 Richard S Boorman,1,2 Ian KY Lo1,21Department of Surgery, 2Sport Medicine Centre, University of Calgary, Calgary, AB, Canada; 3Department of Orthopaedics, University of British Columbia, Vancouver, 4St Joseph's Hospital, Comox, BC, CanadaPurpose: The purpose of this study was to evaluate clinical and anatomic outcomes of patients following transtendon rotator-cuff repair of partial articular supraspinatus tendon avulsion (PASTA) lesions.Patients and methods: Patients in the senior author's practice who had isolated PASTA lesions treated by transtendon rotator-cuff repair were included (n=8) and retrospectively reviewed. All patients were evaluated preoperatively and at a mean of 21.2 months (±9.7 months) postoperatively using standardized clinical evaluation (physical exam, American Shoulder and Elbow Surgeons, and Simple Shoulder Test). All patients underwent postoperative imaging with a magnetic resonance imaging arthrogram.Results: There was a significant improvement in American Shoulder and Elbow Surgeons (42.7±17.5 to 86.9±25.2) and Simple Shoulder Test (4.6±3.2 to 10.1±3.8) scores from pre- to postoperative, respectively. Postoperative imaging demonstrated full-thickness medial cuff tearing in seven patients, and one patient with a persistent partial articular surface defect.Conclusion: Transtendon repair of PASTA lesions may lead to improvements in clinical outcome. However, postoperative imaging demonstrated a high incidence of full-thickness rotator-cuff defects following repair.Keywords: rotator cuff, PASTA lesion, transtendon repair

Social workers and other behavioral health professionals trained to provide prevention, treatment, and recovery services for opioid use disorders (OUD) remain urgently needed in the U.S. particularly in states with widespread health professional shortage areas. To help mitigate this workforce gap, faculty in social work and nursing at a public university in Alabama developed and piloted an innovative HRSA-funded interprofessional traineeship to prepare graduate-level nursing and social work students to assess and treat opioid use disorders (OUD). The yearlong traineeship included specialized coursework on evidenced-based practice in addictions, interprofessional telemedicine and simulation training, and multi-semester field practica in outpatient treatment settings. Impact of the pilot training was evaluated using a pre-experimental one group design. Baseline and post-training surveys assessed knowledge, attitudes, and skills related to OUD and interprofessional practice and perceived program impact. Significant increases were observed for trainees' self-reported knowledge, attitudes, and skills. Moreover, at graduation students reported that the traineeship had improved their abilities to interact with underserved populations, collaborate interprofessionally, and understand ethical issues in SUD treatment as well as enhancing their professional competence, clinical problem-solving, and health workforce skills. Findings suggest that the interprofessional training program may prepare social work and nursing graduate students to effectively serve clients with OUD and help to address a critical workforce gap in medically underserved communities.

Impacts of long-term fertilization and cultivation were evaluated on nematode communities associated with tall fescue turfgrass following 11 years of treatment applications. Fertilizer treatments of biosolid, synthetic, and plant-based fertilizers and cultivation treatments of 0×, 1×, and 2× aerification passes were applied to randomized and replicated tall fescue plots at the University of Maryland Paint Branch Turfgrass facility in College Park, Maryland. Free-living and plant-parasitic nematodes were identified, enumerated, and categorized into functional groups. Nematode count data were compared using generalized linear mixed modeling with negative binomial distribution and two-way ANOVA was used to compare nematode ecological indices. Biosolid treatments resulted in lower omnivore-predator densities than plant-based fertilizer treatments ( p  ≤ .001) and significantly greater Hoplolaimus densities than plant-based fertilizer plots ( p  ≤ .05). Synthetic fertilizer applications resulted in the greatest Eucephalobus ( p  ≤ .05) and total bacterivore densities ( p  ≤ .001) of all fertilizer treatments. Plant-based fertilizer-treated plots had the largest Maturity Index cp 2-5 and Structure Index ( p  ≤ .05). Cultivation of 1× resulted in fewer total bacterivore densities than 2× ( p  ≤ .01) while omnivore-predator densities were greater in 1× than 0× ( p  ≤ .001). Plant health, as measured by NDVI, was lowest in biosolid-treated turfgrass ( p  ≤ .05). These findings suggest that long-term turfgrass management practices can have variable impacts on nematode abundance and community structure in tall fescue and provide insights into ecological impacts of turfgrass management practices., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Neonicotinoid-contaminated sugar stores can have both near term and long term effects on honey bees due to their persistence in honey stores. Effects of imidacloprid food stores contaminants were examined in subtropical colonies that experience reduced brood rearing and foraging during overwintering. Colonies were given treatment sugar syrup containing 0 ppb (control), 20 ppb (field relevant), or 100 ppb (above field relevant) imidacloprid over six weeks to simulate contaminated fall nectar. Colonies were evaluated immediately (post-treatment) and 10 weeks (mid-winter) after treatment to compare proximal and latent effects. Post-treatment 0 ppb and 20 ppb colonies had more workers than 100 ppb colonies while 0 ppb colonies more brood than 20 ppb or 100 ppb colonies. Mid-winter 0 ppb and 20 ppb colonies had more workers than 100 ppb colonies and 0 ppb colonies more brood than 100 ppb colonies. Colonies experienced seasonal declines in stored pollen but no treatment effects. Lower 100 ppb colony performance was associated with reduced effort rather than lifespan. RFID (Radio Frequency Identification) tracking revealed that workers had similar adult lifespans across treatments; however, 100 ppb workers engaged in activities outside the colony for less time than 0 ppb workers. Imidacloprid exposure affected queen but not worker nutritional physiology. Nurses retained well-developed hypopharyngeal glands (as indicated by head protein) across treatments. Mid-winter queens from 0 ppb colonies had marginally higher ovary protein than queens from 100 ppb colonies and more ovary lipids than queens from 20 ppb colonies. However, queen nutrient stores in non-reproductive tissues (fat bodies) did not differ across treatments. Queens from different treatments were attended by comparable numbers of retinue workers and had similar gland contents of four QMP (Queen Mandibular Pheromone) components essential to queen care. High levels of imidacloprid in sugar stores can negatively affect colony performance months after initial storage., Competing Interests: The lead/corresponding author serves as an Academic Editor for PLOS ONE., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Honey bee colonies maintain viable queens in part through communication with Queen Mandibular Pheromone (QMP), a mixture that signals the queen's presence and reproductive quality to workers. In turn, workers are thought to provide retinue queen care or replace queens partially based on QMP profiles. We examined the effects of seasonal dearth (overwintering in a warm subtropical location) on queen-worker interactions. Retinue worker responses to continuously ovipositing queens were considered in view of QMP signaling and queen reproductive quality. QMP signaling was estimated from QMP residues recovered from nest worker bodies, which is the primary mode of QMP transfer from the queen to the colony at large. QMP residues varied seasonally but not at all with queen reproductive quality (spermatheca sperm storage, ovary protein and lipid contents). 9-HDA and 9-ODA were lower in January than other months. HOB decreased from July to January, while HVA, a component associated with mated queens, increased sharply in January. Despite these seasonal signaling differences, retinue workers attended queens at similar levels through the months. In terms of reproductive quality, queens did not differ over the months in matedness (spermatheca sperm storage) or physiological age (protein carbonyl content), but varied in nutrient allocation to reproductive and non-reproductive tissues. Queen ovaries contained more protein in September than in November, and more lipid in July and September than in November and January. Queen fat bodies had more protein in July than September or November, but less lipid in July and September than November or January. Retinue worker responses did not vary with seasonal QMP changes, but reflected overall continuous brood rearing efforts and queen matedness throughout the year. The absence of seasonal differences in worker responses to QMP should be considered in the broader context of continuous reproductive efforts in warm subtropical colonies., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interest: the lead author (Mark J. Carroll) serves as an Academic Editor for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Honey bee colony health is a function of the individuals, their interactions, and the environment. A major goal of honey bee research is to understand how colonies respond to stress. Individual-level studies of the bee stress response are tractable, but their results do not always translate to the colony level. Nutritional stress is an important factor in colony declines. Nutrition studies are typically conducted on individual nurse workers (nurses), who are primarily responsible for converting pollen into brood. Nurse physiology is sensitive to both pollen and pheromones, which communicate signals among colony members. Here, we asked whether pheromones influence nurse nutrient pathways involved in brood care, and whether diet influences colony communication. We exposed caged, nurse-aged workers to different combinations of pheromones and pollen, and measured traits related to brood care. We found that pheromones enhanced pollen-dependent processes such as hypopharyngeal gland growth and mrjp1 expression, and buffered the negative effects of starvation. Pollen also enhanced how nurse phenotypes respond to pheromones. Therefore, diet and pheromones interact to influence nurse nutritional physiology and aspects of brood care. These findings have implications for studying colony function and health in an increasingly stressful climate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks.

We announce the complete genome sequences of 14 Serratia bacteriophages isolated from wastewater treatment plants. These phages define two previously undescribed types which we call the Carrot-like phage cluster (phages Carrot, BigDog, LittleDog, Niamh, Opt-148, Opt-169, PhooPhighters, Rovert, Serratianator, Stoker, Swain, and Ulliraptor) and Tlacuache-like phage cluster (Tlacuache and Opt-155).

The accumulation of peritoneal fluid, referred to as ascites, is common in ovarian cancer. This fluid is a complex mixture that may include cells as well as a diverse array of cytokines and growth factors. Here we describe a comprehensive method to process ascites to maximize data collection. The cellular fraction and fluid are first separated by centrifugation. The fluid can be frozen for later analysis of soluble factors or for use in in vitro experiments. The cellular fraction can be processed to analyze its composition or stored for future use., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

How to translate insights gained from studies in one organismal species for what is most likely to be germane in another species, such as from mice to humans, is a ubiquitous challenge in basic biology as well as biomedicine. This is an especially difficult problem when there are few molecular features that are obviously important in both species for a given phenotype of interest. Neuropathologies are a prominent realm of this complication. Schizophrenia is complex psychiatric disorder that affects 1% of the population. Many genetic factors have been proposed to drive the development of schizophrenia, and the 22q11 microdeletion (MD) syndrome has been shown to dramatically increase this risk. Due to heterogeneity of presentation of symptoms, diagnosis and formulation of treatment options for patients can often be delayed, and there is an urgent need for novel therapeutics directed toward the treatment of schizophrenia. Here, we present a novel computational approach, Translational Pathways Classification (TransPath-C), that can be used to identify shared pathway dysregulation between mouse models and human schizophrenia cohorts. This method uses variation of pathway activation in the mouse model to predict both mouse and human disease phenotype. Analysis of shared dysregulated pathways called out by both the mouse and human classifiers of TransPath-C can identify pathways that can be targeted in both preclinical and human cohorts of schizophrenia. In application to the 22q11 MD mouse model, our findings suggest that PAR1 pathway activation found upregulated in this mouse phenotype is germane for the corresponding human schizophrenia cohort such that inhibition of PAR1 may offer a novel therapeutic target., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Mouse models are vital for preclinical research on Alzheimer's disease (AD) pathobiology. Many traditional models are driven by autosomal dominant mutations identified from early onset AD genetics whereas late onset and sporadic forms of the disease are predominant among human patients. Alongside ongoing experimental efforts to improve fidelity of mouse model representation of late onset AD, a computational framework termed Translatable Components Regression (TransComp-R) offers a complementary approach to leverage human and mouse datasets concurrently to enhance translation capabilities. We employ TransComp-R to integratively analyze transcriptomic data from human postmortem and traditional amyloid mouse model hippocampi to identify pathway-level signatures present in human patient samples yet predictive of mouse model disease status. This method allows concomitant evaluation of datasets across different species beyond observational seeking of direct commonalities between the species. Additional linear modeling focuses on decoupling disease signatures from effects of aging. Our results elucidated mouse-to-human translatable signatures associated with disease: excitatory synapses, inflammatory cytokine signaling, and complement cascade- and TYROBP-based innate immune activity; these signatures all find validation in previous literature. Additionally, we identified agonists of the Tyro3 / Axl / MerTK (TAM) receptor family as significant contributors to the cross-species innate immune signature; the mechanistic roles of the TAM receptor family in AD merit further dedicated study. We have demonstrated that TransComp-R can enhance translational understanding of relationships between AD mouse model data and human data, thus aiding generation of biological hypotheses concerning AD progression and holding promise for improved preclinical evaluation of therapies., Competing Interests: The 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., (Copyright © 2021 Lee, Wang, Carroll, Brubaker, Hyman and Lauffenburger.)

Background: Genetics-based basket trials have emerged to test targeted therapeutics across multiple cancer types. However, while vemurafenib is FDA-approved for BRAF-V600E melanomas, the non-melanoma basket trial was unsuccessful, suggesting mutation status is insufficient to predict response. We hypothesized that proteomic data would complement mutation status to identify vemurafenib-sensitive tumors and effective co-treatments for BRAF-V600E tumors with inherent resistance., Methods: Reverse Phase Proteomic Array (RPPA, MD Anderson Cell Lines Project), RNAseq (Cancer Cell Line Encyclopedia) and vemurafenib sensitivity (Cancer Therapeutic Response Portal) data for BRAF-V600E cancer cell lines were curated. Linear and nonlinear regression models using RPPA protein or RNAseq were evaluated and compared based on their ability to predict BRAF-V600E cell line sensitivity (area under the dose response curve). Accuracies of all models were evaluated using hold-out testing. CausalPath software was used to identify protein-protein interaction networks that could explain differential protein expression in resistant cells. Human examination of features employed by the model, the identified protein interaction networks, and model simulation suggested anti-ErbB co-therapy would counter intrinsic resistance to vemurafenib. To validate this potential co-therapy, cell lines were treated with vemurafenib and dacomitinib (a pan-ErbB inhibitor) and the number of viable cells was measured., Results: Orthogonal partial least squares (O-PLS) predicted vemurafenib sensitivity with greater accuracy in both melanoma and non-melanoma BRAF-V600E cell lines than other leading machine learning methods, specifically Random Forests, Support Vector Regression (linear and quadratic kernels) and LASSO-penalized regression. Additionally, use of transcriptomic in place of proteomic data weakened model performance. Model analysis revealed that resistant lines had elevated expression and activation of ErbB receptors, suggesting ErbB inhibition could improve vemurafenib response. As predicted, experimental evaluation of vemurafenib plus dacomitinb demonstrated improved efficacy relative to monotherapies., Conclusions: Combined, our results support that inclusion of proteomics can predict drug response and identify co-therapies in a basket setting.

Background: The long-term outcomes following arthroscopic Bankart repair have been rarely reported. Because of its relative novelty, little is known about recurrent instability, postoperative arthritis, and patient satisfaction, particularly for well-established modern procedures. The purpose of the study was to evaluate the long-term outcomes following arthroscopic Bankart repair., Methods: Patients who underwent isolated arthroscopic Bankart repair from 2003 to 2006 were retrospectively reviewed. Recurrent instability, radiographic, and clinical scores (American Shoulder and Elbow Surgeons [ASES], Simple Shoulder Test [SST], and Rowe scores) were evaluated. Patient factors (ie, age, gender, side, number of instability episodes, contact sports, and bone loss) were analyzed to determine the correlation with outcome measures., Results: Among the 98 patients (102 shoulders), we were able to contact 50 patients (51 shoulders, mean age 27.0 years, mean follow-up 121.2 months). Significant bone loss in glenoid and humerus was arthroscopically observed in 16 (31.4%) and 28 (54.9%) shoulders, respectively. Sixteen shoulders (31.4%) experienced recurrent instability. Recent radiographs were obtained for 38 shoulders, 14 (36.8%) of which showed moderate to severe arthritis. Clinical outcomes at follow-up were 89.3, 10.8, and 76.0 for ASES, SST, and Rowe scores, respectively. Neither recurrent instability nor arthritis was correlated with any patient factors., Conclusion: When isolated arthroscopic Bankart repair was used in all patients with shoulder instability regardless of bony defect, postoperative recurrent instability and arthritis rates were unacceptably high. Additional procedures should be chosen after careful consideration of multiple patient factors., (© 2019 Published by Elsevier Inc. on behalf of American Shoulder and Elbow Surgeons.)

Methoxyfenozide is an insect growth regulator (IGR) commonly used in agriculture to simultaneously control pests and preserve beneficial insect populations; however, its impact on honey bees in not fully understood. We conducted field and laboratory experiments to investigate bee health in response to field-relevant concentrations of this pesticide. Significant effects were observed in honey bee colony flight activity and thermoregulation after being exposed over 9 weeks to supplemental protein patty containing methoxyfenozide. Compared to bee colonies in the control group, colonies fed pollen patty with 200 ppb methoxyfenozide (as measured by residue analysis) had: 1) a significantly reduced rate of weight loss due to forager departure in the morning; and 2) higher temperature variability during the winter. Colonies in the 100 ppb (as measured by residue analysis) treatment group had values between the 200 ppb group and control for both response variables. The dusk break point, which is the time associated with the end of forager return, differed among all treatment groups but may have been confounded with direction the hives were facing. Bee colony metrics of adult bee mass and brood surface area, and measurements of bee head weight, newly-emerged bee weight, and hypopharyngeal gland size were not significantly affected by methoxyfenozide exposure, suggesting that there may be significant effects on honey bee colony behavior and health in the field that are difficult to detect using standard methods for assessing bee colonies and individuals. The second experiment was continued into the following spring, using the same treatment groups as in the fall. Fewer differences were observed among groups in the spring than the fall, possibly because of abundant spring forage and consequent reduced treatment patty consumption. Residue analyses showed that: 1) observed methoxyfenozide concentrations in treatment patty were about 18-60% lower than the calculated concentrations; 2) no residues were observed in wax in any treatment; and 3) methoxyfenozide was detected in bee bread only in the 200 ppb treatment group, at about 1-2.5% of the observed patty concentration., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To systematically review the literature and determine the rate of radiographic tear progression of nonoperatively treated full-thickness rotator cuff tears., Methods: The PubMed, Embase, and Cochrane Library databases were systematically reviewed to identify all articles related to nonoperatively treated rotator cuff tears. English-language studies of Level I through IV evidence examining chronic, full-thickness rotator cuff tears in adults were included. Partial-thickness tears were excluded. Rotator cuff tears were analyzed according to the presence or absence of symptoms. The primary outcome was radiographic tear progression defined as an increase in tear size of 5 mm or greater on magnetic resonance imaging or ultrasound., Results: Eight studies were included for statistical analysis, and 411 tears were analyzed for progression. No difference in the rate of tear progression was detected between the asymptomatic and symptomatic groups (40.6% at 46.8 months and 34.1% at 37.8 months, respectively; P = .65). Calculation of the number needed to treat showed that for an 8% retear rate at 2-year follow-up, approximately 7 patients with rotator cuff tears would have to undergo operative repair to prevent 1 tear from progressing radiographically., Conclusions: This study showed that with the data available, asymptomatic and symptomatic rotator cuff tears carry similar rates of tear progression over time. Most of these tears will not progress significantly over short- to intermediate-term follow-up., Level of Evidence: Level IV, systematic review of Level I through IV evidence., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Honey bees (Apis mellifera) provide vital pollination services for a variety of agricultural crops around the world and are known to host a consistent core bacterial microbiome. This symbiotic microbial community is essential to many facets of bee health, including likely nutrient acquisition, disease prevention and optimal physiological function. Being that the bee microbiome is likely involved in the digestion of nutrients, we either provided or excluded honey bee colonies from supplemental floral forage before being used for almond pollination. We then used 16S rRNA gene sequencing to examine the effects of forage treatment on the bees' microbial gut communities over four months. In agreement with previous studies, we found that the honey bee gut microbiota is quite stable over time. Similarly, we compared the gut communities of bees from separate colonies and sisters sampled from within the same hive over four months. Surprisingly, we found that the gut microbial communities of individual sisters from the same colony can exhibit as much variation as bees from different colonies. Supplemental floral forage had a subtle effect on the composition of the microbiome during the month of March only, with strains of Gilliamella apicola, Lactobacillus, and Bartonella being less proportionally abundant in bees exposed to forage in the winter. Collectively, our findings show that there is unexpected longitudinal variation within the gut microbial communities of sister honey bees and that supplemental floral forage can subtly alter the microbiome of managed honey bees.

Honey bee colony nutritional ecology relies on the acquisition and assimilation of floral resources across a landscape with changing forage conditions. Here, we examined the impact of nutrition and queen age on colony health across extended periods of reduced forage in a southern climate. We measured conventional hive metrics as well as colony-level gene expression of eight immune-related genes and three recently identified homologs of vitellogenin (vg), a storage glycolipoprotein central to colony nutritional state, immunity, oxidative stress resistance and life span regulation. Across three apiary sites, concurrent longitudinal changes in colony-level gene expression and nutritional state reflected the production of diutinus (winter) bees physiologically altered for long-term nutrient storage. Brood production by young queens was significantly greater than that of old queens, and was augmented by feeding colonies supplemental pollen. Expression analyses of recently identified vg homologs (vg-like-A, -B, and -C) revealed distinct patterns that correlated with colony performance, phenology, and immune-related gene transcript levels. Our findings provide new insights into dynamics underlying managed colony performance on a large scale. Colony-level, molecular physiological profiling is a promising approach to effectively identify factors influencing honey bee health in future landscape and nutrition studies.

Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a coculture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAM) influence the adhesion of tumor cells to mesothelial cells. We found that AAM-secreted MIP-1β activates CCR5/PI3K signaling in mesothelial cells, resulting in expression of P-selectin on the mesothelial cell surface. Tumor cells attached to this de novo P-selectin through CD24, resulting in increased tumor cell adhesion in static conditions and rolling underflow. C57/BL6 mice treated with MIP-1β exhibited increased P-selectin expression on mesothelial cells lining peritoneal tissues, which enhanced CaOV3 adhesion ex vivo and ID8 adhesion in vivo Analysis of samples from patients with HGSOC confirmed increased MIP-1β and P-selectin, suggesting that this novel multicellular mechanism could be targeted to slow or stop metastasis in HGSOC by repurposing anti-CCR5 and P-selectin therapies developed for other indications. Significance: This study reports novel insights on the peritoneal dissemination occurring during progression of ovarian cancer and has potential for therapeutic intervention. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3560/F1.large.jpg Cancer Res; 78(13); 3560-73. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Patterns in within-day hive weight data from two independent datasets in Arizona and California were modeled using piecewise regression, and analyzed with respect to honey bee colony behavior and landscape effects. The regression analysis yielded information on the start and finish of a colony's daily activity cycle, hive weight change at night, hive weight loss due to departing foragers and weight gain due to returning foragers. Assumptions about the meaning of the timing and size of the morning weight changes were tested in a third study by delaying the forager departure times from one to three hours using screen entrance gates. A regression of planned vs. observed departure delays showed that the initial hive weight loss around dawn was largely due to foragers. In a similar experiment in Australia, hive weight loss due to departing foragers in the morning was correlated with net bee traffic (difference between the number of departing bees and the number of arriving bees) and from those data the payload of the arriving bees was estimated to be 0.02 g. The piecewise regression approach was then used to analyze a fifth study involving hives with and without access to natural forage. The analysis showed that, during a commercial pollination event, hives with previous access to forage had a significantly higher rate of weight gain as the foragers returned in the afternoon, and, in the weeks after the pollination event, a significantly higher rate of weight loss in the morning, as foragers departed. This combination of continuous weight data and piecewise regression proved effective in detecting treatment differences in foraging activity that other methods failed to detect., Competing Interests: The authors have declared that no competing interests exist.

Background: Radiology reporting is a clinically oriented form of documentation that reflects critical information for patients about their health care processes. Realizing its importance, many medical institutions have started providing radiology reports in patient portals. The gain, however, can be limited because of medical language barriers, which require a way for customizing these reports for patients. The open-access, collaborative consumer health vocabulary (CHV) is a terminology system created for such purposes and can be the basis of lexical simplification processes for clinical notes., Objective: The aim of this study was to examine the comprehensibility and suitability of CHV in simplifying radiology reports for consumers. This was done by characterizing the content coverage and the lexical similarity between the terms in the reports and the CHV-preferred terms., Methods: The overall procedure was divided into the following two main stages: (1) translation and (2) evaluation. The translation process involved using MetaMap to link terms in the reports to CHV concepts. This is followed by replacing the terms with CHV-preferred terms using the concept names and sources table (MRCONSO) in the Unified Medical Language System (UMLS) Metathesaurus. In the second stage, medical terms in the reports and general terms that are used to describe medical phenomena were selected and evaluated by comparing the words in the original reports with the translated ones. The evaluation includes measuring the content coverage, investigating lexical similarity, and finding trends in missing concepts., Results: Of the 792 terms selected from the radiology reports, 695 of them could be mapped directly to CHV concepts, indicating a content coverage of 88.5%. A total of 51 of the concepts (53%, 51/97) that could not be mapped are names of human anatomical structures and regions, followed by 28 anatomical descriptions and pathological variations (29%, 28/97). In addition, 12 radiology techniques and projections represented 12% of the unmapped concepts, whereas the remaining six concepts (6%, 12/97) were physiological descriptions. The rate of lexical similarity between the CHV-preferred terms and the terms in the radiology reports was approximately 72.6%., Conclusions: The CHV covered a high percentage of concepts found in the radiology reports, but unmapped concepts are associated with areas that are commonly found in radiology reporting. CHV terms also showed a high percentage of lexical similarity with terms in the reports, which contain a myriad of medical jargon. This suggests that many CHV terms might not be suitable for lay consumers who would not be facile with radiology-specific vocabulary. Therefore, further patient-centered content changes are needed of the CHV to increase its usefulness and facilitate its integration into consumer-oriented applications., (©Basel Qenam, Tae Youn Kim, Mark J Carroll, Michael Hogarth. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 18.12.2017.)

Population-level estimates of species' distributions can reveal fundamental ecological processes and facilitate conservation. However, these may be difficult to obtain for mobile species, especially colonial central-place foragers (CCPFs; e.g., bats, corvids, social insects), because it is often impractical to determine the provenance of individuals observed beyond breeding sites. Moreover, some CCPFs, especially in the marine realm (e.g., pinnipeds, turtles, and seabirds) are difficult to observe because they range tens to ten thousands of kilometers from their colonies. It is hypothesized that the distribution of CCPFs depends largely on habitat availability and intraspecific competition. Modeling these effects may therefore allow distributions to be estimated from samples of individual spatial usage. Such data can be obtained for an increasing number of species using tracking technology. However, techniques for estimating population-level distributions using the telemetry data are poorly developed. This is of concern because many marine CCPFs, such as seabirds, are threatened by anthropogenic activities. Here, we aim to estimate the distribution at sea of four seabird species, foraging from approximately 5,500 breeding sites in Britain and Ireland. To do so, we GPS-tracked a sample of 230 European Shags Phalacrocorax aristotelis, 464 Black-legged Kittiwakes Rissa tridactyla, 178 Common Murres Uria aalge, and 281 Razorbills Alca torda from 13, 20, 12, and 14 colonies, respectively. Using Poisson point process habitat use models, we show that distribution at sea is dependent on (1) density-dependent competition among sympatric conspecifics (all species) and parapatric conspecifics (Kittiwakes and Murres); (2) habitat accessibility and coastal geometry, such that birds travel further from colonies with limited access to the sea; and (3) regional habitat availability. Using these models, we predict space use by birds from unobserved colonies and thereby map the distribution at sea of each species at both the colony and regional level. Space use by all four species' British breeding populations is concentrated in the coastal waters of Scotland, highlighting the need for robust conservation measures in this area. The techniques we present are applicable to any CCPF., (© 2017 by the Ecological Society of America.)

Purpose: Given its extremely poor prognosis, there is a pressing need for an improved understanding of the biology of glioblastoma multiforme (GBM), including the roles of tumor subpopulations that may contribute to their growth rate and therapy resistance. The most malignant phenotypes of GBM have been ascribed to the presence of subpopulations of cancer stem cells (CSCs), which are resistant to chemotherapeutic drugs and ionizing radiation and which promote invasiveness and metastasis. The mechanisms by which the CSC state is obtained and by which it promotes tumor maintenance are only beginning to emerge. We hypothesize that M2 polarized macrophages may affect CSC phenotypes via cell-cell communication., Methods: We investigated the interplay between glioma CSCs and macrophages via co-culture. The invasiveness of CSCs in the absence and presence of macrophages was assessed using collagen degradation and Transwell migration assays. The role of STAT3 as a CSC phenotypic mediator was assessed using siRNA-mediated gene silencing., Results: We found that the levels of a M2 macrophage-specific secreted cytokine, TGF-β1, were elevated in the presence of CSCs, regardless of whether the cells were plated as contacting or non-contacting co-cultures. In addition, we found that the co-culture resulted in enhanced expression of M2 markers in macrophages that were previously polarized to the M1 phenotype. siRNA-mediated STAT3 silencing was found to reduce the chemo-responsiveness and migratory abilities of the CSCs. Combination treatment of STAT3 siRNA and DNA alkylating agents was found to further abrogate CSC functions., Conclusions: Our data indicate that the co-culture of CSCs and macrophages results in bi-directional signaling that alters the phenotypes of both cell types. These results provide an explanation for recently observed effects of macrophages on GBM tumor cell growth, motility and therapeutic resistance, and suggest potential therapeutic strategies to disrupt the CSC phenotype by impairing its communication with macrophages.

Honey bees (Apis mellifera) collect and store both honey and pollen in preserved forms. Pollen storage involves the addition of honey or nectar and oral secretions to pollen granules. It is controversial whether the duration of pollen storage alters the palatability or nutritive value of the pollen storage medium. We examined how bees utilize different-aged stored pollen during an extended pollen flow. The deposition of pollen into wax cells and subsequent consumption were monitored daily on 18 brood frames from 6 colonies over an 8d observation period. Despite a greater abundance of older stored pollen cells on brood frames, bees showed a marked preference for the consumption of freshly-stored pollen. Two to four day-old pollen cell contents were significantly more likely to be consumed, while pollen cell contents more than seven days old were eaten at much lower rates. Similar experiments that controlled for cell abundance and spatial effects using cage assays yielded the same result. One day-old stored pollen was consumed approximately three times more often than 10d-old stored pollen, and two times more often than 5d-old stored pollen. These consumption preferences for freshly-stored pollen occurred despite a lack of clear developmental advantages. Young adult workers reared for 7 days on 1d-, 5d-, or 10d-old stored pollen showed no difference in body mass, stored pollen consumption, hindgut fecal material accumulation, or hypopharyngeal gland (HPG) protein titers, suggesting that different-aged pollen stores did not vary in their nutritional value to adult bees. These findings are inconsistent with the hypothesis promoting a period of microbially-mediated, "beebread maturation" that results in greater palatability or nutritive value for aged pollen stores. Rather, stored pollen that is not eaten in the first few days accumulates as excess stores preserved in a less preferred, but nutritionally-similar state.

Imidacloprid is a neonicotinoid pesticide heavily used by the agricultural industry and shown to have negative impacts on honey bees above certain concentrations. We evaluated the effects of different imidacloprid concentrations in sugar syrup using cage and field studies, and across different environments. Honey bee colonies fed sublethal concentrations of imidicloprid (0, 5, 20 and 100 ppb) over 6 weeks in field trials at a desert site (Arizona), a site near intensive agriculture (Arkansas) and a site with little nearby agriculture but abundant natural forage (Mississippi) were monitored with respect to colony metrics, such as adult bee and brood population sizes, as well as pesticide residues. Hive weight and internal hive temperature were monitored continuously over two trials in Arizona. Colonies fed 100 ppb imidacloprid in Arizona had significantly lower adult bee populations, brood surface areas and average frame weights, and reduced temperature control, compared to colonies in one or more of the other treatment groups, and consumption rates of those colonies were lower compared to other colonies in Arizona and Arkansas, although no differences in capped brood or average frame weight were observed among treatments in Arkansas. At the Mississippi site, also rich in alternative forage, colonies fed 5 ppb imidacloprid had less capped brood than control colonies, but contamination of control colonies was detected. In contrast, significantly higher daily hive weight variability among colonies fed 5 ppb imidacloprid in Arizona suggested greater foraging activity during a nectar flow post treatment, than any other treatment group. Imidacloprid concentrations in stored honey corresponded well with the respective syrup concentrations fed to the colonies and remained stable within the hive for at least 7 months after the end of treatment., Competing Interests: The authors have declared that no competing interests exist.

In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1 macrophages correlates with poor patient prognosis. The mechanisms driving poor tumor outcome as a result of the presence of M2 macrophages in the tumor microenvironment remain unclear and are challenging to study with current techniques. Therefore, in this study we utilized a micro-culture device previously developed by our lab to model concentrated paracrine signaling in order to address our hypothesis that interactions between M2 macrophages and ovarian cancer cells induce tumor cell proliferation. Using the micro-culture device, we determined that co-culture with M2-differentiated primary macrophages or THP-1 increased OVCA433 proliferation by 10-12%. This effect was eliminated with epidermal growth factor receptor (EGFR) or heparin-bound epidermal growth factor (HB-EGF) neutralizing antibodies and HBEGF expression in peripheral blood mononuclear cells from ovarian cancer patients was 9-fold higher than healthy individuals, suggesting a role for HB-EGF in tumor progression. However, addition of HB-EGF at levels secreted by macrophages or macrophage-conditioned media did not induce proliferation to the same extent, indicating a role for other factors in this process. Matrix metalloproteinase-9, MMP-9, which cleaves membrane-bound HB-EGF, was elevated in co-culture and its inhibition decreased proliferation. Utilizing inhibitors and siRNA against MMP9 in each population, we determined that macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased MMP9 in OVCA433, resulting in a positive feedback loop to drive HB-EGF release and increase proliferation in co-culture. Identification of multi-cellular interactions such as this may provide insight into how to most effectively control ovarian cancer progression.

In order for a chemical plant protection product to be authorised for sale a registration dossier has to be assembled to demonstrate safety and efficacy to the satisfaction of government regulators. These studies and tests are protected for a period of 10 years in Europe, North America and some other jurisdictions from the date of first product authorisation so that only the data owner can gain commercial benefit from the data. Subsequent regulatory reviews which require new studies should not result in further periods of regulatory data protection exclusive use for the new data but compensation should be payable to the data generator. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: The purpose of this study was to evaluate and to compare the size and morphologic patterns among normal and osteoarthritic (OA) humeral heads., Methods: This comparative anatomic imaging study evaluated 150 humeral heads that were separated into 3 cohorts: normal, OA with symmetric glenoid erosion, and OA with asymmetric (type B2) glenoid erosion. Three-dimensional models were created of the humeral head from computed tomography data, and point coordinates were extracted for evaluation. Parameters measured were diameter (sphere fit and circle fit), chord distance (superoinferior and anteroposterior), and humeral head height., Results: The sphere-fit diameter of the humeral head for the entire OA cohort (100 patients; mean diameter, 59 ± 9 mm) was significantly greater (P < .001) than that of the normal cohort (50 patients; mean diameter, 49 ± 5 mm). Similarly, the humeral head circle-fit diameters in the superoinferior and anteroposterior planes were significantly greater (P < .001) in the combined OA cohorts (59 ± 9 mm and 56 ± 10 mm, respectively) compared with the normal cohort (51 ± 5 mm and 47 ± 5 mm, respectively). However, there were no significant differences (P ≥ .099) between the symmetric and asymmetric OA cohorts in sphere-fit or circle-fit diameters. The mean values of humeral head heights were not significantly different (P = .382) between cohorts, 19 ± 2 mm, 18 ± 2 mm, and 18 ± 2 mm for the normal, symmetric, and asymmetric cohorts, respectively., Discussion: Although OA humeral head morphology varies significantly from normal, it does not vary as a function of the Walch classification between symmetric and asymmetric glenoids. Understanding of the morphologic variability of the pathologic humeral head may provide insight into the pathoanatomy of osteoarthritis and the development of various erosion patterns., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Tribocorrosion at the modular taper connections of total hip implants has been associated with trunnionosis and adverse local tissue reactions. Modularity is also widely used in shoulder arthroplasty implants, but little information exists about the potential for tribocorrosion. This study hypothesized that there would be mild or no tribocorrosion in a series of retrieved shoulder implants., Methods: A total of 28 implants with a mean implantation time of 6.2 ± 6.0 years were evaluated using a validated damage scoring method. Implant tapers on the head and stem were divided into upper (deepest) and lower zones and independently scored for fretting and corrosion damage from 1 (none) to 4 (severe)., Results: Corrosion was present on 32% of heads and 38% of stems, whereas fretting was present on 36% of heads and 46% of stems. There was significantly greater (P = .02) corrosion in the lower zone of the retrieved stems (1.4 ± 0.5) than there was in the upper zone (1.1 ± 0.3). Correlation between the head and stem corrosion for lower zone was moderate (r = 0.41; P = .04)., Discussion: Tribocorrosion was present on the heads and stems of some of the retrieved shoulder implants examined in this study. The incidence of tribocorrosion in shoulder implants was lower than in reported cases of retrieved hip implants. The greatest damage was in the lower zone of the taper, where the connection may be exposed to the surrounding joint fluid. It remains to be seen whether this leads to any clinical presentation of trunnionosis., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Fractures of the capitellum and trochlea account for a small proportion of elbow trauma. Clinicians need to be vigilant in their assessment as they are commonly associated with other injuries about the elbow. To optimize outcomes, the goals of management include a stable, anatomic reduction and early range of motion. Closed reduction of noncomminuted fractures may be successful but requires close follow-up. Open reduction and internal fixation is the preferred management of displaced capitellum-trochlear fractures. Elbow stiffness is the most commonly reported complication in operatively treated fractures. Arthroscopic-assisted reduction and internal fixation and arthroplasty are evolving management options., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Climate change has the capacity to alter physical and biological ecosystem processes, jeopardizing the survival of associated species. This is a particular concern in cool, wet northern peatlands that could experience warmer, drier conditions. Here we show that climate, ecosystem processes and food chains combine to influence the population performance of species in British blanket bogs. Our peatland process model accurately predicts water-table depth, which predicts abundance of craneflies (keystone invertebrates), which in turn predicts observed abundances and population persistence of three ecosystem-specialist bird species that feed on craneflies during the breeding season. Climate change projections suggest that falling water tables could cause 56-81% declines in cranefly abundance and, hence, 15-51% reductions in the abundances of these birds by 2051-2080. We conclude that physical (precipitation, temperature and topography), biophysical (evapotranspiration and desiccation of invertebrates) and ecological (food chains) processes combine to determine the distributions and survival of ecosystem-specialist predators.

Honey bee hives are filled with stored pollen, honey, plant resins and wax, all antimicrobial to differing degrees. Stored pollen is the nutritionally rich currency used for colony growth and consists of 40-50% simple sugars. Many studies speculate that prior to consumption by bees, stored pollen undergoes long-term nutrient conversion, becoming more nutritious 'bee bread' as microbes predigest the pollen. We quantified both structural and functional aspects associated with this hypothesis using behavioural assays, bacterial plate counts, microscopy and 454 amplicon sequencing of the 16S rRNA gene from both newly collected and hive-stored pollen. We found that bees preferentially consume fresh pollen stored for <3 days. Newly collected pollen contained few bacteria, values which decreased significantly as pollen were stored >96 h. The estimated microbe to pollen grain surface area ratio was 1:1 000 000 indicating a negligible effect of microbial metabolism on hive-stored pollen. Consistent with these findings, hive-stored pollen grains did not appear compromised according to microscopy. Based on year round 454 amplicon sequencing, bacterial communities of newly collected and hive-stored pollen did not differ, indicating the lack of an emergent microbial community co-evolved to digest stored pollen. In accord with previous culturing and 16S cloning, acid resistant and osmotolerant bacteria like Lactobacillus kunkeei were found in greatest abundance in stored pollen, consistent with the harsh character of this microenvironment. We conclude that stored pollen is not evolved for microbially mediated nutrient conversion, but is a preservative environment due primarily to added honey, nectar, bee secretions and properties of pollen itself., (© 2014 John Wiley & Sons Ltd.)

Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion.

Functional outcomes of biceps tendon rupture may be optimized with operative treatment. We conducted a retrospective study to determine the neurologic complications of using 1-incision Endobutton fixation to repair distal biceps tendon ruptures. Patients with distal biceps tendon ruptures treated with a 1-incision technique and Endobutton fixation were included. The primary outcome measure was frequency of neurologic complications. All 50 patients in the study were men. Mean age was 45 years. Twenty-one patients (42%) had at least 1 complication. Injury to the lateral antebrachial cutaneous nerve (LACN) was the most common (36%). Mean time to diagnosis was 17 days (range, 0 to 40 days). Posterior interosseous, anterior interosseous, and superficial radial nerve palsies each occurred at a 4% rate. Mean follow-up was 133 days. This study involved the largest cohort of patients with distal biceps tendon rupture repaired with Endobutton fixation using a 1-incision technique. The LACN injury rate (36%) was higher than in other studies using the same technique (0% to 22%). Injury rates for other neural structures near the elbow were comparable to those in the literature.

Interactions between different cell types play critical roles in normal development and disease, but remain challenging to analyse. Here, a co-culture system is described that overcomes many of the limitations of existing methods, is simple to construct and modify, and is compatible with standard cellular and molecular assays.

Purpose. The purpose of this study was to compare the accuracy of the conventional method for determining the percentage of partial thickness rotator cuff tears to a method using an intra-articular depth guide. The clinical utility of the intra-articular depth guide was also examined. Methods. Partial rotator cuff tears were created in cadaveric shoulders. Exposed footprint, total tendon thickness, and percentage of tendon thickness torn were determined using both techniques. The results from the conventional and intra-articular depth guide methods were correlated with the true anatomic measurements. Thirty-two patients were evaluated in the clinical study. Results. Estimates of total tendon thickness (r = 0.41, P = 0.31) or percentage of thickness tears (r = 0.67, P = 0.07) using the conventional method did not correlate well with true tendon thickness. Using the intra-articular depth guide, estimates of exposed footprint (r = 0.92, P = 0.001), total tendon thickness (r = 0.96, P = 0.0001), and percentage of tendon thickness torn (r = 0.88, P = 0.004) correlated with true anatomic measurements. Seven of 32 patients had their treatment plan altered based on the measurements made by the intra-articular depth guide. Conclusions. The intra-articular depth guide appeared to better correlate with true anatomic measurements. It may be useful during the evaluation and development of treatment plans for partial thickness articular surface rotator cuff tears.

Plants respond to insect herbivory through the production of biochemicals that function as either direct defenses or indirect defenses via the attraction of natural enemies. While attack by closely related insect pests can result in distinctive levels of induced plant defenses, precise biochemical mechanisms responsible for differing responses remain largely unknown. Cowpea (Vigna unguiculata) responds to Fall armyworm (Spodoptera frugiperda) herbivory through the detection of fragments of chloroplastic ATP synthase γ-subunit proteins, termed inceptin-related peptides, present in larval oral secretions (OS). In contrast to generalists like Fall armyworm, OS of the legume-specializing velvetbean caterpillar (VBC; Anticarsia gemmatalis) do not elicit ethylene production and demonstrate significantly lower induced volatile emission in direct herbivory comparisons. Unlike all other Lepidoptera OS examined, which preferentially contain inceptin (Vu-In; +ICDINGVCVDA-), VBC OS contain predominantly a C-terminal truncated peptide, Vu-In(-A) (+ICDINGVCVD-). Vu-In(-A) is both inactive and functions as a potent naturally occurring antagonist of Vu-In-induced responses. To block antagonist production, amino acid substitutions at the C terminus were screened for differences in VBC gut proteolysis. A valine-substituted peptide (Vu-In(ΔV); +ICDINGVCVDV-) retaining full elicitor activity was found to accumulate in VBC OS. Compared with the native polypeptide, VBC that previously ingested 500 pmol of the valine-modified chloroplastic ATP synthase γ-subunit precursor elicited significantly stronger plant responses in herbivory assays. We demonstrate that a specialist herbivore minimizes the activation of defenses by converting an elicitor into an antagonist effector and identify an amino acid substitution that recovers these induced plant defenses to a level observed with generalist herbivores.