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Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasiv

Interdisciplinary collaboration is viewed as a critical factor in delivering quality patient care. The purpose of this study was to describe nurse-physician perceptions of collaboration relationship on general medical-surgical units. [ABSTRACT FROM AUTHOR]

Hypothesis: Ginseng root extracts and the biologically active ginsenosides have been shown to inhibit proliferation of human cancer cell lines, including breast cancer. However, there are conflicting data that suggest that ginseng extracts (GEs) may or may not have estrogenic action, which might be contraindicated in individuals with estrogen-dependent cancers. The current study was designed to address the hypothesis that the extraction method of American ginseng (Panax quinquefolium) root will dictate its ability to produce an estrogenic response using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell model. METHODS: MCF-7 cells were treated with a wide concentration range of either methanol-(alc-GE) or water-extracted (w-GE) ginseng root for 6 days. Cells were grown in media containing either normal or charcoal-stripped fetal calf serum to limit exposure to exogenous estrogen. Thus, an increase in MCF-7 cell proliferation by GE indicated potential estrogenicity. This was confirmed by blocking GE-induced MCF-7 cell proliferation with ER antagonists ICI 182,780 (1 nM) and 4-hydroxytamoxifen (0.1 microM). Furthermore, the ability of GE to bind ERalpha or ERbeta and stimulate estrogen-responsive genes was examined. RESULTS: Alc-GE, but not w-GE, was able to increase MCF-7 cell proliferation at low concentrations (5-100 mcirog/mL) when cells were maintained under low-estrogen conditions. The stimulatory effect of alc-GE on MCF-7 cell proliferation was blocked by the ER antagonists ICI 182,780 or 4-hydroxyta-moxifen. At higher concentrations of GE, both extracts inhibited MCF-7 and ER-negative MDA-MB-231 cell proliferation regardless of media conditions. Binding assays demonstrated that alc-GE, but not w-GE, was able to bind ERalpha and ERbeta. Alc-GE (50 microg/mL) also induced an approximate 2.5-fold increase in expression of the estrogen-responsive pS2 gene, as well as progesterone receptor (PgR) gene expression, whereas w-GE was without effect. CONCLUSION: These data indicate that low concentrations of alc-GE, but not w-GE, elicit estrogenic effects, as evidenced by increased MCF-7 cell proliferation, in a manner antagonized by ER antagonists, interactions of alc-GE with estrogen receptors, and increased expression of estrogen-responsive genes by alc-GE. Thus, discrepant results between different laboratories may be due to the type of GE being analyzed for estrogenic activity. [ABSTRACT FROM AUTHOR]

Because headache is a common side effect of electroconvulsive therapy (ECT), this study sought to determine the effectiveness of cryotherapy (i.e., a frozen gel band) in relieving pain in patients with post-ECT headaches, and whether headache intensity and physiological measurements could predict use of an alternative analgesic (rescue medication). We used a quasi-experimental, crossover design to collect data from 31 patients ages 24 to 85 who had been referred for ECT at two medical facilities in San Diego, California. Measurements of patients' pain intensity were made at three intervals: upon perceiving headache, and at 30 and 60 minutes following the cryotherapy or acetaminophen interventions, based on the order of the crossover design. Data were analyzed using Hotelling's T2 and logistic regression. No significant difference was found between cryotherapy and acetaminophen in relieving ECT-induced headaches (p = .420). There was no influence due to the crossover design (p = .313), nor where there significant changes in physiological measures from treatment (p = .420). Logistic regression showed that 50% of patients required rescue medication after 60 minutes for both treatments (R2 = .498, p = .001), and 66% required rescue medication based on pain level and physiological measures (R2 = .662, p < .008). Based on these results, cryotherapy is an alternative treatment that may be helpful to some patients with ECT-induced headaches. [ABSTRACT FROM AUTHOR]

Background: Inulin and inulin-derived fructooligosaccharides (FOS) are well-known prebiotics for use in companion animals and livestock. The mechanisms by which FOS contribute to health has not been fully established. Further, the fine chemistry of fructan structures from diverse sources, such as graminan-type fructans found in cereal crops, has not been fully elucidated. New methods to study fructan structure and microbial responses to these complex carbohydrates will be key for evaluating the prebiotic potency of cereal fructans found in cattle feeds. As the rumen microbiome composition is closely associated with their metabolic traits, such as feed utilization and waste production, prebiotics and probiotics represent promising additives to shift the microbial community toward a more productive state., Results: Within this study, inulin, levan, and graminan-type fructans from winter wheat, spring wheat, and barley were used to assess the capacity of rumen-derived Bifidobacterium boum, Bifidobacterium merycicum, and Lactobacillus vitulinus to metabolize diverse fructans. Graminan-type fructans were purified and structurally characterized from the stems and kernels of each plant. All three bacterial species grew on FOS, inulin, and cereal crop fructans in pure cultures. L. vitulinus was the only species that could metabolize levan, albeit its growth was delayed. Fluorescently labelled polysaccharides (FLAPS) were used to demonstrate interactions with Gram-positive bacteria and confirm fructan metabolism at the single-cell level; these results were in agreement with the individual growth profiles of each species. The prebiotic potential of inulin was further investigated within naïve rumen microbial communities, where increased relative abundance of Bifidobacterium and Lactobacillus species occurred in a dose-dependent and temporal-related manner. This was supported by in situ analysis of rumen microbiota from cattle fed inulin. FLAPS probe derived from inulin and fluorescent in situ hybridization using taxon-specific probes confirmed that inulin interacts with Bifidobacteria and Lactobacilli at the single-cell level., Conclusion: This research revealed that rumen-derived Bifidobacteria and Lactobacilli vary in their metabolism of structurally diverse fructans, and that inulin has limited prebiotic potential in the rumen. This knowledge establishes new methods for evaluating the prebiotic potential of fructans from diverse plant sources as prebiotic candidates for use in ruminants and other animals., (© 2024. His Majesty the King in Right of Canada, as represented by the Minister of Agriculture and Agri-Food Canada, and Greta Reintjes and Trushar R. Patel 2024.)

The development of vaccines for COVID-19 occurred at an unprecedented pace, and 32 vaccines using a broad range of technologies had received authorization for use on an emergency basis by the end of 2021, from either a national regulatory authority or the World Health Organization. However, 27 of those 32 vaccines had little impact on the global course of the pandemic. Only five vaccines, from AstraZeneca, Pfizer/BioNTech, Sinovac, Moderna, and Sinopharm, were manufactured, authorized, and distributed in time to significantly impact the number of deaths worldwide. Together, these five vaccines averted an estimated 17 million deaths in the first year of the vaccination campaign. The shared characteristic of these five manufacturers was their ability to rapidly develop and scale up vaccine production to deliver the large manufacturing volumes required to immunize large segments of the global population. Because the development and manufacturing of these vaccines was generally on the critical path to authorization and supply, the technical activities involved with development, scale-up, testing, technology transfer, and full-scale manufacturing, as well as aspects of the Chemistry, Manufacturing, and Controls (CMC) regulatory interactions, are examined for each vaccine and technology for which information is available in the public domain to provide lessons learned and recommendations on proactive actions to better prepare us for a future pandemic response. The critical success factors include prior experience with commercialization and approval, robust quality systems, rigorous process development strategies, flexible manufacturing facilities with a skilled workforce, collaboration, access to consumables, reagents, and adjuvants (if relevant), and an equitable distribution of the global vaccine manufacturing network., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Consultant for BMGF, Shares of stock in Merck (USA), Bristol Myers Squibb, and Moderna. Coalition of Epidemic Preparedness (CEPI) – Vice Chair of Scientific Advisory Committee and member of Portfolio Strategy Management Board. Global Alliance for Vaccine Immunization (GAVI) – Observer Independent Product Group., (Copyright © 2023 The Author. Published by Elsevier Ltd.. All rights reserved.)

Carbohydrates are chemically and structurally diverse biomolecules, serving numerous and varied roles in agricultural ecosystems. Crops and horticulture products are inherent sources of carbohydrates that are consumed by humans and non-human animals alike; however carbohydrates are also present in other agricultural materials, such as soil and compost, human and animal tissues, milk and dairy products, and honey. The biosynthesis, modification, and flow of carbohydrates within and between agricultural ecosystems is intimately related with microbial communities that colonize and thrive within these environments. Recent advances in -omics techniques have ushered in a new era for microbial ecology by illuminating the functional potential for carbohydrate metabolism encoded within microbial genomes, while agricultural glycomics is providing fresh perspective on carbohydrate-microbe interactions and how they influence the flow of functionalized carbon. Indeed, carbohydrates and carbohydrate-active enzymes are interventions with unrealized potential for improving carbon sequestration, soil fertility and stability, developing alternatives to antimicrobials, and circular production systems. In this manner, glycomics represents a new frontier for carbohydrate-based biotechnological solutions for agricultural systems facing escalating challenges, such as the changing climate., Competing Interests: Declaration of Competing Interest The authors have no conflicts to declare., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

IPUMS Demographic and Health Surveys (IPUMS DHS), through its intuitive website (http://dhs.ipums.org/), eliminate barriers to overtime and cross-national analyses with the DHS. IPUMS DHS recently released simplified reproductive calendar data. These calendar data are harmonized across samples, distinguish "not in universe" cases from "no" responses, and do not require destringing. Variable names are hot links to important documentation, such as survey-question text and comparability concerns. Analysts can also select consistently coded variables relating to the woman, her household, and her social and environmental context without merging files., (© 2023 The Authors. Studies in Family Planning published by Wiley Periodicals LLC on behalf of Population Council.)

Objective: To determine if laser speckle contrast imaging (LSCI) mitigates variations and subjectivity in the use and interpretation of indocyanine green (ICG) fluorescence in the current visualization paradigm of real-time intraoperative tissue blood flow/perfusion in clinically relevant scenarios., Methods: De novo laparoscopic imaging form-factor detecting real-time blood flow using LSCI and blood volume by near-infrared fluorescence (NIRF) of ICG was compared to ICG NIRF alone, for dye-less real-time visualization of tissue blood flow/perfusion. Experienced surgeons examined LSCI and ICG in segmentally devascularized intestine, partial gastrectomy, and the renal hilum across six porcine models. Precision and accuracy of identifying demarcating lines of ischemia/perfusion in tissues were determined in blinded subjects with varying levels of surgical experience., Results: Unlike ICG, LSCI perfusion detection was real time (latency < 150 ms: p < 0.01), repeatable and on-demand without fluorophore injection. Operating surgeons (n = 6) precisely and accurately identified concordant demarcating lines in white light, LSCI, and ICG modes immediately. Blinded subjects (n = 21) demonstrated similar spatial-temporal precision and accuracy with all three modes ≤ 2 min after ICG injection, and discordance in ICG mode at ≥ 5 min in devascularized small intestine (p < 0.0001) and in partial gastrectomy (p < 0.0001)., Conclusions: Combining LSCI for near real-time blood flow detection with ICG fluorescence for blood volume detection significantly improves precision and accuracy of perfusion detection in tissue locations over time, in real time, and repeatably on-demand than ICG alone., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Allowing students to ask and answer questions is a common practice employed by college science instructors. However, recent literature has identified that women participate in whole-class discussions less often than men. One hypothesized reason for this gender gap is that women may be less comfortable participating. However, no studies have examined students' comfort with asking and answering questions in large-enrollment science courses, identified what about these practices might make students uncomfortable, or explored whether there are gender differences with regard to student comfort. To answer these questions, we surveyed 417 undergraduates at an R1 institution about their experiences asking and answering questions in large-enrollment college science courses. Students answered questions about the extent to which they felt comfortable both asking and answering questions and selected possible factors that could make them uncomfortable participating. Using binary logistic regression, we tested whether student demographics predicted their opinions about these practices. Over half of students reported feeling uncomfortable both asking and answering questions in front of college science classes, and women were significantly less comfortable than men both asking and answering questions. Furthermore, we identified student confidence regarding their knowledge of the material and a concern that other students would judge them as some of the primary factors that could cause students to feel uncomfortable asking and answering questions in front of the whole class. This work highlights factors that instructors can target in hopes of maximizing student comfort participating in large-enrollment college science courses., (Copyright © 2021 Nadile et al.)

The human diet is temporally and spatially dynamic, and influenced by culture, regional food systems, socioeconomics, and consumer preference. Such factors result in enormous structural diversity of ingested glycans that are refractory to digestion by human enzymes. To convert these glycans into metabolizable nutrients and energy, humans rely upon the catalytic potential encoded within the gut microbiome, a rich collective of microorganisms residing in the gastrointestinal tract. The development of high-throughput sequencing methods has enabled microbial communities to be studied with more coverage and depth, and as a result, cataloging the taxonomic structure of the gut microbiome has become routine. Efforts to unravel the microbial processes governing glycan digestion by the gut microbiome, however, are still in their infancy and will benefit by retooling our approaches to study glycan structure at high resolution and adopting next-generation functional methods. Also, new bioinformatic tools specialized for annotating carbohydrate-active enzymes and predicting their functions with high accuracy will be required for deciphering the catalytic potential of sequence datasets. Furthermore, physiological approaches to enable genotype-phenotype assignments within the gut microbiome, such as fluorescent polysaccharides, has enabled rapid identification of carbohydrate interactions at the single cell level. In this review, we summarize the current state-of-knowledge of these methods and discuss how their continued development will advance our understanding of gut microbiome function., 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 Her Majesty the Queen in Right of Canada, as represented by the Minister of Agriculture and Agri-Food Canada.)

Allowing students to voluntarily ask and answer questions in front of the whole class are common teaching practices used in college science courses. However, few studies have examined college science students' perceptions of these practices, the extent to which students choose to engage in these practices, and what discourages students from participating. In this study, we surveyed 417 undergraduates at a research-intensive institution about their experiences asking and answering questions in large-enrollment college science courses. Specifically, students answered questions about to what extent they perceive voluntarily asking and answering questions in large-enrollment science courses is helpful to them and why. They also answered questions about to what extent they engage in asking and answering questions in large-enrollment college science courses and what factors could discourage them from participating. Using binary logistic regression, we examined whether there were differences among students of different demographic groups regarding their opinions about asking and answering questions. We found that overwhelmingly students reported that other students voluntarily asking and answering instructor questions is helpful to them. Notably, compared to continuing generation students, first-generation students were more likely to perceive other students asking questions to be helpful. Despite perceiving asking and answering questions to be helpful, over half of students reported that they never ask or answer questions in large-enrollment college science courses during a semester, and women were more likely than men to report never asking questions. We identified fear of negative evaluation, or students' sense of dread associated with being unfavorably evaluated, as a primary factor influencing their decision to answer instructor questions. This work adds to a growing body of literature on student participation in large-enrollment college science courses and begins to uncover underlying factors influencing student participation., Competing Interests: The authors have declared that no competing interests exist.

Canola meal (CM), the protein-rich by-product of canola oil extraction, has shown promise as an alternative feedstuff and protein supplement in poultry diets, yet its use has been limited due to the abundance of plant cell wall fibre, specifically non-starch polysaccharides (NSP) and lignin. The addition of exogenous enzymes to promote the digestion of CM NSP in chickens has potential to increase the metabolizable energy of CM. We isolated chicken cecal bacteria from a continuous-flow mini-bioreactor system and selected for those with the ability to metabolize CM NSP. Of 100 isolates identified, Bacteroides spp. and Enterococcus spp. were the most common species with these capabilities. To identify enzymes specifically for the digestion of CM NSP, we used a combination of glycomics techniques, including enzyme-linked immunosorbent assay characterization of the plant cell wall fractions, glycosidic linkage analysis (methylation-GC-MS analysis) of CM NSP and their fractions, bacterial growth profiles using minimal media supplemented with CM NSP, and the sequencing and de novo annotation of bacterial genomes of high-efficiency CM NSP utilizing bacteria. The SACCHARIS pipeline was used to select plant cell wall active enzymes for recombinant production and characterization. This approach represents a multidisciplinary innovation platform to bioprospect endogenous CAZymes from the intestinal microbiota of herbivorous and omnivorous animals which is adaptable to a variety of applications and dietary polysaccharides.

Background and Aims: Variceal hemorrhage can be a life-threatening adverse event of chronic liver disease. In contrast to the well-described guidelines for the management of portal hypertension (PH) in adults, there is limited evidence about the optimal prophylactic management of variceal bleeding in children. This study was carried out to assess the efficacy of endoscopic variceal ligation (EVL) as primary prophylaxis to prevent upper GI bleeding in children with PH., Methods: From January 2014 to April 2018, all pediatric patients with PH disease and medium to large esophageal varices or reddish spots, regardless of the grade of the varix, were prospectively included in the protocol of primary prophylaxis with EVL. A second retrospective group of patients was made after reviewing medical records of 32 pediatric patients with PH that presented esophageal varices in the upper endoscopy and had received propranolol as primary prophylaxis., Results: Twenty-four patients (75%) reached varices eradication in the EVL group, with a median of 2 procedures (range, 1-4) before eradication and a median time to eradication of 3.40 months (range, 1.10-13.33). No EVL-related adverse events were observed. Statistically significant differences were observed in the bleeding rate at 3 years between propranolol and EVL groups (6/32 [21.9%] vs 1/32 [3.2%], P < .02). The hazard ratio for bleeding for patients treated with propranolol compared with those treated with EVL was 2.6 (95% confidence interval, 1.53-3.67)., Conclusions: EVL is a safe and effective treatment to prevent upper GI bleeding in pediatric patients with PH. (Clinical trial registration number: NCT03943784.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The Demographic and Health Surveys (DHS) are the most important source of comparative information on the health of women and young children in low- and middle-income countries and are well-suited for studies of the relationship between environmental factors and health. However, barriers have limited the use of the DHS for these purposes. IPUMS DHS, an online data dissemination tool, overcomes these barriers, simplifying comparative analyses with DHS. IPUMS DHS recently incorporated environmental variables that can easily be attached to individual or household records, facilitating the use of DHS data for the study of population and environment issues. We provide a brief introduction to IPUMS DHS, describe the current and anticipated environmental variables and how to use them, and provide an example of the novel research possibilities facilitated by this latest IPUMS DHS development. IPUMS-DHS is available free online at dhs.ipums.org.

Yeast α-mannan (YM) is a densely branched N-linked glycan that decorates the surface of yeast cell walls. Owing to the high degree of branching, cleavage of the backbone of YM appears to rely on the coupled action of side-chain-cleaving enzymes. Upon examining the genome sequences of bovine-adapted Bacteroides thetaiotaomicron strains, isolated for their ability to degrade YM, we have identified a tandem pair of genes inserted into an orphan pathway predicted to be involved in YM metabolism. Here, we investigated the activity of one of these enzymes, a predicted endo-mannanase from glycoside hydrolase (GH) family 76 (BtGH76-MD40). Purified recombinant BtGH76-MD40 displayed activity on structurally distinct YMs from Saccharomyces cerevisiae and Schizosaccharomyces pombe. Linkage analysis of released oligosaccharide products from S. cerevisiae and S. pombe mannan determined BtGH76-MD40 targets a specific linkage that is conserved in structurally diverse YM substrates. In addition, using two differential derivatization methods, we have shown that there is an absolute requirement for undecorated d-mannopyranose in the -1 subsite. Determination of the BtGH76-MD40 X-ray crystal structure and structural superimposition and molecular docking of a branched alpha-mannopentatose substrate supported these findings. In contrast, BtGH76-MD40 can accommodate extended side chains in the +1 and -2 subsites, highlighting that a single alpha-1,6-mannosyl residue is a prerequisite for activity, and cleavage occurs at the reducing end of the undecorated monosaccharide. Collectively these results demonstrate how acquisition of new enzymes within extant pathways contributes to the functional abilities of saccharolytic bacteria persisting in complex digestive ecosystems., (Copyright © 2020. Published by Elsevier Ltd.)

The current study focused on the degree to which decision context (deliberative vs. affective) differentially impacted the use of available information about uncertainty (i.e., probability, positive and negative outcome magnitudes, expected value, and variance/risk) when older adults were faced with decisions under risk. In addition, we examined whether individual differences in general mental ability and executive function moderated the associations between age and information use. Participants ( N = 96) completed a neuropsychological assessment and the hot (affective) and cold (deliberative) versions of an explicit risk task. Our results did not find a significant Age × Hot/Cold Condition interaction on overall risk-taking. However, we found that older adults were less likely to use the full decision information available regardless of the decision context. This finding suggested more global age differences in information use. Moreover, older adults were less likely to make expected-value sensitive decisions, regardless of the hot/cold context. Finally, we found that low performance on measures of executive functioning, but not general mental ability, appears to be a risk factor for lower information use. This pattern appears in middle age and progressively becomes stronger in older age. The current work provides evidence that common underlying decision processes may operate in risk tasks deemed either affective or deliberative. It further suggests that underlying mechanisms such as information use may be paramount, relative to differences in the affective context. Additionally, individual differences in neuropsychological function may act as a moderator in the tendency to use available information across affective context. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.

The BAP1 tumor suppressor is mutated in many human cancers such as uveal melanoma, leading to poor patient outcome. It remains unclear how BAP1 functions in normal biology or how its loss promotes cancer progression. Here, we show that Bap1 is critical for commitment to ectoderm, mesoderm, and neural crest lineages during Xenopus laevis development. Bap1 loss causes transcriptional silencing and failure of H3K27ac to accumulate at promoters of key genes regulating pluripotency-to-commitment transition, similar to findings in uveal melanoma. The Bap1-deficient phenotype can be rescued with human BAP1, by pharmacologic inhibition of histone deacetylase (HDAC) activity or by specific knockdown of Hdac4. Similarly, BAP1-deficient uveal melanoma cells are preferentially vulnerable to HDAC4 depletion. These findings show that Bap1 regulates lineage commitment through H3K27ac-mediated transcriptional activation, at least in part, by modulation of Hdac4, and they provide insights into how BAP1 loss promotes cancer progression.

BACKGROUND Transformation of primary cutaneous follicle center lymphoma (PCFCL), a low-grade B-cell non-Hodgkin lymphoma (NHL), into a high-grade NHL is rare with uncertain prognosis and treatment. A case is reported of a 40-year-old man who presented with a scalp mass that was diagnosed histologically as PCFCL. Imaging of the head and neck identified diffuse large B-cell lymphoma (DLBCL) involving the parotid gland and cervical lymph nodes, which responded well to radiation therapy. CASE REPORT A 40-year-old African American man presented with a two-year history of a progressively enlarging scalp mass that measured 10.5×7.1×6.6 cm. Histology showed a low-grade lymphoma with a follicular pattern. Immunohistochemistry was positive for B-cell markers and Bcl-6, consistent with a diagnosis of PCFCL. Computed tomography (CT) identified a 4.9×3.7×3.4 cm mass in the left parotid gland with bilateral cervical lymphadenopathy that had been present for the previous two or three months. The diagnosis of DLBCL was made on histology from a needle biopsy. Treatment began with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy, followed by radiation therapy to the scalp, both sides of the neck, and left parotid gland. At four-month follow-up, combined positron emission tomography (PET) and CT showed only diffuse low-level uptake in the scalp and parotid gland. CONCLUSIONS Transformation of low-grade PCFCL to high-grade DLBCL is rare, and the approach to treatment varies. This case showed a good response to chemotherapy and radiation therapy.

Numerous factors have been reported to underlie the representation of complex images in high-level human visual cortex, including categories (e.g. faces, objects, scenes), animacy, and real-world size, but the extent to which this organization reflects behavioral judgments of real-world stimuli is unclear. Here, we compared representations derived from explicit behavioral similarity judgments and ultra-high field (7T) fMRI of human visual cortex for multiple exemplars of a diverse set of naturalistic images from 48 object and scene categories. While there was a significant correlation between similarity judgments and fMRI responses, there were striking differences between the two representational spaces. Behavioral judgements primarily revealed a coarse division between man-made (including humans) and natural (including animals) images, with clear groupings of conceptually-related categories (e.g. transportation, animals), while these conceptual groupings were largely absent in the fMRI representations. Instead, fMRI responses primarily seemed to reflect a separation of both human and non-human faces/bodies from all other categories. Further, comparison of the behavioral and fMRI representational spaces with those derived from the layers of a deep neural network (DNN) showed a strong correspondence with behavior in the top-most layer and with fMRI in the mid-level layers. These results suggest a complex relationship between localized responses in high-level visual cortex and behavioral similarity judgments - each domain reflects different properties of the images, and responses in high-level visual cortex may correspond to intermediate stages of processing between basic visual features and the conceptual categories that dominate the behavioral response., (Published by Elsevier Inc.)

What it means to be well and to achieve well-being is fundamental to the human condition. Scholars of many disciplines have attempted to define well-being and to investigate the behavioral and neural correlates of well-being. Despite many decades of inquiry into well-being, much remains unknown. The study of well-being has evolved over time, shifting in focus and methodology. Many recent investigations into well-being have taken a neuroscientific approach to try to bolster understanding of this complex construct. A growing body of literature has directly examined the association between well-being and the brain. The current review synthesizes the extant literature regarding the neural correlates of trait-like well-being (i.e., the propensity to live according to one's true nature). Although reported associations between well-being and the brain varied, some notable patterns were evidenced in the literature. In particular, the strongest and most consistent association emerged between well-being and the anterior cingulate cortex. In addition, patterns of association between well-being and the orbitofrontal cortex, posterior cingulate cortex, superior temporal gyrus, and thalamus emerged. These regions largely comprise the salience and default mode networks, suggesting a possible relationship between well-being and brain networks involved in the integration of relevant and significant stimuli. Various methodological concerns are addressed and recommendations for future research are discussed.

In most species, early germline development occurs in the absence of transcription with germline determinants subject to complex translational and post-translational regulations. Here, we report for the first time that early germline development is influenced by dynamic regulation of the proteasome system, previously thought to be ubiquitously expressed and to serve 'housekeeping' roles in controlling protein homeostasis. We show that proteasomes are present in a gradient with the highest levels in the animal hemisphere and extending into the vegetal hemisphere of Xenopus oocytes. This distribution changes dramatically during the oocyte-to-embryo transition, with proteasomes becoming enriched in and restricted to the animal hemisphere and therefore separated from vegetally localized germline determinants. We identify Dead-end1 (Dnd1), a master regulator of vertebrate germline development, as a novel substrate of the ubiquitin-independent proteasomes. In the oocyte, ubiquitin-independent proteasomal degradation acts together with translational repression to prevent premature accumulation of Dnd1 protein. In the embryo, artificially increasing ubiquitin-independent proteasomal degradation in the vegetal pole interferes with germline development. Our work thus reveals novel inhibitory functions and spatial regulation of the ubiquitin-independent proteasome during vertebrate germline development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host's first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.

The Balbiani body (Bb) is a large membrane-less organelle, densely packed with mitochondria, endoplasmic reticulum, proteins, and RNA. The Bb is present in many vertebrate female gametes. In frogs, the Bb is established early during oogenesis and operates as a maternal inherited embryonic determinant that specifies germline identity through the formation of germplasm. We describe here two techniques to isolate the Bb/germplasm from Xenopus laevis primary oocytes.

Dead-end1 (Dnd1) expression is restricted to the vertebrate germline where it is believed to activate translation of messenger RNAs (mRNAs) required to protect and promote that unique lineage. Nanos1 is one such germline mRNA whose translation is blocked by a secondary mRNA structure within the open reading frame (ORF). Dnd1 contains a canonical RNA recognition motif (RRM1) in its N-terminus but also contains a less conserved RRM2. Here we provide a mechanistic picture of the nanos1 mRNA-Dnd1 interaction in the Xenopus germline. We show that RRM1, but not RRM2, is required for binding nanos1. Similar to the zebrafish homolog, Xenopus Dnd1 possesses ATPase activity. Surprisingly, this activity appears to be within the RRM2, different from the C-terminal region where it is found in zebrafish. More importantly, we show that RRM2 is required for nanos1 translation and germline survival. Further, Dnd1 functions as a homodimer and binds nanos1 mRNA just downstream of the secondary structure required for nanos1 repression. We propose a model in which the RRM1 is required to bind nanos1 mRNA while the RRM2 is required to promote translation through the action of ATPase. Dnd1 appears to use RRMs to mimic the function of helicases., (© 2018 Wiley-Liss, Inc.)

Natural and human-induced seabed sediment disturbances affect wide areas of the global coastal ocean. These recurrent to chronic disturbances mobilize significant amounts of material, including substances that have the potential to significantly harm the environment once re-released. This very challenging issue is difficult to deal with if sub-surface contaminant concentrations are unknown. Based on the analysis of 11 new, up to 5-m long sediment cores taken offshore in the Gulf of Cadiz, the contamination history (using the trace elements lead and zinc) is well documented over major parts of the gulf. Ore mining and metal processing industries on the southwestern Iberian Peninsula started five thousand years ago and experienced a first peak during the Roman Period, which can be detected over the entire gulf. The Industrial Era added a massive, shelf-wide heavy metal excursion of unprecedented dimension. This metal contamination to the coastal ocean decreased in the 1990s and appears to be today limited to larger areas off the Tinto/Odiel and Guadiana River mouths. The unforeseen, significant finding of this study is that the gulf-wide, peak heavy metal concentration, stemming from the Industrial Era, is widely overlain by a modern sediment veneer just thick enough to cover the contaminant horizon, but thin enough to have this layer within the reach of natural or human-induced sediment mobilization events., (Published by Elsevier B.V.)

Background: In 2014, the American Association of Cardiovascular and Pulmonary Rehabilitation Quality of Care Committee was asked to develop performance measures (PMs) to assess program quality and aid in program improvement and certification., Methods: A 3-step process was used to prioritize, develop, and then validate new PMs for both cardiac and pulmonary rehabilitation programs. First, we surveyed national leadership, medical directors, and program directors to identify and rank various American Association of Cardiovascular and Pulmonary Rehabilitation potential PM topics. Then, the face validity of the drafted PMs was assessed in a second national survey. Finally, we assessed the inter- and intrarater reliability and feasibility of each PM by abstracting patient charts at programs throughout the United States. At each step, modifications were made to refine and improve the measures for clarity, reliability, and consistency., Results: Through survey answers received from 302 people (19% response rate), we identified 5 categories for PM development: optimal blood pressure control, tobacco use cessation, and improvement in functional capacity, depression, and sensation of dyspnea. After drafting the PMs, a second survey with 82 respondents (57% response rate), found that the proposed PMs had good face validity. Finally, we found excellent inter- and intrarater reliability for the blood pressure, functional capacity, depression, and dyspnea measures (κ generally >0.80.) However, validity concerns were raised about the tobacco intervention PM as written, and it continues to undergo further refinement and testing., Conclusions: We developed and validated 5 new PMs for use in cardiac and pulmonary rehabilitation program quality assessment, improvement, and certification.

The current study examined child preference for presession therapeutic conditions. A 4-year-old female diagnosed with autism spectrum disorder (ASD) was exposed to three conditions in a concurrent-chains arrangement: presession pairing (PSP) prior to the onset of discrete-trial instruction (DTI), free play (FP) prior to DTI, or immediate onset of DTI. Initial link selections in the concurrent-chains arrangement suggested a relative preference for the PSP condition across multiple therapists. Negative vocalizations decreased across all conditions following implementation of the concurrent-chains arrangement with no differentiation between therapeutic conditions., Competing Interests: No authors have a conflict.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically diagnosed in the toddler and preschool years. Intensive early intervention (EI) using applied behavior analytic procedures is the evidenced-based intervention most effective in improving developmental outcomes. Unfortunately, there are numerous barriers to accessing EI services for toddlers with ASD. This article addresses (a) the process of developing an EI program using primarily applied behavior analytic services with multidisciplinary health care providers, (b) a description of the service delivery provided, (c) educational and training programs to increase qualified staff, and (d) advocacy efforts to improve community capacity. The EI program has sustained growth, improved child developmental outcomes, served as a training ground for EI providers, and yielded high parent satisfaction ratings. Suggestions for continued advocacy, education, research, and policy development related to the lack of access to EI for children with ASD is offered for pediatric health care providers., (Copyright © 2017 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Xenopus oocytes and oocyte extracts are the starting material for a variety of experimental approaches. Oocytes are obtained by surgical removal of the ovary from anesthetized females. Although oocytes may be used while they remain within their ovarian follicle, it is more practical to work with defolliculated oocytes. Defolliculation can be performed either manually or enzymatically. Here we present a protocol for the isolation and separation of Xenopus oocytes at various developmental stages, and guidelines for maintaining oocytes in culture., (© 2018 Cold Spring Harbor Laboratory Press.)

Microinjection of Xenopus oocytes has proven to be a valuable tool in a broad array of studies that require expression of DNA or RNA into functional protein. These studies are diverse and range from expression cloning to receptor-ligand interaction to nuclear programming. Oocytes offer a number of advantages for such studies, including their large size (∼1.2 mm in diameter), capacity for translation, and enormous nucleus (0.3-0.4 mm). They are cost effective, easily manipulated, and can be injected in large numbers in a short time period. Oocytes have a large maternal stockpile of all the essential components for transcription and translation. Consequently, the investigator needs only to introduce by microinjection the specific DNA or RNA of interest for synthesis. Oocytes translate virtually any exogenous RNA regardless of source, and the translated proteins are folded, modified, and transported to the correct cellular locations. Here we present procedures for the efficient microinjection of oocytes and their subsequent care., (© 2018 Cold Spring Harbor Laboratory Press.)

Xenopus primordial germ cells (PGCs) are determined by the presence of maternally derived germ plasm. Germ plasm components both protect PGCs from somatic differentiation and begin a unique gene expression program. Segregation of the germline from the endodermal lineage occurs during gastrulation, and PGCs subsequently initiate zygotic transcription. However, the gene network(s) that operate to both preserve and promote germline differentiation are poorly understood. Here, we utilized RNA-sequencing analysis to comprehensively interrogate PGC and neighboring endoderm cell mRNAs after lineage segregation. We identified 1865 transcripts enriched in PGCs compared with endoderm cells. We next compared the PGC-enriched transcripts with previously identified maternal, vegetally enriched transcripts and found that ∼38% of maternal transcripts were enriched in PGCs, including sox7 PGC-directed sox7 knockdown and overexpression studies revealed an early requirement for sox7 in germ plasm localization, zygotic transcription and PGC number. We identified pou5f3.3 as the most highly expressed and enriched POU5F1 homolog in PGCs. We compared the Xenopus PGC transcriptome with human PGC transcripts and showed that 80% of genes are conserved, underscoring the potential usefulness of Xenopus for understanding human germline specification., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Functional magnetic resonance imaging (fMRI) is a powerful tool used in cognitive neuroscientific research. fMRI is noninvasive, safe, and relatively accessible, making it an ideal method to draw inferences about the brain-behavior relationship. When conducting fMRI research, scientists must consider risks associated with brain imaging. In particular, the risk of potentially identifying an abnormal brain finding in an fMRI research scan poses a complex problem that researchers should be prepared to address. This article illustrates how a social constructivism decision-making model can be used as a framework to guide researchers as they develop protocols to address this issue.

Background: The limited neurobiological understanding of posttraumatic stress disorder (PTSD) has been partially attributed to the need for improved animal models. Stress-enhanced fear learning (SEFL) in rodents recapitulates many PTSD-associated behaviors, including stress-susceptible and stress-resilient subgroups in outbred rats. Identification of subgroups requires additional behavioral phenotyping, a confound to mechanistic studies., Methods: We employed a SEFL paradigm in inbred male and female C57BL/6 mice that combines acute stress with fear conditioning to precipitate traumatic-like memories. Extinction and long-term retention of extinction were examined after SEFL. Further characterization of SEFL effects on male mice was performed with additional behavioral tests, determination of regional activation by Fos immunofluorescence, and RNA sequencing of the basolateral amygdala., Results: Stressed animals displayed persistently elevated freezing during extinction. While more uniform in females, SEFL produced male subgroups with differential susceptibility that were identified without posttraining phenotyping. Additional phenotyping of male mice revealed PTSD-associated behaviors, including extinction-resistant fear memory, hyperarousal, generalization, and dysregulated corticosterone in stress-susceptible male mice. Altered Fos activation was also seen in the infralimbic cortex and basolateral amygdala of stress-susceptible male mice after remote memory retrieval. Key behavioral outcomes, including susceptibility, were replicated by two independent laboratories. RNA sequencing of the basolateral amygdala revealed transcriptional divergence between the male subgroups, including genes with reported polymorphic association to patients with PTSD., Conclusions: This SEFL model provides a tool for development of PTSD therapeutics that is compatible with the growing number of mouse-specific resources. Furthermore, use of an inbred strain allows for investigation into epigenetic mechanisms that are expected to critically regulate susceptibility and resilience., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)