Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental forcing and predator consumption outweigh the nonconsumptive effects of multiple predators on oyster reefs.

The ability to predict how predators structure ecosystems has been shown to depend on identifying both consumptive effects (CEs) and nonconsumptive effects (NCEs) of predators on prey fitness. Prey populations may also be affected by interactions between multiple predators across life stages of the prey, and by environmental factors such as disturbance. However, the intersection of these multiple drivers of prey dynamics has yet to be empirically evaluated. We addressed this knowledge gap using eastern oysters (Crassostrea virginica), a species known to suffer NCEs, as the focal prey. Over four months, we manipulated orthogonally the life stage (none, juvenile, adult, or both) at which oysters experienced simulated predation (CE) and exposure to olfactory cues of a juvenile oyster predator (crab), adult predator (conch), sequentially the crab and then the conch, or none. We replicated this experiment at three sites along an environmental gradient in a Florida (USA) estuary. For both juvenile and adult oysters, survival was reduced solely by CEs, and variation in growth was best explained by among-site variation in water flow, with a much smaller and negative effect of predator cue. Adults exposed to conch cue exhibited reduced growth (an NCE), but this effect was outweighed by a positive CE on growth: surviving oysters grew faster at lower densities. Finally, conch cue reduced larval settlement (another NCE), but this was swamped by among-site variation in larval supply. This research highlights how strong environmental gradients and predator CEs may outweigh the influence of NCEs, even in prey known to respond to predator cues. These findings serve as a cautionary tale for the importance of evaluating NCE processes over temporal scales and across environmental gradients relevant to prey demography.
A Cross-Sectoral Comparison of Prevalence and Predictors of Symptoms of Depression Over Time Among Older Adults in Ontario, Canada

Objectives: Late-life depression, a common mental health issue, poses a significant burden of illness globally. We investigated factors associated with symptoms of depression among older adults across 3 health sectors in Ontario, Canada. Method: Electronic health assessment data on older adults aged 60 years+ in home care (HC; N = 359 217), long-term care (LTC; N = 125 496), and palliative care (PC; N = 29 934) were examined. Change in symptoms of depression, measured using the interRAI Depression Rating Scale (DRS), over time was examined, including predictors of the development of depression. Results: At baseline, symptoms of depression were observed in 19.1% (HC), 24.2% (LTC), and 11.9% (PC). This increased to 20.6% (HC), 33.8% (LTC), and 13.2% (PC) at follow-up. For most older adults, DRS scores remained the same across sectors over time. Three independent variables emerged consistently across sectors as the main risk and protective factors for symptoms of depression. Conclusion: Although variations in the risk and protective factors for late-life depression were demonstrated across each sector, some commonalities emerged including unmanaged pain, symptoms of depression at baseline, social connectedness, and activity.
Bayesian spatio-temporal models for mapping TB mortality risk and its relationship with social inequities in a region from Brazilian Legal Amazon.

BACKGROUND Reducing TB mortality is a great challenge in Brazil due to its territorial extension, cultural variations and economic and political crises, which impact the health system. This study aimed to estimate in space and time the risk of TB mortality and test its relationship with social inequities. METHODS This was an ecological study that included deaths from TB between 2006 and 2016 in Cuiabá, Brazilian Legal Amazon. Bayesian models based on the integrated nested Laplace approximation approach were used to estimate spatio-temporal RRs. RRs for TB mortality were obtained according to the covariables representative of social inequities. RESULTS The risk of TB mortality was stable between 2006 and 2016 and high-risk areas were identified throughout the municipality studied. Regarding social inequities, income was an important factor associated with TB mortality risk, as an increase of 1 SD in income resulted in a 35.4% (RR 0.646; CI 95% 0.476 to 0.837) decrease in risk. CONCLUSIONS The results provided evidence of areas with higher TB mortality risks that have persisted over time and are related to social inequities. Advancing social policies and protections in these areas will contribute to achieving the WHO's End TB strategy.
Biomechanical determinants of placekicking success in professional Rugby Union players

ABSTRACT The ability to score from placekicks discriminates winning from losing Rugby Union teams. We aimed to identify which biomechanical variables related to successful placekicking in professional Rugby Union players, and use self-organising maps (SOM) to determine whether meaningful sub-groups existed. Three professional placekickers performed 10 kicks outdoors. Placekicks were categorised into best, worst, and typical performances based on outcomes and coach and player perceptions. Seven 3D biomechanical variables consistently and meaningfully (moderate Cohen’s effect size) discriminated best from worst placekicks in all players. The three-cluster solution from SOM on these seven variables highlighted differences between players rather than best, worst, and typical attempts. Within-clusters, however, the best and worst placekicks tended to be represented in separate map regions. The seven variables identified using standardised effect sizes can be useful for group-level coaching of placekicking skills in absence of individual data, and translated in an applied setting using verbal and visual cues to promote overall placekicking performance. However, players’ idiosyncrasies formed the main SOM boundaries, indicating that optimising placekicking success would benefit from an individualised approach and numerous effective movement templates may exist.
The Development Of An Indirect CT Lymphography Protocol For Sentinel Lymph Node Detection In Head And Neck Cancer and Comparison to Other Sentinel Lymph Node Mapping Techniques.

Identification of metastatic disease critically impacts the care and prognosis of patients with neoplasia. Multiple techniques exist for identifying the sentinel or first lymph node(s) that receive draining tumor lymph. Identification of the sentinel lymph node enables accurate tissue sampling for determination of lymphatic metastasis. The aims of this study were to develop a CT protocol for identifying the sentinel lymph node in dogs with tumors of the head and neck. In addition, indirect CT lymphography was compared to lymphoscintigraphy and vital dye injection to determine which technique more reliably identified the sentinel lymph node. CT indirect lymphography using intratumoral injection of iodinated contrast identified draining lymphatic vessels in 8 of 18 dogs and identified the sentinel lymph node in 5 of 18 dogs. CT indirect lymphography employing four quadrant peritumoral injection of iodinated contrast identified draining lymphatic vessels in 18 of 20 dogs and identified the sentinel lymph node in 11 of 20 dogs. Vital dye injection and lymphoscintigraphy identified the sentinel lymph node in 17 of 18 and 20 of 20dogs, respectively. Identified sentinel lymph nodes were either ipsilateral or bilateral to the primary tumor. Both CT techniques were found to be safe and simple. Peritumoral injection has the greatest promise for the detection of sentinel lymph nodes in various head and neck cancers using CT, while lymphoscintigraphy had the greatest success of the compared techniques. This article is protected by copyright. All rights reserved.
Dignity-conserving care for persons with palliative care needs — identifying outcomes studied in research: An integrative review

Abstract Objectives With people living longer, palliative care may be required for lengthier periods of time. This puts demands on healthcare organizations to provide optimal palliative care. Maintaining dignity is central for any person's health and quality of life, but especially for a person with palliative care needs. Dignity-conserving care needs to be evaluated to increase knowledge about outcomes and how to assess these. The purpose of this integrative review was to identify outcomes studied within dignity-conserving care and how these have been operationalized. Methods An integrative review was conducted in 26 quantitative or mixed-method studies and study protocols. Thematic synthesis with an abductive approach was used for analysis. Results Seven themes of studied outcomes were identified, as well as four cluster themes: themes related to Illness-Related Concerns, themes related to the Dignity-Conserving Repertoire, themes related to the Social Dignity Inventory, and themes regarding Overarching Dignity Issues. Most outcomes studied dealt with Illness-Related Concerns within the themes of “Performance, symptoms and emotional concerns” and “End-of-life and existential aspects”. Themes linked to the Social Dignity Inventory had the lowest number of outcomes studied. Outcomes regarding overarching dignity issues such as “Dignity-related distress” and “Quality of life” were common. However, the results lacked concrete communication outcomes. Significance of results The results will underpin future research in which dignity-conserving care is implemented and evaluated, and contribute to the provision of evidence-based palliative care. A greater focus on outcomes within cluster themes related to the Dignity-Conserving Repertoire and the Social Dignity Inventory is needed, as is more focus on communication outcomes.
The Utility of Expanded Conclusion Scales During Latent Print Examinations

During fingerprint comparisons, a latent print examiner visually compares two impressions to determine whether or not they originated from the same source. They consider the amount of perceived detail in agreement or disagreement and accumulate evidence toward same source and different sources propositions. This evidence is then mapped to one of three conclusions: Identification, Inconclusive, or Exclusion. A limitation of this 3‐conclusion scale is it can lose information when translating the conclusion from the internal strength‐of‐evidence value to one of only three possible conclusions. An alternative scale with two additional values, support for different sources and support for common sources, has been proposed by the Friction Ridge Subcommittee of OSAC. The expanded scale could lead to more investigative leads but could produce complex trade‐offs in both correct and erroneous identifications. The aim of the present study was to determine the consequences of a shift to expanded conclusion scales in latent print comparisons. Latent print examiners each completed 60 comparisons using one of the two scales, and the resulting data were modeled using signal detection theory to measure whether the expanded scale changed the threshold for an “Identification” conclusion. When using the expanded scale, examiners became more risk‐averse when making “Identification” decisions and tended to transition both the weaker Identification and stronger Inconclusive responses to the “Support for Common Source” statement. The results demonstrate the utility of an expanded conclusion scale and also provide guidance for the adoption of these or similar scales.
Flagellin-Stimulated Production of Interferon-β Promotes Anti-Flagellin IgG2c and IgA Responses

Flagellin, a major structural protein of the flagellum found in all motile bacteria, activates the TLR5- or NLRC4 inflammasome-dependent signaling pathway to induce innate immune responses. Flagellin can also serve as a specific antigen for the adaptive immune system and stimulate anti-flagellin antibody responses. Failure to recognize commensal-derived flagellin in TLR5-deficient mice leads to the reduction in anti-flagellin IgA antibodies at steady state and causes microbial dysbiosis and mucosal barrier breach by flagellated bacteria to promote chronic intestinal inflammation. Despite the important role of anti-flagellin antibodies in maintaining the intestinal homeostasis, regulatory mechanisms underlying the flagellin-specific antibody responses are not well understood. In this study, we show that flagellin induces interferon-β (IFN-β) production and subsequently activates type I IFN receptor signaling in a TLR5- and MyD88-dependent manner in vitro and in vivo. Internalization of TLR5 from the plasma membrane to the acidic environment of endolysosomes was required for the production of IFN-β, but not for other pro-inflammatory cytokines. In addition, we found that anti-flagellin IgG2c and IgA responses were severely impaired in interferon-alpha receptor 1 (IFNAR1)-deficient mice, suggesting that IFN-β produced by the flagellin stimulation regulates anti-flagellin antibody class switching. Our findings shed a new light on the regulation of flagellin-mediated immune activation and may help find new strategies to promote the intestinal health and develop mucosal vaccines.
Exogenous Spermidine Promotes γ-Aminobutyric Acid Accumulation and Alleviates the Negative Effect of NaCl Stress in Germinating Soybean (Glycine max L.)

We investigated the effects of exogenous spermidine (Spd) on the physiological status, γ-aminobutyric acid (GABA) synthase activity, and gene expressions in germinating soybeans under NaCl stress. The results show that Spd significantly increases sprout growth and biomass, decreases malonaldehyde and H2O2 contents, and markedly promotes the activities of superoxide dismutase, catalase, peroxidase, and glutathione peroxidase of germinating soybeans. The harmful effect of NaCl stress was alleviated by exogenous Spd. GABA accumulation in germinating soybeans was caused by the activation of diamine oxidase, polyamine oxidase, aminoaldehyde dehydrogenase, and glutamate decarboxylase activities and by up-regulating their gene expression under Spd-NaCl treatment. The GABA content decreased by 57% and 46% in germinating soybeans with the application of aminoguanidine under Spd and Spd-NaCl treatments, respectively. In conclusion, spermidine induces the accumulation of GABA and increases sprouts biomass, thereby enhancing the functional quality of germinating soybeans.
Methods for the reliable induction of heterotopic ossification in the conditional Alk2Q207D mouse

Objective: Conditional ALK2Q207D-floxed (caALK2fl) mice have previously been used as a model of heterotopic ossification (HO). However, HO formation in this model can be highly variable, and it is unclear which methods reliably induce HO. Hence, these studies report validated methods for reproducibly inducing HO in caALK2fl mice. Methods: Varying doses of Adex-cre and cardiotoxin (CTX) were injected into the calf muscles of 9, 14, or 28-day-old caALK2fl/- or caALK2fl/fl mice. HO was measured by planar radiography or microCT at 14-28 days post-injury. Results: In 9-day-old caALK2fl/- or caALK2fl/fl mice, single injections of 109 PFU Adex-cre and 0.3 µg of CTX were sufficient to induce extensive HO within 14 days post-injury. In 28-day-old mice, the doses were increased to 5 x 109 PFU Adex-cre and 3.0 µg of CTX to achieve similar consistency, but at a slower rate versus younger mice. Using a crush injury, instead of CTX, also provided consistent induction of HO. Finally, the Type 1 BMPR inhibitor, DMH1, significantly reduced HO formation in 28-day-old caALK2fl/fl mice. Conclusions: These data illustrate multiple methods for reliable induction of localized HO in the caALK2fl mouse that can serve as a starting point for new laboratories utilizing this model.
Nucleotides released from palmitate-activated murine macrophages attract neutrophils

Obesity and elevation of circulating free fatty acids are associated with an accumulation and proinflammatory polarization of macrophages within metabolically active tissues, such as adipose tissue, muscle, liver, and pancreas. Beyond macrophages, neutrophils also accumulate in adipose and muscle tissues during high-fat diets and contribute to a state of local inflammation and insulin resistance. However, the mechanisms by which neutrophils are recruited to these tissues are largely unknown. Here we used a cell culture system as proof of concept to show that, upon exposure to a saturated fatty acid, palmitate, macrophages release nucleotides that attract neutrophils. Moreover, we found that palmitate up-regulates pannexin-1 channels in macrophages that mediate the attraction of neutrophils, shown previously to allow transfer of nucleotides across membranes. These findings suggest that proinflammatory macrophages release nucleotides through pannexin-1, a process that may facilitate neutrophil recruitment into metabolic tissues during obesity.
Practice Makes Transfer Imperfect: Evidence From Auditory Learning.

BACKGROUND Evidence from motor and visual studies suggests that the ability to generalize learning gains to untrained conditions decreases as the training progresses. This decrease in generalization was suggested to reflect a shift from higher to lower levels of neuronal representations of the task following prolonged training. In the auditory modality, however, the few studies that tested the influence of prolonging training on generalization ability showed no decrease and sometimes even an increase in generalization. OBJECTIVE To test the impact of extending training in a basic psychoacoustic task on the ability to generalize the gains attained in training to untrained conditions. DESIGN Eighty-two young adults participated in two experiments that differed in the specific training regimen. In both experiments, training was conducted using a difference limen for frequency (DLF) task with an adaptive forced-choice procedure, for either a single- or nine-session training. Following training, generalization to the untrained ear and to an untrained frequency was assessed. RESULTS (a) Training induced significant learning (i.e., smaller DLF thresholds) following a single session of training, and more so following nine training sessions; (b) results from the combined data from both experiments showed that the ability to generalize the learning gains to the untrained ear and frequency was limited after the extended DLF training; (c) larger improvements under the trained condition resulted in smaller generalization to the untrained conditions. CONCLUSIONS The findings of increased specificity with training in the auditory modality support the notion that gradual changes, both quantitative and qualitative, occur in the neural representations of an auditory task during its acquisition. These findings suggest common underlying mechanisms in basic skill learning across different modalities.
Carboxy-Terminal Phosphoregulation of the Long Splice Isoform of Free-Fatty Acid Receptor-4 Mediates β-Arrestin Recruitment and Signaling to ERK1/2

Free-fatty acid receptor-4 (FFA4), previously termed GPR120, is a G protein–coupled receptor (GPCR) for medium and long-chained fatty acids, agonism of which can regulate a myriad of metabolic, sensory, inflammatory, and proliferatory signals. Two alternative splice isoforms of FFA4 exist that differ by the presence of an additional 16 amino acids in the longer (FFA4-L) transcript, which has been suggested to be an intrinsically β-arrestin–biased GPCR. Although the shorter isoform (FFA4-S) has been studied more extensively, very little is known about mechanisms of regulation or signaling of the longer isoform. Because β-arrestin recruitment is dependent on receptor phosphorylation, in the current study, we used the endogenous agonist docosahexaenoic acid (DHA) to examine the mechanisms of FFA4-L phosphorylation, as well as DHA-dependent β-arrestin recruitment and DHA-dependent extracellular-signal regulated kinase-1/2 (ERK1/2) signaling in human embryonic kidney 293 cells. Our results reveal differences in basal phosphorylation of the two FFA4 isoforms, and we show that DHA-mediated phosphorylation of FFA4-L is primarily regulated by G protein–coupled receptor kinase 6, whereas protein kinase-C can also contribute to agonist-induced and heterologous phosphorylation. Moreover, our data demonstrate that FFA4-L phosphorylation occurs on the distal C terminus and is directly responsible for recruitment and interactions with β-arrestin-2. Finally, using CRISPR/Cas9 genome-edited cells, our data reveal that unlike FFA4-S, the longer isoform is unable to facilitate phosphorylation of ERK1/2 in cells that are devoid of β-arrestin-1/2. Together, these results are the first to demonstrate phosphoregulation of FFA4-L as well as the effects of loss of phosphorylation sites on β-arrestin recruitment and ERK1/2 activation. SIGNIFICANCE STATEMENT Free-fatty acid receptor-4 (FFA4) is a cell-surface G protein–coupled receptor for medium and long-chained fatty acids that can be expressed as distinct short (FFA4-S) or long (FFA4-L) isoforms. Although much is known about FFA4-S, the longer isoform remains virtually unstudied. Here, we reveal the mechanisms of docosahexaenoic acid–induced phosphorylation of FFA4-L and subsequent β-arrestin-2 recruitment and extracellular-signal regulated kinase-1/2 activity.
New and emerging pharmacotherapy for duchenne muscular dystrophy: a focus on synthetic therapeutics

ABSTRACT Introduction Duchenne muscular dystrophy (DMD) is the result of X-chromosome-linked mutations to the dystrophin protein gene that prevent the normal development and repair of muscles leading to muscle deterioration. The condition affects nearly 1 in 3,500 males worldwide. Current therapeutics have not been sufficient in providing a cure or resulting in a significant extension in life expectancy, but many therapeutic options are currently under investigation. Areas covered This article provides an overview of the current and emerging therapies for DMD giving particular focus to synthetic therapeutic options. The authors further provide their expert opinion. Expert opinion Many discrepancies in primary outcomes of trials have led to questions of efficacy for medications, as well as difficulty in securing FDA approval. A standardization of primary outcome strategies, as well as better access to investigational medications, may alleviate some of the controversy and pressures that exist on medication approvals. Many trials have identified cohorts who responded more favorably to medications, despite a lack of significance in the overall intent-to-treat populations. This indicates that more medication screening and personalized treatment with patient-specific targeting might deliver more clinically significant results.