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Abstract Increases in species richness with habitat area (species–area relationship, or SAR) and increases in ecosystem function with species richness (biodiversity–ecosystem functioning, or BEF) are widely studied ecological patterns. Incorporating functional trait analysis into assemblage datasets may help clarify interpretations of SAR and BEF relationships in natural ecological systems. For example, life history theory can be used to make predictions about what species are most important in generating ecosystem function given a certain set of environmental conditions. We used quantitative assemblage data for freshwater mussels at nine sites in western Alabama, USA, to test for SAR and BEF relationships. At each site, we calculated species richness, mussel assemblage density, and two fundamental metrics of ecosystem function: biomass and secondary production. We also tested whether the proportional biomass and production contributions from species belonging to each of three life history strategies—opportunistic strategists adapted to unstable or frequently disturbed habitats, periodic strategists adapted to habitats subject to predictable large‐scale disturbances, and equilibrium strategists adapted to stable habitats—varied longitudinally with stream drainage area, a proxy for habitat area. Species richness increased with stream size (SAR), and both biomass and production increased with species richness (BEF) and mussel density. There were few longitudinal changes in the proportional contributions of the different life history strategy classifications that we used, but the invasive clam Corbicula fluminea contributed proportionally more biomass and production at sites that had smaller drainage areas. This study provides further evidence for a clear longitudinal SAR in stream‐dwelling taxa. It also suggests BEF relationships for biomass and secondary production in natural assemblages but underscores the importance of assemblage density in BEF studies that use observational field data. Variation in proportional biomass and production contributions by different life history strategies was likely limited by the size of the stream size gradient in our study, as contributions were uniformly high for species with life history traits better adapted to stable and productive habitats such as mid‐sized rivers with low or predictable hydrologic disturbance frequencies. This highlights the need to understand how organisms' functional traits govern their relationships to the environment at different scales.

Objective: Cancer treatment misinformation (CTM) is pervasive and impacts patient health outcomes. Cancer clinicians play an essential role in addressing CTM. We previously identified four self-reported responses that characterize the communication process clinicians engage in to address CTM. Clinicians 1) work to understand the misinformation; 2) correct the misinformation through education; 3) advise about future online searches; and 4) preserve the clinician-patient relationship. We sought to confirm and expand on the model we developed by observing cancer clinicians' communication while addressing CTM with a standardized patient (SP). Methods: 17 cancer clinicians were audio recorded in a SP encounter, in which a breast cancer SP asked three questions based on CTM. We thematically analyzed transcriptions of the recordings. Results: Clinicians used four responses with associated strategies and skills to address CTM in a standardized clinical encounter, confirming the previously developed model. The four responses were: (1) work to understand the misinformation; (2) correct the misinformation through education; (3) advise about future online searches; and (4) preserve the clinician-patient relationship. This observational approach allowed us to refine strategies within each response and identify communication skills clinicians enact to address CTM. Conclusion: These findings provide a strong foundation for the Misinformation Response Model for cancer clinicians. Future research should examine which components of the model are most effective in improving patient outcomes. Innovation: This is the first study observing clinicians' communication through simulated practice with SPs about CTM.

Abstract The United States of America has a diverse collection of freshwater mussels comprising 301 species distributed among 59 genera and two families (Margaritiferidae and Unionidae), each having a unique suite of traits. Mussels are among the most imperilled animals and are critical components of their ecosystems, and successful management, conservation and research requires a cohesive and widely accessible data source. Although trait-based analysis for mussels has increased, only a small proportion of traits reflecting mussel diversity in this region has been collated. Decentralized and non-standardized trait information impedes large-scale analysis. Assembling trait data in a synthetic dataset enables comparison across species and lineages and identification of data gaps. We collated data from the primary literature, books, state and federal reports, theses and dissertations, and museum collections into a centralized dataset covering information on taxonomy, morphology, reproductive ecology and life history, fish hosts, habitats, thermal tolerance, geographic distribution, available genetic information, and conservation status. By collating these traits, we aid researchers in assessing variation in mussel traits and modelling ecosystem change.

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson’s disease, and it is characterized by membrane organelles arranged in tubulo-vesicular structures. These areas, appearing as clusters of vesicles, have never been defined concerning the presence of specific organelles. Therefore, the present study aimed to identify the relative and absolute area of specific membrane-bound organelles following a moderate dose (100 µM) of METH administered to catecholamine-containing PC12 cells. Organelles and antigens were detected by immunofluorescence, and they were further quantified by plain electron microscopy and in situ stoichiometry. This analysis indicated an increase in autophagosomes and damaged mitochondria along with a decrease in lysosomes and healthy mitochondria. Following METH, a severe dissipation of hallmark proteins from their own vesicles was measured. In fact, the amounts of LC3 and p62 were reduced within autophagy vacuoles compared with the whole cytosol. Similarly, LAMP1 and Cathepsin-D within lysosomes were reduced. These findings suggest a loss of compartmentalization and confirm a decrease in the competence of cell clearing organelles during catecholamine degeneration. Such cell entropy is consistent with a loss of energy stores, which routinely govern appropriate subcellular compartmentalization.

The use of predators and predator odor as stressors is an important and ecologically relevant model for studying the impact of behavioral responses to threat. Here we summarize neural substrates and behavioral changes in rats resulting from predator exposure. We briefly define the impact predator exposure has on neural targets throughout development (neonatal, juvenile, and adulthood). These findings allow us to conceptualize the impact of predator exposure in the brain, which in turn may have broader implications for human disorders such as PTSD. Importantly, inclusion of sex as a biological variable yields distinct results that may indicate neural substrates impacted by predator exposure differ based on sex.

Antecedentes: Las ventajas de la cirugía mínimamente invasiva debido a las incisiones pequeñas en comparación con la cirugía tradicional están descritas en la literatura, sin embargo, no existe una medida establecida en cuanto al tamaño de la herida en cirugía tradicional. Objetivo: Comparar el tamaño de las incisiones quirúrgicas entre distintos abordajes. Método: Estudio observacional, transversal, retrospectivo. Medición de incisiones quirúrgicas en fotografías clínicas de 182 pacientes operados con técnica tradicional de 2015 a 2017. Resultados: El promedio obtenido para un nivel de fijación y artrodesis fue de 6.64 cm con una muestra del 51.09% de la población. Con cirugía solo descompresiva es de 3 cm en promedio. Dos niveles, 8.5 cm, con 32.4%, 3 niveles 9.34 cm con 9.8%, 4 niveles 13.1 cm con 4.39% y para 5 niveles 15cm. El tamaño de la herida está relacionado con el diagnóstico (r = 0.392) p = 0001, mientras que el tamaño de la herida está relacionado con los segmentos operados (r = 0.695) p = 0001. Conclusiones: El tamaño de la incisión obtenida en cirugía tradicional no actúa como desventaja en comparación con múltiples incisiones realizadas en cirugía mínimamente invasiva, considerando que varios procedimientos se realizan a través de una sola incisión.

Abstract Background Incarcerated youth are characterized by particularly high rates of childhood trauma, a significant risk factor for outcomes including risky behaviors and recidivism. Trauma-based interventions can ameliorate the negative effects of childhood trauma; however, a critical part of success is careful trauma screening. Due to the limitations associated with commonly used self-report trauma assessments, our team developed the Trauma Checklist (TCL), a trained-rater assessment of childhood trauma specifically created for use with forensic populations. The TCL is designed to provide a more comprehensive assessment of trauma, incorporating categories that are of specific relevance for incarcerated individuals (e.g., traumatic loss). Here, we discuss the continued development made to our original trauma assessment and explore the psychometric properties of this expanded assessment (herein termed the TCL 2.0). Method We examined relationships between TCL 2.0 scores, measures of psychopathology, and psychopathic traits in a sample of incarcerated male juvenile offenders (n = 237). In addition, we examined whether TCL 2.0 scores were associated with time to felony re-offense via Cox proportional-hazard regression analyses. Results We examined dimensionality of the TCL 2.0 using a principal component analysis (PCA), the results of which were confirmed via exploratory structural equation modeling; the PCA yielded a two-component solution (i.e., PC1 and PC2). We observed that PC1 (Experienced Trauma) scores were positively correlated with mood disorder diagnoses. TCL 2.0 total scores were positively correlated with post-traumatic stress disorder symptomatology and psychopathic traits. Finally, higher PC2 (Community Trauma) scores were associated with faster time to felony re-offending. Conclusions These results suggest that the TCL 2.0 may be a beneficial screening tool to provide high-risk youth with appropriate trauma-informed treatment.

Interventions are needed to increase low HPV vaccination rates within rural areas in the United States, particularly in the state of Florida, which has the seventh highest number of HPV-related cancers. Florida also ranks low compared to other states in terms of HPV vaccination. Rural-residing parents may benefit from two evidence-based strategies to increase vaccination rates: reminder messages informing and prompting vaccination appointments and mobile clinics to reduce transportation barriers. We sought to identify parental attitudes towards (1) message features that promote rural-residing parents’ receptivity to HPV vaccination; (2) parents’ acceptability of three reminder message modalities (text, postcard, phone); and (3) implementation factors that promote parents’ acceptability of using a mobile clinic for vaccination. We recruited 28 rural-residing parents of 9- to 12-year-old children (unvaccinated for HPV) for focus group and individual interviews and thematically analyzed transcripts. Three features promoted parents’ receptivity to HPV vaccination messages: source credibility, specific information coverage, and personalization (name and birthday wishes). Parents most preferred text messages and identified three factors promoting parents’ mobile clinic use: convenience and feasibility, trustworthiness, and detailed information. The findings indicate rural-residing parents’ acceptability of reminder messages and mobile clinics as well as the importance of trust and feasibility when implementing these evidence-based strategies for rural-residing parents.

The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes cancer progression. Therefore, the development of strategies inhibiting the interplay between CAFs and cancer cells is considered a winning approach for the development of effective anti-cancer drugs. Among other factors, the signal transducer and activator of transcription-3 (STAT3) has been reported as a key mediator of CAF oncogenic actions, representing a promising therapeutic target. Here, we applied an aptamer-based conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the platelet-derived growth factor receptor (PDGFR)β, to obtain STAT3-specific silencing and interfere with CAF pro-tumorigenic functions. We demonstrated that this molecule effectively delivers the STAT3 siRNA in NSCLC cells, and blocks CAF-induced cancer cell growth and migration and reduced spheroid dimension. In addition, we found that Gint4.T-STAT3 alters CAF phenotype, thus functioning as a double-acting molecule able to inhibit the entire tumor bulk. Our data provide a proof of principle for the targeting of CAF pro-tumor functions through an aptamer-based drug, and can open innovative horizons in NSCLC therapy.

Rationale: Parents of a child or adolescent (CA) or young adult (YA) diagnosed with a hematologic cancer often face uncertainty. Managing uncertainty is critical to reduce the psychosocial burden of illness-related stressors. Objective: This study sought to identify: 1) sources of uncertainty among parents of a child diagnosed with a hematologic cancer, 2) strategies used by parents to manage uncertainty, and 3) clinicians' responses to parents' online information-seeking approach to managing uncertainty. Methods: Parents of CAs/YAs diagnosed with a hematologic cancer within the past 1–18 months and living in the U.S. participated in an in-depth, semi-structured phone interview (n = 20). Data were analyzed thematically. Results: Parents reported uncertainty about treatment (options, efficacy, and side effects or risks) and uncertainty about the future (recurrence, whether worry would subside, and how to approach the child's future). Parents managed uncertainty by seeking information online, talking to clinicians, and joining support groups. Clinicians' responses to online information-seeking were described as supportive and unsupportive. Conclusion: Parents described struggling with uncertainty across the cancer continuum (from primary treatment to survivorship). Parents' psychosocial health may benefit from individual and systems level interventions that help address and manage uncertainty, especially interventions focusing on parent caregiver-clinician communication.

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz were normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2-to-AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to an LPS injury prevented AT1 cell regeneration, led to intraalveolar collagen deposition, and resulted in persistent innate inflammation. These findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

Light fields are one of the emerging 3D representation formats with an effective potential to offer very realistic and immersive visual experiences. This capability comes at the cost of a very large amount of acquired data which practical use requires efficient coding solutions. This need was already addressed by the JPEG Pleno Light Field Coding standard for static light fields, which has specified two coding modes, named 4D-Transform and 4D-Prediction. While the first offers better compression performance for smaller baseline light fields, the second excels for larger baseline light fields. This paper intends to propose a novel light field coding mode, the Slanted 4D-Transform coding mode, which extends the 4D-Transform coding mode based on the conventional 4D-DCT, to offer better compression performance than both the available JPEG Pleno coding modes, independently of the baseline. The key idea is to apply first to each 4D block in the light field an adaptive, hierarchical geometric transformation, which makes the data in the block more energy-compaction friendly for the following 4D-DCT. The rate-distortion performance results show that the proposed Slanted 4D-Transform codec is able to outperform both the already standardized JPEG Pleno coding modes, showing BD-Rates gains of 31.03% and 28.30% for the 4D-Transform and 4D-Prediction modes, respectively, thus implying that a single coding mode can efficiently code all types of light fields.

Here the authors generate an RNA-based platform to neutralize the major epigenetic player DNMT1. Using this targeted approach, aberrant DNA methylation in cancer can be corrected.

The Centers for Disease Control and Prevention recommends a COVID-19 vaccine booster dose for all persons >18 years of age. We analyzed data from the National Immunization Survey–Adult COVID Module collected during February 27–March 26, 2022 to assess COVID-19 booster dose vaccination coverage among adults. We used multivariable logistic regression analysis to assess factors associated with vaccination. COVID-19 booster dose coverage among fully vaccinated adults increased from 25.7% in November 2021 to 63.4% in March 2022. Coverage was lower among non-Hispanic Black (52.7%), and Hispanic (55.5%) than non-Hispanic White adults (67.7%). Coverage was 67.4% among essential healthcare personnel, 62.2% among adults who had a disability, and 69.9% among adults who had medical conditions. Booster dose coverage was not optimal, and disparities by race/ethnicity and other factors are apparent in coverage uptake. Tailored strategies are needed to educate the public and reduce disparities in COVID-19 vaccination coverage.

In conventional injection molding, low mold temperatures are used; however, the thermal conditions, which vary during the processing, affect the properties of the injection molded parts and the injection molding process parameters. Due to the rapid cooling of the molten polymer against the mold wall, the flow resistance of the molten polymer increases, and the hydraulic injection pressure is directly affected by this. The rapid cooling of the plastic parts affects the quality of the parts, which can result in surface defects.Using the rapid heat cycle molding (RHCM) approach, a simple convection heating and cooling system was added to a conventional injection molding process to study the potential of RHCM technology. We assessed the influence of the mold temperature on the part's morphological features (namely, the frozen layer) and mechanical properties (namely, the Young's modulus), as well as the hydraulic injection pressure.Using RHCM to heat the molding surface up to 100 °C was found to entirely prevent the formation of a frozen layer, with an expected positive effect on the previously mentioned defects. Note that while the decrease of the frozen layer could have been expected to reduce Young's modulus, this did not happen, which is a very positive outcome related to the specific orientation at which the frozen layer is formed and its morphology. The higher the mold surface temperature, the lower the hydraulic injection pressure, which means less strict structural requirements for the mold. These results highlight the potential of RHCM technology in injection molding, namely as a strategy to mitigate or solve molding defects.

Previous work in incarcerated boys and adult men and women suggest that individuals scoring high on psychopathic traits show altered resting-state limbic/paralimbic, and default mode functional network properties. However, it is unclear whether similar results extend to high-risk adolescent girls with elevated psychopathic traits. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist: Youth Version (PCL:YV)] were associated with altered inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of low-frequency fluctuations (ALFFs) across resting-state networks among high-risk incarcerated adolescent girls (n = 40). Resting-state networks were identified by applying group independent component analysis (ICA) to resting-state fMRI scans, and a priori regions of interest included limbic, paralimbic, and default mode network components. We tested the association of psychopathic traits (PCL:YV Factor 1 measuring affective/interpersonal traits and PCL:YV Factor 2 assessing antisocial/lifestyle traits) to these three resting-state measures. PCL:YV Factor 1 scores were associated with increased low-frequency and decreased high-frequency fluctuations in components corresponding to the default mode network, as well as increased intra-network FNC in components corresponding to cognitive control networks. PCL:YV Factor 2 scores were associated with increased low-frequency fluctuations in sensorimotor networks and decreased high-frequency fluctuations in default mode, sensorimotor, and visual networks. Consistent with previous analyses in incarcerated adult women, our results suggest that psychopathic traits among incarcerated adolescent girls are associated with altered intra-network ALFFs—primarily that of increased low-frequency and decreased high-frequency fluctuations—and connectivity across multiple networks including paralimbic regions. These results suggest stable neurobiological correlates of psychopathic traits among women across development.

Antimicrobials and heavy metals are commonly used in the animal feed industry. The role of in-feed antimicrobials on the evolution and persistence of resistance in enteric bacteria is not well described. Whole-Genome Sequencing (WGS) is widely used for genetic characterizations of bacterial isolates, including antimicrobial resistance, heavy metal tolerance, virulence factors, and relatedness to other sequenced isolates. The goals of this study were to i) use WGS to characterize Salmonella enterica (n = 33) and Escherichia coli (n = 30) isolated from swine feed and feed mill environments; and ii) investigate their genotypic and phenotypic antimicrobial and heavy metal tolerance. Salmonella isolates belonged to 10 serovars, the most common being Cubana, Senftenberg, and Tennessee. E. coli isolates were grouped into 22 O groups. Phenotypic resistance to at least one antimicrobial was observed in 19 Salmonella (57.6%) and 17 E. coli (56.7%) isolates, whereas multidrug resistance (resistant to ≥3 antimicrobial classes) was observed in four Salmonella (12%) and two E. coli (7%) isolates. Antimicrobial resistance genes were identified in 17 Salmonella (51%) and 29 E. coli (97%), with 11 and 29 isolates possessing genes conferring resistance to multiple antimicrobial classes. Phenotypically, 53% Salmonella and 58% E. coli presented resistance to copper and arsenic. All isolates that possessed the copper resistance operon were resistant to the highest concentration tested (40 mM). Heavy metal tolerance genes to copper and silver were present in 26 Salmonella isolates. Our study showed a strong agreement between predicted and measured resistances when comparing genotypic and phenotypic data for antimicrobial resistance, with an overall concordance of 99% and 98.3% for Salmonella and E. coli, respectively.

Abstract Background In the United States, human papillomavirus (HPV) vaccination rates remain low. The President’s Cancer Panel suggests that effective messaging about the HPV vaccination focus on the vaccine’s safety, efficacy, ability to prevent cancer, and recommendation at ages 11- to 12-years. We aimed to develop messages about HPV vaccine that include the President Cancer Panel’s suggestions and were acceptable to caregivers of adolescents. Methods From August to October 2020, we conducted one-hour, Zoom videoconference focus groups with caregivers who lived in Florida, had an 11- to 12-year-old child, and had not had any of their children receive the HPV vaccine. Focus group moderators asked caregivers to react to three videos of clinician (i.e., MD, DO, APRN, PA) recommendations and three text message reminders. Thematic analysis was conducted using the constant comparative method and led by one author with qualitative analysis expertise. Two additional authors validated findings. Results Caregivers (n = 25 in six groups) were primarily non-Hispanic white (84%) and educated (64% had at least an Associate’s degree). Approximately a third of caregivers had delayed (44%) or decided against a vaccine for their child (36%). Caregivers described six preferred message approaches: recognize caregivers’ autonomy, balanced benefits and risks, trustworthy sources, increased feasibility of appointment scheduling, information prior to decision point, and preferred personalized information. Caregivers expressed a desire to have the follow-up doses mentioned in the introduction. Conclusions HPV vaccine messages, whether delivered by a clinician or via text message, will be more acceptable to caregivers if they approach HPV vaccination as the caregivers’ decision, and include information from trusted sources to help caregivers make an informed choice.

Abstract Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.

To identify demographic factors associated with delaying or not receiving a second dose of the 2-dose primary mRNA COVID-19 vaccine series, we matched 323 million single Pfizer-BioNTech (https://www.pfizer.com) and Moderna (https://www.modernatx.com) COVID-19 vaccine administration records from 2021 and determined whether second doses were delayed or missed. We used 2 sets of logistic regression models to examine associated factors. Overall, 87.3% of recipients received a timely second dose (≤42 days between first and second dose), 3.4% received a delayed second dose (>42 days between first and second dose), and 9.4% missed the second dose. Persons more likely to have delayed or missed the second dose belonged to several racial/ethnic minority groups, were 18–39 years of age, lived in more socially vulnerable areas, and lived in regions other than the northeastern United States. Logistic regression models identified specific subgroups for providing outreach and encouragement to receive subsequent doses on time.

Abstract Winterkill is a major concern for turf‐type bermudagrasses [Cynodon dactylon (L.) Pers. and C. dactylon (L.) Pers. × C. transvaalensis Burtt‐Davy] when cultivated in the US transition zone and frequently occurring drought conditions challenge bermudagrass management. Therefore, developing new bermudagrasses with both drought resistance and winter survivability are needed for the future sustainability of the turfgrass industry in the transition zone. How these two traits interact within bermudagrass populations is not widely reported. Accordingly, the objectives of this study were to estimate reliability for spring green‐up (SG) (as an indicator of winter survivability) and drought response in turf‐type bermudagrasses. A total of 77 experimental genotypes and 7 cultivars were planted in a randomized complete block design with 3 replications over 2 years in Goodwell, OK, USA. Substantial genetic variations were found for drought response and SG parameters when analyzed by year, but variations for SG parameters and leaf firing were not significant when analyzed across years. The reliability estimates for drought response ranged from low to moderate (i2 = 0.24–0.61), whereas the subsequent estimates for SG were low (i2 = 0.13–0.33), suggesting poor reliability. The low‐to‐moderate reliability values in SG were likely due to antecedent drought injuries, indicating that winter survivability and drought resistance may need to be evaluated in separate trials.

Summary: Background: Most cancer drugs enter the US market first. US Food and Drug Administration (FDA) approvals of new cancer drugs may influence regulatory decisions in other settings. The study examined whether characteristics of available evidence at FDA approval influenced time-to-marketing authorisation (MA) in Brazil, and price differences between the two countries. Methods: All new FDA-approved cancer drugs from 2010 to 2019 were matched to drugs with MA and prices approved in Brazil by December 2020. Characteristics of main studies, availability of randomised controlled trials (RCTs), overall survival (OS) benefit, added therapeutic benefit, and prices were compared. Findings: Fifty-six FDA-approved cancer drugs with matching indications received a MA at the Brazilian Health Regulatory Agency (Anvisa) after a median of 522 days following US approval (IQR: 351–932). Earlier authorisation in Brazil was associated with availability of RCT (median: 506 vs 760 days, p = 0.031) and evidence of OS benefit (390 vs 543 days, p = 0.019) at FDA approval. At Brazilian marketing authorisation, a greater proportion of cancer drugs had main RCTs (75% vs 60.7%) and OS benefit (42.9% vs 21.4%) than that in the US. Twenty-eight (50%) drugs did not demonstrate added therapeutic benefit over drugs for the same indication in Brazil. Median approved prices of new cancer drugs were 12.9% lower in Brazil compared to the US (adjusted by Purchasing Power Parity). However, for drugs with added therapeutic benefit median prices were 5.9% higher in Brazil compared to the US, while 17.9% lower for those without added benefit. Interpretation: High-quality clinical evidence accelerated the availability of cancer medicines in Brazil. The combination of marketing and pricing authorisation in Brazil may favour the approval of cancer drugs with better supporting evidence, and more meaningful clinical benefit albeit with variable degree of success in achieving lower prices compared to the US. Funding: None.

Abstract Ecological theory posits that higher species richness should be associated with greater exploitation of resources and niche packing resulting from either increasing species niche overlap or specialization of species' niches. Research evaluating niche theory in animals tends to focus on organisms among functional feeding guilds, while resource partitioning might be more critical within functional groups. Freshwater mussels (Family: Unionidae) are a diverse and imperiled group of animals that are ideal models to test niche occupancy due to their functional similarity as filter‐feeders and their occurrence in spatially and temporally stable multispecies aggregations. We evaluated the relationship between species richness and the trophic niche area for 25 mussel species occurring in 22 aggregations in the southeastern United States using stable isotope analysis (δ13C and δ15N) of soft tissue (n = 1057). Mean species standard ellipse area decreased with species richness, whereas ellipse overlap was not related to richness, indicating increased niche specialization may be the primary mechanism allowing coexistence in species‐rich communities. Total community isotopic area increased with richness, suggesting species‐rich communities also use a broader range of resources and may not be species‐saturated. Overall, our data support the niche‐packing hypothesis by illustrating the importance of niche partitioning within a species‐rich guild of aquatic animals.

The use of environmental DNA (eDNA) to assess aquatic biodiversity is a growing field with great potential for monitoring and managing threatened species, like freshwater mussel (Unionidae) populations. Freshwater mussels are globally imperiled and serve essential roles in aquatic systems as a food source and as a natural water filter making their management essential for ecosystem health. Unfortunately, mussel populations are often understudied, and challenges exist to accurately and efficiently describe the full suite of species present. Multispecies eDNA approaches may also be more challenging where freshwater mussel populations are most diverse due to ongoing and significant taxonomic restructuring that has been further complicated by molecular phylogenies using mitochondrial genes. For this study, we developed a microfluidic metabarcoding array that targets a wide range of species, from invertebrates to fishes, with an emphasis on detecting unionid mussels known to be present in the Sipsey River, Alabama. We compared mussel species diversity across six sites with well-studied mussel assemblages using eDNA surveys and traditional quadrat surveys in 2016. We examined how factors such as mussel population density, biomass and location in the river substrate impacted our ability to detect certain species; and investigated unexpected eDNA detections through phylogenetic analysis. Our eDNA results for fish and mussel species were broadly consistent with the data from traditional electrofishing and quadrat-based field surveys, although both community eDNA and conventional sampling detected species unique to that method. Our phylogenetic analysis agreed with other studies that treat Pleurobema decisum and P. chattanoogaense as synonymous species; however, they are still listed as unique species in molecular databases which complicates their identity in a metabarcoding assay. We also found that Fusconaia flava and F. cerina are indistinguishable from one another using a portion of the NADH dehydrogenase Subunit 1 (ND1) marker, which may warrant further investigation into whether or not they are synonymous. Our results show that many factors impacted our ability to detect and correctly identify Unionidae mussel species. Here we describe the obstacles we faced, including the murky phylogeny of Unionidae mussels and turbid river conditions, and our development of a potentially impactful freshwater mussel monitoring eDNA assay.

Freshwater mussels are important indicators of the overall health of their environment but have suffered declines that have been attributed to factors such as habitat degradation, a loss of fish hosts, climate change, and excessive nutrient inputs. The loss of mussel biodiversity can negatively impact freshwater ecosystems such that understanding the mussel’s gut microbiome has been identified as a priority topic for developing conservation strategies. In this study, we determine whether ethanol-stored specimens of freshwater mussels can yield representative information about their gut microbiomes such that changes in the microbiome through time could potentially be determined from museum mussel collections. A short-term preservation experiment using the invasive clam Corbicula fluminea was used to validate the use of ethanol as a method for storing the bivalve microbiome, and the gut microbiomes of nine native mussel species that had been preserved in ethanol for between 2 and 9 years were assessed. We show that ethanol preservation is a valid storage method for bivalve specimens in terms of maintaining an effective sequencing depth and the richness of their gut bacterial assemblages and provide further insight into the gut microbiomes of the invasive clam C. fluminea and nine species of native mussels. From this, we identify a “core” genus of bacteria (Romboutsia) that is potentially common to all freshwater bivalve species studied. These findings support the potential use of ethanol-preserved museum specimens to examine patterns in the gut microbiomes of freshwater mussels over long periods.

Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression.

Individuals with acute and chronic traumatic brain injury (TBI) are associated with unique white matter (WM) structural abnormalities, including fractional anisotropy (FA) differences. Our research group previously used FA as a feature in a linear support vector machine (SVM) pattern classifier, observing high classification between individuals with and without acute TBI (i.e., an area under the curve [AUC] value of 75.50%). However, it is not known whether FA could similarly classify between individuals with and without history of chronic TBI. Here, we attempted to replicate our previous work with a new sample, investigating whether FA could similarly classify between incarcerated men with (n = 80) and without (n = 80) self-reported history of chronic TBI. Additionally, given limitations associated with FA, including underestimation of FA values in WM tracts containing crossing fibers, we extended upon our previous study by incorporating neurite orientation dispersion and density imaging (NODDI) metrics, including orientation dispersion (ODI) and isotropic volume (Viso). A linear SVM based classification approach, similar to our previous study, was incorporated here to classify between individuals with and without self-reported chronic TBI using FA and NODDI metrics as separate features. Overall classification rates were similar when incorporating FA and NODDI ODI metrics as features (AUC: 82.50%). Additionally, NODDI-based metrics provided the highest sensitivity (ODI: 85.00%) and specificity (Viso: 82.50%) rates. The current study serves as a replication and extension of our previous study, observing that multiple diffusion MRI metrics can reliably classify between individuals with and without self-reported history of chronic TBI.

Abstract Objective: Hospital-acquired infection (HAI) rates were negatively affected by the the coronavirus disease 2019 (COVID-19) pandemic. We describe the incidence of HAIs, main pathogens, and multidrug-resistant organisms (MDROs) isolated in cancer patients before and during the pandemic. Design: This retrospective, comparative study included patients with HAIs. We compared 2 periods: the prepandemic period (2018, 2019, and the first 3 months of 2020) with the pandemic period (April–December 2020 and all of 2021). Setting: Instituto Nacional de Cancerología, a tertiary-care oncology public hospital in Mexico City, Mexico. Methods: Patients with the following HAIs were included: nosocomial pneumonia, ventilator-associated pneumonia (VAP), secondary bloodstream infection (BSI), central-line–associated bloodstream infection (CLBSI), and Clostridioides difficile infection (CDI). Demographic data, clinical characteristics, pathogens isolated, and MDRO data were included. Results: We identified 639 HAIs: 381 (7.95 per 100 hospital discharges) in the prepandemic period and 258 (7.17 per 100 hospital discharges) in the pandemic period. Hematologic malignancy was documented in 263 (44.3%) patients; 251 (39.2%) were in cancer progression or relapse. Nosocomial pneumonia was more frequent during the pandemic period (40.3% vs 32.3%; P = .04). Total episodes of VAP were not different between the 2 periods (28.1% vs 22.1%; P = .08), but during the pandemic period, the VAP rate was higher among COVID-19 patients than non–COVID-19 patients (72.2% vs 8.8%; P < .001). Escherichia coli, Stenotrophomonas maltophilia, and Staphylococcus aureus bacteremia cases were more frequent in the pandemic period. Extended-spectrum β-lactamases (ESBL)–E. coli was the only MDRO that occurred more frequently during the pandemic period. Conclusions: In cancer patients, nosocomial pneumonia was more frequent during the pandemic period. We did not observe a significant impact on other HAIs. MDROs did not significantly increase during the pandemic.

Individuals with history of childhood trauma are characterized by aberrant resting-state limbic and paralimbic functional network connectivity. However, it is unclear whether specific subtypes of trauma (i.e., experienced vs observed or community) showcase differential effects. This study examined whether subtypes of childhood trauma (assessed via the Trauma Checklist [TCL] 2.0) were associated with aberrant intra-network amplitude of fluctuations and connectivity (i.e., functional coherence within a network), and inter-network connectivity across resting-state networks among incarcerated juvenile males (n = 179). Subtypes of trauma were established via principal component analysis of the TCL 2.0 and resting-state networks were identified by applying group independent component analysis to resting-state fMRI scans. We tested the association of subtypes of childhood trauma (i.e., TCL Factor 1 measuring experienced trauma and TCL Factor 2 assessing community trauma), and TCL Total scores to the aforementioned functional connectivity measures. TCL Factor 2 scores were associated with increased high-frequency fluctuations and increased intra-network connectivity in cognitive control, auditory, and sensorimotor networks, occurring primarily in paralimbic regions. TCL Total scores exhibited similar neurobiological patterns to TCL Factor 2 scores (with the addition of aberrant intra-network connectivity in visual networks), and no significant associations were found for TCL Factor 1. Consistent with previous analyses of community samples, our results suggest that childhood trauma among incarcerated juvenile males is associated with aberrant intra-network amplitude of fluctuations and connectivity across multiple networks including predominately paralimbic regions. Our results highlight the importance of accounting for traumatic loss, observed trauma, and community trauma in assessing neurobiological aberrances associated with adverse experiences in childhood, as well as the value of trained-rater trauma assessments compared to self-report.

Background: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients Methods: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients’ self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) at baseline and after 2-weeks. The primary aim was to assess feasibility; secondary aims included satisfaction with the APP, association between meditation frequency and length with self-reported symptoms, and change in symptom measures (symptoms, anxiety, depression, and sleep). Results: Our study included 35 participants (17 meditation group; 18 controls) who were primarily female (94%) with breast cancer (60%). The 61% enrollment rate and 71% adherence rate met pre-specified feasibility criteria. Most meditation group participants described the APP as “Useful” to “Very Useful” and would “Probably” or “Definitely” recommend its use. Mixed model analysis revealed a statistically significant association between meditation length (5, 10, or 15 minutes) and change in anxiety, with 15-minute sessions associated with greater reductions in anxiety. In the exit survey, more meditation group vs. control group participants reported improved focus, mood, and sleep. Study groups differed significantly by ESAS fatigue score change; the meditation group decreased a median of 1.5 pts (IQR 2.5) and the control group increased a median of 0.5 points (IQR 2). The meditation group, but not the control group, experienced statistically significant improvement in ESAS fatigue, depression, anxiety, appetite, and physical, psychological, and global distress. Change in PSQI and HADS anxiety and depression scores did not reveal any statistically significant between-group differences. Conclusions: This pilot study demonstrated the feasibility and acceptability of a meditation APP for cancer patients. Meditation APP users reported improvement in several measures of symptom distress. Future studies should explore ways to enhance the APP’s usability and clinical benefit.

This research focuses on understanding the effectiveness of a university-based induction support program (ISP) instituted to support the graduates of an urban university who completed their preparation during the COVID-19 pandemic. We framed the evaluation of our ISP as participatory action research (PAR) and chose a critical theoretical perspective of adult learning and development as our theoretical lens because of the close alignment with this perspective to our college’s conceptual framework on social justice and equity. Primary data sources consisted of individual interviews with 15 key informants identified by the ISP research team. Data analyses occurred through a recursive and generative process moving between open coding using Nvivo and reflection on the literature related to critical adult learning theory and research on effective induction and coaching models. Findings included (a) the ISP as a liberating space to engage with other educators, (b) the ISP’s role as a university-based program for urban educators, (c) the ISP program’s impact on stakeholders’ professional identity, and (d) the ISP and the concept of criticality. The study also underscored the advantages of using PAR designs for program evaluation and/or accreditation inquiries focusing on continuous improvement.

For many diagnosed mothers and their daughters, breast cancer is a shared experience. However, they struggle to talk about cancer. This is particularly true when the daughter is in adolescence or young adulthood, as they tend to be more avoidant, which is associated with poorer biopsychosocial outcomes. When daughters are their mother’s caregivers, daughters’ burden and distress are heightened. Young adult caregiving daughters (YACDs) are the second most common family caregiver and encounter more distress and burden than other caregiver types. Yet, YACDs and their diagnosed mothers receive no guidance on how to talk about cancer. Thirty-nine mother/YACD pairs participated in an online survey to identify challenging topics and strategies for talking about cancer, and to explore associations between openness/avoidance and psychosocial outcomes. YACDs and mothers reported the same challenging topics (death, treatment-related issues, negative emotions, relational challenges, YACDs’ disease risk) but differed on why they avoided the topic. YACDs and mothers identified the same helpful approaches to navigate conversations (openness, staying positive, third-party involvement, avoidance). Avoidance was correlated with more distress whereas openness was correlated with better psychosocial outcomes. These results provide a psychosocial map for a mother-YACD communication skills intervention, which is key to promoting healthy outcomes.

Objective: Family members are important sources of support for patients with cancer. They access, evaluate, and engage with online information and discuss it with a cancer clinician. This study validates the 4-dimensions, 18-item Transactional eHealth Literacy Instrument (TeHLI) and proposed to include Clinical eHealth Literacy as a 5th dimension. Methods: The Leukemia & Lymphoma Society (LLS) disseminated an online survey to 121 family member caregivers between March-June 2020. We conducted confirmatory factor analyses (1) to examine model fit for the 4-factor TeHLI in the cancer caregiver population, and (2) to examine the model fit when adding the 5th factor. Results: The 4-dimension model yielded acceptable model fit (RMSEA = 0.09; 90% CI = 0.08-0.11; CFI = 0.98; TLI = 0.98; SRMR = 0.07). The 5-dimension model also yielded acceptable model fit (RMSEA = 0.08; 90% CI = 0.07-0.10; CFI = 0.97; TLI = 0.97; SRMR = 0.08), supporting the expansion of the TeHLI within this population. Conclusion: The five-dimension TeHLI is a valid and reliable measure of eHealth literacy among blood cancer caregiver populations. Innovation: The TeHLI can be used as an outcome measure for communication skills training for caregivers, patients, and clinicians.

CDK4/6 inhibitors in combination with endocrine therapy has shown efficacy in ER + breast cancer patients but resistance can occur. Here, the authors demonstrate that co-targeting CDK4/6 and AKT with endocrine therapy prevents acquired resistance and therapy adaptation.

Some state health departments in the United States are in the process of increasing access to immediate postpartum long-acting reversible contraception (LARC), an evidence based approach to preventing unintended pregnancy. Changing state Medicaid policies for immediate postpartum LARC reimbursement has proven insufficient for overcoming access barriers, so states developed implementation strategies to conduct multiple, coordinated systems changes. This research was conducted to understand the roles of social networks in implementing a complex health systems change. In 2015 and 2018, semi-structured telephone interviews were conducted with state teams engaged in increasing access to immediate postpartum LARC. Transcriptions of interviews were coded based on the Consolidated Framework for Implementation Research and implementation strategies, then themes were refined through discussion. A web-based assessment in 2018 evaluated degree of implementation accomplishment. Teams found that increased formal or informal social engagement among members aided timeliness, resource coordination, accountability, and enthusiasm, and over the course of 2 years, reduced disruptions due to staff turnover. The composition of the team influenced the social ties it could draw upon. Preexisting relationships were the most common source of social networking. Bridging social ties connected state teams to novel information and instrumental aid used to seek funding, conduct consumer awareness activities, and train healthcare providers. Cultivating and maintaining relationships among agencies and organizations as part of routine operations enables them to be available for future implementation efforts. Multi-agency teams may benefit from prioritizing time for internal and external relationship-building to enhance implementation progress.

The common bean (Phaseolus vulgaris L.) is the most important grain legume in the human diet, mainly in Africa and Latin America. Argentina is one of the five major producers of the common bean in the world, and the main cultivation areas are concentrated in the northwestern provinces of this country. Crop production of the common bean is often affected by biotic factors like some endemic fungal diseases, which exert a major economic impact on the region. The most important fungal diseases affecting the common bean in Argentina are white mold caused by Sclerotinia sclerotiorum, angular leaf spot caused by Pseudocercospora griseola, web blight and root rot caused by Rhizoctonia solani, which can cause production losses of up to 100% in the region. At the present, the most effective strategy for controlling these diseases is the use of genetic resistance. In this sense, population study and characterization of fungal pathogens are essential for developing cultivars with durable resistance. In this review we report diversity studies carried out on these three fungal pathogens affecting the common bean in northwestern Argentina, analyzing more than 200 isolates by means of molecular, morphological and pathogenic approaches. Also, the screening of physiological resistance in several common bean commercial lines and wild native germplasm is reviewed. This review contributes to the development of sustainable management strategies and cultural practices in bean production aimed to minimize yield losses due to fungal diseases in the common bean.

BackgroundAdult child caregivers of parents with cancer may face challenges when communicating with the patient and other family members, communicating during clinical interactions, and navigating web-based information seeking. ObjectiveWe developed and pilot-tested the Healthy Communication Practice program for adult child caregivers of parents with a blood cancer, which aims to help participants learn and implement communication skills central to caregiving. We assessed the feasibility and acceptability of the training. MethodsEligible participants completed a preprogram survey. We assessed the feasibility of participants completing the intervention in the allotted time. Participants had 2 weeks to complete the 2-part, 90-minute online program and completed a postprogram survey that included program evaluation items and the Acceptability of Intervention Measure (AIM) using a 1-5 rating scale (5=strongly agree). ResultsOf 50 caregivers who initially expressed interest, 34 consented, and 30 completed the program and both surveys (88% completion rate). Caregivers had a mean age of 45.07 (SD 11.96) years and provided care for parents who had a mean age of 73.31 (SD 9.38) years. Caregivers were primarily daughters (n=22, 73%). Overall, scores on the AIM scale were high (mean 4.48, SD 0.67). Specifically, caregivers felt the content met their communication needs (mean 4.58, SD 0.62) and their own needs as a caregiver of a parent with a blood cancer (mean 4.39, SD 0.72). ConclusionsWe demonstrated the feasibility and acceptability of the Healthy Communication Practice program, which aims to enhance family and clinical communication skills among caregivers of a parent with a blood cancer. Future studies will examine the efficacy of the program and its impact on both caregiver and patient communication and health outcomes.

Chagas disease is a tropical zoonosis caused by Trypanosoma cruzi. After infection, the host present an acute phase, usually asymptomatic, in which an extensive parasite proliferation and intense innate immune activity occurs, followed by a chronic phase, characterized by low parasitemia and development of specific immunity. Most individuals in the chronic phase remain without symptoms or organ damage, a state called indeterminate IND form. However, 20 to 40% of individuals develop cardiac or gastrointestinal complications at any time in life. Cardiomyocytes have an important role in the development of Chronic Chagas Cardiomyopathy (CCC) due to transcriptional and metabolic alterations that are crucial for the parasite survival and replication. However, it still not clear why some infected individuals progress to a cardiomyopathy phase, while others remain asymptomatic. In this work, we used hiPSCs-derived cardiomyocytes (hiPSC-CM) to investigate patterns of infection, proliferation and transcriptional response in IND and CCC patients. Our data show that T. cruzi infection and proliferation efficiency do not differ significantly in PBMCs and hiPSC-CM from both groups. However, RNA-seq analysis in hiPSC-CM infected for 24 hours showed a significantly different transcriptional response to the parasite in cells from IND or CCC patients. Cardiomyocytes from IND showed significant differences in the expression of genes related to antigen processing and presentation, as well as, immune co-stimulatory molecules. Furthermore, the downregulation of collagen production genes and extracellular matrix components was significantly different in these cells. Cardiomyocytes from CCC, in turn, showed increased expression of mTORC1 pathway and unfolded protein response genes, both associated to increased intracellular ROS production. These data point to a differential pattern of response, determined by baseline genetic differences between groups, which may have an impact on the development of a chronic outcome with or without the presentation of cardiac symptoms.

In this study, we sequenced the first complete chloroplast (cp) genome of a Peruvian chili pepper landrace, “arnacucho” (Capsicum chinense). This cp genome has a 156,931 bp in length with typical quadripartite structure, containing a large single copy (LSC) region (87,325 bp) and a 17,912 bp small single-copy (SSC) region, separated by two inverted repeat (IR) regions (25,847 bp); and the percentage of GC content was 37.71%. Arnaucho chili pepper chloroplast genome possesses 133 genes that consists of 86 protein-coding genes, 37 tRNA, eight rRNA, and two pseudogenes. Phylogenetic analysis revealed that this Peruvian chili pepper landrace is closely related to the undomesticated species C. galapagoense; all belong to the Capsiceae tribe.

Adult-child caregivers of an aging parent living with a blood cancer describe struggling to communicate with one another and within the family system. They may avoid critical care conversations, which may impede care and their ability to receive social support. We examined what approaches adult-child caregivers of a parent diagnosed with a blood cancer use to enhance their family communication, the topics they find most challenging to discuss, and the roles of openness and support. We used qualitative and quantitative approaches to analyze data from a larger online survey study. In partnership with the Leukemia & Lymphoma Society, we recruited 121 adult-child caregivers. Responses to one open-ended item were analyzed to capture strategies used to enhance communication with their parent and family. They reported utilizing digital communication modalities, prioritizing frequent communication, engaging in openness, establishing boundaries, kinkeeping, and enacting support. Within the quantitative data, we further explored two of these themes (openness and support) and their relationships to other variables using t-tests and regression analysis. Adult-child caregivers and diagnosed parents avoid talking about mortality and negative feelings. Openness in the family about cancer was linked to caregivers’ perceptions of receiving social support. Findings demonstrate that cultivating openness between midlife adult children and diagnosed parents may enhance opportunities to receive support.

The present article discusses the role of light in altering autophagy, both within the outer retina (retinal pigment epithelium, RPE, and the outer segment of photoreceptors) and the inner choroid (Bruch’s membrane, BM, endothelial cells and the pericytes of choriocapillaris, CC). Here autophagy is needed to maintain the high metabolic requirements and to provide the specific physiological activity sub-serving the process of vision. Activation or inhibition of autophagy within RPE strongly depends on light exposure and it is concomitant with activation or inhibition of the outer segment of the photoreceptors. This also recruits CC, which provides blood flow and metabolic substrates. Thus, the inner choroid and outer retina are mutually dependent and their activity is orchestrated by light exposure in order to cope with metabolic demand. This is tuned by the autophagy status, which works as a sort of pivot in the cross-talk within the inner choroid/outer retina neurovascular unit. In degenerative conditions, and mostly during age-related macular degeneration (AMD), autophagy dysfunction occurs in this area to induce cell loss and extracellular aggregates. Therefore, a detailed analysis of the autophagy status encompassing CC, RPE and interposed BM is key to understanding the fine anatomy and altered biochemistry which underlie the onset and progression of AMD.

Plain English summary This paper presents a roadmap for patient-oriented research in mental health in Canada. At the level of laboratory science, the direct involvement of patients and their collaboration with researchers on experimental development and dissemination of results has been scarce. With voices of collaborative patient partners, graduate students and the principal-investigator, it makes a clear case for involving people with lived experience within translational mental health research, which has shown positive outcomes that could potentially shape public policy and future practice. Starting with the premise that meaningful engagement spurs meaningful results, the paper addresses current literature, a discussion of the challenges faced by researchers and patient partners and includes a consideration of COVID-19 consequences. Ending with clear recommendations, this paper is an exciting call to action for involving patient partners in the full research cycle of mental health research and beyond.

Introduction: Early drinkers have been found to have higher risk of developing alcohol use disorder; however, the association of early drinking with progression to problematic alcohol involvement that does not meet disorder criteria (i.e., subclinical problems) or to severe stages of alcohol involvement, sex-specific associations, and relationship of early drinking with alcohol recovery have rarely been investigated. Methods: Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we applied latent transition analyses to investigate the impact of weekly drinking before age 18 on alcohol progression and recovery operationalized as three classes of alcohol involvement using abuse and dependence indicators. We analyzed data separately for male (n = 12,276) and female (n = 14,750) drinkers and applied propensity score methods to address confounding. Results: We observed significant associations between early, weekly drinking and alcohol involvement class membership at Wave 1 for both males and females. For males, early, weekly drinking was also associated with greater odds of transitioning from moderate to severe alcohol problems (aOR = 3.19, 95% CI = 1.72, 5.35). For females, early, weekly drinking predicted the transition from no to severe problems (aOR = 2.98, 95% CI = 1.11–8.00). Contrary to our hypothesis, early, weekly drinking was associated with greater likelihood of transition from severe to no problems for males (aOR = 3.23, 95% CI = 1.26, 8.26). Discussion: Frequent, early drinking seems to be an important indicator of drinking progression with differential associations by sex. This information is useful to identify those at greater risk of progressing to severe drinking problems to intervene appropriately.

Working dogs are widely used by service professionals and the military for diverse roles that include sentry, patrol, messenger, tracking, search and rescue, law enforcement, apprehension, as well as explosives and narcotics detection. The expected tasks performed are in many ways determined by the breed, which is customarily a German Shepherd, Dutch Shepherd, Golden Retriever, Border Collie, Labrador Retriever, Beagle, or Belgium Malinois. Working dogs may be subject to injury from dangerous work environments or harmful agent exposure. Personal protective equipment (PPE) has been developed for such dogs, but may impede performance of duties or be poorly tolerated. Canine-specific field-use ready decontamination techniques and kits are therefore needed for use on working dogs that have encountered a harmful agent exposure. This report briefly reviews the development of the military working dog and examines personal protective equipment and decontamination techniques for working dogs after exposure to harmful biologic or chemical agents.

The Asian clam Corbicula fluminea (Family: Cyneridae) has aggressively invaded freshwater habitats worldwide, resulting in dramatic ecological changes and declines of native bivalves such as freshwater mussels (Family: Unionidae), one of the most imperiled faunal groups. Despite increases in our knowledge of invasive C. fluminea biology, little is known of how intrinsic and extrinsic factors, including co-occurring native species, influence its microbiome. We investigated the gut bacterial microbiome across genetically differentiated populations of C. fluminea in the Tennessee and Mobile River Basins in the Southeastern United States and compared them to those of six co-occurring species of native freshwater mussels. The gut microbiome of C. fluminea was diverse, differed with environmental conditions and varied spatially among rivers, but was unrelated to host genetic variation. Microbial source tracking suggested that the gut microbiome of C. fluminea may be influenced by the presence of co-occurring native mussels. Inferred functions from 16S rRNA gene data using PICRUST2 predicted a high prevalence and diversity of degradation functions in the C. fluminea microbiome, especially the degradation of carbohydrates and aromatic compounds. Such modularity and functional diversity of the microbiome of C. fluminea may be an asset, allowing to acclimate to an extensive range of nutritional sources in invaded habitats, which could play a vital role in its invasive success.

Many studies have shown that morphological knowledge has effects on reading comprehension separate from other aspects of language knowledge. This has implications for reading instruction and assessment: it suggests that children could have reading comprehension difficulties that are due to a lack of morphological knowledge, and thus, that explicit instruction of morphology might be helpful for them, indeed for all children. To find children who might especially benefit from specific instruction in morphology, we would need good tests of morphological knowledge. We evaluated a set of morphological awareness assessments to determine whether they conclusively tapped into morphological knowledge, and found that it was not possible to be certain that they were accurately targeting morphological knowledge.

This 5-year mathematics professional development project involves 27 elementary teachers prepared and supported as Elementary Mathematics Specialists (EMSs) in high-need, urban schools. Our inquiry centers on their experiences in the EMS preparation program and the development of important outcomes, specifically productive beliefs and teacher leadership. Data were gathered at the end of Year 1 via surveys of mathematical beliefs, coaching beliefs, and coaching practices, as well as individual and focus group interviews. The findings provide insights into participants' growth and work as a "more knowledgeable other," illuminating specific emphases of their efforts and influences of the project. When it comes to mathematical beliefs, as participants shifted toward embracing cognitively-oriented pedagogical beliefs, they became more efficacious in this learner-centered pedagogy. The findings also show variability in specific mathematics coaching practices, including those most participants were and were not using, and areas for improvement. Several themes are evident in the interview data: "growing confidence for the uncomfortable," "creating and finding spaces for stepping up," "advocating for learned mathematics pedagogy," and "building teacher capacity through interactions."

Abstract Background Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself. Methods To study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant. Results We found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival. Conclusions These data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.