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Abstract Background Interpreting services bridge language barriers that may prevent patients and clinicians from understanding each other, impacting quality of care and health outcomes. Despite this, there is limited up-to-date evidence regarding the barriers to and facilitators of uptake in primary care. The aim of this study was to ascertain current national uptake and experience of interpreting services in primary care (general practice) by South Asian communities in England. Methods We conducted a national cross-sectional survey in 2023 with people with limited or no English language proficiency (n = 609). Multilingual researchers interviewed people from Bangladeshi (n = 213), Indian (n = 200), and Pakistani (n = 196) backgrounds from four regions in England (Greater London, Midlands, Yorkshire and the Humber, North West). Results Sixty-three percent of participants reported using professional interpreting services in primary care. The most common modality was face-to-face interpreting (55%), followed by telephone (17%) and video (8%). Multivariable analysis identified several correlates of lower uptake: participants from Indian backgrounds, those living in the Midlands, and those whose family member/friend interpreted for them within the past year were less likely to have used a professional interpreter provided by their general/family practice. Participants who had visited primary care within the last 12 months, had requested an interpreter but were told they could not have one, were informed about professional interpreting services, and were given choice in their language support were more likely to have used a professional interpreter. Conclusions Our approach provides novel data on professional interpreting service use and evidence about the factors that may play a role in patient uptake and experience.

Abstract Breathing patterns (respiratory kinematics) contain vital prognostic information. This dimension of physiology is not captured by conventional vital signs. We sought to determine the feasibility and utility of quantifying respiratory kinematics. Using inertial sensors, we analyzed upper rib, lower rib, and abdominal motion of 108 patients with respiratory symptoms during a hospital encounter (582 two-minute recordings). We extracted 34 features based on an explainable correspondence with well-established breathing patterns. K-means clustering revealed that respiratory kinematics had three dimensions apart from the respiratory rate. We represented these dimensions using respiratory rate variability, respiratory alternans (rib-predominant breaths alternating with abdomen-predominant ones), and recruitment of accessory muscles (increased upper rib excursion). Latent profile analysis of the kinematic measures revealed two profiles consistent with the established clinical constructs of labored and unlabored breathing. In logistic regression, the labored breathing profile improved model discrimination for critical illness beyond the Sequential Organ Failure Assessment (SOFA) score (AUROC 0.77 v/s 0.72; p = 0.02). These findings quantitatively confirm the prior understanding that the respiratory rate alone does not adequately represent the complexity of respiratory kinematics; they demonstrate that high-dimensional signatures of labored breathing can be quantified in routine practice settings, and they can improve predictions of clinical deterioration.

Abstract Background Pemetrexed is combined with cisplatin to treat cancer. Whether pemetrexed-cisplatin combination chemotherapy exacerbates cisplatin nephrotoxicity is unclear. Here, we investigated kidney injury in mice administered a non-lethal low-dose regimen of pemetrexed or cisplatin alone and compared it with a pemetrexed-cisplatin combination. Methods Mice were randomly divided into four groups and administered intraperitoneally the experimental drugs solubilized in captisol (sulfobutylether β-cyclodextrin). Group 1 received captisol, Group 2 pemetrexed (10 mg/kg), Group 3 cisplatin (1 mg/kg), and Group 4 pemetrexed (10 mg/kg) plus cisplatin (1 mg/kg). The mice were treated every other day for two weeks, three times per week. Glomerular filtration rate (GFR) was determined on the third day after the last treatment, followed by a necropsy. Results Whereas the relative kidney weight was comparable in the control vs. pemetrexed or cisplatin alone group, it was significantly increased in the combination group. Mice treated with cisplatin and pemetrexed-cisplatin combination exhibited reduced GFR. The pemetrexed-cisplatin combination caused significant increases in the plasma or urinary levels of kidney injury biomarkers, renal lipid peroxidation, and nitrosative stress compared with pemetrexed or cisplatin alone. Histopathology revealed that pemetrexed or cisplatin alone had minimal effects on the kidneys. By contrast, the pemetrexed-cisplatin combination caused tubular degeneration, dilatation, and granular casts. Live-cell imaging showed that the pemetrexed-cisplatin combination caused more severe apoptosis of primary renal epithelial cells than individual concentrations. Conclusions These findings suggest that combining pemetrexed and cisplatin causes oxidative kidney damage at individual doses that do not cause significant nephrotoxicity. Hence, the renal function of patients undergoing treatment with the pemetrexed-cisplatin combination needs extensive monitoring.

Abstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Objective: This cross-sectional study utilized structural equation modeling to examine effects of COVID-19 stress on food insecurity and fruit and vegetable consumption mediated through personal agency and behavioral intention. Participants: Students (n = 749) enrolled at one federally designated Hispanic-serving public university during the fall 2020 semester. Methods: A 34-item survey was developed and administered. Results: COVID-19 stress had a statistically significant impact on food insecurity (B = 0.341; p < 0.001) and an inverse impact on personal agency to consume fruit and vegetables (B = -0.283; p < 0.001). Personal agency (B = 0.389; p < 0.001) and behavioral intention to consume fruit and vegetables were directly associated while food insecurity inversely impacted behavioral intention (B = -0.076; p = 0.034). Conclusions: Pandemic-related stress impacts nutrition behaviors among the student population already at risk of poor fruit and vegetable intake. During periods of high pandemic-related stress, college students need adequate access to fruits and vegetables and health promotion programs emphasizing stress management and healthy dietary behaviors.

In this study, we examine whether students in violent neighborhoods actively avoid their local school as a form of social and physical protection. Specifically, we use 10 years of administrative data (2010-2020) from the high school choice open enrollment program in the Baltimore City Public School System to evaluate the interaction between neighborhood violence and geographic proximity when predicting choice behavior. We find that, adjusting for observed school characteristics and constant unobserved student characteristics, students from more violent neighborhoods are substantially less likely to choose their closest school than are students in safer neighborhoods; even when the closest school is listed, it is ranked lower for students from more violent neighborhoods than for students in safer ones. These findings have implications for how we think about the relationship between neighborhoods and educational opportunity in an era of choice.

Capacity strengthening activities -- be that in the form of courses, workshops, seminars -- have become embedded in research projects as a requirement for funding and as a means for researchers to demonstrate positive societal impacts. We apply qualitative research techniques including interviews, questionnaires and observations to scrutinise and document an international capacity strengthening course aimed at informing and supporting environmental management practice and policy in the Philippines. We appraise power gradients and dynamics between course instructors and participants from different cultures and geographical locations in the design and delivery of this course. We identify five key factors that course instructors should consider as part of their pedagogy: (i) active learning, (ii) knowledge scaffolding and consolidation, and (iii) situated learning, as well as being attuned to (iv) the language dynamics and (v) expertise and networking within the room when teaching the course. Practical efforts to address these issues require that instructors work with participants to co-produce knowledge, rather than assuming epistemic authority and imposing knowledge. This entails reflexive and adaptable practices before, during and after the course. It is recommended that such practices should be central to projects that include capacity strengthening activities, whether delivered locally or internationally.

Abstract DNA methyltransferase 3 A mutations (DNMT3A MT) are frequent in myeloid neoplasia (MN) and mostly heterozygous. However, cases with multiple DNMT3A MT can be also encountered but their clinical and genetic landscape remains unexplored. We retrospectively analyzed 533 cases with DNMT3A MT identified out of 5,603 consecutive MNs, of whom 8.4% had multiple DNMT3A MT hits. They were most frequent in acute myeloid leukemia (AML) with R882 variant accounting for 13.3% of the multi-hits. Multiple DNMT3A MT more likely coincided with IDH2 (P = 0.005) and ETV6 (P = 0.044) mutations compared to patients with single DNMT3A MT. When the sum of variant allele frequencies (VAFs) for multiple DNMT3A MT exceeded 60%, we found a significant positive clonal burden correlation of the two DNMT3A variants (P

Abstract The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.S.) from March 13th 2020 to July 3rd 2023. Our sequencing protocol (‘Virseq’) utilizes wet and dry lab procedures to generate mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control and Prevention national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale.

Abstract Background A prediction model can be a useful tool to quantify the risk of a patient developing dementia in the next years and take risk-factor-targeted intervention. Numerous dementia prediction models have been developed, but few have been externally validated, likely limiting their clinical uptake. In our previous work, we had limited success in externally validating some of these existing models due to inadequate reporting. As a result, we are compelled to develop and externally validate novel models to predict dementia in the general population across a network of observational databases. We assess regularization methods to obtain parsimonious models that are of lower complexity and easier to implement. Methods Logistic regression models were developed across a network of five observational databases with electronic health records (EHRs) and claims data to predict 5-year dementia risk in persons aged 55–84. The regularization methods L1 and Broken Adaptive Ridge (BAR) as well as three candidate predictor sets to optimize prediction performance were assessed. The predictor sets include a baseline set using only age and sex, a full set including all available candidate predictors, and a phenotype set which includes a limited number of clinically relevant predictors. Results BAR can be used for variable selection, outperforming L1 when a parsimonious model is desired. Adding candidate predictors for disease diagnosis and drug exposure generally improves the performance of baseline models using only age and sex. While a model trained on German EHR data saw an increase in AUROC from 0.74 to 0.83 with additional predictors, a model trained on US EHR data showed only minimal improvement from 0.79 to 0.81 AUROC. Nevertheless, the latter model developed using BAR regularization on the clinically relevant predictor set was ultimately chosen as best performing model as it demonstrated more consistent external validation performance and improved calibration. Conclusions We developed and externally validated patient-level models to predict dementia. Our results show that although dementia prediction is highly driven by demographic age, adding predictors based on condition diagnoses and drug exposures further improves prediction performance. BAR regularization outperforms L1 regularization to yield the most parsimonious yet still well-performing prediction model for dementia.

Climate change poses a significant threat to sea turtles. In particular, beach erosion due to sea-level rise endangers sea turtle nests and can hinder the inland movement of nesting females. This study highlights an overlooked indirect hazard in the context of sea-level rise, namely the risk of nesting turtles to lethal falls from rocky cliffs exposed by beach erosion. We provide evidence of mortality of nine nesting green turtles (Chelonia mydas) found upside-down on the base of cliff ledges in Breem Island (locally known as جزيرة بريم), located along the northern Saudi Arabian Red Sea coast. One additional turtle was found flipped over but still alive. Our observations suggest that in areas where there is a continuum from the beach to the rocky cliffs (contrary to very steep cliffs bordering beaches), these structures pose a substantial hazard to nesting sea turtles when they attempt to return to the sea. Moreover, mean daily air temperatures of 31 ˚C (max. 44 ˚C) in the northern Red Sea likely exacerbate heat exhaustion of turtles that fall off the cliffs, providing a very narrow window for the animals to be rescued. This study underscores the need to integrate these indirect effects of sea-level rise into sea turtle vulnerability assessments, as well as the importance of implementing timely mitigation measures. Such steps are essential to meet the goals of the Kunming-Montreal Global Biodiversity Framework and support the survival of breeding sea turtles amidst climate change challenges.

The study of beach morphology holds significant importance in coastal management, offering insights into coastal and environmental processes. It involves analyzing physical characteristics and beach features such as profile shape, slope, sediment composition, and grain size, as well as changes in elevation due to both erosion and accretion over time. Furthermore, studying changes in beach morphology is essential in predicting and monitoring coastal inundation events, especially in the context of rising sea levels and subsidence in some areas. However, having access to high-frequency oblique imagery and beach elevation datasets to document and confirm coastal forcing events and understand their impact on beach morphology is a notable challenge. This paper describes a one-year dataset comprising bi-monthly topographic surveys and imagery collected daily at 30 min increments at the beach adjacent to Horace Caldwell Pier in Port Aransas, Texas. The data collection started in February 2023 and ended in January 2024. The dataset includes 18 topographic surveys, 6879 beach images, and ocean/wave videos that can be combined with colocated National Oceanic and Atmospheric Administration metocean measurements. The one-year temporal span of the dataset allows for the observation and analysis of seasonal variations, contributing to a deeper understanding of coastal dynamics in the study area. Furthermore, a study that combines survey measurements with camera imagery is rare and provides valuable information on conditions before, after, and between surveys and periods of inundation. The imagery enables monitoring of inundation events, while the topographic surveys facilitate the analysis of their impact on beach morphology, including beach erosion and accretion. Various products, including beach profiles, contours, slope maps, triangular irregular networks, and digital elevation models, were derived from the topographic dataset, allowing in depth analysis of beach morphology. Additionally, the dataset contains a time series of four wet/dry shoreline delineations per day and their corresponding elevation extracted by combining the imagery with the digital elevation models. Thus, this paper provides a high-frequency morphological dataset and a machine learning-ready dataset suitable for predicting coastal inundation.

The ‘social death’ metaphor is used to reflect ostracism’s severity and death-related themes often influence ostracism research. To determine its accuracy, we examined the similarity of ostracism and mortality salience (MS) outcomes. To manipulate these constructs, we used writing prompts in Study 1, and Cyberball and a novel MS manipulation, ‘Cybergrave,’ in studies 2, 3a, and 3b. In Study 4, we correlated chronic ostracism and death-thought accessibility. Ostracism uniquely threatened psychological needs, whereas MS uniquely activated death thoughts. Moreover, the correlation between chronic ostracism and death-thought accessibility was small and non-significant when controlling for related variables. Results suggest the death metaphor may not always be accurate. Death-related language may bias how ostracism is conceptualized and studied, emphasizing pain over recovery.

IntroductionAmyloid-specific antibodies have been shown to opsonize and enhance amyloid clearance in systemic amyloidosis mouse models. However, the immunological mechanisms by which amyloid is removed have not been clearly defined. Previous reports from preclinical in vivo studies suggest polymorphonuclear cells (i.e., neutrophils) can affect amyloid removal. Therefore, we sought to analyze how neutrophils may contribute to the clearance of human AL amyloid extracts, using a murine amyloidoma model.MethodsImmunocompromised nude mice injected subcutaneously with patient-derived AL amyloid extract (generating a localized “amyloidoma”) were used to circumvent confounding factors contributed by the adaptive immune system and served as the model system. Two representative AL amyloid extracts were used, ALλ(CLA), which is refractory to clearance, and ALκ(TAL), which is readily cleared in mice. Neutrophil recruitment to the amyloid masses, cellular activation, and propensity to engulf amyloid were assessed.ResultsImmunophenotyping of amyloidomas from animals implanted with 2 mg of either ALλ or ALκ revealed that more neutrophils were recruited to ALκ amyloid masses as compared to the ALλ material, which was generally devoid of neutrophils. Ex vivo analyses indicated neutrophils do not efficiently phagocytose amyloid directly. However, histological evaluation of the ALκ amyloidoma revealed the abundant presence of neutrophil extracellular traps, which were absent in the ALλ amyloidomas. Using neutrophil depletion experiments in mice, we determined that mice devoid of neutrophils cleared the human amyloid lesions less efficiently. Moreover, mice devoid of neutrophils also had significantly reduced intra-amyloid expression of inflammatory cytokines.DiscussionNeutrophils may not directly mediate amyloid clearance through phagocytosis; however, these cells can be stimulated by the amyloid and may function to facilitate phagocytosis and amyloid clearance by professional phagocytes (e.g., macrophages).

Abstract Human‐carnivore conflicts pose significant challenges in the management and conservation of carnivores across the globe. Abundant research has led to generalizable insights into the causes of such conflicts. For example, conflicts predictably occur when carnivores have access to human food resources, particularly when their natural foods are scarce. However, similar insights into the effectiveness of interventions aimed at coexistence remains comparatively scarce. We hypothesized that this disparity might be reflected in a bias toward research focused on causes of conflict rather than interventions to address it. To test our hypothesis, we evaluated the content of studies on human–carnivore conflicts and coexistence in Canada and the United States from 2010 to 2021. We found that studies disproportionately focused on causes of conflict, with that discrepancy increasing through our study period. We also found a disproportionate focus on black bears and wolves and western jurisdictions, and a disproportionate use of observational (vs. experimental) approaches. Studies on conflict interventions were primarily directed at the carnivores themselves (e.g., lethal approaches) versus human elements (e.g., attractant management, policies), despite evidence that the latter are more effective. We expect that a shift in focus toward solutions‐oriented research, integrating insights across geographies, taxa, social contexts, and disciplines, would facilitate effective interventions and foster coexistence, improving outcomes for people and carnivores alike.

Summary: The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1+TCF-1+ neoAg-specific CD8 T cells in tumors. Anti-CTLA-4 and/or anti-PD-1 ICT promotes intratumoral TCF-1− neoAg-specific CD8 T cells, although their phenotype depends in part on the specific ICT used. Anti-CTLA-4 also prompts substantial changes to CD4 T cells, including induction of ICOS+Bhlhe40+ T helper 1 (Th1)-like cells. Although neoAg vaccines or ICTs expand iNOS+ macrophages, neoAg vaccines maintain CX3CR1+CD206+ macrophages expressing the TREM2 receptor, unlike ICT, which suppresses them. TREM2 blockade enhances neoAg vaccine efficacy and is associated with fewer CX3CR1+CD206+ macrophages and induction of neoAg-specific CD8 T cells. Our findings highlight different mechanisms underlying neoAg vaccines and different forms of ICT and identify combinatorial therapies to enhance neoAg vaccine efficacy.

Background Charles Bonnet syndrome (CBS) is a condition characterized by vivid, complex visual hallucinations in individuals with visual impairment. Despite its prevalence among the elderly and those with degenerative eye diseases, CBS remains underdiagnosed and undertreated due to a lack of awareness and misconceptions surrounding its etiology and management. Case Report A 51-year-old man presented to the emergency room after falling off his bicycle without wearing a helmet. Head imaging revealed a small right frontoparietal traumatic subarachnoid hemorrhage with an associated trace subdural hematoma along the right parietal convexity. Subsequently, he developed non-light perceiving vision loss, after which he began experiencing visual hallucinations. Conclusion CBS is frequently overlooked or left untreated. Research on diagnosing and managing CBS following head trauma is limited. Therefore, clear diagnostic criteria for CBS and a better understanding of its underlying mechanisms are needed to improve diagnosis and management strategies.

Abstract Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson’s disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like α-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to α-syn aggregation and a greater understanding of both processes and their role in α-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS.

Abstract Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning algorithm extends the depth-of-field, allowing rapid acquisition of in-focus images from large areas of tissue even when the tissue surface is highly irregular. Finally, a semi-supervised generative adversarial network virtually stains DeepDOF-SE fluorescence images with hematoxylin-and-eosin appearance, facilitating image interpretation by pathologists without significant additional training. We developed the DeepDOF-SE platform using a data-driven approach and validated its performance by imaging surgical resections of suspected oral tumors. Our results show that DeepDOF-SE provides histological information of diagnostic importance, offering a rapid and affordable slide-free histology platform for intraoperative tumor margin assessment and in low-resource settings.

Abstract Contributory science—including citizen and community science—allows scientists to leverage participant‐generated data while providing an opportunity for engaging with local community members. Data yielded by participant‐generated biodiversity platforms allow professional scientists to answer ecological and evolutionary questions across both geographic and temporal scales, which is incredibly valuable for conservation efforts. The data reported to contributory biodiversity platforms, such as eBird and iNaturalist, can be driven by social and ecological variables, leading to biased data. Though empirical work has highlighted the biases in contributory data, little work has articulated how biases arise in contributory data and the societal consequences of these biases. We present a conceptual framework illustrating how social and ecological variables create bias in contributory science data. In this framework, we present four filters—participation, detectability, sampling and preference—that ultimately shape the type and location of contributory biodiversity data. We leverage this framework to examine data from the largest contributory science platforms—eBird and iNaturalist—in St. Louis, Missouri, the United States, and discuss the potential consequences of biased data. Lastly, we conclude by providing several recommendations for researchers and institutions to move towards a more inclusive field. With these recommendations, we provide opportunities to ameliorate biases in contributory data and an opportunity to practice equitable biodiversity conservation. Read the free Plain Language Summary for this article on the Journal blog.

Rare earth metals are considered to be some of the most critical raw materials on the planet due to their use in many products and technologies, the difficulty in isolating the individual elements from ores and each other, and the market restrictions that threaten their supply. However, despite this, the recycling rates for rare earth metals remain low. Hydrometallurgy has been proposed to hold the greatest potential for the recovery of rare earth metals from waste materials. However, the design of hydrometallurgical processes for the recovery of rare earth elements from waste requires a good understanding of the behaviour of the rare earth metals between different phases.In this study, the distribution coefficients of two rare earth metals, yttrium, and neodymium, between an organic solvent; bis(2-ethylhexyl) phosphate, diluted in n-dodecane at between 0.25 M and 1 M; and an aqueous nitric acid solution at concentrations of between 0.1 M and 2.8 M were measured. Distribution measurements were performed using a series of liquid–liquid extraction cells at a constant temperature of 298.2 K. The concentration of the rare earth metals was measured using ICP-OES analysis. The distribution coefficients and the acid concentration were found to be inversely related to each other. Conversely, the distribution coefficients were directly proportional to the concentration of the solvent in the organic phase.The data reported in this paper will be used to design a counter-current liquid–liquid extraction column for the recovery of neodymium from waste permanent magnet powder.

Over the last 5 years, IR-MALDESI-MS (Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry) has been demonstrated for use in a range of high-throughput biochemical and cellular assays with remarkable sample acquisition rates up to 22 Hz for a single 384-well assay plate. With such high single plate acquisition rates, the rate limiting step becomes how fast subsequent plates can be presented to the MS for analysis. To make this transfer as fast as possible while maintaining safe operation in a laboratory environment, we developed a collaborative robotic plate transfer system (CRPTS) that combines a 6-axis robot with dual plate grippers, a 7th axis conveyor stage, and a 420-plate capacity sample loading window. As a demonstration of the throughput and flexibility of CRPTS, we performed a biochemical assay that monitored the oxidation of tris(2-carboxyethyl)phosphine (TCEP) to screen for nuisance compounds. Using continuous and step motion scan profiles, we analyzed 158,799 compounds contained in 448 assay plates over the course of 12.5 h (Z-Factor=0.87) and 17.5 h (Z-factor=0.99), respectively. Extrapolating these results enables the screening of a million compounds within 6–7 working days.

Background:. Geographic information systems are powerful tools for characterizing the geospatial factors influencing access to care. As patients with cleft lip and/or palate (CL/P) require long-term care, with numerous operations and therapies, access to timely, quality care is extremely important. This study uses population level analysis and geographic information systems to identify United States counties with limited access to American Cleft Palate Association–approved cleft teams. Methods:. Natality data were queried from the National Vital Statistics System. Population and geographic data were obtained from the US Census Bureau. The Social Vulnerability Index (SVI) was utilized to account for social inequality. Total births with CL/P, population estimates, SVI, distance to the nearest center, and total centers within 50 km were used to generate the cleft care demand index (CCDI). Results:. Ninety-two counties had CCDIs between 66.7 and 100. The highest scoring county, Hidalgo County, Texas, had 62 births with CL/P, population estimate of 888,367 persons, distance to the nearest cleft center of 368.4 km, and SVI of 0.99. Conclusions:. This study demonstrates the power of geographic information systems for identifying areas with limited access to approved cleft teams. The CCDI measures cleft burden, socioeconomic disadvantage, and geographic barriers to quantify the demand for approved cleft care in each county. Utilizing these scores can help direct future interventions, outreach efforts, and cleft care center planning.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax naïve and resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.

Abstract The Southeast Tropical Indian Ocean (SETIO), dominated by the Indian Ocean monsoon, is an important source region for strong mesoscale eddies. To date, the impacts of the Indian Ocean monsoon on mesoscale eddies have not been clarified. Here we report on the dipole response of mesoscale eddy formation to monsoon transition in the SETIO, using satellite and reanalysis data sets. During the summer monsoon season, anticyclonic eddies are mainly concentrated north of 12°S, while cyclonic eddies are south of 12°S. This situation reverses during the winter monsoon season. We attribute this dipole feature to the oceanic perturbations and current shear during the different monsoon periods. A geographical boundary along 12°S aligns with meridional changes in eddy potential energy, which delineates the generation and direction of the newly‐formed eddies. The hot spot region, rich in eddy energy properties, tends to promote eddy formation and endurance during the monsoon periods.

Background: Health inequalities in African American communities have been further exacerbated by COVID-19. Public health departments and other safety-net providers across the United States have partnered with community-based organizations to address barriers to COVID-19 testing in disproportionately impacted communities. This narrative review summarizes lessons learned from published examples of these community-based COVID-19 testing efforts. Methods: We searched online databases for peer-reviewed articles on community-based COVID-19 testing interventions in the United States aimed at increasing COVID-19 testing among African American populations. We abstracted information about each example and synthesized the primary lessons learned and key aspects that contributed to their success. Results: Seven examples of community-based COVID-19 testing aimed at increasing testing among African Americans and other underserved populations were identified and described, across various U.S. locations and involving multiple types of partners (1) St. Paul, MN (faith, health centers, Mayo Clinic); (2) Chicago, IL (university hospital and health centers); (3) NC (health centers, Community Advisory Board); (4) Baltimore, MD (hospitals, community clinic, mobile clinic); (5) Marion County, FL (health department and community partners); (6) New Orleans, LA (health department and health system); and (7) New York City, NY health and hospital system, mobile clinic). Discussion: Several key aspects of the COVID-19 testing models included the following: (1) close proximity of the testing site to affected communities and availability of walk-up and drive-through testing options; (2) partnerships between safety-net providers and broad community networks, which facilitated outreach and trust; (3) increased resources for safety-net providers; and (4) the use of data to identify areas of need and track impact. The merging of resources and relationships among well-equipped, safety-net providers and other health care institutions and culture-rich, community-centered organizations, to jointly address structural and systemic inequities, is key to cultivating health equity in the distribution of COVID-19 testing and other essential public health services.

Abstract Murine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named ‘PoWeR’, was previously developed to serve as a more translatable alternative to involuntary resistance‐type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic‐to‐oxidative shift in muscle fibre type. Thus, PoWeR reflects a blended resistance/endurance model. In an attempt to bias PoWeR further towards resistance‐type exercise, we developed a novel heavy PoWeR model (hPoWeR) utilizing higher wheel loads (max of 12.5 g vs 6 g). Adult male C57BL/6 mice voluntarily performed an 8‐week progressive loading protocol (PoWeR or hPoWeR). Running distance peaked at ∼5–6 km day−1 in both treatments and was maintained by PoWeR mice, but declined in the hPoWeR mice as load increased beyond 7.5 g. Peak isometric force of the gastrocnemius–soleus–plantaris complex tended to increase in wheel running treatments. Soleus mass increased by 19% and 24% in PoWeR and hPoWeR treatments, respectively, and plantaris fibre cross‐sectional area was greater in hPoWeR, compared to PoWeR. There were fewer glycolytic and more oxidative fibres in the soleus and plantaris muscles in the PoWeR treatment, but not hPoWeR. Collectively, these data suggest hPoWeR may modestly alter skeletal muscle supporting the aim of better reflecting typical resistance training adaptations, in line with decreased running volume and exposure to higher resistance. Regardless, PoWeR remains an effective hypertrophic concurrent training model in mice.

Novel quantum materials offer the opportunity to expand next-generation computers, high-precision sensors, and new energy technologies. Among the most important factors influencing the development of quantum materials research is the ability of inorganic and materials chemists to grow high-quality single crystals. Here, the synthesis, structure characterization and magnetic properties of Na2Cu3(SeO3)4 are reported. It exhibits a novel two-dimensional (2D) structure with isolated layers of Cu nets. Single crystals of Na2Cu3(SeO3)4 were grown using a low-temperature hydrothermal method. Single-crystal X-ray diffraction reveals that Na2Cu3(SeO3)4 crystallizes in the monoclinic crystal system and has space group symmetry of P21/n (No.14) with a unit cell of a = 8.1704(4) Å, b = 5.1659(2) Å, c = 14.7406(6) Å, β = 100.86(2), V = 611.01(5) Å3 and Z = 2. Na2Cu3(SeO3)4 comprises a 2D Cu-O-Cu lattice containing two unique copper sites, a CuO6 octahedra and a CuO5 square pyramid. The SeO3 groups bridge the 2D Cu-O-Cu layers isolating the neighboring Cu-O-Cu layers, thereby enhancing their 2D nature. Magnetic properties were determined by measuring the magnetic susceptibility of an array of randomly oriented single crystals of Na2Cu3(SeO3)4. The temperature-dependent magnetic measurement shows an antiferromagnetic transition at TN = 4 K. These results suggest the fruitfulness of hydrothermal synthesis in achieving novel quantum materials and encourage future work on the chemistry of transition metal selenite.

Abstract Long-read sequencing is revolutionizing de-novo genome assemblies, with continued advancements making it more readily available for previously understudied, non-model organisms. Stony corals are one such example, with long-read de-novo genome assemblies now starting to be publicly available, opening the door for a wide array of ‘omics-based research. Here we present a new de-novo genome assembly for the endangered Caribbean star coral, Orbicella faveolata, using PacBio circular consensus reads. Our genome assembly improved the contiguity (51 versus 1,933 contigs) and complete and single copy BUSCO orthologs (93.6% versus 85.3%, database metazoa_odb10), compared to the currently available reference genome generated using short-read methodologies. Our new de-novo assembled genome also showed comparable quality metrics to other coral long-read genomes. Telomeric repeat analysis identified putative chromosomes in our scaffolded assembly, with these repeats at either one, or both ends, of scaffolded contigs. We identified 32,172 protein coding genes in our assembly through use of long-read RNA sequencing (ISO-seq) of additional O. faveolata fragments exposed to a range of abiotic and biotic treatments, and publicly available short-read RNA-seq data. With anthropogenic influences heavily affecting O. faveolata, as well as its increasing incorporation into reef restoration activities, this updated genome resource can be used for population genomics and other ‘omics analyses to aid in the conservation of this species.

Exercise performance tends to suffer during the morning compared to the evening, which may decrease potential training adaptations. Currently, it is unclear how nutritional interventions may affect this phenomenon and whether supplementation may allow for the attainment of optimal performance regardless of the time of day. The purpose of this study was to investigate the effects of acute yohimbine ingestion on morning-associated decrements in performance and psychophysiological responses to exercise. Physically active females (n = 16) were recruited to participate in three total visits, each with a different treatment: (1) placebo-morning (PL-AM), (2) yohimbine-morning (YHM-AM; oral 2.5 mg), and (3) placebo-afternoon (PM). The morning and afternoon visits occurred between 7:00–8:00 h and 16:00–17:00 h, respectively. The experimental treatments in the morning were ingested 20 min prior to capillary blood collection, which was completed pre- and post-exercise. Following a warm-up, participants completed a 2000 m time trial on a rowing ergometer. Power output, heart rate (HR), and rating of perceived exertion (RPE) were recorded every minute. Time to competition (TTC) and subjective energy, focus, and alertness were documented post-exercise. Pre- and post-exercise blood lactate (La) and plasma hypoxanthine (HX) levels were also assessed. The trials were separated by a 48 h washout period. The results showed that power output (p = 0.010) was lower and TTC (p = 0.003) was significantly slower with PL-AM compared to PM. Furthermore, YHM-AM resulted in higher power output (p = 0.035) and faster TTC (p = 0.007) compared to PL-AM, with no differences compared to PM (p > 0.05). Post-exercise La was significantly lower with YHM-AM compared to PL-AM (p = 0.046) and PM (p = 0.001). Pre-exercise plasma HX, as measured via conversion to xanthine, was significantly higher with PM (p = 0.039), while the levels trended higher with YHM-AM (p = 0.060) compared to PL-AM. Subjective energy was higher with YHM-AM (p = 0.045) and PM (p = 0.009) compared to PL-AM, while alertness was only higher for YHM-AM compared to PL-AM (p = 0.045). No statistical differences between the treatments were found for RPE or HR (p > 0.05). These findings indicate that YHM ingestion attenuates performance decrements in the morning. Improvements in performance may be underpinned by improved feelings of energy and alterations in metabolism. Practically, YHM may represent an effective ergogenic aid to combat a lack of energy and low performance during the morning.

Abstract The offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica’s ice shelves, both now and into the future.

Background and Aims: Colorectal cancer (CRC) polygenic risk scores (PRS) may help personalize CRC prevention strategies. We investigated whether an existing PRS was associated with advanced neoplasia (AN) in a population undergoing screening and follow-up colonoscopy. Methods: We evaluated 10-year outcomes in the Cooperative Studies Program #380 screening colonoscopy cohort, which includes a biorepository of selected individuals with baseline AN (defined as CRC or adenoma ≥10 mm or villous histology, or high-grade dysplasia) and matched individuals without AN. A PRS was constructed from 136 prespecified CRC-risk single nucleotide polymorphisms. Multivariate logistic regression was used to evaluate the PRS for associations with AN prevalence at baseline screening colonoscopy or incident AN in participants with at least one follow-up colonoscopy. Results: The PRS was associated with AN risk at baseline screening colonoscopy (P = .004). Participants in the lowest PRS quintile had more than a 70% decreased risk of AN at baseline (odds ratio 0.29, 95% confidence interval 0.14–0.58; P < .001) compared to participants with a PRS in the middle quintile. Using a PRS cut-off of more than the first quintile to indicate need for colonoscopy as primary screening, the sensitivity for detecting AN at baseline is 91.8%. We did not observe a relationship between the PRS and incident AN during follow-up (P = .28). Conclusion: A PRS could identify individuals at low risk for prevalent AN. Ongoing work will determine whether this PRS can identify a subset of individuals at sufficiently low risk who could safely delay or be reassured about noninvasive screening. Otherwise, more research is needed to augment these genetic tools to predict incident AN during long-term follow-up.

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

The Totten Ice Shelf (TIS) and Moscow University Ice Shelf (MUIS), along the Sabrina Coast of Wilkes Land, are the floating seaward terminuses of the second-largest freshwater reservoir in the East Antarctic Ice Sheet. Being a marine ice sheet, it is vulnerable to the surrounding ocean conditions. Recent comprehensive oceanographic observations, including bathymetric measurements off the Sabrina Coast, have shed light on the widespread intrusion of warm modified Circumpolar Deep Water (mCDW) onto the continental shelf and the intense ice–ocean interaction beneath the TIS. However, the spatiotemporal coverage of the observation is very limited. Here, we use an ocean–sea ice–ice shelf model with updated bathymetry to better understand the regional ocean circulations and ocean–cryosphere interactions. The model successfully captured the widespread intrusions of mCDW, local sea ice production and the ocean heat and volume transports into the TIS cavity, facilitating an examination of the overturning ocean circulation within the ice shelf cavities and the resultant basal melting. We found notable differences in the temporal variability in ice shelf basal melting across the two adjacent ice shelves of the TIS and the western part of the MUIS. Ocean heat transport by mCDW controls the low-frequency interannual-to-decadal variability in ice–ocean interactions, but the sea ice production in the Dalton Polynya strongly modifies the signals, explaining the regional difference between the two ice shelves. The formation of a summertime eastward-flowing undercurrent beneath the westward-flowing Antarctic Slope Current is found to play an important role in the seasonal delivery of ocean heat to the continental shelf.