Carbonate-Metal Reactions in the Lower Mantle.

Carbonates are important carbon-bearing phases in the mantle. While their role in upper mantle petrologic processes has been well studied, their effect on phase relations, melting, and transport properties in the lower mantle is less understood. The stability of carbonates in the mantle depends on a host of factors, including pressure, temperature, oxygen fugacity, and reactions with surrounding mantle phases. To understand the stability of carbonates in the presence of metal in the lower mantle, carbonate-metal reaction experiments on the Fe-Si-Ca-Mg-C-O system were conducted up to 124 GPa and 3200 K. We find that carbonates react with iron alloys to form silicates, iron carbides, and oxides. However, the temperature at which these reactions occur increases with pressure, indicating that along a geotherm in the lowermost mantle carbonates are the stable carbon-bearing phase. Carbon is found to be less siderophilic at high-pressure compared to silicon.

Altered Mental Status and Cardiac Failure Due to Thiamine Deficiency in an Overweight Teen.

We describe an overweight but otherwise previously healthy 17-year-old female who presented with altered mental status and rapidly progressive weakness. She was ultimately diagnosed with Wernicke encephalopathy and wet beriberi resulting from severe thiamine deficiency. She required admission to the pediatric ICU because of hypoventilation with progressive weakness and worsening encephalopathy and was found to have impaired cardiac function as assessed by echocardiography. Her heart function and encephalopathy improved on initiation of thiamine repletion. She remained in inpatient rehabilitation for 10 months but still remained weak at discharge. Thiamine deficiency is not commonly considered in the United States as a diagnosis other than in patients with severe alcohol use disorder. However, thiamine may be depleted in as little as 2 weeks if nutrition is inadequate. In such a setting, thiamine deficiency is an important etiology to consider early in the pediatric patient with altered mentation especially because it can be readily and safely treated.

Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.

PURPOSE: The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression-based subtyping remain unknown. EXPERIMENTAL DESIGN: In this study, we conducted 126 PET scans using four different metabolic PET tracers, [18F]fluorodeoxy-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), and [11C]acetate ([11C]ACE), using a spectrum of five preclinical colon cancer models with varying genetics (BMT, AKPN, AK, AKPT, KPN), at three sites (subcutaneous, orthograft, autochthonous) and at two tumor stages (primary vs. metastatic). RESULTS: The results demonstrate that imaging signatures are influenced by genotype, tumor environment, and stage. PET imaging signatures exhibited significant heterogeneity, with each cancer model displaying distinct radiotracer profiles. Oncogenic Kras and Apc loss showed the most distinctive imaging features, with [18F]FLT and [18F]FET being particularly effective, respectively. The tissue environment notably impacted [18F]FDG uptake, and in a metastatic model, [18F]FET demonstrated higher uptake. CONCLUSIONS: By examining factors contributing to PET-imaging phenotype, this study establishes the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. It lays the foundation for further exploration of PET-based subtyping in human cancer, thereby facilitating noninvasive molecular diagnosis.

Loneliness in the Daily Lives of People With Mood and Psychotic Disorders.

BACKGROUND AND HYPOTHESIS: Loneliness, the subjective experience of feeling alone, is associated with physical and psychological impairments. While there is an extensive literature linking loneliness to psychopathology, limited work has examined loneliness in daily life in those with serious mental illness. We hypothesized that trait and momentary loneliness would be transdiagnostic and relate to symptoms and measures of daily functioning. STUDY DESIGN: The current study utilized ecological momentary assessment and passive sensing to examine loneliness in those with schizophrenia (N = 59), bipolar disorder (N = 61), unipolar depression (N = 60), remitted unipolar depression (N = 51), and nonclinical comparisons (N = 82) to examine relationships of both trait and momentary loneliness to symptoms and social functioning in daily life. STUDY RESULTS: Findings suggest that both trait and momentary loneliness are higher in those with psychopathology (F(4,284) = 28.00, P < .001, ηp2 = 0.27), and that loneliness significantly relates to social functioning beyond negative symptoms and depression (ß = -0.44, t = 6.40, P < .001). Furthermore, passive sensing measures showed that greater movement (ß = -0.56, t = -3.29, P = .02) and phone calls (ß = -0.22, t = 12.79, P = .04), but not text messaging, were specifically related to decreased loneliness in daily life. Individuals higher in trait loneliness show stronger relationships between momentary loneliness and social context and emotions in everyday life. CONCLUSIONS: These findings provide further evidence pointing to the importance of loneliness transdiagnostically and its strong relation to social functioning. Furthermore, we show that passive sensing technology can be used to measure behaviors related to loneliness in daily life that may point to potential treatment implications or early detection markers of loneliness.

Characterizing Neutrophil Subtypes in Cancer Using scRNA Sequencing Demonstrates the Importance of IL1ß/CXCR2 Axis in Generation of Metastasis-specific Neutrophils.

Neutrophils are a highly heterogeneous cellular population. However, a thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing of human and murine datasets, both publicly available and independently generated, to identify neutrophil transcriptomic subtypes and developmental lineages in health and malignancy. Datasets of lung, breast, and colorectal cancer were integrated to establish and validate neutrophil gene signatures. Pseudotime analysis was used to identify genes driving neutrophil development from health to cancer. Finally, ligand-receptor interactions and signaling pathways between neutrophils and other immune cell populations in primary colorectal cancer and metastatic colorectal cancer were investigated. We define two main neutrophil subtypes in primary tumors: an activated subtype sharing the transcriptomic signatures of healthy neutrophils; and a tumor-specific subtype. This signature is conserved in murine and human cancer, across different tumor types. In colorectal cancer metastases, neutrophils are more heterogeneous, exhibiting additional transcriptomic subtypes. Pseudotime analysis implicates IL1ß/CXCL8/CXCR2 axis in the progression of neutrophils from health to cancer and metastasis, with effects on T-cell effector function. Functional analysis of neutrophil-tumoroid cocultures and T-cell proliferation assays using orthotopic metastatic mouse models lacking Cxcr2 in neutrophils support our transcriptional analysis. We propose that the emergence of metastatic-specific neutrophil subtypes is driven by the IL1ß/CXCL8/CXCR2 axis, with the evolution of different transcriptomic signals that impair T-cell function at the metastatic site. Thus, a better understanding of neutrophil transcriptomic programming could optimize immunotherapeutic interventions into early and late interventions, targeting different neutrophil states. SIGNIFICANCE: We identify two recurring neutrophil populations and demonstrate their staged evolution from health to malignancy through the IL1ß/CXCL8/CXCR2 axis, allowing for immunotherapeutic neutrophil-targeting approaches to counteract immunosuppressive subtypes that emerge in metastasis.

The Reel Health Care Professionals of Instagram: A Systematic Review.

Social media and health research have covered the benefits for the public and patients as users. Specifically, this has focused on searching for health information, connecting with others experiencing similar health issues, and communicating with their health professionals. Recently, there has been a shift in research to focus on health care professionals as users as they participate in professional development, improve communication with patients, and contribute to health research and service. However, such research has predominantly focused on text-based platforms, namely Facebook and Twitter. The scope of this article is a systematic review of publications on health care professionals' use of the image-based platform Instagram, according to the preferred reporting items for systematic reviews and meta-analyses guidelines. This study, drawing from 51 articles, shows how health care professionals use Instagram, and reveals that these professionals utilize the platform to address health concerns that may not necessarily align with their specific expertise. Images were the common format of posts created by health care professionals, with six content types identified: (a) educational, (b) promotional, (c) patient experience, (d) personal, (e) emotion based, and (f) other. Three measures of post engagement were used by researchers, including (a) likes and comments, (b) use of hashtags, and (c) number of followers. This study also identified the dangers of misleading users, including (a) lack of credentials reported, (b) edited images, (c) quality of content, and (d) patient and client confidentiality issues. In conclusion, insights into the advantages of health care professionals' use of Instagram and ways in which they can maximize its use to reach and engage with their target audience are provided.

Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5+ stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1+ stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease. These PDS3 phenotypic traits are evident across numerous bulk and single-cell datasets, and demark a series of subtle biological states that are currently under-represented in pre-clinical models and are not identified using existing subtyping classifiers.

Empowering Pacific Patients on the Weight Loss Surgery Pathway: A Co-designed Evaluation Study.

PURPOSE: Despite having the highest medical needs by population for weight loss treatment, Pacific patients in Aotearoa New Zealand face substantial levels of attrition in publicly funded weight loss surgery programs. In collaboration with the Auckland City Hospital bariatric surgery team, a Pacific-led preoperative weight loss surgery program was co-designed, delivered, and evaluated between 2020 and 2023. MATERIALS AND METHODS: This was a single-arm, prospective co-designed evaluation study that took place at Auckland City Hospital in Aotearoa New Zealand. Participants were Pacific patients (n = 14) referred to the weight loss surgery program. Survey and video diaries were analyzed to determine if the program had the potential to increase Pacific patient retention through the preoperative stage of weight loss surgery, increase surgery completion rates, and improve the quality of treatment experiences. RESULTS: Nine out of 14 participants attended all preoperative sessions. Six participants subsequently underwent weight loss surgery. Program components that had positive impacts on patient success and satisfaction were accessibility, information quality, having Pacific role models, cultural safety, and the group support system. The patients found the program to be culturally anchored and there was support for the implementation of the program going forward. CONCLUSION: This study demonstrated how a culturally anchored intervention can increase patient retention for those patients who may not respond to mainstream treatment. Adjusting existing preoperative weight loss surgery programs to integrate Pacific-led models of healthcare has the potential to increase Pacific patient resiliency to follow through with surgery.

Identifying mechanisms of persecutory ideation maintenance with smartphone technology: Examining threat importance, certainty, rumination, and behavior change.

Previous cross-sectional and laboratory research has identified risk factors for persecutory ideation including rumination, negative affect, and safety-seeking behaviors. Questions remain about what in-the-moment factors link general negative affect to PI as well as which maintain PI over time. In the present study, N = 219 individuals completed momentary assessments of PI as well as four factors (attributing threats as certain and important, ruminating, and changing one's behavior in response) proposed to maintain PI over time. Linear mixed effects models were used to analyze multiple time-varying relationships, including these factors predicting negative affect and vice versa, as well as factors predicting maintenance of PI over time. Linear mixed effects models were used to analyze multiple time-varying relationships, examining each PI-related factor predicting negative affect, negative affect predicting each PI-related factor, as well as each factor predicting maintenance of PI over time. All four factors were associated with increases in subsequent day self-reported severity of PI, suggesting all four increased the likelihood of maintaining or worsening next-day PI. Results of this study confirm that the proposed factors are key in maintaining a cycle by which PI and negative affect are maintained over time. These factors may represent targets for momentary interventions.

Depressive symptoms as a heterogeneous and constantly evolving dynamical system: Idiographic depressive symptom networks of rapid symptom changes among persons with major depressive disorder.

Major depressive disorder (MDD) is conceptualized by individual symptoms occurring most of the day for at least two weeks. Despite this operationalization, MDD is highly variable with persons showing greater variation within and across days. Moreover, MDD is highly heterogeneous, varying considerably across people in both function and form. Recent efforts have examined MDD heterogeneity byinvestigating how symptoms influence one another over time across individuals in a system; however, these efforts have assumed that symptom dynamics are static and do not dynamically change over time. Nevertheless, it is possible that individual MDD system dynamics change continuously across time. Participants (N = 105) completed ratings of MDD symptoms three times a day for 90 days, and we conducted time varying vector autoregressive models to investigate the idiographic symptom networks. We then illustrated this finding with a case series of five persons with MDD. Supporting prior research, results indicate there is high heterogeneity across persons as individual network composition is unique from person to person. In addition, for most persons, individual symptom networks change dramatically across the 90 days, as evidenced by 86% of individuals experiencing at least one change in their most influential symptom and the median number of shifts being 3 over the 90 days. Additionally, most individuals had at least one symptom that acted as both the most and least influential symptom at any given point over the 90-day period. Our findings offer further insight into short-term symptom dynamics, suggesting that MDD is heterogeneous both across and within persons over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Space object identification and classification from hyperspectral material analysis.

This paper presents a data processing pipeline designed to extract information from the hyperspectral signature of unknown space objects. The methodology proposed in this paper determines the material composition of space objects from single pixel images. Two techniques are used for material identification and classification: one based on machine learning and the other based on a least square match with a library of known spectra. From this information, a supervised machine learning algorithm is used to classify the object into one of several categories based on the detection of materials on the object. The behaviour of the material classification methods is investigated under non-ideal circumstances, to determine the effect of weathered materials, and the behaviour when the training library is missing a material that is present in the object being observed. Finally the paper will present some preliminary results on the identification and classification of space objects.

KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo.

Oncogenic KRAS mutations are well-described functionally and are known to drive tumorigenesis. Recent reports describe a significant prevalence of KRAS allelic imbalances or gene dosage changes in human cancers, including loss of the wild-type allele in KRAS mutant cancers. However, the role of wild-type KRAS in tumorigenesis and therapeutic response remains elusive. We report an in vivo murine model of colorectal cancer featuring deletion of wild-type Kras in the context of oncogenic Kras. Deletion of wild-type Kras exacerbates oncogenic KRAS signalling through MAPK and thus drives tumour initiation. Absence of wild-type Kras potentiates the oncogenic effect of KRASG12D, while incidentally inducing sensitivity to inhibition of MEK1/2. Importantly, loss of the wild-type allele in aggressive models of KRASG12D-driven CRC significantly alters tumour progression, and suppresses metastasis through modulation of the immune microenvironment. This study highlights the critical role for wild-type Kras upon tumour initiation, progression and therapeutic response in Kras mutant CRC.

Health Professionals' Use of Online Communities for Interprofessional Peer Education.

Online communities in health care are well established as technologies for facilitating interactions between patients with common conditions and communication between patients and health professionals. Less well known is how health professionals use these platforms to connect with their peers, particularly for interprofessional education or support. We present early results from our exploratory international mixed methods (survey and interview) study of health professionals' experience of engaging with online communities for interprofessional peer education. Our results show that health professionals had relatively high levels of confidence engaging with multiple platforms. They used the platforms to formally and informally share evidence-based content, engage in collegial debate and connect with international colleagues. Health professionals are keen to engage with online communities for education and are aware of how these sites' functionality can promote engagement with interdisciplinary peers.

Improved motif-scaffolding with SE(3) flow matching.

Protein design often begins with knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds for a diverse range of motifs. However, the generated scaffolds tend to lack structural diversity, which can hinder success in wet-lab validation. In this work, we extend FrameFlow, an SE(3) flow matching model for protein backbone generation, to perform motif-scaffolding with two complementary approaches. The first is motif amortization, in which FrameFlow is trained with the motif as input using a data augmentation strategy. The second is motif guidance, which performs scaffolding using an estimate of the conditional score from FrameFlow, and requires no additional training. Both approaches achieve an equivalent or higher success rate than previous state-of-the-art methods, with 2.5 times more structurally diverse scaffolds. Code: https://github.com/microsoft/frame-flow.

Exploring Discussions About Virtual Reality on Twitter to Inform Brain Injury Rehabilitation: Content and Network Analysis.

BACKGROUND: Virtual reality (VR) use in brain injury rehabilitation is emerging. Recommendations for VR development in this field encourage end user engagement to determine the benefits and challenges of VR use; however, existing literature on this topic is limited. Data from social networking sites such as Twitter may further inform development and clinical practice related to the use of VR in brain injury rehabilitation. OBJECTIVE: This study collected and analyzed VR-related tweets to (1) explore the VR tweeting community to determine topics of conversation and network connections, (2) understand user opinions and experiences of VR, and (3) identify tweets related to VR use in health care and brain injury rehabilitation. METHODS: Publicly available tweets containing the hashtags #virtualreality and #VR were collected up to twice weekly during a 6-week period from July 2020 to August 2020 using NCapture (QSR International). The included tweets were analyzed using mixed methods. All tweets were coded using inductive content analysis. Relevant tweets (ie, coded as "VR in health care" or "talking about VR") were further analyzed using Dann's content coding. The biographies of users who sent relevant tweets were examined descriptively. Tweet data networks were visualized using Gephi computational analysis. RESULTS: A total of 260,715 tweets were collected, and 70,051 (26.87%) were analyzed following eligibility screening. The sample comprised 33.68% (23,596/70,051) original tweets and 66.32% (46,455/70,051) retweets. Content analysis generated 10 main categories of original tweets related to VR (ie, advertising and promotion, VR content, talking about VR, VR news, general technology, VR industry, VR live streams, VR in health care, VR events, and VR community). Approximately 4.48% (1056/23,596) of original tweets were related to VR use in health care, whereas 0.19% (45/23,596) referred to VR in brain injury rehabilitation. In total, 14.86% (3506/23,596) of original tweets featured commentary on user opinions and experiences of VR applications, equipment, and software. The VR tweeting community comprised a large network of 26,001 unique Twitter users. Users that posted tweets related to "VR in health care" (2124/26,001, 8.17%) did not form an interconnected VR network, whereas many users "talking about VR" (3752/26,001, 14.43%) were connected within a central network. CONCLUSIONS: This study provides valuable data on community-based experiences and opinions related to VR. Tweets showcased various VR applications, including in health care, and identified important user-based considerations that can be used to inform VR use in brain injury rehabilitation (eg, technical design, accessibility, and VR sickness). Limited discussions and small user networks related to VR in brain injury rehabilitation reflect the paucity of literature on this topic and the potential underuse of this technology. These findings emphasize that further research is required to understand the specific needs and perspectives of people with brain injuries and clinicians regarding VR use in rehabilitation.

Time to surgery and outcomes following open reduction and internal fixation of both-bone forearm fractures.

PURPOSE: To determine the effect of time to surgery on outcomes following open reduction and internal fixation (ORIF) of both-bone forearm fractures (BBFFs). METHODS: Ninety-nine patients who underwent ORIF of BBFFs in a single academic medical center over a 16-year time period were retrospectively reviewed. Demographic and clinical data including age, sex, current smoking status, time from injury to surgery (tsurg), presence of open injury, polytrauma status, and complications were obtained. Radiographs of the affected extremity were reviewed for fracture morphology, reduction quality, and time to union (or presence of nonunion). In addition to descriptive statistics, Chi-square and Wilcoxon-Mann-Whitney tests were used to compare categorical and interval, respectively, with a significance level of 0.05. RESULTS: A tsurg > 48 h was associated with increased rate of delayed unions (tsurg < 48 h: 25% vs tsurg > 48 h: 59%, p = 0.03), but not complications (tsurg < 48 h: 44% vs tsurg > 48 h: 47%, p = 0.79). Open BBFFs were not associated with increased rates of delayed unions (closed: 16% vs open: 19%, p = 0.77) or complications (closed: 42% vs open: 53%, p = 0.29). A trend toward increased time to union with tsurg > 48 h was also seen, but did not reach significance (tsurg < 48 h: 13.5 weeks vs tsurg > 48 h: 15.7 weeks, p = 0.11). CONCLUSION: A tsurg > 48 h is associated with an increased rate of delayed union, but not complications, after ORIF of BBFFs. LEVEL OF EVIDENCE: Therapeutic Level III (Retrospective Cohort).

The Burden of Sickle Cell Disease on Children and Their Caregivers: Caregiver Reports of Children's Health-Related Quality of Life and School Experiences, Caregiver Burden, and Their Association with Frequency of Vaso-Occlusive Crises.

Background: Children with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain. Methods: A cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months-11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months-4 years, the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5-11 years, and a study-specific survey of school experiences. Results: Children with SCD 2 months-4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p<0.001) than a normative sample of children; across domains, differences ranged from 18.73-45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5-11 years had lower scores on all CHQ-PF50 domains than the normative sample (p<0.001); differences ranged from 6.78-36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p<0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months-4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5-11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups. Conclusion: VOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.

The Great Masquerader: Mycotoxins.

No Abstract Available.

Pain Frequency and Health Care Utilization Patterns in Women with Sickle Cell Disease Experiencing Menstruation-Associated Pain Crises.

Background: Pain crises in sickle cell disease (SCD) lead to high rates of health care utilization. Historically, women have reported higher pain burdens than men, with recent studies showing a temporal association between pain crisis and menstruation. However, health care utilization patterns of SCD women with menstruation-associated pain crises have not been reported. We studied the frequency, severity, and health care utilization of menstruation-associated pain crises in SCD women. Materials and Methods: A multinational, cross-sectional cohort study of the SCD phenotype was executed using a validated questionnaire and medical chart review from the Consortium for the Advancement of Sickle Cell Research (CASiRe) cohort. Total number of pain crises, emergency room/day hospital visits, and hospitalizations were collected from a subcohort of 178 SCD women within the past 6 months and previous year. Results: Thirty-nine percent of women reported menstruation-associated pain crises in their lifetime. These women were significantly more likely to be hospitalized compared with those who did not (mean 1.70 vs. 0.67, p = 0.0005). Women reporting menstruation-associated pain crises in the past 6 months also experienced increased hospitalizations compared with those who did not (mean 1.71 vs. 0.75, p = 0.0016). Forty percent of women reported at least four menstruation-associated pain crises in the past 6 months. Conclusions: Nearly 40% of SCD women have menstruation-associated pain crises. Menstruation-associated pain crises are associated with high pain burden and increased rates of hospitalization. Strategies are needed to address health care disparities within gynecologic care in SCD.