Phylogeny and historical biogeography of the swallow family (Hirundinidae) inferred from comparisons of thousands of UCE loci.

Swallows (Hirundinidae) are a globally distributed family of passerine birds that exhibit remarkable similarity in body shape but tremendous variation in plumage, sociality, nesting behavior, and migratory strategies. As a result, swallow species have become models for empirical behavioral ecology and evolutionary studies, and variation across the Hirundinidae presents an excellent opportunity for comparative analyses of trait evolution. Exploiting this potential requires a comprehensive and well-resolved phylogenetic tree of the family. To address this need, we estimated swallow phylogeny using genetic data from thousands of ultraconserved element (UCE) loci sampled from nearly all recognized swallow species. Maximum likelihood, coalescent-based, and Bayesian approaches yielded a well-resolved phylogenetic tree to the generic level, with minor disagreement among inferences at the species level, which likely reflect ongoing population genetic processes. The UCE data were particularly useful in helping to resolve deep nodes, which previously confounded phylogenetic reconstruction efforts. Divergence time estimates from the improved swallow tree support a Miocene origin of the family, roughly 13 million years ago, with subsequent diversification of major groups in the late Miocene and Pliocene. Our estimates of historical biogeography support the hypothesis that swallows originated in the Afrotropics and have subsequently expanded across the globe, with major in situ diversification in Africa and a secondary major radiation following colonization of the Neotropics. Initial examination of nesting and sociality indicates that the origin of mud nesting - a relatively rare nest construction phenotype in birds - was a major innovation coincident with the origin of a clade giving rise to over 40% of extant swallow diversity. In contrast, transitions between social and solitary nesting appear less important for explaining patterns of diversification among swallows.

Articulated ankle-foot-orthosis improves inter-limb propulsion symmetry during walking adaptability task post-stroke.

BACKGROUND: Community ambulation involves complex walking adaptability tasks such as stepping over obstacles or taking long steps, which require adequate propulsion generation by the trailing leg. Individuals post-stroke often have an increased reliance on their trailing nonparetic leg and favor leading with their paretic leg, which can limit mobility. Ankle-foot-orthoses are prescribed to address common deficits post-stroke such as foot drop and ankle instability. However, it is not clear if walking with an ankle-foot-orthosis improves inter-limb propulsion symmetry during adaptability tasks. This study sought to examine this hypothesis. METHODS: Individuals post-stroke (n = 9) that were previously prescribed a custom fabricated plantarflexion-stop articulated ankle-foot-orthosis participated. Participants performed steady-state walking and adaptability tasks overground with and without their orthosis. The adaptability tasks included obstacle crossing and long-step tasks, leading with both their paretic and nonparetic leg. Inter-limb propulsion symmetry was calculated using trailing limb ground-reaction-forces. FINDINGS: During the obstacle crossing task, ankle-foot-orthosis use resulted in a significant improvement in inter-limb propulsion symmetry. The orthosis also improved ankle dorsiflexion during stance, reduced knee hyperextension, increased gastrocnemius muscle activity, and increased peak paretic leg ankle plantarflexor moment. In contrast, there were no differences in propulsion symmetry during steady-state walking and taking a long-step when using the orthosis. INTERPRETATION: Plantarflexion-stop articulated ankle-foot-orthoses can improve propulsion symmetry during obstacle crossing tasks in individuals post-stroke, promoting paretic leg use and reduced reliance on the nonparetic leg.

Using machine learning to dissect host kinases required for Leishmania internalization and development.

The Leishmania life cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes ( i.e. , neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators of Leishmania promastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique and overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several host kinases that regulate receptor-mediated phagocytosis and/or the uptake of L. amazonensis . Findings included kinases previously implicated in Leishmania uptake (such as SRC family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)); we also uncovered many novel kinases. These methods also predicted kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course of Leishmania infection, and that the kinases required for the parasite's life cycle substantially differ depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that preferentially regulate the uptake of parasites over beads, indicating that the methods required for Leishmania to be internalized by macrophages differ significantly from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.

Desire for Gender-Affirming Medical Care Before Age 18 in Transgender and Nonbinary Young Adults.

Purpose: We aimed to understand transgender and nonbinary (TNB) young adults' desire to receive gender-affirming medical care (GAMC) before age 18 and identify barriers and facilitators to receiving this care in adolescence. Methods: A cross-sectional survey was administered to TNB young adults presenting for care between ages 18 and 20 in 2023. Descriptive statistics characterized the sample, χ2 tests with post hoc pairwise comparisons identified differences in desire for gender-affirming medications, outness, and parental consent by gender identity and sex assigned at birth, and t-tests evaluated differences in barriers and facilitators to receiving care by outness to parents. Results: A total of 230 TNB respondents had complete data. Nearly all (94.3%) indicated they desired GAMC before age 18. Half (55.7%) of the respondents reported being out about their gender identity to a parent before age 18. Outness, discussing desire for GAMC, and asking for consent to receive GAMC from a parent were significantly more common among participants who identified as men compared to those who identified as women and among those assigned female at birth compared to those assigned male at birth. No such differences emerged when comparing nonbinary individuals to those who identified as men or women. Lack of parental willingness to consent for GAMC was cited as the primary contributor of not having received care in adolescence. Conclusions: Many TNB young adults desire GAMC in adolescence; however, lack of parental support is a key barrier to receiving this care, suggesting a need for more readily available resources for parents to support TNB adolescents.

Telehealth and Telemedicine: Regulatory and Medicolegal Landscape.

ABSTRACT: Telehealth and telemedicine experienced remarkable growth during and after the recent COVID-19 pandemic. Telehealth is generally defined as nonclinical services that employ telecommunication technology. Telemedicine refers more specifically to remote clinical services including diagnosis, monitoring, and treatment. Nuclear medicine is no exception in employing telemedicine increasingly in clinical practice for image interpretation and treatment consultation and care delivery supervision. There is no doubt that soon, the use of tele-nuclear medicine will increase, comparable to the employment of telecommunication in other fields of medicine. We review the medicolegal and regulatory aspects of the evolution in the clinical practice of medicine through telehealth and telemedicine.

Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy.

The non-physiological nutrient levels found in traditional culture media have been shown to affect numerous aspects of cancer cell physiology, including how cells respond to certain therapeutic agents. Here, we comprehensively evaluated how physiological nutrient levels impact therapeutic response by performing drug screening in human plasma-like medium (HPLM). We observed dramatic nutrient-dependent changes in sensitivity to a variety of FDA-approved and clinically trialed compounds including rigosertib, an experimental cancer therapeutic that has recently failed in phase 3 clinical trials. Mechanistically, we found that the ability of rigosertib to destabilize microtubules is strongly inhibited by the purine metabolism end product uric acid, which is uniquely abundant in humans relative to traditional in vitro and in vivo cancer models. These results demonstrate the broad and dramatic effects nutrient levels can have on drug response, and how incorporation of human-specific physiological nutrient media might help to identify compounds whose efficacy could be impacted in humans.

Caregiver perspectives on receiving gender-affirming care with their transgender and gender diverse adolescents via telemedicine.

Telemedicine may help improve access to gender-affirming care for transgender and gender diverse (TGD) adolescents. Parents or guardians (i.e., caregivers) of TGD adolescents play a critical role in supporting TGD adolescents in accessing this care. The purpose of this study was to explore caregivers' perspectives regarding their adolescent receiving pediatric gender-affirming care via telemedicine to help providers and health systems optimize this modality for future care delivery. Caregivers (n=18) of TGD adolescents ages 14-17 participated in semi-structured, individual interviews that were transcribed and analyzed qualitatively. Caregivers cited participating in visits from their home environment, decreased anxiety, COVID safety, ability to have more family members attend, no transportation demands, and effective delivery of care as advantages of telemedicine. Disadvantages included dysphoria or discomfort with self-image, impersonal provider-patient interactions, video teleconferencing fatigue, difficulty with portal navigation, connectivity issues, and lack of privacy. Caregivers largely deferred to their child's preference regarding the choice of visit modality, but many reported a preference for the first to be conducted in-person, and follow-up and less complex visits via telemedicine. Health systems should consider these perspectives as they adapt telemedicine infrastructure to better meet the needs of patients and their families.

Estimating Transgender and Gender-Diverse Youth Populations in Health Systems and Survey Data.

OBJECTIVES: To identify and examine demographic variation in estimates of gender-diverse youth (GDY) populations from the PEDSnet learning health system network and the Youth Risk Behavior Survey (YRBS). METHODS: The PEDSnet sample included 14- to 17-years-old patients who had ≥2 encounters at a member institution before March 2022, with at least 1 encounter in the previous 18 months. The YRBS sample included pooled data from 14- to 17-year-old in-school youth from the 2017, 2019, and 2021 survey years. Adjusted logistic regression models tested for associations between demographic characteristics and gender dysphoria (GD) diagnosis (PEDSnet) or self-reported transgender identity (YRBS). RESULTS: The PEDSnet sample included 392 348 patients and the YRBS sample included 270 177 youth. A total of 3453 (0.9%) patients in PEDSnet had a GD diagnosis and 5262 (1.9%) youth in YRBS self-identified as transgender. In PEDSnet, adjusted logistic regression indicated significantly lower likelihood of GD diagnosis among patients whose electronic medical record-reported sex was male and among patients who identified as Asian, Black/African American, and Hispanic/Latino/a/x/e. In contrast, in the YRBS sample, only youth whose sex was male had a lower likelihood of transgender identity. CONCLUSIONS: GDY are underrepresented in health system data, particularly those whose electronic medical record-reported sex is male, and Asian, Black/African American, and Hispanic/Latino/a/x/e youth. Collecting more accurate gender identity information in health systems and surveys may help better understand the health-related needs and experiences of GDY and support the development of targeted interventions to promote more equitable care provision.

Directed conservation of the world's reef sharks and rays.

Many shark populations are in decline around the world, with severe ecological and economic consequences. Fisheries management and marine protected areas (MPAs) have both been heralded as solutions. However, the effectiveness of MPAs alone is questionable, particularly for globally threatened sharks and rays ('elasmobranchs'), with little known about how fisheries management and MPAs interact to conserve these species. Here we use a dedicated global survey of coral reef elasmobranchs to assess 66 fully protected areas embedded within a range of fisheries management regimes across 36 countries. We show that conservation benefits were primarily for reef-associated sharks, which were twice as abundant in fully protected areas compared with areas open to fishing. Conservation benefits were greatest in large protected areas that incorporate distinct reefs. However, the same benefits were not evident for rays or wide-ranging sharks that are both economically and ecologically important while also threatened with extinction. We show that conservation benefits from fully protected areas are close to doubled when embedded within areas of effective fisheries management, highlighting the importance of a mixed management approach of both effective fisheries management and well-designed fully protected areas to conserve tropical elasmobranch assemblages globally.

Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC.

Cysteine metabolism occurs across cellular compartments to support diverse biological functions and prevent the induction of ferroptosis. Though the disruption of cytosolic cysteine metabolism is implicated in this form of cell death, it is unknown whether the substantial cysteine metabolism resident within the mitochondria is similarly pertinent to ferroptosis. Here, we show that despite the rapid depletion of intracellular cysteine upon loss of extracellular cystine, cysteine-dependent synthesis of Fe-S clusters persists in the mitochondria of lung cancer cells. This promotes a retention of respiratory function and a maintenance of the mitochondrial redox state. Under these limiting conditions, we find that glutathione catabolism by CHAC1 supports the mitochondrial cysteine pool to sustain the function of the Fe-S proteins critical to oxidative metabolism. We find that disrupting Fe-S cluster synthesis under cysteine restriction protects against the induction of ferroptosis, suggesting that the preservation of mitochondrial function is antagonistic to survival under starved conditions. Overall, our findings implicate mitochondrial cysteine metabolism in the induction of ferroptosis and reveal a mechanism of mitochondrial resilience in response to nutrient stress.

Properties That Potentially Limit High-Level Blends of Biomass-Based Diesel Fuel.

While today's biomass-based diesel fuels are used at relatively low blend levels in petroleum diesel, decarbonization of the heavy-duty trucking and off-road sectors is driving increasing use of higher level blends and the combination of hydroprocessing-derived renewable diesel (RD) with biodiesel (fatty acid methyl esters) to create a 100% renewable fuel. However, little data are available on the properties of biodiesel blends over 20 vol % into RD or conventional diesel, despite the potential for properties to fall well outside the normal range for diesel fuels. Here, we evaluate the properties of 20-80% blends of a soy-derived biodiesel into RD and petroleum diesel. Properties measured were flash point, cloud point, cetane number, surface tension, density, kinematic viscosity, distillation curve, lower heating value, water content, water solubility in the fuel, lubricity, and oxidation stability. Density and viscosity were measured over a wide temperature range. A key objective was to reveal properties that might limit blending of biodiesel and any differences between biodiesel blends into RD versus petroleum diesel and to understand research needed to advance the use of high-level blends and 100% renewable fuel. Properties that may limit blending include the cloud point, viscosity, distillation curve, and oxidation stability. Meeting cloud point requirements can be an issue for all distillate fuels. For biodiesel, reducing the blend level and use of lower cloud point hydrocarbon blendstocks, such as No. 1 diesel or kerosene, can be used in winter months. Alternatively, a heated fuel system that allows for starting the vehicle on conventional diesel before switching to pure biodiesel (B100) or a high-level blend has been successfully demonstrated in the literature. Some biodiesels can have kinematic viscosity above the upper limit for diesel fuels (4.1 mm2/s), which will limit the amount that can be blended. Biodiesel boils in a narrow range at the very high end of the No. 2 diesel range. Additional research is needed to understand how the high T90 of B100 and high-level blends and the very low distillation range of B100, some RD samples, and high-level biodiesel blends impact lube oil dilution, engine deposits, and diesel oxidation catalyst light-off. Blending with No. 1 diesel or kerosene or biodiesel-specific engine calibrations may mitigate these issues. Oxidation stability of higher level blends is poorly understood but may be addressed through the increased use of antioxidant additives. Finally, high-level biodiesel blends and B100 will have significantly higher density, viscosity, and surface tension compared to conventional diesel. In combination with the high boiling point, these properties may impact fuel spray atomization and evaporation, and additional research is needed in this area.

Mechanically induced localisation of SECONDARY WALL INTERACTING bZIP is associated with thigmomorphogenic and secondary cell wall gene expression.

Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

Telemedicine-Based Provision of Adolescent Gender-Affirming Medical Care to Promote Equitable Access.

Purpose: To explore transgender and nonbinary (TNB) young adults' (1) interest in receiving gender-affirming medications through telemedicine before age 18 years and (2) willingness to initiate this care with primary care providers (PCPs). Methods: Data were from a survey of TNB young adults who had not received gender-affirming medications before age 18 years. Chi-square and Wald tests identified demographic differences in telemedicine interest and willingness to initiate medications with their PCP as minors. Results: Among 280 respondents, 82.5% indicated interest in telemedicine and 42.0% were willing to initiate medications with their PCP. Black/African American respondents were more likely to indicate interest in telemedicine than White and multiracial respondents. Respondents from rural areas were more likely to indicate willingness to initiate medications with their PCP than those from urban areas. Conclusions: Telemedicine expansion and further support for PCPs may represent critical opportunities to promote equitable access to adolescent gender-affirming care.

The Caribbean and Mesoamerica Biogeochemical Isotope Overview (CAMBIO).

The Caribbean & Mesoamerica Biogeochemical Isotope Overview (CAMBIO) is an archaeological data community designed to integrate published biogeochemical data from the Caribbean, Mesoamerica, and southern Central America to address questions about dynamic interactions among humans, animals, and the environment in the region over the past 10,000 years. Here we present the CAMBIO human dataset, which consists of more than 16,000 isotopic measurements from human skeletal tissue samples (δ13C, δ15N, δ34S, δ18O, 87Sr/86Sr, 206/204Pb, 207/204Pb, 208/204Pb, 207/206Pb) from 290 archaeological sites dating between 7000 BC to modern times. The open-access dataset also includes detailed chronological, contextual, and laboratory/sample preparation information for each measurement. The collated data are deposited on the open-access CAMBIO data community via the Pandora Initiative data platform ( https://pandoradata.earth/organization/cambio ).

Physical impairment during and between migraine attacks: A daily diary study of patients with chronic migraine.

OBJECTIVE: While a substantial body of research describes the disabling impacts of migraine attacks, less research has described the impacts of migraine on physical functioning between migraine attacks. The objective of this study is to describe physical impairment during and between migraine attacks as a dimension of burden experienced by people living with chronic migraine. METHODS: The physical impairment domain of the Migraine Physical Function Impact Diary was recorded in headache diaries from the Medication Overuse Treatment Strategy trial. Days with moderate to severe headache were used to approximate migraine attacks. Factor analysis and regression analysis were used to describe associations between migraine and physical impairment. RESULTS: 77,662 headache diary entries from 720 participants were analyzed, including 25,414 days with moderate to severe headache, 19,149 days with mild headache, and 33,099 days with no headache. Mean physical impairment score was 41.5 (SD = 26.1) on days with moderate to severe headache, 12.8 (SD = 15.0) on days with mild headache, and 5.2 (SD = 13.1) on days with no headache. Physical impairment on days with mild headache and days with no headache was significantly associated with days since last moderate to severe headache, physical impairment with last moderate to severe headache, mild headache (compared to no headache), depression, hypersensitivities and cranial autonomic symptoms. CONCLUSIONS: Physical impairment occurs on migraine and non-migraine days. Study participants with frequent headaches, symptoms of depression, hypersensitivities and cranial autonomic symptoms experience physical impairment at a higher rate on days with no headache and days with mild headache.Clinical Trial Registration: ClinicalTrials.gov (NCT02764320).

A Comparative Review of Oral Board Delivery Across Procedural Disciplines.

OBJECTIVE: Despite its ubiquity in the certification process among surgical specialties, there is little data regarding oral board delivery across various procedural fields. In this study we sought to determine the specifics of oral board exam administration across surgical disciplines with the goal of highlighting common practices, differences, and areas of innovation. This comparative analysis might further serve to identify unifying principles that undergird the oral board examination process across specialties. DESIGN: A standardized questionnaire was developed that included domains of exam structure/administration, content development, exam prerequisites, information about examiners, scoring, pass/failure rates, and emerging technologies. Between December 2022 and February 2023 structured interviews were conducted to discuss specifics of various oral board exams. Interview answers were compared between various specialties to extrapolate themes and to highlight innovative or emerging techniques among individual boards. SETTING: Interviews were conducted virtually. PARTICIPANTS: Executive members of 9 procedural medical boards including anesthesiology, neurosurgery, obstetrics, and gynecology, ophthalmology, orthopaedic surgery, otolaryngology-head and neck surgery, plastic surgery, general surgery, and urology RESULTS: Common themes include assessment of pre-, intra- and postoperative care; all testing involved candidate examination by multiple examiners and psychometricians were used by all organizations. Important differences included virtual versus in person administration (3 out of 9), inclusion and discussion of candidates' case logs as part of the exam (4 out of 9), formal assessment of professionalism (4 out of 9), and inclusion of an objective structured clinical examination (2 out of 9). CONCLUSIONS: While there are common themes and practices in the oral board delivery process between various surgical fields, and important differences continue to exist. Ongoing efforts to standardize exam administration and determine best practices are needed to ensure oral board exams continue to effectively establish that candidates meet the qualifications required for board certification.

An Analysis of American Urological Association Census Trends: Earlier Planned Retirement and Practice Pattern Changes May Exacerbate the Urology Workforce Shortage.

OBJECTIVE: To explore how changes in planned retirement age, practice setting, and physician productivity may impact the workforce shortage in urology. METHODS: We compared data between the 2015 and 2022 American Urological Association census, a specialty-wide annual survey which collects data on demographics, practice patterns, and procedures from a representative sample of U.S. urologists. Workforce productivity was measured by the self-reported number of hours worked per week and patients seen per week. A novel formula was developed to demonstrate how planned retirement age and productivity impact the workforce's production capacity. RESULTS: The total number of practicing urologists increased during the period from 2015 to 2022 (11,990 to 13,976), while the mean age of practicing urologists decreased slightly (55.0 to 54.5years; P < .002). During this period, the mean planned age of retirement for all urologists decreased from 68.9years to 67.7 (P < .001). Urologists in solo practice had a significantly higher planned age of retirement at 71.9years (P < .001) as compared to all other practice models. The number of patients seen per week for all urologists decreased from 78.7 to 72.9 (P < .001). The amount of hours worked per week remained relatively constant between the study periods. The maximum possible number of patients seen by the workforce prior to retirement increased by only 2.4% during the study interval. CONCLUSION: Though the U.S. urology workforce is growing and the mean age is decreasing, decreases in planned retirement age and productivity may offset these gains and intensify the physician shortage for U.S. urologists.

CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival.

Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type. In the context of pancreatic cancer, we have previously reported that CD200 is expressed in the pancreatic tumor microenvironment (TME), and that targeting CD200 in murine tumor models reduces tumor burden. We hypothesized that CD200 is overexpressed on tumor and stromal populations in the pancreatic TME and that circulating levels of soluble CD200 (sCD200) have prognostic value for overall survival. We discovered that CD200 was overexpressed on immune, stromal, and tumor populations in the pancreatic TME. Particularly, single-cell RNA-sequencing indicated that CD200 was upregulated on inflammatory cancer-associated fibroblasts. Cytometry by time of flight analysis of PBMCs indicated that CD200 was overexpressed on innate immune populations, including monocytes, dendritic cells, and monocytic myeloid-derived suppressor cells. High sCD200 levels in plasma correlated with significantly worse overall and progression-free survival. Additionally, sCD200 correlated with the ratio of circulating matrix metalloproteinase (MMP) 3: tissue inhibitor of metalloproteinase (TIMP) 3 and MMP11/TIMP3. This study highlights the importance of CD200 expression in pancreatic cancer and provides the rationale for designing novel therapeutic strategies that target this protein.

Impact of a resilience-building energy management intervention for people with systemic sclerosis: a mixed methods study.

Objectives: People with SSc often experience fatigue, which significantly affects daily life functioning and quality of life. We aimed to explore participants' experiences of a peer health-coached resilience-building energy management to enhance well-being (RENEW) intervention on symptoms and well-being and to use mixed methods to compare how SSc duration influenced the experiences of participants who had clinically significant fatigue improvement vs those who did not. Methods: Semi-structured interviews were conducted with 21 participants from the parent clinical trial randomized to the RENEW intervention. Data were analysed using the rigorous and accelerated data reduction technique combined with thematic content analysis. A mixed methods approach used a joint display to identify themes related to the impact of SSc duration on fatigue improvement status. Participants were categorized into short/improvement, short/limited improvement, long/improvement, and long/limited improvement. Results: Our team generated four themes: participant and peer health-coach relationship, physical and psychological well-being improvement, need for a tailored approach and easy program access through technology. Mixed methods analysis revealed that, regardless of SSc duration, participants with improved fatigue reported increasing self-awareness of SSc-related symptoms and learning coping strategies to manage fatigue. Participants in the short/improvement group reported preferences for slower pacing of the program and pairing with a coach with similar symptom severity. Participants in the long/limited improvement group sought SSc-specific symptom management information. Conclusion: Incorporating peer health coaches and technology is beneficial for self-management interventions for people with SSc. Future tailoring of RENEW based on SSc duration and symptom severity is needed. Clinical trial registration number: clinicatrials.gov, NCT04908943.