Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins. HAQERs are enriched for bivalent chromatin states, particularly in gastrointestinal and neurodevelopmental tissues, and genetic variants linked to neurodevelopmental disease. We developed a multiplex, single-cell in vivo enhancer assay to discover that rapid sequence divergence in HAQERs generated hominin-unique enhancers in the developing cerebral cortex. We propose that a lack of pleiotropic constraints and elevated mutation rates poised HAQERs for rapid adaptation and subsequent susceptibility to disease.

Epigenetic Regulator CoREST Controls Social Behavior in Ants.

Ants acquire distinct morphological and behavioral phenotypes arising from a common genome, underscoring the importance of epigenetic regulation. In Camponotus floridanus, "Major" workers defend the colony, but can be epigenetically reprogrammed to forage for food analogously to "Minor" workers. Here, we utilize reprogramming to investigate natural behavioral specification. Reprogramming of Majors upregulates Minor-biased genes and downregulates Major-biased genes, engaging molecular pathways fundamental to foraging behavior. We discover the neuronal corepressor for element-1-silencing transcription factor (CoREST) is upregulated upon reprogramming and required for the epigenetic switch to foraging. Genome-wide profiling during reprogramming reveals CoREST represses expression of enzymes that degrade juvenile hormone (JH), a hormone elevated upon reprogramming. High CoREST, low JH-degrader expression, and high JH levels are mirrored in natural Minors, revealing parallel mechanisms of natural and reprogrammed foraging. These results unveil chromatin regulation via CoREST as central to programming of ant social behavior, with potential far-reaching implications for behavioral epigenetics.

Species invasions shift microbial phenology in a two-decade freshwater time series.

Invasive species impart abrupt changes on ecosystems, but their impacts on microbial communities are often overlooked. We paired a 20 y freshwater microbial community time series with zooplankton and phytoplankton counts, rich environmental data, and a 6 y cyanotoxin time series. We observed strong microbial phenological patterns that were disrupted by the invasions of spiny water flea (Bythotrephes cederströmii) and zebra mussels (Dreissena polymorpha). First, we detected shifts in Cyanobacteria phenology. After the spiny water flea invasion, Cyanobacteria dominance crept earlier into clearwater; and after the zebra mussel invasion, Cyanobacteria abundance crept even earlier into the diatom-dominated spring. During summer, the spiny water flea invasion sparked a cascade of shifting diversity where zooplankton diversity decreased and Cyanobacteria diversity increased. Second, we detected shifts in cyanotoxin phenology. After the zebra mussel invasion, microcystin increased in early summer and the duration of toxin production increased by over a month. Third, we observed shifts in heterotrophic bacteria phenology. The Bacteroidota phylum and members of the acI Nanopelagicales lineage were differentially more abundant. The proportion of the bacterial community that changed differed by season; spring and clearwater communities changed most following the spiny water flea invasion that lessened clearwater intensity, while summer communities changed least following the zebra mussel invasion despite the shifts in Cyanobacteria diversity and toxicity. A modeling framework identified the invasions as primary drivers of the observed phenological changes. These long-term invasion-mediated shifts in microbial phenology demonstrate the interconnectedness of microbes with the broader food web and their susceptibility to long-term environmental change.

Peptide diffusion in biomolecular condensates.

Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion constant for simple model systems of peptides GGGGG, GGQGG, and GGVGG in aqueous solutions after phase separation by simulating atomic-level models. These solutions readily separate into aqueous and peptide-rich droplet phases. We noted the effect of the peptides being in a solvated, surface, or droplet state on the peptide's diffusion coefficients. Both sequence and peptide conformational distribution were found to influence diffusion and condensate turnover in these systems, with sequence dominating the magnitude of the differences. We found that the most compact structures for each sequence diffused the fastest in the peptide-rich condensate phase. This model result may have implications for turnover dynamics in signaling systems.

Effects of exercise training on ANGPTL3/8 and ANGPTL4/8 and their associations with cardiometabolic traits.

Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of regular exercise on ANGPTL3/8 and ANGPTL4/8 are unknown. We characterized ANGPTL3/8 and ANGPTL4/8 and their relationship with in vivo measurements of lipase activities and cardiometabolic traits before and after a 5-month endurance exercise training intervention in 642 adults from the HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study. At baseline, higher levels of both ANGPTL3/8 and ANGPTL4/8 were associated with a worse lipid, lipoprotein, and cardiometabolic profile, with only ANGPTL3/8 associated with postheparin LPL and HL activities. ANGPTL3/8 significantly decreased with exercise training, which corresponded with increases in LPL activity and decreases in HL activity, plasma triglycerides, apoB, visceral fat, and fasting insulin (all P < 5.1 × 10-4). Exercise-induced changes in ANGPTL4/8 were directly correlated to concomitant changes in total cholesterol, LDL-C, apoB, and HDL-triglycerides and inversely related to change in insulin sensitivity index (all P < 7.0 × 10-4). In conclusion, exercise-induced decreases in ANGPTL3/8 and ANGPTL4/8 were related to concomitant improvements in lipase activity, lipid profile, and cardiometabolic risk factors. These findings reveal the ANGPTL3-4-8 model as a potential molecular mechanism contributing to adaptations in lipid metabolism in response to exercise training.

Characteristics and Outcomes of US Veterans With Immunocompromised Conditions at High Risk of SARS-CoV-2 Infection With or Without Receipt of Oral Antiviral Agents.

OBJECTIVES: Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US veterans with immunocompromised conditions prescribed oral antivirals with those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: This was a retrospective, observational, nationwide propensity-matched analysis of US veterans with immunocompromised conditions who developed documented SARS-CoV-2 infection. The primary outcome was the composite of any hospitalization or death within 30 days of diagnosis. Secondary outcomes included 30-day comparative rates of (1) any hospitalization, (2) death, (3) intensive care requirement, and (4) subset analyses of outcomes by oral antiviral used and vaccination status. RESULTS: The composite primary outcome was significantly lower in patients receiving oral antiviral therapy compared with those who did not (23/390 [5.9%] vs 57/390 [14.6%]; odds ratio, 0.37; 95% confidence interval, .22-.61). This difference was driven largely by fewer deaths in the oral antiviral group (1/390 [0.3%] vs 19/390 [4.9%]; odds ratio, 0.05; 95% confidence interval, .007-.38). There was no significant difference in rate of intensive care requirement. The composite outcome was improved in vaccinated patients (completing the first series or first booster dose) who received oral antiviral agents compared with those who did not receive oral antiviral agents. Compared with those prescribed nirmatrelvir-ritonavir, patients given molnupiravir were older, had a higher incidence of cautions/contraindications, greater prevalence of tobacco use, and more cardiovascular complications. CONCLUSIONS: Use of molnupiravir or nirmatrelvir-ritonavir was associated with lower incidences of hospitalization or death within 30 days of diagnosis in US veterans with immunocompromised conditions, regardless of vaccination status. These findings support the use of either oral antiviral in this patient population.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Patient-reported observations on medical procedure timeliness (PROMPT) in breast cancer: a qualitative study.

PURPOSE: Timeliness of care is an important healthcare outcome measure. The objective of this study was to explore patient perspectives on the timeliness of breast cancer diagnosis and treatment at accredited breast cancer centers. METHODS: In this qualitative study, 1 hour virtual interviews were conducted with participants 18-75 years old who were diagnosed and treated for stage 0-III breast cancer at a National Accreditation Program for Breast Centers facility from 2018 to 2022. Thematic analysis was used to identify key themes of participant experiences. RESULTS: Twenty-eight participants were interviewed. Two thematic domains were identified: etiologies of expedited or delayed care and the impact of delayed or expedited care on patients. Within these domains, multiple themes emerged. For etiologies of expedited or delayed care, participants discussed (1) the effect of scheduling appointments, (2) the COVID-19 pandemic, (3) dissatisfaction with the timeline for various parts of the diagnostic workup, and (4) delays related to patient factors, including socioeconomic status. For the impact of expedited or delayed care, patients discussed (1) the emotional and mental impact of waiting, (2) the importance of communication and clear expectations, and (3) the impact of electronic health portals. Patients desired each care interval (e.g., the time from mammogram to breast biopsy) to be approximately 7 days, with longer intervals sometimes preferred prior to surgery. CONCLUSION: These patient interviews identify areas of delay and provide patient-centered, actionable items to improve the timeliness of breast cancer care.

Gonomics: uniting high performance and readability for genomics with Go.

SUMMARY: Many existing software libraries for genomics require researchers to pick between competing considerations: the performance of compiled languages and the accessibility of interpreted languages. Go, a modern compiled language, provides an opportunity to address this conflict. We introduce Gonomics, an open-source collection of command line programs and bioinformatic libraries implemented in Go that unites readability and performance for genomic analyses. Gonomics contains packages to read, write, and manipulate a wide array of file formats (e.g. FASTA, FASTQ, BED, BEDPE, SAM, BAM, and VCF), and can convert and interface between these formats. Furthermore, our modular library structure provides a flexible platform for researchers developing their own software tools to address specific questions. These commands can be combined and incorporated into complex pipelines to meet the growing need for high-performance bioinformatic resources. AVAILABILITY AND IMPLEMENTATION: Gonomics is implemented in the Go programming language. Source code, installation instructions, and documentation are freely available at https://github.com/vertgenlab/gonomics.

Hedonic hunger, ultra-processed food consumption, and the moderating effects of impulsivity in pregnant individuals with body mass index ≥ 25.

Evidence suggests higher hedonic hunger (preoccupation with/desire to consume food for pleasure) is associated with greater ultra-processed food (UPF) consumption in non-pregnant individuals with higher, but not lower, self-report impulsivity or delay discounting. The current study tested the association between hedonic hunger and UPF consumption, and the moderating effects of self-report impulsivity and delay discounting, during pregnancy. Individuals (N = 220) with body mass index (BMI)≥25 completed the Power of Food Scale, 24-h dietary recalls, and Barratt Impulsiveness Scale-Version 11 in early-mid pregnancy. A subset enrolled in an ancillary study (n = 143) completed a Delay Discounting Task. Linear regression and moderation models covaried for age, gestational age, pre-pregnancy BMI, and socioeconomic status. The association between hedonic hunger and UPF consumption was nonsignificant (p = 0.47). Self-report impulsivity was not a significant moderator (p = 0.11), but delay discounting was (p = 0.01). Simple slopes analysis revealed a one-unit increase in hedonic hunger was associated with 7% lower UPF intake among participants with lower (M+1SD) delay discounting (p = 0.01) and 1% higher UPF intake among those with higher (M-1SD) delay discounting (p = 0.57). Findings contrast those from research with non-pregnant samples and indicate lower delay discounting may serve as a protective factor, associated with reduced UPF consumption at higher levels of hedonic hunger, during pregnancy.

A longitudinal investigation of breastfeeding planning, initiation, and duration among individuals with pre-pregnancy overweight or obesity.

Individuals with a body mass index (BMI)≥25 kg/m2 are less likely to initiate and continue breastfeeding than are those with BMIs<25. Given the intergenerational health benefits of breastfeeding, it is important to understand breastfeeding behaviors and their correlates among individuals with BMIs≥25. Thus, in an observational cohort with BMI≥25 (N = 237), we aimed to characterize longitudinal relationships among breastfeeding planning, initiation, and duration and their sociodemographic/clinical correlates and determine if pre-pregnancy BMI predicts breastfeeding planning, initiation, and duration. Breastfeeding behaviors, weight/BMI, and sociodemographic/clinical characteristics were assessed in early, mid, and late pregnancy, and at six-months postpartum. Most participants planned to (84%) and initiated (81%) breastfeeding, of which 37% breastfed for ≥6 months. Participants who were married, first-time parents, higher in education/income, and had never smoked tobacco were more likely to plan, initiate, and achieve ≥6 months of breastfeeding. Higher pre-pregnancy BMI was not associated with breastfeeding planning or initiation but was associated with lower adjusted odds of breastfeeding for ≥6 months relative to <6 months. Findings suggest that support aimed at extending breastfeeding among those with elevated pre-pregnancy BMI may be warranted. Future interventions should also address sociodemographic and clinical inequities in breastfeeding.

The Large Language Model ChatGPT-4 Demonstrates Excellent Triage Capabilities and Diagnostic Performance for Patients Presenting with Various Causes of Knee Pain.

PURPOSE: To provide a proof-of-concept analysis of the appropriateness and performance of ChatGPT-4 to triage, synthesize differential diagnoses, and generate treatment plans concerning common presentations of knee pain. METHODS: Twenty knee complaints warranting triage and expanded scenarios were input into ChatGPT-4, with memory cleared prior to each new input to mitigate bias. For the 10 triage complaints, ChatGPT-4 was asked to generate a differential diagnosis which was graded for accuracy and suitability in comparison to a differential created by two orthopaedic sports medicine physicians. For the 10 clinical scenarios, ChatGPT-4 was prompted to provide treatment guidance for the patient, which was again graded. To test the higher-order capabilities of ChatGPT-4, further inquiry into these specific management recommendations was performed and graded. RESULTS: All ChatGPT-4 diagnoses were deemed appropriate within the spectrum of potential pathologies on a differential. The top diagnosis on the differential was identical between surgeons and ChatGPT-4 for 70% of scenarios, and the top diagnosis provided by the surgeon appeared as either the first or second diagnosis in 90% of scenarios. Overall, 16/30 (53.3%) of diagnoses in the differential were identical. When provided with 10 expanded vignettes with a single diagnosis, the accuracy of ChatGPT-4 increased to 100%, with the suitability of management graded as appropriate in 90% of cases. Specific information pertaining to conservative management, surgical approaches, and related treatments was appropriate and accurate in 100% of cases. CONCLUSION: ChatGPT-4 provided clinically reasonable diagnoses to triage patient complaints of knee pain due to various underlying conditions that was generally consistent with differentials provided by sports medicine physicians. Diagnostic performance was enhanced when providing additional information, allowing ChatGPT-4 to reach high predictive accuracy for recommendations concerning management and treatment options. However, ChatGPT-4 may demonstrate clinically important error rates for diagnosis depending on prompting strategy and information provided; therefore, further are necessary to prior to implementation into clinical workflows.

Fast and friendly: The role of vocal cues in adolescents' responses to and perceptions of peer provocation.

Adolescents self-report using different strategies to respond to peer provocation. However, we have a limited understanding of how these responses are behaviorally enacted and perceived by peers. This study examined the extent to which adolescents' self-reported responses to peer provocation (i.e., aggressive, assertive, and withdrawn) predicted how their vocal enactments of standardized responses to peer provocation were perceived by other adolescents. Three vocal cues relevant to the communication of emotional intent-average pitch, average intensity, and speech rate-were explored as moderators of these associations. Adolescent speakers (n = 39; Mage = 12.67; 66.7% girls) completed a self-report measure of how they would choose to respond to scenarios involving peer provocation; they also enacted standardized vocal responses to hypothetical peer provocation scenarios. Recordings of speakers' vocal responses were presented to a separate sample of adolescent listeners (n = 129; Mage = 12.12; 52.7% girls) in an online listening task. Speakers who self-reported greater use of assertive response strategies enacted standardized vocal responses that were rated as significantly friendlier by listeners. Vocal responses enacted with faster speech rates were also rated as significantly friendlier by listeners. Speakers' self-reported use of aggression and withdrawal was not significantly related to listeners' ratings of their standardized vocal responses. These findings suggest that adolescents may be perceived differently by their peers depending on the way in which their response is enacted; specifically, faster speech rate may be perceived as friendlier and thus de-escalate peer conflict. Future studies should consider not only what youth say and/or do when responding to peer provocation but also how they say it.

Comparing the compensatory reserve metric obtained from invasive arterial measurements and photoplethysmographic volume-clamp during simulated hemorrhage.

PURPOSE: The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. METHODS: Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. RESULTS: The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. CONCLUSION: There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM.

Associations of pelvic floor dysfunction and postnatal mental health: a systematic review.

BACKGROUND: Postpartum mental health conditions are common and can have devastating effects for both mother and infant. Adverse birth outcomes increase the risk of postnatal mental health conditions. Pelvic floor dysfunction (PFD) is a common adverse pregnancy outcome that may be a risk factor for postnatal mental health conditions. There are many studies reporting associations between PFD and postnatal mental health conditions, but no reports have synthesised the current literature as it relates to pregnancy and the postpartum period. METHODS: A research librarian conducted systematic literature searches using terms concerning PFD, postnatal mental health conditions, and pregnancy. Searches were conducted within PubMed, Embase, CINAHL, Cochrane, and Scopus. Two reviewers independently rated each study for inclusion and study quality. No studies were excluded based on quality. RESULTS: A total of 47 studies were included for review. Articles addressed sexual dysfunction (n = 11), incontinence (n = 21), perineal laceration (n = 13), pelvic organ prolapse (n = 2), and general pelvic floor symptoms (n = 2) and associations with postnatal mental health conditions. Two articles addressed more than one type of PFD. The majority (44 studies) reported associations between PFD and adverse postnatal mental health conditions. DISCUSSION: Most studies included for review found consistent associations between PFD and adverse mental health conditions. Healthcare providers should screen for PFD and postnatal mental health conditions early in the postpartum period. Future research should investigate whether the treatment of PFD can modify the associations between PFD and postnatal mental health conditions.

Furthering development of the Eating Disorder Examination-Pregnancy Version (EDE-PV): Exploratory factor analysis and psychometric performance among a community sample of pregnant individuals with body mass index ≥ 25.

Psychometrically sound measures of disordered eating during pregnancy are needed, particularly for pregnant individuals with body mass index (BMI) ≥ 25, who are at high risk for disordered eating attitudes/behaviors. We previously adapted the Eating Disorder Examination (EDE) for use among pregnant individuals with BMI ≥ 25. This study examined the factor structure of the EDE-Pregnancy Version (EDE-PV) in a community sample of pregnant individuals with BMI ≥ 25. The EDE-PV was administered to 257 pregnant individuals with pre-pregnancy BMI ≥ 25 between 12 and 20 weeks gestation. The EDE-PV factor structure was determined using an exploratory factor analysis with oblique geomin rotation, internal consistency coefficients were calculated, and convergent and discriminant validity of the EDE-PV factors were assessed. An 11-item, two-factor solution produced an acceptable model fit. The subscales did not replicate those of the EDE and were interpreted as Pregnancy Eating and Weight Change Concerns and Pregnancy Shape and Weight Concerns (αs=.67 and .85; ωs=.70 and .85, respectively). These subscales showed small-to-moderate, positive correlations with weight and psychosocial distress measures and differentiated between participants with and without lifetime histories of any eating disorder diagnosis, demonstrating adequate convergent and discriminant validity. The results indicate that the EDE-PV can more reliably identify factors associated with disordered eating attitudes/behaviors among pregnant individuals with BMI ≥ 25 compared to the EDE and support our call for the development and use of new and/or adapted measures to appropriately assess disordered eating during pregnancy.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.

Comparison of cardiac magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in the assessment of myocardial viability: meta-analysis and systematic review.

AIM: Contrast-enhanced cardiac magnetic resonance (Ce-CMR) and Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are frequently utilized in clinical practice to assess myocardial viability. However, studies evaluating direct comparison between Ce-CMR and FDG-PET have a smaller sample size, and no clear distinction between the two imaging modalities has been defined. To address this gap, we conducted a meta-analysis of studies comparing Ce-CMR and FDG-PET for the assessment of myocardial viability. METHODS: We searched PubMed, EMBASE, Scopus, and Web of Science databases from their inception to 4/20/2022 with search terms "viability" AND "heart diseases" AND "cardiac magnetic resonance imaging" AND "positron-emission tomography." We extracted patient characteristics, segment level viability assessment according to Ce-CMR and FDG-PET, and change in regional wall motion abnormalities (RWMA) at follow-up. RESULTS: We included four studies in the meta-analysis which provided viability assessment with Ce-CMR and FDG-PET in all patients and change in RWMA at follow-up. There were 82 patients among the four included studies, and 585 segments were compared for viability assessment. There were 59 (72%) males, and mean age was 65 years. The sensitivity (95% confidence interval-CI) and specificity (CI) of Ce-CMR for predicting myocardial recovery were 0.88 (0.66-0.96) and 0.64 (0.49-0.77), respectively. The sensitivity (CI) and specificity (CI) of FDG-PET for predicting myocardial recovery were 0.91 (0.63-0.99) and 0.67 (0.49-0.81), respectively. CONCLUSION: FDG-PET and Ce-CMR have comparable diagnostic parameters in myocardial viability assessment and are consistent with prior research.

Maximal Rashba-like spin splitting via kinetic-energy-coupled inversion-symmetry breaking.

Engineering and enhancing the breaking of inversion symmetry in solids-that is, allowing electrons to differentiate between 'up' and 'down'-is a key goal in condensed-matter physics and materials science because it can be used to stabilize states that are of fundamental interest and also have potential practical applications. Examples include improved ferroelectrics for memory devices and materials that host Majorana zero modes for quantum computing. Although inversion symmetry is naturally broken in several crystalline environments, such as at surfaces and interfaces, maximizing the influence of this effect on the electronic states of interest remains a challenge. Here we present a mechanism for realizing a much larger coupling of inversion-symmetry breaking to itinerant surface electrons than is typically achieved. The key element is a pronounced asymmetry of surface hopping energies-that is, a kinetic-energy-coupled inversion-symmetry breaking, the energy scale of which is a substantial fraction of the bandwidth. Using spin- and angle-resolved photoemission spectroscopy, we demonstrate that such a strong inversion-symmetry breaking, when combined with spin-orbit interactions, can mediate Rashba-like spin splittings that are much larger than would typically be expected. The energy scale of the inversion-symmetry breaking that we achieve is so large that the spin splitting in the CoO2- and RhO2-derived surface states of delafossite oxides becomes controlled by the full atomic spin-orbit coupling of the 3d and 4d transition metals, resulting in some of the largest known Rashba-like spin splittings. The core structural building blocks that facilitate the bandwidth-scaled inversion-symmetry breaking are common to numerous materials. Our findings therefore provide opportunities for creating spin-textured states and suggest routes to interfacial control of inversion-symmetry breaking in designer heterostructures of oxides and other material classes.

A 4-week morning light treatment with stable sleep timing for individuals with fibromyalgia: a randomized controlled trial.

OBJECTIVES: Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing. METHODS: Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing). RESULTS: Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed. CONCLUSIONS: Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects.