Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Descriptive Analysis of Physician Versus Patient-Directed Gabapentin Usage In Chronic Pain - A Preliminary Report.

BACKGROUND Gabapentin is one of the most common medications employed in Pain Medicine, specifically targeting the management of neuropathic pain. We are most familiar with the incremental dosing strategy where a ceiling dose is eventually attained guided by efficacy and patient tolerance, after which a fixed dosing regimen is prescribed. We propose that autonomous short-term dose variations per patient could have rapid clinically significant effects in the management of chronic pain. OBJECTIVES This study examines the frequency at which patients take gabapentin on a fixed vs variable schedule and how the pattern of gabapentin use correlates with efficacy, side effects, and patient satisfaction. STUDY DESIGN Single institution, cross-sectional observational survey study with data collection performed over 2 phases as a pilot for proof of concept. SETTING Remote contact via telephone with researchers calling from a quiet, private location within the hospital complex conducive for confidential conversation. METHODS Patients recently prescribed gabapentin were queried on the patterns of use and self-perceived efficacy, satisfaction, and side effects in accordance to a standardized oral script. Patients selected met the criteria of being new patients freshly prescribed gabapentin who have been consistently on the medication for at least a month, while having chronic pain symptoms for over 3 months. Responses were collected in the form of a 5-point Likert scale. Statistical analyses were performed using GraphPad Prism. RESULTS Of the 222 patients, 92 patients agreed to participate in the survey for a response rate of 41.4. Of these, 51% had terminated the medication for various reasons. Of the patients still taking gabapentin, 73% were on a fixed schedule, while 27% were on a variable dosing schedule. Variable dosing cohort reported better efficacy (P = 0.027) and satisfaction (P = 0.036), while the side-effect profile between the 2 groups was similar. LIMITATIONS The study is limited by its nature of being a pilot, single-institution study performed on a relatively small sample size. None of the patients we surveyed had been given the autonomy to adjust gabapentin doses by their providers and this could significantly reduce the proportion of patients who would be encouraged to run a variable dosing regimen. CONCLUSIONS This pilot study suggests that a significant portion of patients choose to administer variable doses of gabapentin and associate this with better efficacy and satisfaction. A larger study is needed to confirm this supposition. Based upon this pilot study, the variable dosing option may be an option for improved therapeutic efficacy or as an alternative to those whose lifestyles do not allow for fixed dosing regimens. Discussion of the risks of gabapentin, including respiratory depression, and clear dosage parameters of use, would need to be outlined when considering a variable dose regimen.
Observations of runup and energy flux on a low‐slope beach with high‐energy, long‐period ocean swell

The transformation of surface gravity waves from 11 m depth to runup was observed on the low‐sloped (1/80) Agate Beach, Oregon, with a cross‐shore transect of current meters, pressure sensors, and a scanning lidar. Offshore wave heights H0 ranged from calm (0.5 m) to energetic (>7 m). Runup, measured with pressure sensors and a scanning lidar, increases linearly with (H0L0)1/2, with L0 the deep‐water wavelength of the spectral peak. Runup saturation, in which runup oscillations plateau despite further increases in (H0L0)1/2, is not observed. Infragravity wave shoaling and nonlinear energy exchanges with short waves are included in an infragravity wave energy balance. This balance closes for high‐infragravity frequencies (0.025–0.04 Hz) but not lower frequencies (0.003–0.025 Hz), possibly owing to unmodeled infragravity energy losses of wave breaking and/or bottom friction. Dissipative processes limit, but do not entirely damp, increases in runup excursions in response to increased incident wave forcing.
Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug–Gene Networks: From Biology to Precision Therapeutics

BACKGROUND: Interferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits in vitro exploration of proinflammatory mechanisms and the development of novel immune therapies. We hypothesized that the study of macrophage subpopulations could lead to anti-inflammatory interventions. METHODS: Primary human macrophages activated by IFNγ (M(IFNγ)) underwent analyses by single-cell RNA sequencing, time-course cell-cluster proteomics, metabolite consumption, immunoassays, and functional tests (phagocytic, efferocytotic, and chemotactic). RNA-sequencing data were analyzed in LINCS (Library of Integrated Network-Based Cellular Signatures) to identify compounds targeting M(IFNγ) subpopulations. The effect of compound BI-2536 was tested in human macrophages in vitro and in a murine model of atherosclerosis. RESULTS: Single-cell RNA sequencing identified 2 major clusters in M(IFNγ): inflammatory (M(IFNγ)i) and phagocytic (M(IFNγ)p). M(IFNγ)i had elevated expression of inflammatory chemokines and higher amino acid consumption compared with M(IFNγ)p. M(IFNγ)p were more phagocytotic and chemotactic with higher Krebs cycle activity and less glycolysis than M(IFNγ)i. Human carotid atherosclerotic plaques contained 2 such macrophage clusters. Bioinformatic LINCS analysis using our RNA-sequencing data identified BI-2536 as a potential compound to decrease the M(IFNγ)i subpopulation. BI-2536 in vitro decreased inflammatory chemokine expression and secretion in M(IFNγ) by shrinking the M(IFNγ)i subpopulation while expanding the M(IFNγ)p subpopulation. BI-2536 in vivo shifted the phenotype of macrophages, modulated inflammation, and decreased atherosclerosis and calcification. CONCLUSIONS: We characterized 2 clusters of macrophages in atherosclerosis and combined our cellular data with a cell-signature drug library to identify a novel compound that targets a subset of macrophages in atherosclerosis. Our approach is a precision medicine strategy to identify new drugs that target atherosclerosis and other inflammatory diseases.
Associations Between Headache (Migraine and Tension-Type Headache) and Psychological Symptoms (Depression and Anxiety) in Pediatrics: A Systematic Review and Meta-analysis.

BACKGROUND There have been no recent meta-analysis studies on specific psychological symptoms (depression and anxiety) according to the type of primary headache disorder in children and adolescents. OBJECTIVES We performed a meta-analysis of various psychodiagnostic scales. Psychological symptoms of primary headache disorders have been reported in previous studies. STUDY DESIGN A systematic review and meta-analysis. METHODS We conducted systematic reviews using the PubMed, Embase, Cochrane Library, and Scopus databases up to October 19, 2022. Ten studies were selected by applying the inclusion criteria. The psychological symptoms (depression and anxiety) of children and adolescents with migraine and tension-type headache (TTH) were compared with those of healthy controls using scale scores. All statistical analyses of the pooled data were performed using RevMan 5.3 software. RESULTS Psychodiagnostic tools to assess depression scored higher in patients with migraine than in healthy controls; however, most anxiety-related scores were not significantly different between the migraine and control groups. In contrast, anxiety-related scores were higher in patients with TTH than in healthy controls, but the score to measure the degree of depressive symptoms was not significantly different from the control group in patients with TTH. LIMITATIONS A limited number of studies for each scale were included. In addition, each scale has different sensitivities and specificities, which may have affected the results. In addition, we did not evaluate the differences in psychological symptoms according to the frequency and severity of headaches. CONCLUSIONS Depression is more associated with migraine; whereas, anxiety is more associated with TTH than healthy controls. Therefore, the screening and assessment of psychological symptoms should be performed in children and adolescents with primary headache disorders.
AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging

Abstract Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.
Impact of bimonthly repeated total sleep deprivation and recovery sleep on cardiovascular indices

Since short sleep duration adversely affects cardiovascular (CV) health, we investigated the effects of exposures to total sleep deprivation (TSD), and baseline (BL) and recovery (REC) sleep on CV measures. We conducted a 5‐day experiment at months 2 and 4 in two separate studies (N = 11 healthy adults; 5 females). During these repeated experiments, CV measures [stroke volume (SV), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular ejection time, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure (MAP)] were collected at three assessment time points after: (1) two BL 8 h time‐in‐bed (TIB) sleep opportunity nights; (2) a TSD night; and (3) two REC 8‐10 h TIB nights. CV measures were also collected pre‐study. TSD significantly increased SV and CI, and decreased SVRI, with large effect sizes, which importantly were reversed with recovery, indicating these measures are possible novel biomarkers for assessing the adverse consequences of TSD. Pre‐study SV, CI, SVRI, HR, SBP, and MAP measures also significantly associated with TSD CV responses at months 2 and 4 [Pearson's r: 0.615–0.862; r2: 0.378–0.743], indicating they are robust correlates of future TSD CV responses. Our novel findings highlight the critical impact of sleep on CV health across time.
Deep Fusion of Multi-Template Using Spatio-Temporal Weighted Multi-Hypergraph Convolutional Networks for Brain Disease Analysis

Conventional functional connectivity network (FCN) based on resting-state fMRI (rs-fMRI) can only reflect the relationship between pairwise brain regions. Thus, the hyper-connectivity network (HCN) has been widely used to reveal high-order interactions among multiple brain regions. However, existing HCN models are essentially spatial HCN, which reflect the spatial relevance of multiple brain regions, but ignore the temporal correlation among multiple time points. Furthermore, the majority of HCN construction and learning frameworks are limited to using a single template, while the multi-template carries richer information. To address these issues, we first employ multiple templates to parcellate the rs-fMRI into different brain regions. Then, based on the multi-template data, we propose a spatio-temporal weighted HCN (STW-HCN) to capture more comprehensive high-order temporal and spatial properties of brain activity. Next, a novel deep fusion model of multi-template called spatio-temporal weighted multi-hypergraph convolutional network (STW-MHGCN) is proposed to fuse the STW-HCN of multiple templates, which extracts the deep interrelation information between different templates. Finally, we evaluate our method on the ADNI-2 and ABIDE-I datasets for mild cognitive impairment (MCI) and autism spectrum disorder (ASD) analysis. Experimental results demonstrate that the proposed method is superior to the state-of-the-art approaches in MCI and ASD classification, and the abnormal spatio-temporal hyper-edges discovered by our method have significant significance for the brain abnormalities analysis of MCI and ASD.
Facilitating Harmonization of Variables in Framingham, MESA, ARIC, and REGARDS Studies Through a Metadata Repository

BACKGROUND: High-quality research in cardiovascular prevention, as in other fields, requires inclusion of a broad range of data sets from different sources. Integrating and harmonizing different data sources are essential to increase generalizability, sample size, and representation of understudied populations—strengthening the evidence for the scientific questions being addressed. METHODS: Here, we describe an effort to build an open-access repository and interactive online portal for researchers to access the metadata and code harmonizing data from 4 well-known cohort studies—the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, FHS (Framingham Heart Study), MESA (Multi-Ethnic Study of Atherosclerosis), and ARIC (Atherosclerosis Risk in Communities) study. We introduce a methodology and a framework used for preprocessing and harmonizing variables from multiple studies. RESULTS: We provide a real-case study and step-by-step guidance to demonstrate the practical utility of our repository and interactive web page. In addition to our successful development of such an open-access repository and interactive web page, this exercise in harmonizing data from multiple cohort studies has revealed several key themes. These themes include the importance of careful preprocessing and harmonization of variables, the value of creating an open-access repository to facilitate collaboration and reproducibility, and the potential for using harmonized data to address important scientific questions and disparities in cardiovascular disease research. CONCLUSIONS: By integrating and harmonizing these large-scale cohort studies, such a repository may improve the statistical power and representation of understudied cohorts, enabling development and validation of risk prediction models, identification and investigation of risk factors, and creating a platform for racial disparities research. REGISTRATION: URL: https://precision.heart. org/duke-ninds.
Psychological health of mothers and siblings of children with autism spectrum disorder during COVID-19 pandemic: New evidence in Italian families

Background and aim: Psychological challenges are well recognized in families with a child with Autism Spectrum Disorder (ASD). Instead, less is known about the effects of traumatic scenarios, such as COVID-19, on the psychological health of these families. The main aim of this study was to examine the psychological health of both mothers and typically developing (TD) siblings of children with ASD during the COVID-19 pandemic. We also investigated the relationship between mothers’ psychological resources and their children’s psychological well-being. Method: The sample included 52 mothers and their children: 15 mothers with one child with ASD and at least one TD child (ASD-siblings group) and 37 mothers with one or more TD children (TD control group). The data were collected using an online platform; four standardized questionnaires (GAD-7, BDI-II, CD-RISC 25 and CBCL) were administered. Results: The analyses revealed more internalizing and total behavioral symptoms in the siblings of children with ASD, compared to the TD control group. Regarding the mothers, we did not find differences in depression and anxious symptoms between the two groups. However, the mothers of children with ASD showed a lower resilience than mothers of TD children. Moreover, the psychological well-being of the children was related with the mothers’ anxiety in the ASD-siblings group. Conclusions: Overall, our data show that the COVID-19 outbreak may have been particularly challenging for siblings of children with ASD, and highlight the importance of intensifying the psychological support to these families. (www.actabiomedica.it)
Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?

BACKGROUND: 3′, 5′-cyclic AMP (cAMP) regulates numerous cardiac functions. Various hormones and neurotransmitters elevate intracellular cAMP (i[cAMP]) in cardiomyocytes through activating GsPCRs (stimulatory-G-protein-coupled-receptors) and membrane-bound ACs (adenylyl cyclases). Increasing evidence has indicated that stimulating different GsPCRs and ACs exhibits distinct, even opposite effects, on cardiomyocyte viability. However, the underlying mechanisms are not fully understood. METHODS: We used molecular and pharmacological approaches to investigate how different GsPCR/cAMP signaling differentially regulate cardiomyocyte viability with in vitro, ex vivo, and in vivo models. RESULTS: For prodeath GsPCRs, we explored β1AR (beta1-adrenergic receptor) and H2R (histamine-H2-receptor). We found that their prodeath effects were similarly dependent on AC5 activation, ATP release to the extracellular space via PANX1 (pannexin-1) channel, and extracellular ATP (e[ATP])-mediated signaling involving in P2X7R (P2X purinoceptor 7) and CaMKII (Ca2+/calmodulin-dependent protein kinase II). PANX1 phosphorylation at Serine 206 by cAMP-dependent-PKA (protein-kinase-A) promoted PANX1 activation, which was critical in β1AR- or H2R-induced cardiomyocyte death in vitro and in vivo. β1AR or H2R was localized proximately to PANX1, which permits ATP release. For prosurvival GsPCRs, we explored adenosine-A2-receptor (A2R), CGRPR (calcitonin-gene-related-peptide-receptor), and RXFP1 (relaxin-family peptide-receptor 1). Their prosurvival effects were dependent on AC6 activation, cAMP efflux via MRP4 (multidrug resistance protein 4), extracellular cAMP metabolism to adenosine (e[cAMP]-to-e[ADO]), and e[ADO]-mediated signaling. A2R, CGRPR, or RXFP1 was localized proximately to MRP4, which enables cAMP efflux. Interestingly, exogenously increasing e[cAMP] levels by membrane-impermeable cAMP protected against cardiomyocyte death in vitro and in ex vivo and in vivo mouse hearts with ischemia-reperfusion injuries. CONCLUSIONS: Our findings indicate that the functional diversity of different GsPCRs in cardiomyocyte viability could be achieved by their ability to form unique signaling complexes (signalosomes) that determine the fate of cAMP: either stimulate ATP release by activating PKA or directly efflux to be e[cAMP].
Survey response rates in health sciences education research: A 10‐year meta‐analysis

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta‐analysis evaluated survey trends over one decade (2011–2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta‐analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9–69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.
The Process Model of Stigmatized Loss: Identity-Threatened Experiences of Bereaved Mothers

Despite almost one-third of women suffering from the loss of a baby through miscarriage, stillbirth, or infant loss, it is surprising how little research examines how such loss affects the identity and stigmas experienced by these individuals. Through in-depth, semi-structured interviews with bereaved mothers (in particular, mothers who lost a baby during pregnancy or within one year after birth), this research sheds light on the bereaved mother’s experiences after loss. Specifically, this research applies the identity-threat model of stigma to showcase the process of stigmatized loss. Based on our findings, we also introduce the process model of stigmatized loss that can apply to all types of stigmatized loss. Key themes emerged as we explored stigmatized loss discourses. These include situational cues that trigger stigma, identity-based responses that aim to preserve both a baby’s and mother’s identity, as well as nonvolitional and volitional responses that help restore control and reconstruct identity. Additionally, other themes revolve around positive and negative outcomes stemming from avoiding stigmatized identity activation and identification of triggers that initiate a recursive process through stigmatized baby loss. Importantly, stigma can be perceived as both an identity threat (negative) and an identity confirmation (positive). Findings inform theory and practice alike.