Miracle-dz/UniFAR-FTUs huggingface dataset:
Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants.

BACKGROUND The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that "classic" serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. METHODS This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed. RESULTS Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies-such as engagement of the downstream glutamatergic pathway-the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research. CONCLUSIONS Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.
Analysis of spent ion exchange media: Superlig 639 and Superlig 644

The current BNFL Inc. flowsheet for the pretreatment of the Hanford High-Level tank wastes includes the use of Superlig{reg_sign} materials for the removal of {sup 137}Cs and {sup 99}Tc from the aqueous fraction of the waste. The cesium-selective Superlig{reg_sign} 644 (SL-644) and the technetium-selective Superlig{reg_sign} 639 (SL-639) have been evaluated in tests with actual waste samples. These materials have a finite processing lifetime in the plant and will need to be disposed of. The composition and level of residual radionuclide contamination is important for assessing various disposal pathways for the Superlig{reg_sign} materials. This report contains the results of analyses of subsamples of the SL-639 and SL 644 materials that have been used in small column testing of actual waste samples at the Radiochemical Processing Laboratory. The wastes that have been tested include samples from Tanks 241-AW-101 and 241-AN-107. The analyses of the spent resins include inductively coupled plasma/atomic emission spectrometry (ICP-AES) for metals, cold vapor atomic absorption (CVAA) spectroscopy for mercury, gamma energy analysis (GEA) for radionuclides and inductively coupled plasma/mass spectrometry (ICP-MS) for selected metals and radionuclides. While these results provide an indication of the analyte concentrations that may be left on the spent resin, they do not fullymore » represent the concentrations that may be found after extended plant processing with additional load/elute cycles and different waste compositions. BNFL estimates that the SL-644 may last for 100 load/elute cycles with Envelope A and C wastes and 20 cycles with Envelope B wastes. The number of useable load/elute cycles for the SL-639 is not well defined, but is likely on the order of hundreds. « less
Self-reported seasonality is strongly associated with chronotype and weakly associated with latitude

ABSTRACT The aim of this study was to investigate the association between self-reported seasonality, i.e., seasonal variations in mood and related behavior, and chronotype, and between self-reported seasonality and home address’ latitude. Data were collected from an online questionnaire with 45,338 participants. Seasonality and chronotype were measured with the Global Seasonality Score (GSS) and the Composite Scale of Morningness, respectively. The participants were categorized into extreme morning types, moderate morning types, intermediate types, moderate evening types, and extreme evening types. Furthermore, participants were categorized depending on home address’ latitude. Data were analyzed with chi-square tests and logistic regression analyses adjusting for sex, age, marital status, level of education, and children living at home. Results showed that high seasonality (GSS 11+) was found in 20.9%. The prevalence dose-dependency ranged from 12.2% in extreme morning types to 42.6% in extreme evening types (adjusted OR = 4.21, CI = 3.27–5.41). The prevalence was higher in participants living in North-Norway (latitude from 65 to 71⁰N) versus South-Norway (latitude from 58 to 65⁰N) (23.8% versus 20.7%; adjusted OR = 1.18, CI = 1.08–1.28). When comparing the northernmost (69–71⁰N) to the southernmost (58–59⁰N) counties of Norway, the association was stronger (24.9% versus 18.7%; adjusted OR = 1.37, CI = 1.20–1.56). Among the adjusting variables, high seasonality was associated with female sex, younger age, being unmarried, low level of education, and not having children living at home. In conclusion, about one in five Norwegians reported high seasonality. High seasonality was strongly associated with late chronotype (being an evening type) and weakly associated with living in the north (high latitude).
Malaria is associated with Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in a cohort of western Kenyan children.

BACKGROUND We aimed to determine whether Plasmodium falciparum (Pf) infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children. METHODS Kenyan children (n=144) enrolled at age one month, from two sites with different levels of malaria transmission (stable/high malaria vs. unstable/low malaria transmission) were followed through 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA) (K8.1 and LANA) and a multiplex bead-based assay (K8.1, K10.5, ORF38, ORF50, and LANA) and whole blood tested for Pf DNA using quantitative-PCR. Cox proportional hazards models were used to assess associations between Pf DNA detection, malaria annualized rate (Pf detections/person-years), and enrollment site (malaria-high vs malaria-low) with time to KSHV seroconversion. RESULTS KSHV seroprevalence was 63% by 2 years of age when assessed by multiplex assay. Children with Pf were at increased hazards of earlier KSHV seroconversion and among children with malaria, the hazard of becoming KSHV seropositive increased significantly with increasing malaria annualized rate. Children from the malaria-high transmission region had no significant difference in hazards of KSHV seroconversion at 12 months but were more likely to become KSHV seropositive by 24 months of age. DISCUSSION Malaria exposure increases the risk for KSHV seroconversion early in life.
How does level of personality functioning inform clinical management and treatment? Implications for ICD-11 classification of personality disorder severity

Purpose of review The International Classification of Diseases, 11th Edition (ICD-11) classifies personality disturbance according to levels of severity. This article reviews the literature on levels of personality functioning in relation to clinical management and treatment, and proposes how these findings apply to the ICD-11 classification of personality disorders. Recent findings Findings were primarily derived from studies using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Level of Personality Functioning Scale (LPFS), Kernberg's Level of Personality Organization, and the general P-factor of personality disorder. Severity of personality dysfunction is related to treatment outcome, risk of dropout, therapeutic alliance, readiness for treatment, risk of harm to self or others, risk of dissociation and psychotic-like breaks, coherence in narrative identity, reflective functioning, and epistemic trust. Summary The overall level of personality disorder severity indicates risk of negative outcomes and may be used as decision tool for ‘personalized medicine’ and required treatment intensity (e.g., strength of alliance and the need for establishing epistemic trust). Beyond the ICD-11 guidelines for determining personality disorder severity, these implications also apply to practitioners using comparable frameworks such as the DSM-5 LPFS and Kernberg's Level of Personality Organization. Future research should focus on the interaction of severity with trait qualifiers in relation to clinical management.
Transpalpebral approach for microsurgical clipping of an unruptured basilar apex aneurysm: case report and literature review

Abstract Background and importance The supraorbital “keyhole” approach has been described for the treatment of basilar artery aneurysms. Transpalpebral approach (TPA) is an alternative minimally invasive route to aneurysms of the Circle of Willis with excellent functional and cosmetic outcomes. Clinical presentation 53-years-old female who presented with an incidentally found 6.3 mm BA aneurysm with 3.1 mm neck diameter, admitted to our department of neurovascular surgery. Clipping was performed through TPA, with endoscope assistance and intraoperative ICG angiography. The patient’s postoperative course was uneventful and was discharged home on postoperative day 5 without any complications. Conclusion First time in the literature described keyhole TPA with eyelid incision to BA aneurysm. TPA is technically difficult and requires some experience to work through deep and limited surgical corridor. This technique can be good alternative to traditional fronto-lateral, supraorbital keyhole craniotomies.
Increase in trigeminal ganglion neurons that respond to both CGRP and PACAP in mouse models of chronic migraine and post-traumatic headache.

A large body of animal and human studies indicate that blocking peripheral calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) administration significantly increased the number of CGRP-R and PACAP-R neurons in TG but not dorsal root ganglia. In TG neurons that express endogenous αCGRP, repeated NTG led to a 7-fold increase in the number of neurons that respond to both CGRP and PACAP (CGRP-R&PACAP-R). The majority of these neurons were unmyelinated C-fiber nociceptors. This suggests that a larger fraction of CGRP signaling in TG nociceptors may be mediated through the autocrine mechanism, and the release of endogenous αCGRP can be enhanced by both CGRP and PACAP signaling pathways under chronic migraine condition. The number of CGRP-R&PACAP-R TG neurons was also increased in a mouse model of post-traumatic headache (PTH). Interestingly, low-dose interleukin-2 treatment, which completely reverses chronic migraine- and PTH-related behaviors in mouse models, also blocked the increase in both CGRP-R and PACAP-R TG neurons. Together, these results suggest that inhibition of both CGRP and PACAP signaling in TG neurons may be more effective in treating chronic migraine and PTH than targeting individual signaling pathways.
A Pilot Randomized Clinical Trial of Remote Varenicline Sampling to Promote Treatment Engagement and Smoking Cessation.

INTRODUCTION Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling. METHODS Smokers (N=99), both motivated to quit and not, were recruited and randomized to varenicline sampling vs. not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2-4wks), with minimally suggestive guidance on use. RESULTS Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5mg to 2mg. Relative to control, varenicline sampling increased motivation (p=0.006) and confidence to quit (p=0.02), and decreased cigarette smoking (p=0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in CPD, both immediately following the sampling exercise (Adjusted Odds Ratio/AOR = 4.12; 95% CI: 1.39 - 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 - 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not. CONCLUSIONS Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting. IMPLICATIONS Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that NRT sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial.
The G-Protein Coupled Formyl Peptide Receptors and Their Role in the Progression of Digestive Tract Cancer

Chronic inflammation is a causative factor of many cancers, although it originally acts as a protective host response to the loss of tissue homeostasis. Many inflammatory conditions predispose susceptible cells, most of which are of epithelial origin, to neoplastic transformation. There is a close correlation between digestive tract (DT) cancer and chronic inflammation, such as esophageal adenocarcinoma associated with Barrett’s esophagus, helicobacter pylori infection as the cause of stomach cancer, hepatitis leading to liver cirrhosis and subsequent cancer, and colon cancer linking to inflammatory bowel diseases and schistosomiasis. A prominent feature of malignant transformation of DT tract epithelial cells is their adoption of somatic gene mutations resulting in abnormal expression of proteins that endow the cells with unlimited proliferation as well as increased motility and invasive capabilities. Many of these events are mediated by Gi-protein coupled chemoattractant receptors (GPCRs) including formyl peptide receptors (FPRs in human, Fprs in mice). In this article, we review the current understanding of FPRs (Fprs) and their function in DT cancer types as well as their potential as therapeutic targets.
Intracerebral endotheliitis and microbleeds are neuropathological features of COVID‐19

Coronavirus disease 19 (COVID‐19) is a rapidly evolving pandemic caused by the coronavirus Sars‐CoV‐2. Clinically manifest central nervous system symptoms have been described in COVID‐19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars‐CoV‐2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars‐CoV‐2‐associated endotheliitis, which was associated by elevated levels of the Sars‐CoV‐2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension‐related hemorrhage, critical illness‐associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID‐19 patients could be a consequence of Sars‐ CoV‐2‐induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.
A Synthesis of the Sustainability of Remedial Reading Intervention Effects for Struggling Adolescent Readers

A majority of reading-related intervention studies aiming to remediate struggling readers’ reading outcomes assess student performance immediately following the conclusion of an intervention to determine intervention effects. Few studies collect follow-up data to measure the long-term sustainability of treatment effects. Hence, the aim of the current synthesis was to examine follow-up intervention effects of reading interventions involving adolescent struggling readers in Grades 6 to 12. Our literature search yielded only 10 studies that reported follow-up data for intervention participants, which highlights the dearth of intervention research that examines sustainability of intervention effects. Of the 10 included studies, the weighted mean effect size for all reading outcome measures was gw = 0.78 at immediate posttest and gw = 0.27 at follow-up, in favor of treatment group students. Although the magnitude of difference between treatment and control groups diminished at follow-up time, a comparison of treatment group students’ immediate posttest and follow-up scores showed that students mostly maintained gains made during intervention at follow-up time points.
Cognition, symptom perception, and medication non-adherence in older adults with asthma

Abstract Background Cognitive impairment (CI) is highly prevalent in elderly asthmatics and is associated with worse asthma self-management (SM) and outcomes. CI may also explain why older adults may under-perceive asthma symptoms. We hypothesized that CI would be associated with low medication adherence and asthma symptom under-perception (ASP). We also hypothesized that ASP would mediate the relationship between CI and medication adherence. Methods Participants of this longitudinal cohort study were asthmatics (N = 334) ≥60 years (51% Hispanic, 25% Black). Cognitive measures assessed general cognition, attention, processing speed, executive functioning, memory, and language. Measures of SM were self-reported and electronically measured adherence to controller medications. ASP was assessed for 6 weeks by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter, followed by PEF blows. Participants were blinded to actual PEF values. Percentage of time that participants were in the over-perception zone was calculated as an average. Results In regression analyses, those with impairments in memory and general cognition had lower odds ratios (OR) for self-reported non-adherence (OR: 0.96, 95% CI 0.93 − 0.98 & OR: 0.90, 95% CI 0.83 − 0.96, respectively). CI was not associated with electronically measured non-adherence or ASP. In structural equation modeling, while CI was associated with adherence (β = 0.04, SE = 0.021, p = 0.04), ASP did not mediate this relationship. Conclusions While results confirmed the importance of cognition in asthma SM, these findings were not linked to ASP. Future analyses are needed to understand the role of confounding factors.
Effect‐Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays

Effect‐based trigger (EBT) values for in vitro bioassays are important for surface water quality monitoring because they define the threshold between acceptable and poor water quality. They have been derived for highly specific bioassays, such as hormone‐receptor activation in reporter gene bioassays, by reading across from existing chemical guideline values. This read‐across method is not easily applicable to bioassays indicative of adaptive stress responses, which are triggered by many different chemicals, and activation of nuclear receptors for xenobiotic metabolism, to which many chemicals bind with rather low specificity. We propose an alternative approach to define the EBT from the distribution of specificity ratios of all active chemicals. The specificity ratio is the ratio between the predicted baseline toxicity of a chemical in a given bioassay and its measured specific endpoint. Unlike many previous read‐across methods to derive EBTs, the proposed method accounts for mixture effects and includes all chemicals, not only high‐potency chemicals. The EBTs were derived from a cytotoxicity EBT that was defined as equivalent to 1% of cytotoxicity in a native surface water sample. The cytotoxicity EBT was scaled by the median of the log‐normal distribution of specificity ratios to derive the EBT for effects specific for each bioassay. We illustrate the new approach using the example of the AREc32 assay, indicative of the oxidative stress response, and 2 nuclear receptor assays targeting the peroxisome proliferator–activated receptor gamma and the arylhydrocarbon receptor. The EBTs were less conservative than previously proposed but were able to differentiate untreated and insufficiently treated wastewater from wastewater treatment plant effluent with secondary or tertiary treatment and surface water. Environ Toxicol Chem 2021;40:487–499. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.