Miracle-dz/UniFAR-FTUs huggingface dataset:
Initiating Opioid Agonist Treatment for Opioid use Disorder Nationally in the Veterans Health Administration: Who Gets What?

Background Despite substantial benefits associated with opioid agonist treatment (OAT) with buprenorphine and methadone for opioid use disorder (OUD), only a small proportion of patients with OUD initiate OAT. There is a lack of studies addressing the correlates of OAT initiation among patients with OUD. Methods Using Veterans Health Administration (VHA) national administrative data, we identified veterans with OUD who started OAT with either buprenorphine or methadone maintenance treatment (MMT) in fiscal year (FY) 2012 (first prescription of buprenorphine or first methadone clinic visit after the first 60 days of FY) and those who received no OAT that year. Multivariate logistic regression models including sociodemographic characteristics, diagnoses, and service and psychotropic drug use variables were used to identify independent predictors of OAT initiation. Results Greater age (10-year increments; odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.0.9–0.97) and black race (OR: 0.46, 95% CI: 0.38–0.55) were associated with lower odds of being started on buprenorphine compared with no OAT, but not with MMT initiation. Veterans with cocaine and anxiolytic-sedative hypnotic use disorders had higher odds of being started on both buprenorphine and methadone compared with no OAT. Receipt of any mental health inpatient treatment was associated with higher odds of being started on buprenorphine but not methadone. Overall, we were unable to identify a robust set of patient characteristics associated with initiation of OAT. Conclusion This study points out the stark reality that in the middle of an opioid crisis, we have very little insight into which patients with OUD initiate OAT.
Effects of Age on Peripapillary and Macular Vessel Density Determined Using Optical Coherence Tomography Angiography in Healthy Eyes.

Purpose To evaluate the effect of age on global and sectoral vascular parameters of the peripapillary area and macula in healthy eyes by using optical coherence tomography angiography (OCT-A). Methods This retrospective cross-sectional study included 239 eyes of 172 healthy subjects. Subjects were scanned using the high-definition disc angio scan (4.5 × 4.5 mm), retina angio scan (6 × 6 mm), and optic nerve head/ganglion cell complex (GCC) modes of OCT-A. Global and sectoral circumpapillary vessel density (VD), parafoveal VD, retinal nerve fiber layer (RNFL), and GCC thickness parameters were modeled in terms of age by using linear mixed-effect models incorporating covariates. Normalized slopes were calculated by dividing the absolute slopes by the mean value of the OCT-A parameters. Results All global and sectoral circumpapillary VDs decreased significantly with increasing age, except for those in the temporal superior sector. The steepest slopes in the circumpapillary region were observed in nasal superior (-0.098%/y) and nasal inferior (-0.096%/y) sectors. The global, temporal, and superior macular VDs also decreased with increasing age, while the foveal, nasal, and inferior parameters did not. The temporal quadrant showed the steepest slope among the macular parameters (-0.068%/y). The RNFL and GCC thickness results showed similar trends. Conclusions Age substantially affected VD in most of the peripapillary and macular areas; however, the papillomacular bundle area did not show significant age-related vascular changes. These age-related global and sectoral differences in circumpapillary and macular VDs should be considered when assessing pathologic VD changes over time.
Impact of Medicaid Expansion of the Affordable Care on the Outcomes of Lower Extremity Bypass for Patients With Peripheral Artery Disease in the Vascular Quality Initiative Database.

OBJECTIVE The aim of this study was to evaluate changes in the utilization and outcomes of surgery after Medicaid Expansion (ME) for patients with peripheral artery disease (PAD). SUMMARY BACKGROUND DATA Recent studies have demonstrated increased insurance coverage and improved care with the Affordable Care Act's (ACA) state expansion of Medicaid. METHODS Infrainguinal bypass procedures performed due to occlusive pathology in the Vascular Quality Initiative database between 2010 and 2017 were included. Primary outcomes including postoperative mortality and major adverse limb events (MALE) at 1-year of follow-up were analyzed using interrupted time-series analysis (ITS). RESULTS Out of 26,446 infrainguinal bypass procedures, 13,955 (52.8%) were included in this analysis. ME states witnessed an annual decrease in infrainguinal surgery for acute ischemia [annual change in post vs pre-ME period (95% confidence interval): -4.3% (-7.5% to -1.0%), P = 0.02] and an increase in revascularization for claudication [3.7% (1.7%-5.6%), P = 0.01]. Among nonacute cases, elective procedures increased in ME states [3.9% (0.1%-7.7%), P = 0.05] along with a significant annual decrease in in-hospital mortality [-0.4% (-0.8 to -0.02), P = 0.04) and MALE at 1 year of follow up [-9.0% (-20.3 to 2.3), P = 0.09]. These results were statistically significant after comparing them with the annual trend changes in states which did not adopt ME. CONCLUSIONS The adoption of ME in 2014 was associated with significant increase in the use of infrainguinal bypass for nonsevere and elective cases, along with improved in-hospital mortality and MALE at 1 year. Longer follow-up is needed to evaluate the impact of ME on other aspects of care and longer term outcomes of PAD patients.
Cdc42 defines apical identity and regulates epithelial morphogenesis by promoting apical recruitment of Par6-aPKC and Crumbs

ABSTRACT Cdc42 regulates epithelial morphogenesis together with the Par complex (Baz/Par3-Par6-aPKC), Crumbs (Crb/CRB3) and Stardust (Sdt/PALS1). However, how these proteins work together and interact during epithelial morphogenesis is not well understood. To address this issue, we used the genetically amenable Drosophila pupal photoreceptor and follicular epithelium. We show that during epithelial morphogenesis active Cdc42 accumulates at the developing apical membrane and cell-cell contacts, independently of the Par complex and Crb. However, membrane localization of Baz, Par6-aPKC and Crb all depend on Cdc42. We find that although binding of Cdc42 to Par6 is not essential for the recruitment of Par6 and aPKC to the membrane, it is required for their apical localization and accumulation, which we find also depends on Par6 retention by Crb. In the pupal photoreceptor, membrane recruitment of Par6-aPKC also depends on Baz. Our work shows that Cdc42 is required for this recruitment and suggests that this factor promotes the handover of Par6-aPKC from Baz onto Crb. Altogether, we propose that Cdc42 drives morphogenesis by conferring apical identity, Par-complex assembly and apical accumulation of Crb. Summary: During epithelia morphogenesis in Drosophila, the Rho-GTPase Cdc42 confers apical identity, Par-complex assembly and Crb accumulation to promote epithelial morphogenesis.
Community-informed connectomics of the thalamocortical system in generalized epilepsy

Objective To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. Methods In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. Results Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. Conclusions Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.
Heavy cannabis use, dependence and the brain: a clinical perspective

Abstract Aims To summarize and evaluate our knowledge of the relationship between heavy cannabis use, cannabis use disorder (CUD) and the brain. Methods Narrative review of relevant literature identified through existing systematic reviews, meta‐analyses and a PubMed search. Epidemiology, clinical representations, potential causal mechanisms, assessments, treatment and prognosis are discussed. Results Although causality is unclear, heavy and dependent cannabis use is consistently associated with a high prevalence of comorbid psychiatric disorders and learning and memory impairments that seem to recover after a period of abstinence. Evidence regarding other cognitive domains and neurological consequences, including cerebrovascular events, is limited and inconsistent. Abstinence after treatment is only achieved in a minority of cases; treatment targeted at reduction in use appears have some success. Potential moderators of the impact of CUD on the brain include age of onset, heaviness of use, CUD severity, the ratio of ∆9‐tetrahydrocannabinol to cannabidiol and severity of comorbid disorders. Conclusions Current evidence of long‐term effects of daily cannabis use and cannabis use disorder on brain‐related outcomes is suggestive rather than conclusive, but use is associated with psychiatric morbidity and with cognitive impairments that recover after a period of abstinence.
HO-1 reduces heat stress-induced apoptosis in bovine granulosa cells by suppressing oxidative stress

Heat stress negatively affects reproduction in cattle by disrupting the normal function of ovarian granulosa cells (GCs), ultimately leading to oxidative damage and cell death via apoptosis. Heme oxygenase-1(HO-1) is a member of the heat shock protein family, which are associated with cellular antioxidant defenses and anti-apoptotic functions. Recent studies demonstrated that HO-1 is upregulated in heat-stressed cells. In the present study, we investigated the expression of HO-1 in bovine GCs transiently exposed to heat stress and characterized the expression and activity of key oxidative stress enzymes and molecules. We show that heat stress induced oxidative stress and apoptosis, and enhanced Nrf2 and HO-1 expression in primary GC cultures. Knocking down HO-1 expression using siRNA exacerbated both oxidative stress and apoptosis, whereas pre-treating GCs with hemin, which induces HO-1 expression, partially prevented these effects. These findings demonstrate that HO-1 attenuates heat stress-induced apoptosis in bovine GCs by decreasing production of reactive oxygen species and activating the antioxidant response.
Association of Crohn’s Disease with Aryl Hydrocarbon Receptor Gene Polymorphisms in Patients from Southeast China

ABSTRACT Aims The aryl hydrocarbon receptor (AhR) plays a pivotal role in regulating the innate and the acquired immune systems. The present study aimed to investigate the association of Crohn’s disease (CD) with AhR polymorphisms in a cohort of patients from Southeast China. Methods An improved multiple ligase detection reaction technique was applied to examine the polymorphisms of rs2158041, rs2066853, and rs10249788 in 310 patients with CD and 573 controls. Results Compared to the controls, the variant allele (T) and genotype (CT+TT) of rs2158041 were less frequent in patients with CD (both p < 0.05). Similar conclusions were drawn from patients with ileal CD and with stricture CD as compared to the controls (all p < 0.0083). However, no significant differences were observed in allele and genotype frequencies of rs2066853 and rs10249788 between patients with CD and the controls (all p > 0.05). Although rs2158041 and rs10249788 were in complete linkage disequilibrium with rs2066853, respectively, only the frequency of haplotype (TG) formed by rs2158041 and rs2066853 was significantly lower in patients with CD than that in the controls (p < 0.05). Conclusions AhR (rs2158041) might be a susceptible locus for CD, especially for the two subtypes: ileal CD and stricture CD.
Assessment of the accuracy of salivary cotinine readings from NicAlert strips against a liquid chromatography tandem mass spectrometry assay in self-reported non-smokers who passed carbon monoxide but failed NicAlert validation.

BACKGROUND AND AIMS NicAlert produces semi-quantitative assessments of cotinine levels in saliva or urine for verification of smoking abstinence. This study aimed to assess the accuracy of NicAlert readings against a liquid chromatography tandem mass spectrometry assay, in smokers who had passed expired-air carbon monoxide (CO) verification but failed NicAlert verification. DESIGN Comparison of NicAlert readings against readings from a reference assay using liquid chromatography tandem mass spectrometry. SETTING Geneva, Switzerland PARTICIPANTS: Self-reported non-smokers (n=92) who in previous testing had CO of 0-3 parts per million (indicating no recent smoking) and reported not using any nicotine product but had NicAlert readings >=1 (indicating smoking). MEASUREMENTS NicAlert produces readings of 0, 1 and 2+ which are reported by the manufacturer to correspond to saliva cotinine concentrations of 0-10ng/mL (indicating not smoking), 10-30 ng/mL and 30+ ng/mL respectively. Liquid chromatography tandem mass spectrometry was used as the reference. FINDINGS For 82 participants with NicAlert reading of 1, only two of the liquid chromatography tandem mass spectrometry values were within the purported range of 10-30 ng/mL; 71 were below 4 ng/mL, and half the values were below 0.5 ng/mL. Two of the eight participants with NicAlert readings of 2 had laboratory values within the designated range. None of the two participants with NicAlert of 3 had a cotinine value within the designated range. CONCLUSIONS In people who had passed carbon monoxide verification, NicAlert readings yielded a very high false positive rate in detecting levels of cotinine indicative of smoking.
First Molecular Report of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) guyanensis in Paraguayan Inhabitants Using High-Resolution Melt-PCR.

American tegumentary leishmaniasis is an endemic anthropozoonosis undergoing expansion on the American continent. The disease is caused by several Leishmania species and it is manifested as cutaneous and mucocutaneous leishmaniasis. In this study, we evaluate the viability of high-resolution melt polymerase chain reaction (HRM-PCR) analysis to differentiate four closely related Leishmania species as a routine tool for the diagnosis of leishmaniasis. For this purpose, biopsy specimens from cutaneous and mucocutaneous lesions were taken from 132 individuals from endemic and non-endemic areas for leishmaniasis. Each sample was processed for parasitological, histopathological, and molecular analysis. Positive biopsy samples were analyzed by HRM-PCR of a 144-bp heat-shock protein (hsp70) gene fragment, and new cases were confirmed by sequencing. Of the 132 samples analyzed, 36 (27%) were positive for Leishmania spp. , of which 86% were from cutaneous lesions and 14% from mucocutaneous lesions. We identified Leishmania (Viannia) braziliensis (84%), Leishmania (Leishmania) infantum (13%), and Leishmania (Leishmania) amazonensis (3%) in cutaneous lesions, and L. (V.) braziliensis (40%), L. (L.) infantum (20%), L. (L.) amazonensis (20%), and Leishmania (Viannia) guyanensis (20%) in mucocutaneous lesions. The main purpose of this research was to report for the first time in Paraguay the presence of L. (L.) amazonensis and L. (V.) guyanensis in patients with cutaneous and mucocutaneous lesions, using the HRM-PCR technique. In addition, we report the presence of additional new cases of L. (L.) infantum in cutaneous lesions.
Direct and Indirect Effects of Trait and State Gratitude on Health-Related Quality of Life in a Prospective Design

Gratitude has been consistently linked to well-being, but its influence on health-related functioning is not well understood. Furthermore, research suggests the need to differentiate between-person and within-person effects of personality characteristics, and research on gratitude and health has not typically done so. This prospective study aimed to (1) differentiate the unique effects of trait and state gratitude on health-related quality of life (HRQoL) and (2) test state gratitude as a mediator between baseline trait gratitude and subsequent HRQoL. Undergraduate participants (N = 141) completed a trait gratitude measure at baseline and then repeated measures of weekly state gratitude and HRQoL over eight weeks. Multilevel models examined baseline trait gratitude, state gratitude averaged across the study (person aggregate) as between-person individual differences, and within-person variability in state gratitude (person-centered) as predictors of HRQoL, as well as the indirect effect of trait gratitude on HRQoL via state gratitude. Greater aggregate and person-centered state gratitude each predicted higher HRQoL. Baseline trait gratitude did not have a significant direct effect but prospectively predicted higher HRQoL via higher weekly state gratitude. Results suggest that understanding effects of gratitude on health-related perceptions requires accounting for both between-person individual differences and within-person fluctuation in state gratitude.
Holistic Recollection via Pattern Completion Involves Hippocampal Subfield CA3

Episodic memories typically comprise multiple elements. A defining characteristic of episodic retrieval is holistic recollection, i.e., comprehensive recall of the elements a memorized event encompasses. A recent study implicated activity in the human hippocampus with holistic recollection of multi-element events based on cues (Horner et al., 2015). Here, we obtained ultra-high resolution functional neuroimaging data at 7 tesla in 30 younger adults (12 female) using the same paradigm. In accordance with anatomically inspired computational models and animal research, we found that metabolic activity in hippocampal subfield CA3 (but less pronounced in dentate gyrus) correlated with this form of mnemonic pattern completion across participants. Our study provides the first evidence in humans for a strong involvement of hippocampal subfield CA3 in holistic recollection via pattern completion. SIGNIFICANCE STATEMENT Memories of daily events usually involve multiple elements, although a single element can be sufficient to prompt recollection of the whole event. Such holistic recollection is thought to require reactivation of brain activity representing the full event from one event element (“pattern completion”). Computational and animal models suggest that mnemonic pattern completion is accomplished in a specific subregion of the hippocampus called CA3, but empirical evidence in humans was lacking. Here, we leverage the ultra-high resolution of 7 tesla neuroimaging to provide first evidence for a strong involvement of the human CA3 in holistic recollection of multi-element events via pattern completion.
Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

In this review, we aim to reappraise the organization of intrinsic and extrinsic networks of the entorhinal cortex with a focus on the concept of parallel cortical connectivity streams. The concept of two entorhinal areas, the lateral and medial entorhinal cortex, belonging to two parallel input–output streams mediating the encoding and storage of respectively what and where information hinges on the claim that a major component of their cortical connections is with the perirhinal cortex and postrhinal or parahippocampal cortex in, respectively, rodents or primates. In this scenario, the lateral entorhinal cortex and the perirhinal cortex are connectionally associated and likewise the postrhinal/parahippocampal cortex and the medial entorhinal cortex are partners. In contrast, here we argue that the connectivity matrix emphasizes the potential of substantial integration of cortical information through interactions between the two entorhinal subdivisions and between the perirhinal and postrhinal/parahippocampal cortices, but most importantly through a new observation that the postrhinal/parahippocampal cortex projects to both lateral and medial entorhinal cortex. We suggest that entorhinal inputs provide the hippocampus with high‐order complex representations of the external environment, its stability, as well as apparent changes either as an inherent feature of a biological environment or as the result of navigating the environment. This thus indicates that the current connectional model of the parahippocampal region as part of the medial temporal lobe memory system needs to be revised.
Antimicrobial Desensitization: A Review of Published Protocols

Antimicrobial desensitization represents a last-line option for patients with no alternative therapies, where the benefits of this intensive process must outweigh the potential harm from drug exposure. The goal of antimicrobial desensitization procedures is to establish a temporary state of tolerance to drugs that may otherwise cause hypersensitivity reactions. While no universal antimicrobial desensitization protocols exist, this review critically analyzes previously published desensitization protocols. The purpose of this review is to provide a greater insight for clinicians and institutions to ensure desensitization procedures are efficacious while minimizing potential for patient harm. With an increasing rate of antimicrobial resistance and the critical need to preserve antimicrobial agents, desensitization may represent another option in our antimicrobial stewardship toolkit.