Miracle-dz/UniFAR-FTUs huggingface dataset:
Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants

Abstract Background Lysergic acid diethylamide (LSD) is currently being investigated in psychedelic-assisted therapy. LSD has a long duration of acute action of 8–11 hours. It produces its acute psychedelic effects via stimulation of the serotonin 5-hydroxytryptamine-2A (HT2A) receptor. Administration of the 5-HT2A antagonist ketanserin before LSD almost fully blocks the acute subjective response to LSD. However, unclear is whether ketanserin can also reverse the effects of LSD when administered after LSD. Methods We used a double-blind, randomized, placebo-controlled, crossover design in 24 healthy participants who underwent two 14-hour sessions and received ketanserin (40 mg p.o.) or placebo 1 hour after LSD (100 µg p.o.). Outcome measures included subjective effects, autonomic effects, acute adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 12 hours. Results Ketanserin reversed the acute response to LSD, thereby significantly reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. Ketanserin also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution. Ketanserin reduced adverse cardiovascular effects and mydriasis that were associated with LSD but had no effects on elevations of brain-derived neurotrophic factor levels. Ketanserin did not alter the pharmacokinetics of LSD. Conclusions These findings are consistent with an interaction between ketanserin and LSD and the view that LSD produces its psychedelic effects only when occupying 5-HT2A receptors. Ketanserin can effectively be used as a planned or rescue option to shorten and attenuate the LSD experience in humans in research and LSD-assisted therapy. Trial registry ClinicalTrials.gov (NCT04558294)
Bilateral medial sacrospinous ligament suture for apical suspension through natural spaces: A single‐center study with low perioperative complications

Sacrospinous ligament fixation (SSLF) is one of the most used native tissue approaches for apical suspension with a high rate of perioperative complications. This study aimed to review cases undergoing a modified SSLF and assess its perioperative adverse events. It was a retrospective study of 168 consecutive patients undergoing modified transvaginal SSLF at a single tertiary center from 2017 to 2021. The sutures were placed on the sacrospinous ligament (SSL) approaching the sacrum through natural spaces under direct vision. Moreover, it was performed bilaterally. Patient demographics and perioperative complications were reviewed. The median age was 65 years, and 85.7% (144/168) had stage III–IV prolapse. Among the 168 patients undergoing this modified SSLF, 161 were for uterovaginal prolapse, and seven were for posthysterectomy vaginal vault prolapse. 83.9% (135/161) patients were concomitant with hysterectomy, and 70.2% (118/168) were with anteroposterior colporrhaphy. The median operation time was 82 min (interquartile range [IQR], 61–100 min), and the median intraoperative blood loss was 50 ml (IQR, 30–50 ml). Two cases had pelvic hematoma, and both were cured after expectant treatment. No patient required a homologous blood transfusion, and none complained about buttock or lower limb pain 2 weeks postoperatively. Nor did injury of the ureters, bladder, or rectum occur intraoperatively. This modified transvaginal SSLF procedure was safe and had no severe perioperative complications.
GPR56 S4 variant is required for microglia‐mediated synaptic pruning

ADGRG1 (also called GPR56) plays critical roles in brain development and wiring, including cortical lamination, central nervous system (CNS) myelination, and developmental synaptic refinement. However, the underlying mechanism(s) in mediating such diverse functions is not fully understood. Here, we investigate the function of one specific alternative splicing isoform, the GPR56 splice variant 4 (S4), to test the hypothesis that alternative splicing variants of GPR56 in part support its different functions. We created a new transgenic mouse line, Gpr56∆S4, using CRISPR/Cas9, in which GPR56 S4 was deleted. Detailed phenotype analyses show that Gpr56∆S4 mice manifest no deficits in cortical architecture and CNS myelination compared to controls. Excitingly, they present significantly increased synapse densities, decreased synapse engulfment by microglia, and impaired eye‐segregation. Taken together, our findings support that the GPR56 S4 variant is dispensable for cortical development and CNS myelination but is essential for microglia‐mediated synaptic pruning.
Incidental Coronary Artery Calcium: Opportunistic Screening of Previous Nongated Chest Computed Tomography Scans to Improve Statin Rates (NOTIFY-1 Project)

Background: Coronary artery calcium (CAC) can be identified on nongated chest computed tomography (CT) scans, but this finding is not consistently incorporated into care. A deep learning algorithm enables opportunistic CAC screening of nongated chest CT scans. Our objective was to evaluate the effect of notifying clinicians and patients of incidental CAC on statin initiation. Methods: NOTIFY-1 (Incidental Coronary Calcification Quality Improvement Project) was a randomized quality improvement project in the Stanford Health Care System. Patients without known atherosclerotic cardiovascular disease or a previous statin prescription were screened for CAC on a previous nongated chest CT scan from 2014 to 2019 using a validated deep learning algorithm with radiologist confirmation. Patients with incidental CAC were randomly assigned to notification of the primary care clinician and patient versus usual care. Notification included a patient-specific image of CAC and guideline recommendations regarding statin use. The primary outcome was statin prescription within 6 months. Results: Among 2113 patients who met initial clinical inclusion criteria, CAC was identified by the algorithm in 424 patients. After chart review and additional exclusions were made, a radiologist confirmed CAC among 173 of 194 patients (89.2%) who were randomly assigned to notification or usual care. At 6 months, the statin prescription rate was 51.2% (44/86) in the notification arm versus 6.9% (6/87) with usual care (P<0.001). There was also more coronary artery disease testing in the notification arm (15.1% [13/86] versus 2.3% [2/87]; P=0.008). Conclusions: Opportunistic CAC screening of previous nongated chest CT scans followed by clinician and patient notification led to a significant increase in statin prescriptions. Further research is needed to determine whether this approach can reduce atherosclerotic cardiovascular disease events. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT04789278.
Distress Tolerance in the Comorbid Chronic Pain and Opioid Use Disorder Population

Objectives The risk of opioid addiction among people with chronic pain is elevated in those using opioids to self-medicate physical or emotional pain or distress. The purpose of this study is to test the main effect of distress tolerance (DT) on opioid use disorder (OUD) status in people with chronic pain, and the potential moderating effect of DT in the relationship between known addiction risk factors and the development of OUD. Methods One hundred twenty people with chronic pain were recruited to 1 of 3 groups according to their opioid use status (ie, current methadone or buprenorphine/naloxone for OUD [n = 60], history of OUD but current prolonged opioid abstinence [n = 30, meanabstinence = 121 weeks, SD = 23.3], and opioid naive [n = 30]). Participants completed self-report measures and a cold pressor task. Multinomial logistic regression analyses were used to test if DT associated with OUD status in people with chronic pain and to compare DT to other known indicators of OUD risk. Multinomial linear regression analyses were used to test the moderation effects of DT on the relationship between various risk factors and OUD in people with chronic pain. Results Analyses revealed that DT was significantly related to OUD status but did not moderate the effects of most OUD risk factors. Conclusions These results suggest that decreasing distress (eg, pain levels, craving responses, etc) may be more effective than improving tolerance to distress for the comorbid chronic pain and OUD population.
Constraints on dark matter annihilation and decay from the isotropic gamma-ray background

We study the constraints on dark matter (DM) annihilation/decay from the Fermi-LAT Isotropic Gamma-Ray Background (IGRB) observation. We consider the contributions from both extragalactic and galactic DM components. For DM annihilation, the evolution of extragalactic DM halos is taken into account. We find that the IGRB annihilation constraints under some DM subhalo models can be comparable to those derived from the observations of dwarf spheroidal galaxies and CMB. We also use the IGRB results to constrain the parameter regions accounting for the latest AMS-02 electron-positron anomaly. We find that the majority of DM annihilation/decay channels are strongly disfavored by the latest Fermi-LAT IGRB observation; only DM decays to μ+μ− and 4μ channels may be valid.
Polyphenol-rich Spondias mombin leaf extract abates cerebral ischemia/reperfusion-induced disturbed glutamate-ammonia metabolism and multiorgan toxicity in rats

ABSTRACT Introduction: This study investigated the protective properties of Spondias mombin leaf extract (SML), in cerebral ischemia/reperfusion (I/R) mediated toxicity in the brain, liver, and kidney of male Wistar rats. Materials and methods: Animals were subjected to 30 min of bilateral common carotid artery occlusion followed by 24 h of reperfusion (BCCAO/R). The animals were divided into sham, I/R, and I/R treated with SML (25, 50 and 100 mg/kg) or quercetin (20 mg/kg) groups. Animals were sacrificed after 24 h of reperfusion and markers of organ toxicity (urea creatinine, glutamine synthetase (GS), glutaminase (GA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), acetylcholinesterase (AChE)) were measured in the brain regions (cortex, striatum, and hippocampus), liver, and kidney. Results and discussion: BCCAO/R significantly (p < 0.0001) inhibited the glutamate-glutamine cycle and mediated toxicity in the cerebral cortex, striatum, hippocampus, liver, and kidney of rats. Post-treatment with SML significantly (p < 0.0001) reversed glutamate-glutamine cycle inhibition and ameliorated cerebrohepatorenal toxicity in ischemic rats. Conclusion: Cerebral I/R significantly mediated cerebral, hepatic, and renal toxicity through the inhibition of glutamate-ammonia detoxification in rats, and SML protected against this post-ischemic glutamate-ammonia mediated multiorgan toxicity.
Invariance principle for the random conductance model in a degenerate ergodic environment

We study a continuous time random walk, X, on Zd in an environment of random conductances taking values in (0,∞). We assume that the law of the conductances is ergodic with respect to space shifts. We prove a quenched invariance principle for X under some moment conditions of the environment. The key result on the sublinearity of the corrector is obtained by Moser’s iteration scheme.
A complete description of the antipodal set of most symmetric spaces of compact type

It is known that the antipodal set of a Riemannian symmetric space of compact type $G / K$ consists of a union of $K$-orbits. We determine the dimensions of these $K$-orbits of most irreducible symmetric spaces of compact type. The symmetric spaces we are not going to deal with are those with restricted root system $\mathfrak{a}_r$ and a non-trivial fundamental group, which is not isomorphic to $\mathbb{Z}_2$ or $\mathbb{Z}_{r+1}$. For example, we show that the antipodal sets of the Lie groups $Spin(2r+1)\:\: r\geq 5$, $E_8$ and $G_2$ consist only of one orbit which is of dimension $2r$, 128 and 6, respectively; $SO(2r+1)$ has also an antipodal set of dimension $2r$; and the Grassmannian $Gr_{r,r+q}(\mathbb{R})$ has a $rq$-dimensional orbit as antipodal set if $r\geq 5$ and $q>0$.
Lorentz TEM Imaging of Stripe Structures Embedded in a Soft Magnetic Matrix

N\'eel walls in soft magnetic NiFe/NiFeGa hybrid stripe structures surrounded by a NiFe film are investigated by high resolution Lorentz transmission electron microscopic imaging. An anti-parallel orientation of magnetization in 1000 nm wide neighboring unirradiated-irradiated stripes is observed by forming high angle domain walls during magnetization reversal. Upon downscaling the stripe structure size from 1000 nm to 200 nm a transition from a discrete domain pattern to an effective magnetic medium is observed for external magnetic field reversal. This transition is associated with vanishing ability of hosting high angle domain walls between adjacent stripes. The investigation also demonstrated the potentiality of Lorentz microscopy to image periodic stripe structures well under micron length-scale.
On the Density of $C_7$-Critical Graphs

In 1959, Grotszch famously proved that every planar graph of girth at least 4 is 3-colourable (or equivalently, admits a homomorphism to $C_3$). A natural generalization of this is the following conjecture: for every positive integer $t$, every planar graph of girth at least $4t$ admits a homomorphism to $C_{2t+1}$. This is in fact the planar dual of a well-known conjecture of Jaeger which states that every $4t$-edge-connected graph admits a modulo $(2t+1)$-orientation. Jaeger's original conjecture was disproved by Han et al., but not before Lovasz et al. showed that it holds for $6t$-edge-connected graphs. The latter result implies that every planar graph of girth at least $6t$ admits a homomorphism to $C_{2t+1}$. We improve upon this in the $t=3$ case, by showing that every planar graph of girth at least $16$ admits a homomorphism to $C_7$. We obtain this through a more general result regarding the density of $C_7$-critical graphs: if $G$ is a $C_7$-critical graph with $G \not \in \{C_3, C_5\}$, then $e(G) \geq \tfrac{17v(G)-2}{15}$. Our girth bound is the best known result for Jaeger's Conjecture in the $t=3$ case.
Linear independence of indefinite iterated Eisenstein integrals

We prove linear independence of indefinite iterated Eisenstein integrals over the fraction field of the ring of formal power series $\mathbb{Z}[[q]]$. Our proof relies on a general criterium for linear independence of iterated integrals, which has been established by Deneufch{â}tel, Duchamp, Minh and Solomon. As a corollary, we obtain $\mathbb{C}$-linear independence of indefinite iterated Eisenstein integrals, which has applications to the study of elliptic multiple zeta values, as defined by Enriquez.
Mechanism by Which Inflammation and Oxidative Stress Induce Mineralocorticoid Receptor Gene Expression in Aging Vascular Smooth Muscle Cells

Background: Vascular MR (mineralocorticoid receptor) expression increases with age driving aging-associated vascular stiffness and hypertension. MR has two isoforms (1α and 1β) with distinct 5′-untranslated and promoter sequences (P1 and P2), but the gene regulatory mechanisms remain unknown. We investigated mechanisms driving MR gene transcriptional regulation in aging human smooth muscle cells (SMC). Methods: MR was quantified in aortic tissue and primary human aortic SMC (HASMC) comparing adult and aged donors and adult HASMC treated with H2O2, to induce aging. Predicted transcription factor (TF) binding sites in the MR gene were validated using chromatin immunoprecipitations and reporter assays. The impact of TF inhibitors on MR isoforms and fibrosis target gene expression was examined. Results: Expression of both MR mRNA isoforms increased with donor age or H2O2 treatment in HASMCs. HIF1α (hypoxia-inducible factor) and the inflammatory TF NFκB (nuclear factor kappa B) both increased with age in HASMCs and are predicted to bind MR promoters. H2O2 induced HIF1α and NFκB expression and DNA binding of HIF1α to the MR P1 promoter and of NFκB to both MR promoters in HASMCs. HIF1α inhibition decreased MR-1α isoform expression while NFκB inhibition decreased both MR isoforms. HIF1α, NFκB, and MR inhibition decreased the expression of a SMC-MR target gene implicated in vascular fibrosis. In human aortic tissues, expression of HIF1α and NFκB each positively correlated with donor age and MR expression (P<0.0001). Conclusions: These data implicate the inflammatory TF, NFκB, and oxidative stress-induced TF, HIF1α, in regulating SMC MR transcription in aging HASMCs, which drives aging-related vascular stiffness and cardiovascular disease.
On the fundamental solution and a variational formulation of a degenerate diffusion of Kolmogorov type

In this paper, we construct the fundamental solution to a degenerate diffusion of Kolmogorov type and develop a time-discrete variational scheme for its adjoint equation. The so-called mean squared derivative cost function plays a crucial role occurring in both the fundamental solution and the variational scheme. The latter is implemented by minimizing a free energy functional with respect to the Kantorovich optimal transport cost functional associated with the mean squared derivative cost. We establish the convergence of the scheme to the solution of the adjoint equation generalizing previously known results for the Fokker-Planck equation and the Kramers equation.
The regularization theory of the Krylov iterative solvers LSQR and CGLS for linear discrete ill-posed problems, part I: the simple singular value case

For the large-scale linear discrete ill-posed problem $\min\|Ax-b\|$ or $Ax=b$ with $b$ contaminated by a white noise, the Lanczos bidiagonalization based LSQR method and its mathematically equivalent Conjugate Gradient (CG) method for $A^TAx=A^Tb$ are most commonly used. They have intrinsic regularizing effects, where the number $k$ of iterations plays the role of regularization parameter. However, there has been no answer to the long-standing fundamental concern by Bjorck and Elden in 1979: for which kinds of problems LSQR and CGLS can find best possible regularized solutions? Here a best possible regularized solution means that it is at least as accurate as the best regularized solution obtained by the truncated singular value decomposition (TSVD) method or standard-form Tikhonov regularization. In this paper, assuming that the singular values of $A$ are simple, we analyze the regularization of LSQR for severely, moderately and mildly ill-posed problems. We establish accurate estimates for the 2-norm distance between the underlying $k$-dimensional Krylov subspace and the $k$-dimensional dominant right singular subspace of $A$. For the first two kinds of problems, we then prove that LSQR finds a best possible regularized solution at semi-convergence occurring at iteration $k_0$ and that, for $k=1,2,\ldots,k_0$, (i) the $k$-step Lanczos bidiagonalization always generates a near best rank $k$ approximation to $A$; (ii) the $k$ Ritz values always approximate the first $k$ large singular values in natural order; (iii) the $k$-step LSQR always captures the $k$ dominant SVD components of $A$. For the third kind of problem, we prove that LSQR generally cannot find a best possible regularized solution. Numerical experiments confirm our theory.
Inertial range turbulence in kinetic plasmas

The transfer of turbulent energy through an inertial range from the driving scale to dissipative scales in a kinetic plasma followed by the conversion of this energy into heat is a fundamental plasma physics process. A theoretical foundation for the study of this process is constructed, but the details of the kinetic cascade are not well understood. Several important properties are identified: (a) The conservation of a generalized energy by the cascade; (b) the need for collisions to increase entropy and realize irreversible plasma heating; and (c) the key role played by the entropy cascade—a dual cascade of energy to small scales in both physical and velocity space—to convert ultimately the turbulent energy into heat. A strategy for nonlinear numerical simulations of kinetic turbulence is outlined. Initial numerical results are consistent with the operation of the entropy cascade. Inertial range turbulence arises in a broad range of space and astrophysical plasmas and may play an important role in the th.
Isoconfigurational thermostat

A holonomic constraint is used to enforce a constant instantaneous configurational temperature on an equilibrium system. Three sets of equations of motion are obtained, differing according to the way in which the holonomic constraint is introduced and the phase space distribution function that is preserved by the dynamics. Firstly, Gauss’ principle of least constraint is used, and it is shown that it does not preserve the canonical distribution. Secondly, a modified Hamiltonian is used to find a dynamics that provides a restricted microcanonical distribution. Lastly, we provide equations that are specifically designed to both satisfy the temperature constraint and produce a restricted canonical ensemble.
Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.

Objective: We evaluated associations between vitamin D status and skeletal muscle, strength, and bone mineral density (BMD) outcomes after ACL reconstruction (ACLR) in an observational study. Methods: Serum measures included 25-hydroxyvitamin D (25(OH)D; free and total), vitamin D binding protein (DBP), and 1,25-dihydroxy vitamin D (1,25(OH)2D) at baseline, 1 week, 4 months, and 6 months post-ACLR. Vastus lateralis biopsies were collected from the healthy and ACL-injured limb of 21 young, healthy participants (62% female; 17.8 [3.2] yr, BMI: 26.0 [3.5] kg/m2) during ACLR and the injured limb only at 1 week and 4 month follow ups. RNA and protein were isolated from biopsies and assessed for vitamin D receptor [VDR], and vitamin D-activating enzymes. Quadriceps fiber cross-sectional area (CSA) was determined with immunohistochemistry. BMD of femur and tibia were determined with at baseline and 6 months post-ACLR; strength was assessed with an isokinetic dynamometer. Results: 1,25(OH)2D decreased from baseline to one week after ACLR (21.6 [7.9] vs. 13.8 [5.5] pg/mL; p<0.0001). VDR and 25-hydroxylase transcript abundance and VDR and DBP proteins were elevated one week after ACLR compared with baseline (FDR<0.05; p<0.05). Participants with an average total 25(OH)D <30 ng/mL showed significant decreases in CSA 1 week and 4 months after ACLR (p<0.01; p=0.041 for time x D status interaction), whereas those with total 25(OH)D [≥]30ng/mL showed no significant differences (p>0.05 for all comparisons). BMD and strength measures were lower at follow up but did not associate with vitamin D status. Conclusion: ACLR promotes vitamin D pathways in the quadriceps and low status is associated with loss of skeletal muscle both 1 week and 4 months after ACLR.
The Algebraic Connectivity and the Clique Number of Graphs

This paper investigates some relationship between the algebraic connectivity and the clique number of graphs. We characterize all extremal graphs which have the maximum and minimum the algebraic connectivity among all graphs of order $n$ with the clique number $r$, respectively. In turn, an upper and lower bounds for the clique number of a graph in terms of the algebraic connectivity are obtained. Moreover, a spectral version of the Erd\H{o}s-Stone theorem in terms of the algebraic connectivity of graphs is presented.