Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

Search for exotic decays of the Higgs boson to a pair of pseudoscalars in the and final states.

A search for exotic decays of the Higgs boson () with a mass of 125 to a pair of light pseudoscalars is performed in final states where one pseudoscalar decays to two quarks and the other to a pair of muons or leptons. A data sample of proton-proton collisions at corresponding to an integrated luminosity of 138 recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds.

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo.

Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing.

A PET-CT study on neuroinflammation in Huntington's disease patients participating in a randomized trial with laquinimod.

Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington's disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis and explore the effects of laquinimod treatment.

Effect of Race on Prediction of Brain Amyloidosis by Plasma Aβ42/Aβ40, Phosphorylated Tau, and Neurofilament Light.

Background And Objectives: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.

Methods: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age, ε4 carrier status, and cognitive status. Each participant underwent blood and CSF collection, and amyloid PET was performed in 103 participants (68%).

MC-100093, a Novel -Lactam Glutamate Transporter-1 Enhancer Devoid of Antimicrobial Properties, Attenuates Cocaine Relapse in Rats.

Cocaine use disorder currently lacks Food and Drug Administration-approved treatments. In rodents, the glutamate transporter-1 (GLT-1) is downregulated in the nucleus accumbens after cocaine self-administration, and increasing the expression and function of GLT-1 reduces the reinstatement of cocaine seeking. The -lactam antibiotic ceftriaxone upregulates GLT-1 and attenuates cue- and cocaine-induced cocaine seeking without affecting motivation for natural rewards.

Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.

Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD).

Methods: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease.

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.

Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine.

The nature of the T=T double bond (T = B, Al, Ga, In) in dialumene and its derivatives: topological study of the electron localization function (ELF).

The local electronic structure of the Al=Al bond was studied in dialumene and derivatives of dialumene in which the Al atoms were substituted by B, Ga, or In atoms. DFT calculations were performed using the B3LYP, B3PW91, PBE0, M06-L, and M06-2X functionals. Topological analysis of the electron localization function described the covalent bonds mentioned above using the disynaptic basins V(B,B), V(Al,Al), V(Ga,Ga), and V(In,In).

Self-management of Epilepsy: A Systematic Review.

Background: Although self-management is recommended for persons with epilepsy, its optimal strategies and effects are uncertain.

Purpose: To evaluate the components and efficacy of self-management interventions in the treatment of epilepsy in community-dwelling persons.

Data Sources: English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL in April 2018; the MEDLINE search was updated in March 2019.

Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease.

Objective: To assess the onset, sequence, and rate of progression of comprehensive biomarker and clinical measures across the spectrum of Alzheimer disease (AD) using the Dominantly Inherited Alzheimer Network (DIAN) study and compare these to cross-sectional estimates.

Methods: We conducted longitudinal clinical, cognitive, CSF, and neuroimaging assessments (mean of 2.7 [±1.

A sulfur-free peptide mimic of surfactant protein B (B-YL) exhibits high in vitro and in vivo surface activities.

: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B covalently joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

Background: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.

Methods: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks.

Determination of the Ratio of b-Quark Fragmentation Fractions f(s)/f(d) in pp Collisions at √s=7 TeV with the ATLAS Detector.

With an integrated luminosity of 2.47  fb(-1) recorded by the ATLAS experiment at the LHC, the exclusive decays B(s)(0)→J/ψϕ and B(d)(0)→J/ψK(*0) of B mesons produced in pp collisions at √s=7  TeV are used to determine the ratio of fragmentation fractions f(s)/f(d). From the observed B(s)(0)→J/ψϕ and B(d)(0)→J/ψK(*0) yields, the quantity (f(s)/f(d))[B(B(s)(0)→J/ψϕ)/B(B(d)(0)→J/ψK(*0))] is measured to be 0.

Transcriptome Analysis of Minimal Residual Disease in Subtypes of Pediatric B Cell Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related death in children and adolescents. Minimal residual disease (MRD) is a strong, independent prognostic factor. The objective of this study was to identify molecular signatures distinguishing patients with positive MRD from those with negative MRD in different subtypes of ALL, and to identify molecular networks and biological pathways deregulated in response to positive MRD at day 46.

Measurement of the Bs(0)→μ+ μ- branching fraction and search for B(0)→μ+ μ- decays at the LHCb experiment.

A search for the rare decays Bs(0)→μ+ μ- and B(0)→μ+ μ- is performed at the LHCb experiment. The data analyzed correspond to an integrated luminosity of 1  fb(-1) of pp collisions at a center-of-mass energy of 7 TeV and 2  fb(-1) at 8 TeV. An excess of Bs(0)→μ+ μ- signal candidates with respect to the background expectation is seen with a significance of 4.

Search for Majorana neutrinos in B- → π+ μ- μ- decays.

A search for heavy Majorana neutrinos produced in the B- → π+ μ- μ- decay mode is performed using 3  fb(-1) of integrated luminosity collected with the LHCb detector in pp collisions at center-of-mass energies of 7 and 8 TeV at the LHC. Neutrinos with masses in the range 250 to 5000 MeV and lifetimes from zero to 1000 ps are probed. In the absence of a signal, upper limits are set on the branching fraction B(B- → π+ μ- μ-) as functions of neutrino mass and lifetime.

Observation of the decay B(c)(+) → B(s)(0)π+.

The result of a search for the decay B(c)(+) → B(s)(0) π+ is presented, using the B(s)(0) → D(s)(-)π+ and B(s)(0) → J/ψ Ø channels. The analysis is based on a data sample of pp collisions collected with the LHCb detector, corresponding to an integrated luminosity of 1 fb(-1) taken at a center-of-mass energy of 7 TeV, and 2 fb(-1) taken at 8 TeV. The decay B(c)(+) → B(s)(0)π+ is observed with significance in excess of 5 standard deviations independently in both decay channels.

Search for the lepton-flavor-violating decays B(s)0→e(±)μ(∓) and B0→e(±)μ(∓).

A search for the lepton-flavor-violating decays B(s)0→e(±)μ(∓) and B0→e(±)μ(∓) is performed with a data sample, corresponding to an integrated luminosity of 1.0 fb(-1) of pp collisions at √s=7 TeV, collected by the LHCb experiment. The observed number of B(s)0→e(±)μ(∓) and B0→e(±)μ(∓) candidates is consistent with background expectations.

Search for rare B(0)((s))→μ(+)μ(-)μ(+)μ(-) decays.

A search for the decays B(0)((s))→μ(+)μ(-)μ(+)μ(-) and B(0)→μ(+)μ(-)μ(+)μ(-) is performed using data, corresponding to an integrated luminosity of 1.0 fb(-1), collected with the LHCb detector in 2011. The number of candidates observed is consistent with the expected background and, assuming phase-space models of the decays, limits on the branching fractions are set: B(B(s)(0)→μ(+)μ(-)μ(+)μ(-))<1.

First evidence for the decay B(s)(0)→μ+ μ-.

A search for the rare decays B(s)(0)→μ+ μ- and B(0)→μ+ μ- is performed with data collected in 2011 and 2012 with the LHCb experiment at the Large Hadron Collider. The data samples comprise 1.1  fb(-1) of proton-proton collisions at sqrt[s]=8  TeV and 1.

Observation of B0→D¯(0)K(+)K(-) and evidence for B(s)(0)→D¯(0)K(+)K(-).

The first observation of the decay B0→D¯(0)K(+)K(-) is reported from an analysis of 0.62 fb(-1) of pp collision data collected with the LHCb detector. Its branching fraction is measured relative to that of the topologically similar decay B(0)→D ¯(0)π(+)π(-) to be (B(B(0)→D¯(0)K(+)K(-))/B(B(0)→D¯(0)π(+)π(-))=0.

First observation of the decay B(c)+ → J/ψπ(+) π- π+.

The decay B(c)(+) → J/ψπ(+) π(-) π(+) is observed for the first time, using 0.8 fb(-1) of pp collisions at sqrt[s] = 7 TeV collected by the LHCb experiment. The ratio of branching fractions B(B(c)(+) → J/ψπ(+) π(-) π(+))/B(B(c)(+)→J/ψπ^{+}) is measured to be 2.