A randomized trial of acceptance-based behavioral therapy to improve mental health outcomes for LGBTQ+ persons: Study protocol.

BACKGROUND: During the COVID-19 pandemic, public health measures limited social interactions as an effective and protective intervention for all. For many, however, this social isolation exacerbated mental health symptoms. People who identify as lesbian, gay, bisexual, transgender, and queer (LGBTQ+) were already at elevated risk of anxiety and depression, relative to cisgender and heterosexual populations, and pandemic-related social isolation likely heightened these disparities. In our prior work with sexual and gender minorities, we developed and established feasibility and acceptability of a novel acceptance-based behavioral therapy (ABBT) intervention for HIV treatment. ABBT showed promise in improving social support and reducing mental health symptoms. In the current study, we investigate the efficacy of ABBT, compared to a treatment-as-usual control condition, in a full-scale randomized controlled trial to improve social support for LGBTQ+ persons living with anxiety and depression. METHODS: Two hundred forty LGBTQ+ adults with anxiety and/or depressive symptoms will be recruited and equally randomized to receive: (a) the ABBT intervention, consisting of two 30-40 min sessions plus treatment-as-usual (TAU), or (b) TAU only. Primary outcomes are interviewer-assessed anxiety and depressive symptoms. Secondary outcomes are self-reported anxiety and depressive symptoms. Experiential avoidance and social support are hypothesized mediators and presence of an anxiety and/or depressive disorder is a hypothesized moderator. CONCLUSIONS: ABBT represents a novel, identify-affirming real-world approach to promoting social support as a means of improving mental health among individuals who identify as LGBTQ+. This study will contribute actionable data establishing the impact, mediational mechanisms, and effect modifiers of ABBT. CLINICALTRIALS: govregistration: NCT05540067.

Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy.

Hoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine. Antibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease. Flow cytometry analysis of sera of immune mice that were previously cured of their melanoma through a combined immunotherapy regimen with long-term memory showed strong antibody-binding against melanoma tumor cell lines. Using a high-density whole-proteome peptide array, we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by 2 or more of these 6 mice and exhibited strong antibody binding only by immune, not naive sera. Confirmatory studies were done to validate these results using 2 separate ELISA-based systems. To the best of our knowledge, this is the first study of the "immunome" of protein-based epitopes that are recognized by immune sera from mice cured of cancer via immunotherapy.

Associations between KIR/KIR-ligand genotypes and clinical outcome for patients with advanced solid tumors receiving BEMPEG plus nivolumab combination therapy in the PIVOT-02 trial.

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with clinical outcome. Patients with inhibitory KIR2DL2 and its ligand (HLA-C1) observed significantly greater tumor shrinkage (TS, median change -13.0 vs. 0%) and increased PFS (5.5 vs. 3.3 months) and a trend toward improved OR (31.2 vs. 19.5%) compared to patients with the complementary genotype. Furthermore, patients with KIR2DL2 and its ligand together with inhibitory KIR3DL1 and its ligand (HLA-Bw4) had improved OR (36.5 vs. 19.6%), greater TS (median change -16.1 vs. 0%), and a trend toward prolonged PFS (8.4 vs. 3.6 months) as compared to patients with the complementary genotype. FCγR polymorphisms did not influence OR/PFS/TS.These data show that clinical response to BEMPEG plus nivolumab treatment in the PIVOT-02 trial may be associated with the repertoire of KIR/KIR-ligands an individual inherits. Further investigation and validation of these results may enable KIR/KIR-ligand genotyping to be utilized prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.

Formation of n- and p-type regions in individual Si/SiO2 core/shell nanowires by ion beam doping.

A method for cross-sectional doping of individual Si/SiO2 core/shell nanowires (NWs) is presented. P and B atoms are laterally implanted at different depths in the Si core. The healing of the implantation-related damage together with the electrical activation of the dopants takes place via solid phase epitaxy driven by millisecond-range flash lamp annealing. Electrical measurements through a bevel formed along the NW enabled us to demonstrate the concurrent formation of n- and p-type regions in individual Si/SiO2 core/shell NWs. These results might pave the way for ion beam doping of nanostructured semiconductors produced by using either top-down or bottom-up approaches.

Bistable self-assembly in homogeneous colloidal systems for flexible modular architectures.

This paper presents a homogeneous system of magnetic colloidal particles that self-assembles via two structural patterns of different symmetry. Based on a qualitative comparison between a real magnetic particles system, analytical calculations and molecular dynamics simulations, it is shown that bistability can be achieved by a proper tailoring of an anisotropic magnetization distribution inside the particles. The presented bistability opens new possibilities to form two-dimensionally extended and flexible structures where the connectivity between the particles can be changed in vivo.

Lateral spin transfer torque induced magnetic switching at room temperature demonstrated by x-ray microscopy.

Changing and detecting the orientation of nanomagnetic structures, which can be used for durable information storage, needs to be developed towards true nanoscale dimensions for keeping up the miniaturization speed of modern nanoelectronic components. Therefore, new concepts for controlling the state of nanomagnets are currently in the focus of research in the field of nanoelectronics. Here, we demonstrate reproducible switching of a purely metallic nanopillar placed on a lead that conducts a spin-polarized current at room temperature. Spin diffusion across the metal-metal (Cu to CoFe) interface between the pillar and the lead causes spin accumulation in the pillar, which may then be used to set the magnetic orientation of the pillar. In our experiments, the detection of the magnetic state of the nanopillar is performed by direct imaging via scanning transmission x-ray microscopy (STXM).

Non-monotonic crossover from single-file to regular diffusion in micro-channels.

The diffusion behavior of interacting particles determines the behavior of a large number of systems ranging from pedestrians crossing a road to ions passing through channels in living cells. Here we present a system in which the nature of the diffusion process varies with changes in the external conditions. We find this special behavior in a colloidal model system, consisting of micron sized particles which are confined to narrow channels and interact via induced magnetic dipoles. When the density of these particles is changed, diffusion alternates between normal Fickian behavior and single-file diffusion. This anomalous behavior is induced by the order of the particles in the restricted geometry and does not depend on the exact nature of the inter-particle interactions.

Subharmonic resonant optical excitation of confined acoustic modes in a free-standing semiconductor membrane at GHz frequencies with a high-repetition-rate femtosecond laser.

We propose subharmonic resonant optical excitation with femtosecond lasers as a new method for the characterization of phononic and nanomechanical systems in the gigahertz to terahertz frequency range. This method is applied for the investigation of confined acoustic modes in a free-standing semiconductor membrane. By tuning the repetition rate of a femtosecond laser through a subharmonic of a mechanical resonance we amplify the mechanical amplitude, directly measure the linewidth with megahertz resolution, infer the lifetime of the coherently excited vibrational states, accurately determine the system's quality factor, and determine the amplitude of the mechanical motion with femtometer resolution.

Density reduction and diffusion in driven two-dimensional colloidal systems through microchannels.

The behavior of particles driven through a narrow constriction is investigated in experiment and simulation. The system of particles adapts to the confining potentials and the interaction energies by a self-consistent arrangement of the particles. It results in the formation of layers throughout the channel and of a density gradient along the channel. The particles accommodate to the density gradient by reducing the number of layers one by one when it is energetically favorable. The position of the layer reduction zone fluctuates with time while the particles continuously pass this zone. The flow behavior of the particles is studied in detail. The velocities of the particles and their diffusion behavior reflect the influence of the self-organized order of the system.

Influence of chopped laser light onto the electronic transport through atomic-sized contacts.

This paper reports on the influence of laser irradiation onto the electrical conductance of gold nanocontacts established with the mechanically controllable breakjunction technique. We concentrate here on the study of reversible conductance changes which can be as high as 200%. We investigate the dependence on the initial conductance of the contacts, the wavelength, the intensity and position of the laser spot with respect to the sample. Under most conditions an enhancement of the conductance is observed. We discuss several physical mechanisms which might contribute to the observed effect including thermal expansion, rectification and photon-assisted transport. We conclude that thermal expansion is not the dominating one.

Influence of laser light on electronic transport through atomic-size contacts.

This Letter reports on the influence of laser irradiation onto the electrical conductance of gold nanocontacts established with the mechanically controllable break-junction technique. We concentrate on the study of reversible conductance changes which can be as high as 200%. We investigate the dependence on the initial conductance of the contacts, and on the wavelength, the intensity, and the position of the laser spot with respect to the sample. Under most conditions an enhancement of the conductance is observed. Several physical mechanisms which might contribute to the observed effect including thermal expansion, rectification, plasmon excitation, and photon-assisted transport are discussed, among which the two latter ones are most likely the dominating ones.

Characterization of magnetic colloids by means of magnetooptics.

A new, efficient method for the characterization of magnetic colloids based on the Faraday effect is proposed. According to the main principles of this technique, it is possible to detect the stray magnetic field of the colloidal particles induced inside the magnetooptical layer. The magnetic properties of individual particles can be determined providing measurements in a wide range of magnetic fields. The magnetization curves of capped colloids and paramagnetic colloids were measured by means of the proposed approach. The registration of the magnetooptical signals from each colloidal particle in an ensemble permits the use of this technique for testing the magnetic monodispersity of colloidal suspensions.

Tilt angle of lipid acyl chains in unilamellar vesicles determined by ellipsometric light scattering.

Ellipsometric light scattering (ELS) at room temperature is applied to unilamellar vesicles (approximately 50 nm radius) of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in the gel phase and of 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) in the liquid-crystaline phase. A high sensitivity of this technique to the local anisotropy is found. From the resulting local birefringence, a lower limit of (29 +/-0.5) degrees for the average tilt angle of the lipid chains of DPPC with respect to the membrane normal is estimated. This tilt angle value is slightly lower than literature values for the tilt angle in oriented lipid multi-bilayers on solid substrates.

Layer reduction in driven 2D-colloidal systems through microchannels.

The transport behavior of a system of gravitationally driven superparamagnetic colloidal particles is investigated. The motion of the particles through a narrow channel is governed by magnetic dipole interactions, and a layered structure forms parallel to the walls. The arrangement of the particles is perturbed by diffusion and the motion induced by gravity leading to a density gradient along the channel. Our main result is the reduction of the number of layers. Experiments and Brownian dynamics simulations show that this occurs due to the density gradient along the channel.

Single- and multigrain nanojunctions with a self-assembled monolayer of conjugated molecules.

Systematic conductivity measurements in nanoscale junctions containing a self-assembled monolayer of conjugated molecules are reported. Different conductivity mechanisms are identified depending on the granularity of the metal used as a substrate for assembling the monolayer. Unexpectedly, the energy scale controlling the dominant conductance channels is quite low in comparison with the molecular level spacing. In single-grain junctions, the dominant conductance mechanism is hopping with an energy scale of the order of 10-100 meV determined by the nature of the metal contacts. In the case of multigrain junctions, additional tunnel conductance is observed with low-energy Coulomb-blockade features.

Nanomechanical resonator shuttling single electrons at radio frequencies.

We observe transport of electrons through a metallic island on the tip of a nanomechanical pendulum. The resulting tunneling current shows distinct features corresponding to the discrete mechanical eigenfrequencies of the pendulum. We report on measurements covering the temperature range from 300 down to 4.2 K. We explain the I-V curve, which unexpectedly differs from previous theoretical predictions, with model calculations based on a master equation approach.