Rare GPR37L1 Variants Reveal Potential Association between GPR37L1 and Disorders of Anxiety and Migraine.

GPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare () genetic variants found among 51,289 whole-exome sequences from the DiscovEHR cohort. Rare coding variants were binned according to predicted pathogenicity and analyzed by sequence kernel association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others.

Measurement of the Centrality Dependence of the Dijet Yield in p+Pb Collisions at sqrt[s_{NN}]=8.16 TeV with the ATLAS Detector.

ATLAS measured the centrality dependence of the dijet yield using 165  nb^{-1} of p+Pb data collected at sqrt[s_{NN}]=8.16  TeV in 2016. The event centrality, which reflects the p+Pb impact parameter, is characterized by the total transverse energy registered in the Pb-going side of the forward calorimeter.

Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis.

We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene-peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets.

Ensuring Stakeholder Feedback in the Design and Conduct of Clinical Trials for Rare Diseases: ISCTM Position Paper of the Orphan Disease Working Group.

The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor.

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101).

Background: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.

Objective: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.

Design: Multicenter prospective observational study.

Observation of WZγ Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter reports the observation of WZγ production and a measurement of its cross section using 140.1±1.2  fb^{-1} of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider.

Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC.

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022.

Search for Dark Photons in Rare Z Boson Decays with the ATLAS Detector.

A search for events with a dark photon produced in association with a dark Higgs boson via rare decays of the standard model Z boson is presented, using 139  fb^{-1} of sqrt[s]=13  TeV proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider. The dark boson decays into a pair of dark photons, and at least two of the three dark photons must each decay into a pair of electrons or muons, resulting in at least two same-flavor opposite-charge lepton pairs in the final state. The data are found to be consistent with the background prediction, and upper limits are set on the dark photon's coupling to the dark Higgs boson times the kinetic mixing between the standard model photon and the dark photon, α_{D}ϵ^{2}, in the dark photon mass range of [5, 40] GeV except for the ϒ mass window [8.

Combined Measurement of the Higgs Boson Mass from the H→γγ and H→ZZ^{*}→4ℓ Decay Channels with the ATLAS Detector Using sqrt[s]=7, 8, and 13 TeV pp Collision Data.

A measurement of the mass of the Higgs boson combining the H→ZZ^{*}→4ℓ and H→γγ decay channels is presented. The result is based on 140  fb^{-1} of proton-proton collision data collected by the ATLAS detector during LHC run 2 at a center-of-mass energy of 13 TeV combined with the run 1 ATLAS mass measurement, performed at center-of-mass energies of 7 and 8 TeV, yielding a Higgs boson mass of 125.11±0.

Pancreatic Replacement Therapy for Maladaptive Behaviors in Preschool Children With Autism Spectrum Disorder.

Importance: There is an urgent unmet need for a treatment addressing the core symptoms and associated maladaptive symptoms of autism spectrum disorder (ASD), especially in preschool populations.

Objectives: To evaluate whether treatment of children with ASD aged 3 to 6 years treated with high-protease pancreatic therapy produces long- and short-term improvements in autism-associated maladaptive behaviors.

Design, Setting, And Participants: This cohort study at 32 sites across the US used a double-blind parallel group, delayed-start design comprising a 2-week blinded placebo run-in, and a double-blind, randomized, placebo-controlled segment (12 weeks).

Observation of Single-Top-Quark Production in Association with a Photon Using the ATLAS Detector.

This Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139  fb^{-1} of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) _{-71}^{+75}(syst)  fb, to be compared with the standard model prediction of 515_{-42}^{+36}  fb at next-to-leading order in QCD.

Observation of an Excess of Dicharmonium Events in the Four-Muon Final State with the ATLAS Detector.

A search is made for potential ccc[over ¯]c[over ¯] tetraquarks decaying into a pair of charmonium states in the four muon final state using proton-proton collision data at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} recorded by the ATLAS experiment at LHC. Two decay channels, J/ψ+J/ψ→4μ and J/ψ+ψ(2S)→4μ, are studied. Backgrounds are estimated based on a hybrid approach involving Monte Carlo simulations and data-driven methods.

Observation of the γγ→ττ Process in Pb+Pb Collisions and Constraints on the τ-Lepton Anomalous Magnetic Moment with the ATLAS Detector.

This Letter reports the observation of τ-lepton-pair production in ultraperipheral lead-lead collisions Pb+Pb→Pb(γγ→ττ)Pb and constraints on the τ-lepton anomalous magnetic moment a_{τ}. The dataset corresponds to an integrated luminosity of 1.44  nb^{-1} of LHC Pb+Pb collisions at sqrt[s_{NN}]=5.

A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML.

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine.

Understanding parents uncertainty sources and management strategies while caring for a child diagnosed with a hematologic cancer.

Rationale: Parents of a child or adolescent (CA) or young adult (YA) diagnosed with a hematologic cancer often face uncertainty. Managing uncertainty is critical to reduce the psychosocial burden of illness-related stressors.

Objective: This study sought to identify: 1) sources of uncertainty among parents of a child diagnosed with a hematologic cancer, 2) strategies used by parents to manage uncertainty, and 3) clinicians' responses to parents' online information-seeking approach to managing uncertainty.

Overcoming Barriers to Autologous Stem Cell Transplantation in Multiple Myeloma: Recommendations from a Multidisciplinary Roundtable Discussion.

Autologous stem cell transplantation (ASCT) is a standard of care treatment for patients with multiple myeloma (MM). However, only 20% to 30% of patients with MM for whom the procedure is indicated undergo ASCT. Barriers to ASCT may be informational, financial, logistic, or cultural and may affect patients and treating oncologists.

Strong Constraints on Jet Quenching in Centrality-Dependent p+Pb Collisions at 5.02 TeV from ATLAS.

Jet quenching is the process of color-charged partons losing energy via interactions with quark-gluon plasma droplets created in heavy-ion collisions. The collective expansion of such droplets is well described by viscous hydrodynamics. Similar evidence of collectivity is consistently observed in smaller collision systems, including pp and p+Pb collisions.

Real-world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system.

Background: We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State.

Methods: Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations.

Test of CP Invariance in Higgs Boson Vector-Boson-Fusion Production Using the H→γγ Channel with the ATLAS Detector.

A test of CP invariance in Higgs boson production via vector-boson fusion has been performed in the H→γγ channel using 139  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV collected by the ATLAS detector at the LHC. The optimal observable method is used to probe the CP structure of interactions between the Higgs boson and electroweak gauge bosons, as described by an effective field theory. No sign of CP violation is observed in the data.