Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

Orally bioavailable RORγ/DHODH dual host-targeting small molecules with broad-spectrum antiviral activity.

Host-directed antivirals (HDAs) represent an attractive treatment option and a strategy for pandemic preparedness, especially due to their potential broad-spectrum antiviral activity and high barrier to resistance development. Particularly, dual-targeting HDAs offer a promising approach for antiviral therapy by simultaneously disrupting multiple pathways essential for viral replication. Izumerogant (IMU-935) targets two host proteins, (i) the retinoic acid receptor-related orphan receptor γ isoform 1 (RORγ1), which modulates cellular cholesterol metabolism, and (ii) the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in de novo pyrimidine synthesis.

Novel cathepsin C inhibitor, BI 1291583, intended for treatment of bronchiectasis: Phase I characterization in healthy volunteers.

Novel treatments are needed to reduce inflammation, improve symptoms, address exacerbations, and slow disease progression in bronchiectasis. Cathepsin C (CatC) inhibition promises to achieve this through reduction of neutrophil-derived serine protease (including neutrophil elastase [NE] and proteinase 3 [PR3]) activation. Here, we present the phase I characterization of the novel CatC inhibitor, BI 1291583.

An FDA-Validated, Self-Cleaning Liquid Chromatography-Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium.

As organoids and organ-on-chip (OoC) systems move toward preclinical and clinical applications, there is an increased need for method validation. Using a liquid chromatography-mass spectrometry (LC-MS)-based approach, we developed a method for measuring small-molecule drugs and metabolites in the cell medium directly sampled from liver organoids/OoC systems. The LC-MS setup was coupled to an automatic filtration and filter flush system with online solid-phase extraction (SPE), allowing for robust and automated sample cleanup/analysis.

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.

The preclinical and phase 1 development of the novel oral cathepsin C inhibitor BI 1291583.

https://bit.ly/47PZ8E5.

Platelet dysfunction reversal with cold-stored vs room temperature-stored platelet transfusions.

Platelets are stored at room temperature for 5 to 7 days (room temperature-stored platelets [RSPs]). Because of frequent and severe shortages, the US Food and Drug Administration recently approved up to 14-day cold-stored platelets (CSPs) in plasma. However, the posttransfusion function of CSPs is unknown and it is unclear which donors are best suited to provide either RSPs or CSPs.

A search for decays of the Higgs boson to invisible particles in events with a top-antitop quark pair or a vector boson in proton-proton collisions at .

A search for decays to invisible particles of Higgs bosons produced in association with a top-antitop quark pair or a vector boson, which both decay to a fully hadronic final state, has been performed using proton-proton collision data collected at by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138. The 95% confidence level upper limit set on the branching fraction of the 125 Higgs boson to invisible particles, , is 0.54 (0.

Search for ambient superconductivity in the Lu-N-H system.

Motivated by the recent report of room-temperature superconductivity at near-ambient pressure in N-doped lutetium hydride, we performed a comprehensive, detailed study of the phase diagram of the Lu-N-H system, looking for superconducting phases. We combined ab initio crystal structure prediction with ephemeral data-derived interatomic potentials to sample over 200,000 different structures. Out of the more than 150 structures predicted to be metastable within ~50 meV from the convex hull we identify 52 viable candidates for conventional superconductivity, for which we computed their superconducting properties from Density Functional Perturbation Theory.

Cytomegalovirus cyclin-dependent kinase ortholog vCDK/pUL97 undergoes regulatory interaction with human cyclin H and CDK7 to codetermine viral replication efficiency.

Human cytomegalovirus (HCMV) infection is shaped by a tightly regulated interplay between viral and cellular proteins. Distinct kinase activities, such as the viral cyclin-dependent kinase ortholog (vCDK) pUL97 and cellular CDK7 are both crucial for efficient viral replication. Previously, we reported that both kinases, vCDK/pUL97 and CDK7, interact with cyclin H, thereby achieving an enhanced level of kinase activity and overall functionality in viral replication.

Search for Nonresonant Pair Production of Highly Energetic Higgs Bosons Decaying to Bottom Quarks.

A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.

Search for Higgs Boson and Observation of Z Boson through Their Decay into a Charm Quark-Antiquark Pair in Boosted Topologies in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13  TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138  fb^{-1}. Boosted H→cc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique.

Measurement of the mass dependence of the transverse momentum of lepton pairs in Drell-Yan production in proton-proton collisions at .

The double differential cross sections of the Drell-Yan lepton pair (, dielectron or dimuon) production are measured as functions of the invariant mass , transverse momentum , and . The observable, derived from angular measurements of the leptons and highly correlated with , is used to probe the low- region in a complementary way. Dilepton masses up to 1 are investigated.

Measurements of the associated production of a W boson and a charm quark in proton-proton collisions at .

Measurements of the associated production of a W boson and a charm ( ) quark in proton-proton collisions at a centre-of-mass energy of 8 are reported. The analysis uses a data sample corresponding to a total integrated luminosity of 19.7 collected by the CMS detector at the LHC.

Search for Flavor-Changing Neutral Current Interactions of the Top Quark and Higgs Boson in Final States with Two Photons in Proton-Proton Collisions at sqrt[s]=13 TeV.

Proton-proton interactions resulting in final states with two photons are studied in a search for the signature of flavor-changing neutral current interactions of top quarks (t) and Higgs bosons (H). The analysis is based on data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 137  fb^{-1}. No significant excess above the background prediction is observed.

Effects of COVID-19 Lockdown on Melanoma Diagnosis in Switzerland: Increased Tumor Thickness in Elderly Females and Shift towards Stage IV Melanoma during Lockdown.

At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis.

There and back again: the once and current developments in donor-derived platelet products for hemostatic therapy.

More than 100 years ago, Duke transfused whole blood to a patient with thrombocytopenia to raise the platelet count and prevent bleeding. Since then, platelet transfusions have undergone numerous modifications from whole blood-derived platelet-rich plasma to apheresis-derived platelet concentrates. The storage time and temperature have also changed.

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton-proton collisions at .

A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a boson. The search uses proton-proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 , at a center-of-mass energy .

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at .

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data.

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at .

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 at the CERN LHC, corresponding to an integrated luminosity of 137 collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented.

Precision luminosity measurement in proton-proton collisions at in 2015 and 2016 at CMS.

The measurement of the luminosity recorded by the CMS detector installed at LHC interaction point 5, using proton-proton collisions at in 2015 and 2016, is reported. The absolute luminosity scale is measured for individual bunch crossings using beam-separation scans (the van der Meer method), with a relative precision of 1.3 and 1.

Search for a heavy vector resonance decaying to a boson and a Higgs boson in proton-proton collisions at .

A search is presented for a heavy vector resonance decaying into a boson and the standard model Higgs boson, where the boson is identified through its leptonic decays to electrons, muons, or neutrinos, and the Higgs boson is identified through its hadronic decays. The search is performed in a Lorentz-boosted regime and is based on data collected from 2016 to 2018 at the CERN LHC, corresponding to an integrated luminosity of 137 . Upper limits are derived on the production of a narrow heavy resonance , and a mass below 3.

Search for charged Higgs bosons produced in vector boson fusion processes and decaying into vector boson pairs in proton-proton collisions at .

A search for charged Higgs bosons produced in vector boson fusion processes and decaying into vector bosons, using proton-proton collisions at at the LHC, is reported. The data sample corresponds to an integrated luminosity of 137 collected with the CMS detector. Events are selected by requiring two or three electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass.

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements.

This paper presents new sets of parameters ("tunes") for the underlying-event model of the event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in , and are obtained from a fit to minimum-bias data collected by the CMS experiment at , 7, and . The tunes are based on the NNPDF 3.