Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3.

Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies.

The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax.

Background: B-cell receptor (BCR) signaling is a central driver in chronic lymphocytic leukemia (CLL), along with the activation of pro-survival pathways (e.g., NF-κB) and aberrant anti-apoptotic mechanisms (e.

Prediction of pathological complete response to chemotherapy for breast cancer using deep neural network with uncertainty quantification.

Background: The I-SPY 2 trial is a national-wide, multi-institutional clinical trial designed to evaluate multiple new therapeutic drugs for high-risk breast cancer. Previous studies suggest that pathological complete response (pCR) is a viable indicator of long-term outcomes of neoadjuvant chemotherapy for high-risk breast cancer. While pCR can be assessed during surgery after the chemotherapy, early prediction of pCR before the completion of the chemotherapy may facilitate personalized treatment management to achieve an improved outcome.

Adaptive fine-tuning based transfer learning for the identification of MGMT promoter methylation status.

Glioblastoma Multiforme (GBM) is an aggressive form of malignant brain tumor with a generally poor prognosis.-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to be a predictive bio-marker for resistance to treatment of GBM, but it is invasive and time-consuming to determine methylation status. There has been effort to predict the MGMT methylation status through analyzing MRI scans using machine learning, which only requires pre-operative scans that are already part of standard-of-care for GBM patients.

BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects.

Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects.

Unlabelled: Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.

Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.

Objective: To evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH) genes and systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).

Methods: Targeted sequencing of HLH genes (, , , , , ) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtained (dbGaP:phs000280.

Population and hospital-level COVID-19 measures are associated with increased risk of hospital-onset COVID-19.

A review of hospital-onset COVID-19 cases revealed 8 definite, 106 probable, and 46 possible cases. Correlations between hospital-onset cases and both HCW and inpatient cases were noted in 2021. Rises in community measures were associated with rises in hospital-onset cases.

Adaptive Fine-tuning based Transfer Learning for the Identification of MGMT Promoter Methylation Status.

Glioblastoma Multiforme (GBM) is an aggressive form of malignant brain tumor with a generally poor prognosis. Treatment usually includes a mix of surgical resection, radiation therapy, and akylating chemotherapy but, even with these intensive treatments, the 2-year survival rate is still very low. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to be a predictive bio-marker for resistance to chemotherapy, but it is invasive and time-consuming to determine the methylation status.

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.

Background: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID.

Objective: We sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships.

Observation of Same-Sign WW Production from Double Parton Scattering in Proton-Proton Collisions at sqrt[s]=13 TeV.

The first observation of the production of W^{±}W^{±} bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138  fb^{-1} recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds.

Search for Higgs Boson Decay to a Charm Quark-Antiquark Pair in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→cc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13  TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138  fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed.

Measurements of jet multiplicity and jet transverse momentum in multijet events in proton-proton collisions at .

Multijet events at large transverse momentum () are measured at using data recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of . The multiplicity of jets with that are produced in association with a high- dijet system is measured in various ranges of the of the jet with the highest transverse momentum and as a function of the azimuthal angle difference between the two highest jets in the dijet system. The differential production cross sections are measured as a function of the transverse momenta of the four highest jets.

Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions.

The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization.

Azimuthal correlations in Z +jets events in proton-proton collisions at .

The production of Z bosons associated with jets is measured in collisions at with data recorded with the CMS experiment at the LHC corresponding to an integrated luminosity of 36.3. The multiplicity of jets with transverse momentum is measured for different regions of the Z boson's , from lower than 10 to higher than 100.

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.

Probing Heavy Majorana Neutrinos and the Weinberg Operator through Vector Boson Fusion Processes in Proton-Proton Collisions at sqrt[s]=13 TeV.

The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13  TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138  fb^{-1}. The results are found to agree with the predictions of the standard model.

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.

CMS pythia 8 colour reconnection tunes based on underlying-event data.

New sets of parameter tunes for two of the colour reconnection models, quantum chromodynamics-inspired and gluon-move, implemented in the pythia  8 event generator, are obtained based on the default CMS pythia  8 underlying-event tune, CP5. Measurements sensitive to the underlying event performed by the CMS experiment at centre-of-mass energies and 13, and by the CDF experiment at 1.96 are used to constrain the parameters of colour reconnection models and multiple-parton interactions simultaneously.

Search for light Higgs bosons from supersymmetric cascade decays in collisions at .

A search is reported for pairs of light Higgs bosons () produced in supersymmetric cascade decays in final states with small missing transverse momentum. A data set of LHC collisions collected with the CMS detector at and corresponding to an integrated luminosity of 138 is used. The search targets events where both bosons decay into pairs that are reconstructed as large-radius jets using substructure techniques.

Reconnaissance of Oxygenic Denitrifiers in Agriculturally Impacted Soils.

Row crop production in the agricultural Midwest pollutes waterways with nitrate, and exacerbates climate change through increased emissions of nitrous oxide and methane. Oxygenic denitrification processes in agricultural soils mitigate nitrate and nitrous oxide pollution by short-circuiting the canonical pathway to avoid nitrous oxide formation. Furthermore, many oxygenic denitrifiers employ a nitric oxide dismutase () to create molecular oxygen that is used by methane monooxygenase to oxidize methane in otherwise anoxic soils.

The Evolution of the Sentinel Node Biopsy in Melanoma.

The growing repertoire of approved immune-checkpoint inhibitors and targeted therapy has revolutionized the adjuvant treatment of melanoma. While the treatment of primary cutaneous melanoma remains wide local excision (WLE), the management of regional lymph nodes continues to evolve in light of practice-changing clinical trials and dramatically improved adjuvant therapy. With large multicenter studies reporting no benefit in overall survival for completion lymph node dissection (CLND) after a positive sentinel node biopsy (SLNB), controversy remains regarding patient selection and clinical decision-making.

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.

Novel Function of CtXyn5A from Acetivibrio thermocellus: Dual Arabinoxylanase and Feruloyl Esterase Activity in the Same Active Site.

Enzymes' uncharacterised side activities can have significant effects on reaction products and yields. Hence, their identification and characterisation are crucial for the development of successful reaction systems. Here, we report the presence of feruloyl esterase activity in CtXyn5A from Acetivibrio thermocellus, besides its well-known arabinoxylanase activity, for the first time.