Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response.

Immune checkpoint inhibitors (ICIs) have advanced the treatment of non-small cell lung cancer (NSCLC). This study evaluates the predictive value of CD8 T cell exhaustion in patients with lung adenocarcinoma treated with ICIs. By analyzing tumor samples from 166 patients through multiplex immunofluorescence, we quantify tumor-infiltrating lymphocytes (TILs) expressing exhaustion markers programmed cell death-1 (PD1), lymphocyte activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and T cell immunoglobulin and mucin domain 3 (TIM3).

Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.

Background: The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

Evidence for a New Structure in the J/ψp and J/ψp[over ¯] Systems in B_{s}^{0}→J/ψpp[over ¯] Decays.

An amplitude analysis of flavor-untagged B_{s}^{0}→J/ψpp[over ¯] decays is performed using a sample of 797±31 decays reconstructed with the LHCb detector. The data, collected in proton-proton collisions between 2011 and 2018, correspond to an integrated luminosity of 9  fb^{-1}. Evidence for a new structure in the J/ψp and J/ψp[over ¯] systems with a mass of 4337_{-4}^{+7} _{-2}^{+2}  MeV and a width of 29_{-12}^{+26} _{-14}^{+14}  MeV is found, where the first uncertainty is statistical and the second systematic, with a significance in the range of 3.

Observation of New Resonances Decaying to J/ψK^{+} and J/ψϕ.

The first observation of exotic states with a new quark content cc[over ¯]us[over ¯] decaying to the J/ψK^{+} final state is reported with high significance from an amplitude analysis of the B^{+}→J/ψϕK^{+} decay. The analysis is carried out using proton-proton collision data corresponding to a total integrated luminosity of 9  fb^{-1} collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The most significant state, Z_{cs}(4000)^{+}, has a mass of 4003±6_{-14}^{+4}  MeV, a width of 131±15±26  MeV, and spin parity J^{P}=1^{+}, where the quoted uncertainties are statistical and systematic, respectively.

Observation of a New Excited D_{s}^{+} Meson in B^{0}→D^{-}D^{+}K^{+}π^{-} Decays.

Using pp collision data corresponding to an integrated luminosity of 5.4  fb^{-1} collected with the LHCb detector at a center-of-mass energy of 13 TeV, the B^{0}→D^{-}D^{+}K^{+}π^{-} decay is studied. A new excited D_{s}^{+} meson is observed decaying into the D^{+}K^{+}π^{-} final state with large statistical significance.

Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure.

Background: The cyclic AMP (adenosine monophosphate; cAMP)-hydrolyzing protein PDE4B (phosphodiesterase 4B) is a key negative regulator of cardiac β-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal Ca handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure.

Methods: We measured PDE4B expression in human cardiac tissues and developed 2 transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B and an adeno-associated virus serotype 9 encoding PDE4B.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

Background: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.

Methods: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos.

The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.

Cell fate perturbations underlie many human diseases, including breast cancer. Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors.

Observation of J/ψp Resonances Consistent with Pentaquark States in Λ_{b}^{0}→J/ψK^{-}p Decays.

Observations of exotic structures in the J/ψp channel, which we refer to as charmonium-pentaquark states, in Λ_{b}^{0}→J/ψK^{-}p decays are presented. The data sample corresponds to an integrated luminosity of 3 fb^{-1} acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis of the three-body final state reproduces the two-body mass and angular distributions.

Observation of two new Ξ(b)(-) baryon resonances.

Two structures are observed close to the kinematic threshold in the Ξ(b)(0)π(-) mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0  fb(-1), recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content bds are expected in this mass region: the spin-parity J(P)=(1/2)(+) and J(P)=(3/2)(+) states, denoted Ξ(b)('-) and Ξ(b)(*-).

First observation of the decay Bs2*(5840)(0)→B*+ K- and studies of excited Bs(0) mesons.

The properties of the orbitally excited (L=1) Bs(0) states are studied by using 1.0  fb(-1) of pp collisions at sqrt[s]=7  TeV collected with the LHCb detector. The first observation of the Bs2*(5840)(0) meson decaying to B*+ K- is reported, and the corresponding branching fraction measured relative to the B+ K- decay mode.

Interferon for interferon naive patients with chronic hepatitis C.

Background: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported.

Objectives: To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated.

Interferon for acute hepatitis C.

Background: Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C.

Objectives: The aim of this review was to assess the efficacy of interferon in acute HCV infection.