MicroRNA Profiling during Cardiomyocyte-Specific Differentiation of Murine Embryonic Stem Cells Based on Two Different miRNA Array Platforms

MicroRNA (miRNA) plays a critical role in a wide variety of biological processes. Profiling miRNA expression during differentiation of embryonic stem cells will help to understand the regulation pathway of differentiation, which in turn may elucidate disease mechanisms. The identified miRNAs could then serve as a new group of possible therapeutic targets. In the present paper, miRNA expression profiles were determined during cardiomyocyte-specific differentiation and maturation of murine embryonic stem (ES) cells. For this purpose a homogeneous cardiomyocyte population was generated from a transgenic murine ES cell line. Two high throughput array platforms (Affymetrix and Febit) were used for miRNA profiling in order to compare the effect of the platforms on miRNA profiling as well as to increase the validity of target miRNA identification. Four time points (i.e. day 0, day 12, day 19 and day 26) were chosen for the miRNA profiling study, which corresponded to different stages during cardiomyocyte-specific differentiation and maturation. Fifty platform and pre-processing method-independent miRNAs were identified as being regulated during the differentiation and maturation processes. The identification of these miRNAs is an important step for characterizing and understanding the events involved in cardiomyocyte-specific differentiation of ES cells and may also highlight candidate target molecules for therapeutic purposes

Observation of B(s)0→J/ψpp¯ decays and precision measurements of the B(s)0 masses

The first observation of the decays B 0 ( s ) → J / ψ p ¯ p is reported, using proton-proton collision data corresponding to an integrated luminosity of 5.2     fb − 1 , collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are B ( B 0 → J / ψ p ¯ p ) = [ 4.51 ± 0.40 ( stat ) ± 0.44 ( syst ) ] × 10 − 7 , B ( B 0 s → J / ψ p ¯ p ) = [ 3.58 ± 0.19 ( stat ) ± 0.39 ( syst ) ] × 10 − 6 . For the B 0 s meson, the result is much higher than the expected value of O ( 10 − 9 ) . The small available phase space in these decays also allows for the most precise single measurement of both the B 0 mass as 5279.74 ± 0.30 ( stat ) ± 0.10 ( syst )     MeV and the B 0 s mass as 5366.85 ± 0.19 ( stat ) ± 0.13 ( syst )     MeV

Test of lepton universality in b→sℓ+ℓ−b \rightarrow s \ell^+ \ell^- decays

The first simultaneous test of muon-electron universality using $B^{+}\rightarrow K^{+}\ell^{+}\ell^{-}$ and $B^{0}\rightarrow K^{*0}\ell^{+}\ell^{-}$ decays is performed, in two ranges of the dilepton invariant-mass squared, $q^{2}$. The analysis uses beauty mesons produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 $\mathrm{fb}^{-1}$. Each of the four lepton universality measurements reported is either the first in the given $q^{2}$ interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb public pages

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

First observation of a doubly charged tetraquark and its neutral partner

A combined amplitude analysis is performed for the decays $B^0 \rightarrow \overline{D}^0 D^+_s\pi^-$ and $B^+\rightarrow D^- D^+_s\pi^+$, which are related by isospin symmetry. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13$\,\rm{TeV}$. The full data sample corresponds to an integrated luminosity of 9$\,\rm{fb^{-1}}$. Two new resonant states with masses of $2.908\pm0.011\pm0.020\,\rm{GeV}$ and widths of $0.136\pm0.023\pm0.011\,\rm{GeV}$ are observed, which decay to $D^+_s\pi^+$ and $D^+_s\pi^-$ respectively. The former state indicates the first observation of a doubly charged open-charm tetraquark state with minimal quark content $[c\bar{s}u\bar{d}]$, and the latter state is a neutral tetraquark composed of $[c\bar{s}\bar{u}d]$ quarks. Both states are found to have spin-parity $0^+$, and their resonant parameters are consistent with each other, which suggests that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb public pages

Observation of a resonant structure near the Ds+Ds−D_s^+ D_s^- threshold in the B+→Ds+Ds−K+B^+\to D_s^+ D_s^- K^+ decay

An amplitude analysis of the $B^+\to D_s^+ D_s^- K^+$ decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at centre-of-mass energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as $X(3960)$, is observed in the $D_s^+ D_s^-$ invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width and the quantum numbers of the structure are measured to be $3956\pm5\pm10$ MeV, $43\pm13\pm8$ MeV and $J^{PC}=0^{++}$, respectively, where the first uncertainties are statistical and the second systematic. The properties of the new structure are consistent with recent theoretical predictions for a state composed of $c\bar{c}s\bar{s}$ quarks. Evidence for an additional structure is found around 4140 MeV in the $D_s^+ D_s^-$ invariant mass, which might be caused either by a new resonance with the $0^{++}$ assignment or by a $J/\psi \phi\leftrightarrow D_s^+ D_s^-$ coupled-channel effect.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb public pages

Measurement of the Λb0→Λ(1520)μ+μ−\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-} differential branching fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest$q^{2}$interval,$q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb public pages

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients

Amplitude analysis of the B0 (s)! K0K0 decays and measurement of the branching fraction of the B0! K0K0 decay

The $B^0 \to K^{*0} \overline{K}^{*0}$ and $B^0_s \to K^{*0} \overline{K}^{*0}$ decays are studied using proton-proton collision data corresponding to an integrated luminosity of 3fb$^{-1}$. An untagged and time-integrated amplitude analysis of $B^0_{(s)} \to (K^+\pi^-)(K^-\pi^+)$ decays in two-body invariant mass regions of 150 MeV$/c^2$ around the $K^{*0}$ mass is performed. A stronger longitudinal polarisation fraction in the ${B^0 \to K^{*0} \overline{K}^{*0}}$ decay, ${f_L = 0.724 \pm 0.051 \,({\rm stat}) \pm 0.016 \,({\rm syst})}$, is observed as compared to ${f_L = 0.240 \pm 0.031 \,({\rm stat}) \pm 0.025 \,({\rm syst})}$ in the ${B^0_s\to K^{*0} \overline{K}^{*0}}$ decay. The ratio of branching fractions of the two decays is measured and used to determine $\mathcal{B}(B^0 \to K^{*0} \overline{K}^{*0}) = (8.0 \pm 0.9 \,({\rm stat}) \pm 0.4 \,({\rm syst})) \times 10^{-7}$.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2019-004.html (LHCb public pages