Development of a DNA aptamer for direct and selective homocysteine detection in human serum

l-Homocysteine has been an amino acid intermediate of interest for over 20 years due to its implication in various adverse health conditions, including cardiovascular disease. Here, we report the first in vitro selection and application of high affinity aptamers for the target l-homocysteine. Two novel aptamer sequences were selected following 8 rounds of selection that displayed high affinity binding and selectivity to homocysteine compared to other amino acids. One of the selected aptamers, Hcy 8 (KD = 600 ± 300 nM), was used to develop a gold-nanoparticle biosensor capable of sensitive and selective homocysteine detection in human serum, with a limit of detection of 0.5 μM and a linear range of 0.5-3.0 μM. This biosensor allows rapid detection of free homocysteine in human serum samples at low cost, with little preparation time and could be adapted to be part of a po

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Measurement of the Branching Fraction of B0→J/ψπ0B^{0} \rightarrow J/\psi \pi^{0} Decays

International audienceThe ratio of branching fractions between $B^{0} \rightarrow J/\psi \pi^{0}$ and $B^{+} \rightarrow J/\psi K^{*+}$ decays is measured with proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9 fb$^{-1}$. The measured value is $\frac{\mathcal{B}_{B^{0} \rightarrow J/\psi \pi^{0}}}{\mathcal{B}_{B^{+} \rightarrow J/\psi K^{*+}}} = (1.153 \pm 0.053 \pm 0.048 ) \times 10^{-2}$, where the first uncertainty is statistical and the second is systematic. The branching fraction for $B^{0} \rightarrow J/\psi \pi^{0}$ decays is determined using the branching fraction of the normalisation channel, resulting in $\mathcal{B}_{B^{0} \rightarrow J/\psi \pi^{0}} = (1.670 \pm 0.077 \pm 0.069 \pm 0.095) \times 10^{-5}$, where the last uncertainty corresponds to that of the external input. This result is consistent with the current world average value and competitive with the most precise single measurement to date

First observation and branching fraction measurement of the Λb0→Ds−p {\Lambda}_b^0\to {D}_s^{-}p decay

International audienceThe first observation of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is presented using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}$ = 13 TeV, corresponding to a total integrated luminosity of 6 fb$^{−1}$. Using the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$ decay as the normalisation mode, the branching fraction of the ${\Lambda}_b^0\to {D}_s^{-}p$ decay is measured to be $\mathcal{B}\left({\Lambda}_b^0\to {D}_s^{-}p\right)=\left(12.6\pm 0.5\pm 0.3\pm 1.2\right)\times {10}^{-6}$, where the first uncertainty is statistical, the second systematic and the third due to uncertainties in the branching fractions of the ${\Lambda}_b^0\to {\Lambda}_c^{+}{\pi}^{-}$, ${D}_s^{-}\to {K}^{-}{K}^{+}{\pi}^{-}$ and ${\Lambda}_c^{+}\to p{K}^{-}{\pi}^{+}$ decays.[graphic not available: see fulltext

Observation of the Bs0 ⁣→D∗+D∗−B^0_s\!\to D^{*+}D^{*-} decay

International audienceThe first observation of the ${B}_s^0$→ D$^{∗+}$D$^{∗−}$ decay and the measurement of its branching ratio relative to the B$^{0}$→ D$^{∗+}$D$^{∗−}$ decay are presented. The data sample used corresponds to an integrated luminosity of 9 fb$^{−1}$ of proton-proton collisions recorded by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV between 2011 and 2018. The decay is observed with more than 10 standard deviations and the time-integrated ratio of branching fractions is determined to be$\frac{\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)}{\mathcal{B}\left({B}^0\to {D}^{\ast +}{D}^{\ast -}\right)}=0.269\pm 0.032\pm 0.011\pm 0.008,$where the first uncertainty is statistical, the second systematic and the third due to the uncertainty of the fragmentation fraction ratio f$_{s}$/f$_{d}$. The ${B}_s^0$→ D$^{*+}$D$^{*−}$ branching fraction is calculated to be$\mathcal{B}\left({B}_s^0\to {D}^{\ast +}{D}^{\ast -}\right)=\left(2.15\pm 0.26\pm 0.09\pm 0.06\pm 0.16\right)\times {10}^{-4},$where the fourth uncertainty is due to the B$^{0}$→ D$^{*+}$D$^{*−}$ branching fraction. These results are calculated using the average ${B}_s^0$ meson lifetime in simulation. Correction factors are reported for scenarios where either a purely heavy or a purely light ${B}_s^0$ eigenstate is considered.[graphic not available: see fulltext

A study of C ⁣PC\!P violation in the decays B±→[K+K−π+π−]Dh±B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm} (h=K,πh = K, \pi) and B±→[π+π−π+π−]Dh±B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^{\pm}

The first study of $C\!P$ violation in the decay mode $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm}$, with $h=K,\pi$, is presented, exploiting a data sample of proton-proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9$ fb$^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^{\pm}$ and $B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^{\pm}$ decays.The first study of $C\!P$ violation in the decay mode {{B} ^\pm } \rightarrow [{{K} ^+} {{K} ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm , with $h=K,\pi$, is presented, exploiting a data sample of proton–proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9\text {\,fb} ^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for {{B} ^\pm } \rightarrow [{{K} ^+} {{K} ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm and {{B} ^\pm } \rightarrow [{{\uppi } ^+} {{\uppi } ^-} {{\uppi } ^+} {{\uppi } ^-} ]_{D} h^\pm decays.The first study of $C\!P$ violation in the decay mode $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^\pm$, with $h=K,\pi$, is presented, exploiting a data sample of proton-proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of $9$ fb$^{-1}$. The analysis is performed in bins of phase space, which are optimised for sensitivity to local $C\!P$ asymmetries. $C\!P$-violating observables that are sensitive to the angle $\gamma$ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for $B^\pm\to[K^+K^-\pi^+\pi^-]_D h^\pm$ and $B^\pm\to[\pi^+\pi^-\pi^+\pi^-]_D h^\pm$ decays

Measurement of the <math display="inline"><mrow><msubsup><mrow><mi mathvariant="normal">Λ</mi></mrow><mrow><mi>b</mi></mrow><mrow><mn>0</mn></mrow></msubsup><mo stretchy="false">→</mo><mi mathvariant="normal">Λ</mi><mo stretchy="false">(</mo><mn>1520</mn><mo stretchy="false">)</mo><msup><mrow><mi>μ</mi></mrow><mrow><mo>+</mo></mrow></msup><msup><mrow><mi>μ</mi></mrow><mrow><mo>-</mo></mrow></msup></mrow></math> 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.The branching fraction of the rare decay Λb0→Λ(1520)μ+μ- is measured for the first time, in the squared dimuon mass intervals q2, excluding the J/ψ and ψ(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  fb-1. The result in the highest q2 interval, q2&gt;15.0  GeV2/c4, where theoretical predictions have the smallest model dependence, agrees with the predictions.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

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$

First observation of the <math display="inline"><msup><mi>B</mi><mo>+</mo></msup><mo stretchy="false">→</mo><msubsup><mi>D</mi><mi>s</mi><mo>+</mo></msubsup><msubsup><mi>D</mi><mi>s</mi><mo>-</mo></msubsup><msup><mi>K</mi><mo>+</mo></msup></math> decay

International audienceThe B+→Ds+Ds-K+ decay is observed for the first time using proton-proton collision data collected by the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV, corresponding to an integrated luminosity of 9  fb-1. Its branching fraction relative to that of the B+→D+D-K+ decay is measured to be B(B+→Ds+Ds-K+)B(B+→D+D-K+)=0.525±0.033±0.027±0.034, where the first uncertainty is statistical, the second systematic, and the third is due to the uncertainties on the branching fractions of the Ds±→K∓K±π± and D±→K∓π±π± decays. This measurement fills an experimental gap in the knowledge of the family of Cabibbo-favored b¯→c¯cs¯ transitions and opens the path for unique studies of spectroscopy in future