The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Amplitude analysis and branching fraction measurement of D+s→K−K+π+π0

Relative fractions and phases of the intermediate decays are determined. With the detection efficiency estimated by the results of the amplitude analysis, the branching fraction of Dþ s → K−Kþπþπ0 decay is measured to be ð5.42 0.10stat 0.17systÞ%

Measurements of the center-of-mass energies of e+e- collisions at BESIII

During the 2016-17 and 2018-19 running periods, the BESIII experiment collected 7.5 fb -1 of e+e− collision data at center-of-mass energies ranging from 4.13 to 4.44 GeV. These data samples are primarily used for the study of excited charmonium and charmoniumlike states. By analyzing the di-muon process e+e− (γISR/FSR)µ -> +µ-, we measure the center-of-mass energies of the data samples with a precision of 0.6 MeV. Through a run-by-run study, we find that the center-of-mass energies were stable throughout most of the data-collection period

Measurements of the center-of-mass energies of e+e− collisions at BESIII

During the 2016-17 and 2018-19 running periods, the BESIII experiment collected 7.5~fb−1 of e+e− collision data at center-of-mass energies ranging from 4.13 to 4.44~GeV. These data samples are primarily used for the study of excited charmonium and charmoniumlike states. By analyzing the di-muon process e+e−→(γISR/FSR)μ+μ−, we measure the center-of-mass energies of the data samples with a precision of 0.6 MeV. Through a run-by-run study, we find that the center-of-mass energies were stable throughout most of the data-taking period

Measurement of cross section for e+⁢e−→Ξ−⁢¯Ξ+ near threshold at BESIII

The Born cross sections and effective form factors for process +⁢−→Ξ−⁢¯Ξ+ are measured at eight center-of-mass energies between 2.644 and 3.080 GeV, using a total integrated luminosity of 363.9  pb−1 +⁢− collision data collected with the BESIII detector at BEPCII. After performing a fit to the Born cross section of +⁢−→Ξ−⁢¯Ξ+, no significant threshold effect is observed

Search for an axion-like particle in radiative J/ψ decays

We search for an axion-like particle (ALP) a through the process ψ(3686)→π+π−J/ψ, J/ψ→γa, a→γγ in a data sample of (2.71±0.01)×109 ψ(3686) events collected by the BESIII detector. No significant ALP signal is observed over the expected background, and the upper limits on the branching fraction of the decay J/ψ→γa and the ALP-photon coupling constant gaγγ are set at 95% confidence level in the mass range of 0.165≤ma≤2.84GeV/c2. The limits on B(J/ψ→γa) range from 8.3×10−8 to 1.8×10−6 over the search region, and the constraints on the ALP-photon coupling are the most stringent to date for 0.165≤ma≤1.468GeV/c2

Observation of the decay D_(s)⁺ → ωπ⁺η

Using 7.33 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.128 and 4.226~GeV, we observe for the first time the decay D±s→ωπ±η with a statistical significance of 7.6σ. The measured branching fraction of this decay is (0.54±0.12±0.04)%, where the first uncertainty is statistical and the second is systematic

Measurement of e+e− → ηJ/ψ cross section from √s= 3.808 GeV to 4.951 GeV

Using data samples with an integrated luminosity of 22.42  fb−1 collected by the BESIII detector operating at the BEPCII storage ring, we measure the cross sections of the +⁢−→⁢/ process at center-of-mass energies from 3.808 to 4.951 GeV. Three structures are observed in the line shape of the measured cross sections. A maximum-likelihood fit with ⁡(4040), two additional resonances, and a nonresonant component are performed. The mass and width of the first additional state are (4219.7±2.5±4.5)  MeV/2 and (80.7±4.4±1.4)  MeV, respectively, consistent with the ⁡(4230). For the second state, the mass and width are (4386±13±17)  MeV/2 and (177±32±13)  MeV, respectively, consistent with the ⁡(4360). The first uncertainties are statistical, and the second ones are systematic. The statistical significance of ⁡(4040) is 8.0⁢ and those for ⁡(4230) and ⁡(4360) are more than 10.0⁢

Observation of the anomalous shape of X(1840) in J/ψ → γ3(π⁺π^(−)) indicating a second resonance Near pp̄ threshold

Using a sample of (10087±44)×106 J/ψ events, which is about 45 times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π+π−) decay is performed. A significant distortion at 1.84 GeV/c2 in the line-shape of the 3(π+π−) invariant mass spectrum is observed for the first time, which could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance larger than 10σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c2 and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp¯ bound state