Chagas Cardiomyopathy Manifestations and Trypanosoma cruzi Genotypes Circulating in Chronic Chagasic Patients

Chagas disease caused by Trypanosoma cruzi is a complex disease that is endemic and an important problem in public health in Latin America. The T. cruzi parasite is classified into six discrete taxonomic units (DTUs) based on the recently proposed nomenclature (TcI, TcII, TcIII, TcIV, TcV and TcVI). The discovery of genetic variability within TcI showed the presence of five genotypes (Ia, Ib, Ic, Id and Ie) related to the transmission cycle of Chagas disease. In Colombia, TcI is more prevalent but TcII has also been reported, as has mixed infection by both TcI and TcII in the same Chagasic patient. The objectives of this study were to determine the T. cruzi DTUs that are circulating in Colombian chronic Chagasic patients and to obtain more information about the molecular epidemiology of Chagas disease in Colombia. We also assessed the presence of electrocardiographic, radiologic and echocardiographic abnormalities with the purpose of correlating T. cruzi genetic variability and cardiac disease. Molecular characterization was performed in Colombian adult chronic Chagasic patients based on the intergenic region of the mini-exon gene, the 24Sα and 18S regions of rDNA and the variable region of satellite DNA, whereby the presence of T.cruzi I, II, III and IV was detected. In our population, mixed infections also occurred, with TcI-TcII, TcI-TcIII and TcI-TcIV, as well as the existence of the TcI genotypes showing the presence of genotypes Ia and Id. Patients infected with TcI demonstrated a higher prevalence of cardiac alterations than those infected with TcII. These results corroborate the predominance of TcI in Colombia and show the first report of TcIII and TcIV in Colombian Chagasic patients. Findings also indicate that Chagas cardiomyopathy manifestations are more correlated with TcI than with TcII in Colombia

Luminosity determination using Z boson production at the CMS experiment

Data Availability Statement - This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preser vation of data used by the CMS Collaboration as the basis for publi cations is guidedbytheCMSpolicyasstatedinhttps://cms-docdb.cern. ch/cgibin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSD ataPolicyV1.2.pdf&version=2. CMS data preservation,re-use and open access policy.]The measurement of Z boson production is presented as a method to determine the integrated luminosity of CMS data sets. The analysis uses proton–proton collision data, recorded by the CMS experiment at the CERN LHC in 2017 at a center-of-mass energy of 13 TeV . Events with Z bosons decaying into a pair of muons are selected. The total number of Z bosons produced in a fiducial volume is determined, together with the identification efficiencies and correlations from the same data set, in small intervals of 20 pb-1 of integrated luminosity, thus facilitating the efficiency and rate measurement as a function of time and instantaneous luminosity. Using the ratio of the efficiency-corrected numbers of Z bosons, the precisely measured integrated luminosity of one data set is used to determine the luminosity of another. For the first time, a full quantitative uncertainty analysis of the use of Z bosons for the integrated luminosity measurement is performed. The uncertainty in the extrapolation between two data sets, recorded in 2017 at low and high instantaneous luminosity, is less than 0.5%. We show that the Z boson rate measurement constitutes a precise method, complementary to traditional methods, with the potential to improve the measurement of the integrated luminosity.SCOAP

Search for ZZ and ZH production in the bb̅bb̅ final state using proton-proton collisions at √s = 13TeV

A preprint version of the article is available at arXiv - https://arxiv.org/abs/2403.20241A search for ZZ and ZH production in the bb̅bb̅ final state is presented, where H is the standard model (SM) Higgs boson. The search uses an event sample of proton-proton collisions corresponding to an integrated luminosity of 133fb−1 collected at a center-of-mass energy of 13TeV with the CMS detector at the CERN LHC. The analysis introduces several novel techniques for deriving and validating a multi-dimensional background model based on control samples in data. A multiclass multivariate classifier customized for the bb̅bb̅ final state is developed to derive the background model and extract the signal. The data are found to be consistent, within uncertainties, with the SM predictions. The observed (expected) upper limits at 95% confidence level are found to be 3.8 (3.8) and 5.0 (2.9) times the SM prediction for the ZZ and ZH production cross sections, respectively.SCOAP

Search for nonresonant Higgs boson pair production in the four leptons plus two b jets final state in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.10657v2 [hep-ex], https://arxiv.org/abs/2206.10657 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at this http URL (CMS Public Pages). Report number: CMS-HIG-20-004, CERN-EP-2022-114.The first search for nonresonant production of Higgs boson pairs (HH) with one H decaying into four leptons and the other into a pair of b quarks is presented, using proton-proton collisions recorded at a center-of-mass energy of s = 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 138 fb−1. A 95% confidence level upper limit of 32.4 is set on the signal strength modifier μ, defined as the ratio of the observed HH production rate in the HH→ ZZ∗b b ¯ → 4 ℓb b ¯ decay channel to the standard model (SM) expectation. Possible modifications of the H trilinear coupling λ HHH with respect to the SM value are investigated. The coupling modifier κλ, defined as λ HHH divided by its SM prediction, is constrained to be within the observed (expected) range −8.8 (−9.8) < κλ < 13.4 (15.0) at 95% confidence level. [Figure not available: see fulltext.].SCOAP3

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at s = 13 TeV

A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp→tH/A→ttc‾ and pp→tH/A→ttu‾ processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200–1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM

Search for flavor changing neutral current interactions of the top quark in final states with a photon and additional jets in proton-proton collisions at s=13 TeV

A search for the production of a top quark in association with a photon and additional jets via flavor changing neutral current interactions is presented. The analysis uses proton-proton collision data recorded by the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of Formula Presented. The search is performed by looking for processes where a single top quark is produced in association with a photon, or a pair of top quarks where one of the top quarks decays into a photon and an up or charm quark. Events with an electron or a muon, a photon, one or more jets, and missing transverse momentum are selected. Multivariate analysis techniques are used to discriminate signal and standard model background processes. No significant deviation is observed over the predicted background. Observed (expected) upper limits are set on the branching fractions of top quark decays: Formula Presented (Formula Presented) and Formula Presented (Formula Presented) at 95% confidence level, assuming a single nonzero coupling at a time. The obtained limit for Formula Presented is similar to the current best limit, while the limit for Formula Presented is significantly tighter than previous results

Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fármaco/gen en América Latina y el Caribe

La farmacogenómica (PGx) se considera un campo emergente en los países en desarrollo. La investigación sobre PGx en la región de América Latina y el Caribe (ALC) sigue siendo escasa, con información limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenómico entre la comunidad científica y clínica de ALC y examinamos las barreras para la aplicación clínica. Realizamos una búsqueda de publicaciones y ensayos clínicos en este campo en todo el mundo y evaluamos la contribución de ALC. A continuación, realizamos una encuesta regional estructurada que evaluó una lista de 14 barreras potenciales para la aplicación clínica de biomarcadores en función de su importancia. Además, se analizó una lista emparejada de 54 genes/fármacos para determinar una asociación entre los biomarcadores y la respuesta a la medicina genómica. Esta encuesta se comparó con una encuesta anterior realizada en 2014 para evaluar el progreso en la región. Los resultados de la búsqueda indicaron que los países de América Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clínicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 países respondieron a la encuesta. Se identificaron seis grandes grupos de obstáculos. A pesar de los continuos esfuerzos de la región en la última década, la principal barrera para la implementación de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicación clínica de la farmacogenética/farmacogenómica". Las cuestiones de coste-eficacia se consideran factores críticos en la región. Los puntos relacionados con la reticencia de los clínicos son actualmente menos relevantes. Según los resultados de la encuesta, los pares gen/fármaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricíclicos, CYP2C19/antidepresivos tricíclicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusión, aunque la contribución global de los países de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la región. La percepción de la utilidad de las pruebas PGx en la comunidad biomédica ha cambiado drásticamente, aumentando la concienciación entre los médicos, lo que sugiere un futuro prometedor en las aplicaciones clínicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

An Updated Examination of the Perception of Barriers for Pharmacogenomics Implementation and the Usefulness of Drug/Gene Pairs in Latin America and the Caribbean

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2301.08096v2 [hep-ex], https://arxiv.org/abs/2301.08096 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-003 (CMS Public Pages).A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (t ~1), is presented. The search targets the four-body decay of the t ~1 , which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (χ~10), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(t ~1) and m(χ~10). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(t ~1) − m(χ~10) = 10 and 80 GeV, respectively. [Figure not available: see fulltext.].SCOAP3