Interactions between ribosomal proteins (rproteins) and ribosomal RNA (rRNA) facilitate the formation of functional ribosomes. S15 is a central domain primary binding protein that has been shown to ...trigger a cascade of conformational changes in 16S rRNA, forming the functional structure of the central domain. Previous biochemical and structural studies in vitro have revealed that S15 binds a three-way junction of helices 20, 21, and 22, including nucleotides 652–654 and 752–754. All junction nucleotides except 653 are highly conserved among the Bacteria. To identify functionally important motifs within the junction, we subjected nucleotides 652–654 and 752–754 to saturation mutagenesis and selected and analyzed functional mutants. Only 64 mutants with greater than 10% ribosome function in vivo were isolated. S15 overexpression complemented mutations in the junction loop in each of the partially active mutants, although mutations that produced inactive ribosomes were not complemented by overexpression of S15. Single-molecule Förster or fluorescence resonance energy transfer (smFRET) was used to study the Mg2+- and S15-induced conformational dynamics of selected junction mutants. Comparison of the structural dynamics of these mutants with the wild type in the presence and absence of S15 revealed specific sequence and structural motifs in the central junction that are important in ribosome function.
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•Study identified sequence, structure, and dynamic requirements of central junction.•Cross-junction interactions especially a Watson–Crick base pair of 654:754 are required.•Loss of ribosome function is linked to decreased and improper 30S assembly.•Central domain folding requires S15, Mg2+, and an ability to pivot at junction.•Comprehensive results of central junction study can aid new antibiotic development.
Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among ...drip and ship patients.
Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic.
We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27).
This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.
Multiple myeloma (MM) is accompanied by alterations to the normal plasma cell (PC) proteome, leading to changes to the tumor microenvironment and disease progression. There is a great need for ...understanding the consequences that lead to MM progression and for the discovery of new biomarkers that can aid clinical diagnostics and serve as targets for therapeutics. This study demonstrates the applicability of utilizing the single-cell high-definition liquid biopsy assay (HDSCA) and imaging mass cytometry to characterize the proteomic profile of myeloma. In our study, we analyzed ~87,000 cells from seven patient samples (bone marrow and peripheral blood) across the myeloma disease spectrum and utilized our multiplexed panel to characterize the expression of clinical markers for PC classification, additional potential therapeutic targets, and the tumor microenvironment cells. Our analysis showed BCMA, ICAM3 (CD50), CD221, and CS1 (SLAMF7) as the most abundantly expressed markers on PCs across all myeloma stages, with BCMA, ICAM3, and CD221 having significantly higher expression levels on disease versus precursor PCs. Additionally, we identify significantly elevated levels of expression for CD74, MUM1, CD229, CD44, IGLL5, Cyclin D1, UBA52, and CD317 on PCs from overt disease conditions compared to those from precursor states.
To analyze which ethically relevant biases have been identified by academic literature in artificial intelligence (AI) algorithms developed either for patient risk prediction and triage, or for ...contact tracing to deal with the COVID-19 pandemic. Additionally, to specifically investigate whether the role of social determinants of health (SDOH) have been considered in these AI developments or not. We conducted a scoping review of the literature, which covered publications from March 2020 to April 2021. Studies mentioning biases on AI algorithms developed for contact tracing and medical triage or risk prediction regarding COVID-19 were included. From 1054 identified articles, 20 studies were finally included. We propose a typology of biases identified in the literature based on bias, limitations and other ethical issues in both areas of analysis. Results on health disparities and SDOH were classified into five categories: racial disparities, biased data, socio-economic disparities, unequal accessibility and workforce, and information communication. SDOH needs to be considered in the clinical context, where they still seem underestimated. Epidemiological conditions depend on geographic location, so the use of local data in studies to develop international solutions may increase some biases. Gender bias was not specifically addressed in the articles included. The main biases are related to data collection and management. Ethical problems related to privacy, consent, and lack of regulation have been identified in contact tracing while some bias-related health inequalities have been highlighted. There is a need for further research focusing on SDOH and these specific AI apps.
The Military Macaw (Ara militaris) is not considered within the avifauna of Morelos due to a lack of solid evidence confirming the presence of the species in the state. We conducted systematic ...surveys from elevated viewpoints in the tropical dry forest of the Sierra de Huautla Biosphere Reserve from August to December 2017 and 2020-2022 to confirm the presence of the Military Macaw in the reserve. We obtained 36 records of the Military Macaw, with photographic evidence, and observed a mean of 10.0 ± 11.2 macaws per record, registering flocks of 32-39 individuals on three occasions. We identified sites within the reserve that Military Macaws recurrently used for resting, foraging, and roosting. We also observed macaws foraging in three tree species, with another six plant species reported in the diet by local people. We could not confirm nesting by macaws in the reserve as observations were conducted outside the breeding season. Some sightings occurred outside the biosphere reserve, in an area of the Mixteca Baja Poblana (Puebla) proposed as a new protected area. Our findings provide the first systematic and photographic evidence of the presence of the Military Macaw in Morelos state, confirm the relevance and effectivity of the Sierra de Huautla Biosphere Reserve for regional conservation of the species and the tropical dry forest, and provide additional support for the proposal to create a new protected area and conservation corridor in the Balsas Basin that could benefit the conservation of this endangered bird species.
La Guacamaya Verde (Ara militaris) no se considera dentro de la avifauna de Morelos debido a la falta de evidencia solida que confirme presencia de la especie en el estado. Realizamos censos sistemáticos, desde puntos de observación elevados, en el bosque tropical seco de la Reserva de la Biosfera Sierra de Huautla, Morelos, durante los meses de agosto a diciembre de 2017 y 2020-2022, para confirmar la presencia de la Guacamaya Verde en la reserva. Obtuvimos 36 registros de Guacamaya Verde, con evidencia fotográfica, y observamos un promedio de 10.0 ± 11.2 guacamayas por registro, registrando bandadas de 32-39 individuos en tres ocasiones. Identificamos sitios dentro de la reserva que fueron utilizados recurrentemente por la especie para descansar, alimentarse y posarse. También observamos individuos de Guacamaya Verde alimentándose de tres especies de árboles, y la población local informó sobre otras 6 especies de plantas en la dieta. No pudimos confirmar la anidación de la especie en la reserva ya que las observaciones se realizaron fuera de la temporada de reproducción. Algunos avistamientos se produjeron fuera de la reserva de la biosfera, en una zona de la Mixteca Baja Poblana (Puebla) que ha sido propuesta como nueva área protegida. Nuestros hallazgos proporcionan la primera evidencia sistemática y fotográfica de la presencia de la Guacamaya Verde en el estado de Morelos, confirman la relevancia y efectividad de la Reserva de la Biosfera Sierra de Huautla para la conservación regional de la especie y del bosque tropical seco y brindan apoyo adicional a la propuesta para crear una nueva área protegida y corredor de conservación en la Cuenca del Balsas, en beneficio de la conservación de esta especie de ave amenazada.
Ciclovía Recreativa is a program in which streets are closed off to automobiles so that people have a safe and inclusive space for recreation and for being physically active. The study aims were: (1) ...to compare participant's spatial trajectories in four Ciclovía Recreativa programs in Latin America (Bogotá, Mexico City, Santiago de Cali, and Santiago de Chile) according to socioeconomic characteristics and urban segregation of these cities; and (2) to assess the relationship between participants' physical activity (PA) levels and sociodemographic characteristics. We harmonized data of cross-sectional studies including 3282 adults collected between 2015 and 2019. We found the highest mobility for recreation in Bogotá, followed closely by Santiago de Cali. In these two cities, the maximum SES (socioeconomic status) percentile differences between the neighborhood of origin and the neighborhoods visited as part of the Ciclovía use were 33.58 (
-value < 0.001) and 30.38 (
-value < 0.001), respectively, indicating that in these two cities, participants were more likely to visit higher or lower SES neighborhoods than their average SES-of-neighborhood origin. By contrast, participants from Mexico City and Santiago de Chile were more likely to stay in geographic units similar to their average SES-of-origin, having lower overall mobility during leisure time: maximum SES percentile difference 1.55 (
-value < 0.001) and -0.91 (
-value 0.001), respectively. PA levels of participants did not differ by sex or SES. Our results suggest that Ciclovía can be a socially inclusive program in highly unequal and segregated urban environments, which provides a space for PA whilefacilitat physical proximity, exposure to new communities and environments, and interactions between different socioeconomic groups.
The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal ...adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers.
Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients.
This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018.
Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 interquartile range (IQR) 60-73 years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS.
Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT.
The global polarization of the Λ and Λ hyperons is measured for Pb-Pb collisions at sNN=2.76 and 5.02 TeV recorded with the ALICE at the Large Hadron Collider (LHC). The results are reported ...differentially as a function of collision centrality and hyperon's transverse momentum (pT) for the range of centrality 5-50%, 0.5<pT<5 GeV/c, and rapidity |y|<0.5. The hyperon global polarization averaged for Pb-Pb collisions at sNN=2.76 and 5.02 TeV is found to be consistent with zero, (PH)(%)≈0.01±0.06(stat.)±0.03(syst.) in the collision centrality range 15-50%, where the largest signal is expected. The results are compatible with expectations based on an extrapolation from measurements at lower collision energies at the Relativistic Heavy Ion Collider, hydrodynamical model calculations, and empirical estimates based on collision energy dependence of directed flow, all of which predict the global polarization values at LHC energies of the order of 0.01%.
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