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Three billion years of evolution has produced a tremendous diversity of protein molecules 1 , but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions. To enable this, we introduce a diffusion process that respects the conformational statistics of polymer ensembles, an efficient neural architecture for molecular systems that enables long-range reasoning with sub-quadratic scaling, layers for efficiently synthesizing three-dimensional structures of proteins from predicted inter-residue geometries and a general low-temperature sampling algorithm for diffusion models. Chroma achieves protein design as Bayesian inference under external constraints, which can involve symmetries, substructure, shape, semantics and even natural-language prompts. The experimental characterization of 310 proteins shows that sampling from Chroma results in proteins that are highly expressed, fold and have favourable biophysical properties. The crystal structures of two designed proteins exhibit atomistic agreement with Chroma samples (a backbone root-mean-square deviation of around 1.0 Å). With this unified approach to protein design, we hope to accelerate the programming of protein matter to benefit human health, materials science and synthetic biology. Evolution has produced a range of diverse proteins, and now a generative model called Chroma can expand that set by allowing the user to design new proteins and protein complexes with desired properties and functions.

La inclusión financiera se ha convertido en un instrumento dentro de las políticas públicas que ejercen los países en busca de garantizar el acceso a servicios financieros. En Colombia se ha desarrollado el programa “Banca de las Oportunidades” con este propósito. Sin embargo, el programa no analiza el alcance de estos procesos en el bienestar de la población. En este artículo se analizan los efectos de la inclusión financiera en el desarrollo del departamento del Huila. En este sentido, se implementó una metodología mixta, mediante el método DEXPLIS; en la fase cuantitativa se estimó y analizó un modelo estadístico multivariado, a fin de determinar si existe relación entre inclusión financiera y desarrollo; en la fase cualitativa se aplicaron entrevistas a funcionarios de la Gobernación del Huila. Las técnicas de recolección de información fueron revisión de literatura, bases estadísticas y guía de entrevista. Dentro de los resultados obtenidos se determinó que existe una relación positiva entre el Índice de Desarrollo Humano (IDH) y los indicadores de inclusión financiera. Adicionalmente, se identificó que los indicadores de acceso y de uso repercuten en las dimensiones de salud, educación e ingreso siempre y cuando se garantice el uso de los productos y los servicios financieros.

Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5–17 years, 18–49 years, and ≥50 years). The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3–12·9) of IPD cases in children younger than 5 years and 15·5% (13·4–19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2–65·4) and 45·6% (40·0–50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3–30·0) of IPD cases in children younger than 5 years and 29·5% (27·5–33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2–43·1]) and adults aged 50 years or older (14·8% [11·9–17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1–9·7% for PCV15, 13·5–36·0% for PCV20, 29·9–53·8% for PCV21, 15·6–42·0% for PCV24, and 31·5–50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Canopy lianas differ considerably from trees in terms of wood anatomical structure, and they are suggested to have a demographic advantage—faster growth and higher survival—than trees. However, it remains unclear whether these anatomical and demographic differences persist at the seedling stage, when most liana species are self-standing and, consequently, might be ecologically similar to trees. We assessed how self-standing liana and tree seedlings differ in relation to wood anatomy, growth, and survival. We measured 12 wood traits and monitored seedling growth and survival over one year for 10 self-supporting liana and 10 tree seedling species from three tropical dry forests in Colombia. Liana and tree seedlings exhibited similar survival rates and wood anatomies for traits related to water storage and mechanical support. Yet, for traits associated with water transport, liana seedlings showed greater variability in vessel lumen size, while tree seedlings had higher vessel density. Also, the liana relative growth rate was significantly higher than for trees. These results indicate that, while self-supporting liana and tree seedlings are anatomically similar in terms of mechanical support and water storage—likely contributing to their similar survival rates—liana seedlings have a growth advantage, possibly due to more efficient water transport. These findings suggest that the well-documented anatomical and demographic differences between adult lianas and trees may depend on the liana’s developmental stage, with more efficient water transport emerging as a key trait from early stages.

Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83–99% decline; ≥65 years: 54–96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61–79% decline relative to before any PCV; age ≥65 years: 7–26% decline) but increased at PCV10 sites (age <5 years: 1·6–2·3-fold; age ≥65 years: 3·6–4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3–3·3-fold; age ≥65 years: 1·7–2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58–74%); among adults aged 65 years or older, declines were greater at PCV13 (25–29%) than PCV10 (4–14%) sites, but other differences between sites precluded attribution to product. Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality. In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality. A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84–1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36–0.86). We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions. •A large Colombian COVID-19 patients' cohort studied among 3 epidemic waves.•Less hospitalization in ≥65 and comorbid patients for the 3rd epidemic wave.•No association between in-hospital-mortality and the 3rd epidemic wave.•Lower hazard for mortality in ≥75 in the 3rd epidemic probably due to vaccination.

Background Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population. Methods The MeSO‐CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first‐line chemotherapy among Latin American patients. Results The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first‐line platinum‐based chemotherapy. The overall response rate to first‐line chemotherapy was 40.4%, progression‐free survival to first‐line treatment was 5.7 months (95% CI 4.9–6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0–20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first‐line overall survival. The model to predict response to first‐line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non‐responders. Conclusion This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.

INTRODUCCIÓN: La vitamina D actúa en múltiples tejidos y procesos fisiológicos. El objetivo del estudio fue determinar los niveles de vitamina D en pacientes con epilepsia tratados con anticonvulsivantes. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, de corte transversal en pacientes con diagnóstico de epilepsia que asistieron al servicio de consulta externa de un hospital de tercer nivel de atención de Neiva, Colombia, entre marzo y octubre de 2018. Se midieron los niveles séricos de vitamina D, paratohormona, albúmina y calcio. RESULTADOS: Una muestra de 90 pacientes. La mediana de edad fue de 36,5 (rango 18-81 años), 46 (51,1%) presentaron niveles bajos de vitamina D (38,8% en rango de insuficiencia y 12,2% rango de deficiencia). Se documentó asociación entre el sexo femenino y niveles insuficientes y deficientes de vitamina D, el no realizar ejercicio con niveles insuficientes de vitamina D, la exposición diaria al sol menor de 15 minutos y el no realizar caminata con niveles deficientes de vitamina D. El déficit de vitamina D se asoció con incremento de los niveles de paratohormona, mediana 103,9 pg/ml (rango 30,7-182,9 pg/ml, P <0,01). No se encontraron diferencias entre los niveles de vitamina D y el uso de monoterapia, politerapia, ni con la utilización fármacos inductores enzimáticos. CONCLUSIONES: En pacientes con terapia anticonvulsivante es frecuente encontrar niveles insuficientes/ deficientes de vitamina D aunque no se encontró asociación con el uso de monoterapia, politerapia o inductores enzimáticos hepáticos.

INTRODUCTION:Vitamin D acts in many tissues and different physiological processes. The objective was to determine vitamin D levels in patients with epilepsy treated with anticonvulsants.MATERIALS AND METHOD:Observational, descriptive, cross-section study in consecutive patients with epilepsy who attended the Neurology outpatient service of a university hospital in Neiva, Colombia, between March and October 31, 2018. We obtained serum levels of vitamin D, parathormone, albumin and calcium.RESULTS:There were 90 patients with a median age of 36.5 (range 18-81 years), 46 (51.1%) had low levels of vitamin D (38.8% in the range of insufficiency and 12.2% with deficiency). Females had more insufficient and deficient levels of vitamin D; not exercising was associated with insufficient levels of vitamin D, daily exposure to the sun under 15 minutes and not walking, with deficient levels of vitamin D. Vitamin D deficiency was associated with an increase in parathyroid hormone levels, median 103.9 pg / ml (range 30.7 - 182.9 pg / ml, P <0.01). No difference was found between vitamin D levels and the use of monotherapy, polytherapy, or the use of enzyme-inducing drugs.CONCLUSIONS:In epileptic patients with anticonvulsants it is common to find insufficient / deficient levels of vitamin D although we found no association with the use of monotherapy, polytherapy or hepatic enzyme inducers.