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Phages are one of the key ecological drivers of microbial community dynamics, function, and evolution. Despite their importance in bacterial ecology and evolutionary processes, phage genes are poorly characterized, hampering their usage in a variety of biotechnological applications. Methods to characterize such genes, even those critical to the phage life cycle, are labor intensive and are generally phage specific. Here, we develop a systematic gene essentiality mapping method scalable to new phage-host combinations that facilitate the identification of nonessential genes. As a proof of concept, we use an arrayed genome-wide CRISPR interference (CRISPRi) assay to map gene essentiality landscape in the canonical coliphages λ and P1. Results from a single panel of CRISPRi probes largely recapitulate the essential gene roster determined from decades of genetic analysis for lambda and provide new insights into essential and nonessential loci in P1. We present evidence of how CRISPRi polarity can lead to false positive gene essentiality assignments and recommend caution towards interpreting CRISPRi data on gene essentiality when applied to less studied phages. Finally, we show that we can engineer phages by inserting DNA barcodes into newly identified inessential regions, which will empower processes of identification, quantification, and tracking of phages in diverse applications.
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Bacteriófagos , Bacteriófagos/genética , DNA , Genes Essenciais/genéticaRESUMO
Mixed tin-lead (Sn-Pb) halide perovskites stand out as promising materials for next-generation photovoltaics and near-infrared optoelectronics. However, their sensitivity to oxidative degradation remains a major hurdle toward their widespread deployment. A holistic understanding of their oxidation processes considering all their constituent ions is therefore essential to stabilize these materials. Herein, we reveal that A-site cation choice plays an inconspicuous yet crucial role in determining Sn-Pb perovskite stability toward oxidation. Comparing typical A-site compositions, we show that thin films and solar cells containing cesium are more resistant to oxidative stress relative to their methylammonium analogs. We identify degradation in these compositions to be closely linked to the presence of triiodide, a harmful species evolving from native I2 oxidants. We find that hydrogen bonding between methylammonium and I2 promotes triiodide formation, while the strong polarizing character of cesium limits this process by capturing I2. Inspired from these findings, we design two strategies to boost stability of sensitive methylammonium-based Sn-Pb perovskite films and devices against oxidation. Specifically, we modulate the polarizing character of surface A-sites in perovskite via CsI and RbI coatings, and we incorporate Na2S2O3 as an I2 scavenging additive. These crucial mechanistic insights will pave the way for the design of highly efficient and stable Sn-Pb perovskite optoelectronics.
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BACKGROUND: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. METHODS: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. RESULTS: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). CONCLUSION: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. TRIAL REGISTRATION: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .
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Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estudos Prospectivos , Vesículas Extracelulares/metabolismo , Biópsia Líquida , Biomarcadores Tumorais/genéticaRESUMO
INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.
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Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Metronidazol/uso terapêutico , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto/uso terapêutico , Amoxicilina/uso terapêutico , Tinidazol , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Resistência Microbiana a MedicamentosRESUMO
BACKGROUND: Metastasis is the leading cause of cancer-related deaths. Most studies have focused on the primary tumor or on overt metastatic lesions, leaving a significant knowledge gap concerning blood-borne cancer cell dissemination, a major step in the metastatic cascade. Circulating tumor cells (CTCs) in the blood of patients with solid cancer can now be enumerated and investigated at the molecular level, giving unexpected information on the biology of the metastatic cascade. CONTENT: Here, we reviewed recent advances in basic and translational/clinical research on CTCs as key elements in the metastatic cascade. SUMMARY: Findings from translational studies on CTCs have elucidated the complexity of the metastatic process. Fully understanding this process will open new potential avenues for cancer therapeutic and diagnostic strategies to propose precision medicine to all cancer patients.
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Células Neoplásicas Circulantes , Humanos , Pesquisa Translacional Biomédica , Conhecimento , Medicina de PrecisãoRESUMO
Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioma/tratamento farmacológico , Glioma/patologia , Temozolomida/farmacologia , Temozolomida/uso terapêuticoRESUMO
BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.
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Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.
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Exposição Ambiental , Expossoma , Humanos , Colômbia/epidemiologia , Pré-Escolar , Feminino , Exposição Ambiental/análise , Masculino , Poluentes Atmosféricos/análise , Gravidez , Poluição do Ar/análise , Estudos de CoortesRESUMO
BACKGROUND: Gallstone-related conditions affect a significant portion of the population, with varying prevalence among different ethnic groups. Complications such as pancreatitis and cholangitis are associated with the presence of common bile duct (CBD) stones. Existing guidelines for diagnosing choledocholithiasis lack precision, leading to excessive use of invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A prospective study was conducted at Hospital Central "Dr. Ignacio Morones Prieto," involving 374 patients in the development cohort and 154 patients in the validation cohort. Patients meeting inclusion criteria underwent biochemical testing and ultrasonography. A predictive scoring system was developed using logistic regression and validated in an independent cohort. Clinical and laboratory variables were collected, and model performance was assessed using receiver-operator characteristic (ROC) curves. RESULTS: The predictive model incorporated variables such as age, pancreatitis, cholangitis, bilirubin levels, and CBD stone presence on ultrasound. The model demonstrated an area under the ROC curve (AUC) of 93.81% in the validation dataset. By adjusting the threshold defining high-risk probability to 40%, the model improved specificity and sensitivity compared to existing guidelines. Notably, the model reclassified patients, leading to a more accurate risk assessment. CONCLUSIONS: The developed algorithm accurately predicts choledocholithiasis non-invasively in patients with symptomatic gallstones. This tool has the potential to reduce reliance on costly or invasive procedures like magnetic resonance cholangiopancreatography and ERCP, offering a more efficient and cost-effective approach to patient management. The user-friendly calculator developed in this study could streamline diagnostic procedures, particularly in resource-limited healthcare settings, ultimately improving patient care.
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Coledocolitíase , Humanos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/diagnóstico , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Curva ROC , Valor Preditivo dos Testes , Ultrassonografia , Modelos LogísticosRESUMO
BACKGROUND: Phase angle (PhA) is an indicator of cellular health, function, and integrity. PhA has been considered an indicator of nutritional and health status, but it is uncertain whether it could be used as a fitness or athletic performance indicator. OBJECTIVE: To analyze the relationship between PhA and the fitness and athletic performance of adolescent boxers and to know whether this association is independent of body composition. METHODS: Thirty-seven trained youth boxers (15-18 y old) participated in the study. Participants underwent anthropometry and bioelectrical impedance assessments. The following tests were conducted: Fitness-Gram battery; speed, agility, and quickness; ball throws; punch impact force; bench press maximal strength; and vertical and horizontal jumps. Linear regression models were estimated and adjusted by covariates. RESULTS: The PhA was related to upper-limb strength. Nevertheless, in linear regression models, after adjusting models by body composition, only PhA remained as a predictor of relative maximal strength. The PhA was not a predictor of speed, agility, and quickness; cardiorespiratory fitness; or lower-limb power, in which adiposity was the main predictor of fitness. CONCLUSIONS: In adolescent boxers, PhA can predict upper-limb maximal strength independently of bioelectrical impedance analysis premises. However, compared with mucle mass, PhA is not a better predictor of upper-limb maximal strength.
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One of the main lines of research in distributed learning in recent years is the one related to Federated Learning (FL). In this work, a decentralized Federated Learning algorithm based on consensus (CoL) is applied to Wireless Ad-hoc Networks (WANETs), where the agents communicate with other agents to share their learning model as they are available to the wireless connection range. When deploying a set of agents, it is essential to study whether all the WANET agents will be reachable before the deployment. The paper proposes to explore it by generating a simulation close to the real world using a framework (FIVE) that allows the easy development and modification of simulations based on Unity and SPADE agents. A fruit orchard with autonomous tractors is presented as a case study. The paper also presents how and why the concept of artifact has been included in the above-mentioned framework as a way to highlight the importance of some devices used in the environment that have to be located in specific places to ensure the full connection of the system. This inclusion is the first step to allow Digital Twins to be modeled with this framework, now allowing a Digital Shadow of those devices.
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Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.
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Antioxidantes , Envelhecimento da Pele , Humanos , Antioxidantes/farmacologia , Raios Ultravioleta/efeitos adversos , Pele/metabolismo , Estresse OxidativoRESUMO
BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.
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Duodeno , Mucosa , Humanos , Consenso , Endoscopia do Sistema DigestórioRESUMO
BACKGROUND: Varicella causes a major health burden in many low- to middle-income countries located in tropical regions. Because of the lack of surveillance data, however, the epidemiology of varicella in these regions remains uncharacterized. In this study, based on an extensive dataset of weekly varicella incidence in children ≤10 during 2011-2014 in 25 municipalities, we aimed to delineate the seasonality of varicella across the diverse tropical climates of Colombia. METHODS: We used generalized additive models to estimate varicella seasonality, and we used clustering and matrix correlation methods to assess its correlation with climate. Furthermore, we developed a mathematical model to examine whether including the effect of climate on varicella transmission could reproduce the observed spatiotemporal patterns. RESULTS: Varicella seasonality was markedly bimodal, with latitudinal changes in the peaks' timing and amplitude. This spatial gradient strongly correlated with specific humidity (Mantel statistic = 0.412, P = .001) but not temperature (Mantel statistic = 0.077, P = .225). The mathematical model reproduced the observed patterns not only in Colombia but also México, and it predicted a latitudinal gradient in Central America. CONCLUSIONS: These results demonstrate large variability in varicella seasonality across Colombia and suggest that spatiotemporal humidity fluctuations can explain the calendar of varicella epidemics in Colombia, México, and potentially in Central America.
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Varicela , Criança , Humanos , Varicela/epidemiologia , Colômbia/epidemiologia , Clima , Herpesvirus Humano 3 , Umidade , Estações do Ano , Clima TropicalRESUMO
Discoidal lipid-protein nanoparticles known as nanodiscs are widely used tools in structural and membrane biology. Amphipathic, synthetic copolymers have recently become an attractive alternative to membrane scaffold proteins for the formation of nanodiscs. Such copolymers can directly intercalate into, and form nanodiscs from, intact membranes without detergents. Although these copolymer nanodiscs can extract native membrane lipids, it remains unclear whether native membrane properties are also retained. To determine the extent to which bilayer lipid packing is retained in nanodiscs, we measured the behavior of packing-sensitive fluorescent dyes in various nanodisc preparations compared with intact lipid bilayers. We analyzed styrene-maleic acid (SMA), diisobutylene-maleic acid (DIBMA), and polymethacrylate (PMA) as nanodisc scaffolds at various copolymer-to-lipid ratios and temperatures. Measurements of Laurdan spectral shifts revealed that dimyristoyl-phosphatidylcholine (DMPC) nanodiscs had increased lipid headgroup packing compared with large unilamellar vesicles (LUVs) above the lipid melting temperature for all three copolymers. Similar effects were observed for DMPC nanodiscs stabilized by membrane scaffolding protein MSP1E1. Increased lipid headgroup packing was also observed when comparing nanodiscs with intact membranes composed of binary mixtures of 1-palmitoyl-2-oleoyl-phosphocholine (POPC) and di-palmitoyl-phosphocholine (DPPC), which show fluid-gel-phase coexistence. Similarly, Laurdan reported increased headgroup packing in nanodiscs for biomimetic mixtures containing cholesterol, most notable for relatively disordered membranes. The magnitudes of these ordering effects were not identical for the various copolymers, with SMA being the most and DIBMA being the least perturbing. Finally, nanodiscs derived from mammalian cell membranes showed similarly increased lipid headgroup packing. We conclude that nanodiscs generally do not completely retain the physical properties of intact membranes.
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Dimiristoilfosfatidilcolina , Nanoestruturas , Animais , Fosforilcolina , Bicamadas Lipídicas/química , Maleatos/química , Polímeros/química , Proteínas de Membrana/química , Estireno , Lipossomas Unilamelares , Nanoestruturas/química , MamíferosRESUMO
REM (reproductive meristem) transcription factors have been proposed as regulators of plant reproductive development mainly based on their specific expression patterns in reproductive structures, but their roles are still largely unknown probably because of their redundancy. We selected three REM genes (REM13, REM34 and REM46) for functional analysis, based on their genome position and/or co-expression data.Our results suggest that these genes have a role in flowering time regulation and may modulate cell cycle progression. In addition, protein interaction experiments revealed that REM34 and REM46 interact with each other, suggesting that they might work cooperatively to regulate cell division during inflorescence meristem commitment.Previous attempts of using co-expression data as a guide for functional analysis of REMs were limited by the transcriptomic data available at the time. Our results uncover previously unknown functions of three members of the REM family of Arabidopsis thaliana and open the door to more comprehensive studies of the REM family, where the combination of co-expression analysis followed by functional studies might contribute to uncovering the biological roles of these proteins and the relationship among them.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores , Inflorescência/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Meristema , Regulação da Expressão Gênica de PlantasRESUMO
We had attended a Parkinson's Disease (PD) patient for a non-healing wound who reported a marked decrease in his hand tremor and freezing of gait when his wound was exposed to a ceramic far-field infrared (cFIR) blanket. PD is the most frequent motor disorder and the second most frequent neurodegenerative disease after Alzheimer's Disease (AD). The tremor, rigidity, and slowness of movement associated with Parkinson's disease (PD) affect up to 10 million people throughout the world, and the major contributing factor to the pathogenesis of PD is the accumulation and propagation of pathological α-synuclein (α-Syn) and the death of dopaminergic cells in the Nigrostriatal system. Efforts to slow or stop its spreading have resulted in the development and use of dopaminergic drug replacement therapy. Unfortunately, there is a loss of about 70-80% of substantia nigral dopaminergic neurons in patients by the time they are diagnosed with PD, and various dopaminergic drugs provide only temporary relief of their motor symptoms. There are limitations in treating PD with many conventional medications, necessitating a combination of pharmaceutical and non-pharmacological therapy as an essential adjunct to better address the health and welfare of PD patients. We used male adult A53T alpha-synuclein transgenic mice exposed to a ceramic far-infrared blanket. Motor activity was assessed using the rotarod apparatus, and mouse brains were examined to quantify the fluorescence intensities of the immunostained samples. A53T alpha-synuclein transgenic mice had a significantly shorter time stay on the rotating bar than the wild-type mice (B6C3H). The rotarod performance was significantly improved in A53T alpha-synuclein transgenic mice exposed to cFIR as well as B6C3H healthy wild mice exposed to cFIR. There was a significant statistical and substantive increase in the cellular composition of the Striatum and substantia nigra of cFIR-treated mice. Improvement in motor performance is seen in PD mice and wild mice and is associated with increases in cell volume in the substantia nigra and striatum after treatment.
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BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).
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Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Neoplasias Colorretais/patologia , Colonoscopia/métodos , Pólipos do Colo/patologia , Água , Ressecção Endoscópica de Mucosa/métodos , Mucosa Intestinal/patologiaRESUMO
BACKGROUND: Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. METHODS: A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. RESULTS: We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. CONCLUSION: While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.
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Neoplasias Encefálicas , Neoplasias Meníngeas , Radiocirurgia , Humanos , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/terapia , Neoplasias Encefálicas/cirurgia , Prognóstico , Fatores de Risco , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We present an improved algorithm to solve the near-congruence problem for rigid molecules and clusters based on the iterative application of assignment and alignment steps with biased Euclidean costs. The algorithm is formulated as a quasi-local optimization procedure with each optimization step involving a linear assignment (LAP) and a singular value decomposition (SVD). The efficiency of the algorithm is increased by up to 5 orders of magnitude with respect to the original unbiased noniterative method and can be applied to systems with hundreds or thousands of atoms, outperforming all state-of-the-art methods published so far in the literature. The Fortran implementation of the algorithm is available as an open source library (https://github.com/qcuaeh/molalignlib) and is suitable to be used in global optimization methods for the identification of local minima or basins.