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Objective: This study aimed to investigate the impact of foot orthoses on foot radiological parameters and pain in children diagnosed with flexible flatfoot. Methods: A comprehensive search was conducted across several databases, including PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO, covering publications from the inception of each database up to 8 June 2024. The study focused on randomized controlled trials investigating the use of foot orthoses for treating flexible flat feet in children. Four researchers independently reviewed the identified literature, extracted relevant data, assessed the quality of the studies, and performed statistical analyses using RevMan 5.4 software. Results: Six studies involving 297 participants were included. The methodological quality of the included literature ranged from moderate to high. Radiological parameters of the foot improved significantly in older children with flexible flat feet following foot orthotic intervention compared to controls, particularly in the lateral talar-first metatarsal angle [mean difference (MD) = -2.76, 95% confidence interval (95% CI) -4.30 to -1.21, p = 0.0005], lateral talo-heel angle (MD = -5.14, 95% CI -7.76 to -2.52, p = 0.0001) and calcaneal pitch angle (MD = 1.79, 95% CI 0.88-2.69, p = 0.0001). These differences were statistically significant. Additionally, foot orthoses significantly improved the ankle internal rotation angle and reduced foot pain in children with symptomatic flexible flatfoot (MD = -2.51, 95% CI -4.94 to -0.07, p = 0.04). Conclusion: The use of foot orthoses positively impacts the improvement of radiological parameters of the foot and reduces pain in older children with flexible flat feet. However, in younger children with flexible flat feet, the improvement from foot orthoses was not significant, likely due to challenges in radiological measurements caused by the underdevelopment of the ossification centers in the foot. Further studies are needed. Consequently, the results of this meta-analysis support the implementation of an early intervention strategy using foot orthoses for the management of symptomatic flat feet in older children. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO [CRD42023441229].
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Stereochemically pure saccharides have indispensable roles in fields ranging from medicinal chemistry to materials science and organic synthesis. However, the development of a simple, stereoselective, and efficient glycosylation protocol to access α- and ß-C-glycosides (particularly 2-deoxy entities) remains a persistent challenge. Existing studies have primarily focused on C1 modification of carbohydrates and transformation of glycosyl radical precursors. Here, we innovate by harnessing the in situ generated glycosyl-Ni species to achieve one-pot borylation and glycosylation in a cascade manner, which is enabled by an earth-abundant nickel-catalyzed carboboration of readily accessible glycals without any ligand. This work reveals the potential for the development of a modular and multifunctional glycosylation platform to facilitate the simultaneous introduction of C-C and C-B bonds at the stereogenic center of saccharides, a largely unexploited research area. Preliminary experimental and computational studies indicate that the endocyclic O and the C3 group play important roles in stereoseclectively forging glycosidic bonds. As a result, a diverse range of C-R (R = alkyl, aryl, and alkenyl) and 2-deoxygenated glycosides bearing modifiable boron groups could be rapidly made with excellent stereocontrol and exhibit remarkable functional group tolerance. The synthetic potential is underscored in the late-stage glycosylation of natural products and commercial drugs as well as the facile preparation of various rare sugars, bioactive conjugates, and key intermediates to prorocentin, phomonol, and aspergillide A.
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X-ray communication is a kind of space communication technology which uses X-ray as information carrier. In order to improve the information transmission capacity, communication rate and anti-interference ability of X-ray communication, we proposes to design a novel multi-target X-ray source. The source is composed of a fast switching module of light channels based on FPGA technology and four photoelectric X-ray tubes with different target materials: Cr, Fe, Ni, and Cu. Using Geant4 software, we determined the optimal target thickness for each material, which enabled us to fully leverage the characteristic X-rays for multi-channel signal modulation transmission. Moreover, using CST software for particle trajectory simulation and optimization of the electron beam revealed that at a tube voltage of 20 kV, the focus area measures approximately 1.2 mm×1.2 mm. The simulations show that four kinds of spectra with high distinctiveness can be generated from the Cr, Fe, Ni, and Cu targets. Within a single modulation period, these spectra can be combined in various ways to create 16 different X-ray spectra signals, thereby increasing the number of communication elements and enhancing the information transmission rate.
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Diseño de Equipo , Rayos X , Programas Informáticos , Simulación por ComputadorRESUMEN
The evidence associating traffic-related air pollution (TRAP) with allergic asthma is growing, but the underlying mechanisms for this association remain unclear. The airway epithelium is the primary tissue exposed to TRAP, hence understanding its interactions with TRAP and allergen is important. Diesel exhaust (DE), a paradigm of TRAP, consists of particulate matter (PM) and gases. Modern diesel engines often have catalytic diesel particulate filters to reduce PM output, but these may increase gaseous concentrations, and their benefits on human health cannot be assumed. We conducted a randomized, double-blinded, crossover study using our unique in vivo human exposure system to investigate the effects of DE and allergen co-exposure, with or without particle depletion as a proxy for catalytic diesel particulate filters, on the airway epithelial transcriptome. Participants were exposed for 2 h before an allergen inhalation challenge, with each receiving filtered air and saline (FA-S), filtered air and allergen (FA-A), DE and allergen (DE-A), or particle-depleted DE and allergen (PDDE-A), over four different occasions, each separated by a 4-week washout period. Endobronchial brushings were collected 48 h after each exposure, and total RNA was sequenced. Differentially expressed genes (DEGs) were identified using DESeq2, followed by GO enrichment and pathway analysis. FA-A, DE-A, and PDDE-A exposures significantly modulated genes relative to FA-S, with 462 unique DEGs identified. FA-A uniquely modulated the highest number (↑178, ↓155), followed by DE-A (↑44, ↓23), and then PDDE-A exposure (↑15, ↓2); 6 DEGs (↑4, ↓2) were modulated by all three conditions. Exposure to PDDE-A resulted in modulation of 285 DEGs compared to DE-A exposure, further revealing 26 biological process GO terms, including "cellular response to chemokine" and "inflammatory response". The transcriptional epithelial response to diesel exhaust and allergen co-exposure is enriched in inflammatory mediators, the pattern of which is altered upon particle depletion.
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Contaminantes Atmosféricos , Alérgenos , Material Particulado , Transcriptoma , Emisiones de Vehículos , Emisiones de Vehículos/toxicidad , Humanos , Transcriptoma/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad , Material Particulado/toxicidad , Pulmón/efectos de los fármacos , Estudios Cruzados , Adulto , Masculino , Exposición por Inhalación/efectos adversos , Femenino , Método Doble CiegoRESUMEN
BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.
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Glucólisis , Proteínas HSP90 de Choque Térmico , Ratones Endogámicos C57BL , Células Th17 , Animales , Células Th17/inmunología , Células Th17/efectos de los fármacos , Células Th17/metabolismo , Glucólisis/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Ratones , Masculino , Metilación de ADN/efectos de los fármacos , Sulfato de Dextran , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Colitis Ulcerosa/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , HumanosRESUMEN
OBJECTIVE: This study aimed to investigate the clinical efficacy of percutaneous endoscopic suprapedicular decompression in treatment of down-migrated lumbar disc herniation. METHODS: The clinical data of 43 patients with down-migrated lumbar disc herniation treated with endoscopic surgery at our hospital between January 2022 and January 2023 were retrospectively analyzed. Twenty-two and 21 patients underwent percutaneous endoscopic decompression using the suprapedicular and transforaminal endoscopic surgical system approaches, respectively. The perioperative, follow-up, and imaging data of the groups were compared. RESULTS: Surgery was uneventful in both groups. The number of intraoperative fluoroscopies and duration of surgery were significantly lower in the suprapedicular group (P < 0.05). The patients in both groups were followed up for at least 12 months. At the last follow-up, lumbar pain and leg pain visual analog scale, Oswestry Disability Index, and 36-Item Short Form Health Survey scores were significantly improved in both groups compared with preoperative values (P < 0.05); the differences in these indexes between the 2 groups were not significant preoperatively (P > 0.05). However, at the last postoperative follow-up, lumbar pain visual analog scale scores were significantly better in the suprapedicular group (0.83 ± 0.85 vs. 2.54 ± 1.32, P < 0.05). There was no significant change in intervertebral space height or lumbar lordotic angle compared with preoperative values in either group at the last follow-up (P > 0.05). However, the spinal canal cross-sectional area significantly increased (P < 0.05). CONCLUSIONS: The treatment of down-migrated lumbar disc herniation via a suprapedicular approach enabled the incision of the superior margin of the pedicle as needed under direct vision, involved less fluoroscopy while preserving facet joint stability, and enabled targeted removal of the herniated nucleus pulposus, thus greatly reducing residual nucleus pulposus. This surgical procedure was safe, rapid, and showed satisfactory therapeutic efficacy.
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Descompresión Quirúrgica , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Humanos , Femenino , Desplazamiento del Disco Intervertebral/cirugía , Masculino , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Descompresión Quirúrgica/métodos , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , Endoscopía/métodos , Discectomía Percutánea/métodos , Neuroendoscopía/métodos , AncianoRESUMEN
Cognitive impairment is a core symptom of schizophrenia. The gut microbiota (GM) and oxidative stress may play important roles in the pathophysiological mechanisms of cognitive impairment. This study aimed to explore the relationship between GM and oxidative stress in the cognitive function of schizophrenia. GM obtained by 16S RNA sequencing and serum superoxide dismutase (SOD) levels from schizophrenia patients (N = 68) and healthy controls (HCs, N = 72) were analyzed. All psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Correlation analysis was used to explore the relationship between GM, SOD, and cognitive function. Machine learning models were used to identify potential biomarkers. Compared to HCs, the relative abundances of Collinsella, undefined Ruminococcus, Lactobacillus, Eubacterium, Mogibacterium, Desulfovibrio, Bulleidia, Succinivibrio, Corynebacterium, and Atopobium were higher in patients with schizophrenia, but Faecalibacterium, Anaerostipes, Turicibacter, and Ruminococcus were lower. In patients with schizophrenia, the positive factor, general factor, and total score of MCCB positively correlated with Lactobacillus, Collinsella, and Lactobacillus, respectively; SOD negatively correlated with Eubacterium, Collinsella, Lactobacillus, Corynebacterium, Bulleidia, Mogibacterium, and Succinivibrio, but positively correlated with Faecalibacterium, Ruminococcus, and MCCB verbal learning index scores; Faecalibacterium and Turicibacter were positively correlated with MCCB visual learning index scores and speed of processing index scores, respectively. Our findings revealed a correlation between SOD and GM and confirmed that cognitive dysfunction in patients with schizophrenia involves abnormal SOD levels and GM changes.
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Disfunción Cognitiva , Microbioma Gastrointestinal , Estrés Oxidativo , Esquizofrenia , Humanos , Esquizofrenia/fisiopatología , Esquizofrenia/microbiología , Esquizofrenia/complicaciones , Microbioma Gastrointestinal/fisiología , Masculino , Femenino , Estrés Oxidativo/fisiología , Adulto , Proyectos Piloto , China , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/microbiología , Superóxido Dismutasa/sangre , Persona de Mediana Edad , Adulto Joven , Aprendizaje AutomáticoRESUMEN
Stress is a crucial factor affecting social decision-making. However, its impacts on the behavioral and neural processes of females' unfairness decision-making remain unclear. Combining computational modeling and functional near-infrared spectroscopy (fNIRS), this study attempted to illuminate the neurocomputational signature of unfairness decision-making in females. We also considered the effect of trait stress coping styles. Forty-four healthy young females (20.98 ± 2.89 years) were randomly assigned to the stress group (n = 21) and the control group (n = 23). Acute psychosocial stress was induced by the Trier Social Stress Test (TSST), and participants then completed the one-shot ultimatum game (UG) as responders. The results showed that acute psychosocial stress reduced the adaptability to fairness and lead to more random decision-making responses. Moreover, in the stress group, a high level of negative coping style predicted more deterministic decision. fNIRS results showed that stress led to an increase of oxy-hemoglobin (HbO) peak in the right temporoparietal junction (rTPJ), while decreased the activation of left middle temporal gyrus (lMTG) when presented the moderately unfair (MU) offers. This signified more involvement of the mentalization and the inhibition of moral processing. Moreover, individuals with higher negative coping scores showed more deterministic decision behaviors under stress. Taken together, our study emphasizes the role of acute psychosocial stress in affecting females' unfairness decision-making mechanisms in social interactions, and provides evidences for the "tend and befriend" pattern based on a cognitive neuroscience perspec.
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Rechargeable aqueous zinc-ion batteries (AZIBs) have been highly desired due to their low cost, intrinsic safety, environmental friendliness, and great potential in large-scale power storage systems. However, their practical applications are impeded by unstable long-term electrochemical performances induced by microstructure degradation of the cathode material, hydrogen evolution reaction in the electrolyte, and dendritic growth on the zinc anode upon cycling. In this work, rubidium cations (Rb+) are introduced to synthesize an Rb+-preintercalated NH4V4O10 (NVO-Rb) composite. The contribution of Rb+ ions as pillars in V-O interlayers to facilitating Zn2+ storage is investigated first, and then the influences of partial Rb+ ions from the NVO-Rb cathode on the aqueous electrolyte and zinc anode are specially inspected from different viewpoints. Based on a series of characterization results, it is comprehensively elucidated that the partial Rb+ ions into the electrolyte suppress the generation of byproducts on the cathode and regulate the dendrite growth on the zinc anode, thus effectively promoting the long-term electrochemical performances of NVO-based AZIBs. The assembled Znâ¥Zn(CF3SO3)2â¥NVO-Rb cell can exhibit a high specific capacity and optimized Zn2+ diffusion kinetics, especially an improved electrochemical cyclability with a capacity retention of 87.6% at 5 A g-1 over 10000 cycles. This study enlightens the multiple roles of cation-preintercalation in the layered structure material and provides a feasible strategy for the development of high-performance aqueous batteries.
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The purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723-0.828) in the derivation cohort and 0.846 (95% CI: 0.790-0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.
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Trasplante de Células Madre Hematopoyéticas , Sepsis , Humanos , Klebsiella pneumoniae , Estudios Retrospectivos , Modelos Estadísticos , Pronóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Described here is a mild and stereoselective protocol for the synthesis of [3]dendralenes via the intermolecular dimerization of allenes. With the proper choice of a ruthenium catalyst, a range of unactivated 1,1-disubstituted allenes, without prefunctionalization in the allylic position, reacted efficiently to provide rapid access to densely substituted [3]dendralenes. An intermolecular C-C bond and three different types of CâC double bonds (di-, tri-, and tetrasubstituted) embedded in an acyclic structure were constructed with good to high E/Z stereocontrol. This is in contrast to the known catalytic protocols that focus on allenes with prefunctionalization at the allylic position and/or monosubstituted allenes, which would proceed by a different mechanism or require less stereocontrol. The silyl-substituted dendralene products are precursors of other useful dendralene molecules. Density functional theory (DFT) studies and control experiments supported a mechanism involving oxidative cyclometalation, ß-H elimination (the rate-determining step), and reductive elimination.
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The microbiome-gut-brain axis (MGBA) plays a critical role in schizophrenia (SZ). However, the underlying mechanisms of the interactions among the gut microbiome, brain networks, and symptom severity in SZ patients remain largely unknown. Fecal samples, structural and functional magnetic resonance imaging (MRI) data, and Positive and Negative Syndrome Scale (PANSS) scores were collected from 38 SZ patients and 38 normal controls, respectively. The data of 16S rRNA gene sequencing were used to analyze the abundance of gut microbiome and the analysis of human brain networks was applied to compute the nodal properties of 90 brain regions. A total of 1,691,280 mediation models were constructed based on 261 gut bacterial, 810 nodal properties, and 4 PANSS scores in SZ patients. A strong correlation between the gut microbiome and brain networks (r = 0.89, false discovery rate (FDR) -corrected p < 0.05) was identified. Importantly, the PANSS scores were linearly correlated with both the gut microbiome (r = 0.5, FDR-corrected p < 0.05) and brain networks (r = 0.59, FDR-corrected p < 0.05). The abundance of genus Sellimonas significantly affected the PANSS negative scores of SZ patients via the betweenness centrality of white matter networks in the inferior frontal gyrus and amygdala. Moreover, 19 significant mediation models demonstrated that the nodal properties of 7 brain regions, predominately from the systems of visual, language, and control of action, showed significant mediating effects on the PANSS scores with the gut microbiome as mediators. Together, our findings indicated the tripartite relationships among the gut microbiome, brain networks, and PANSS scores and suggested their potential role in the neuropathology of SZ.
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Microbioma Gastrointestinal , Esquizofrenia , Humanos , Esquizofrenia/patología , Análisis de Mediación , ARN Ribosómico 16S , Encéfalo , Imagen por Resonancia Magnética/métodosRESUMEN
INTRODUCTION: Mandibular asymmetry has negative impacts on maxillofacial aesthetics and psychological well-being. This study investigated the effects of unilateral injection of botulinum toxin type A (BTX-A) into the masseter muscle on mandibular symmetry. METHODS: Forty Wistar rats (4-week-old) were divided into 4 groups (n = 10): control, group 1 (1U BTX-A), group 2 (3U BTX-A), and group 3 (1U BTX-A for 3 times). BTX-A was injected into the right masseter of treatment groups. Cone-beam computerized tomography scans were taken before the injection and then at 2 weeks, 4 weeks, and 6 weeks after injection. Histologic and immunohistochemical staining were done for the condylar cartilage. RNA sequencing and quantitative reverse transcription polymerase chain reaction were used to detect gene expression in the angular process. RESULTS: In Groups 2 and 3, the right angular process length and the ramus height were reduced 4 weeks after injection, resulting in the mandibular midline deviating to the right side; the right condylar cartilage had reduced thickness and decreased expression of RUNX2, SOX9, and COL II (P <0.05). Two hundred sixty-one genes were differentially expressed (256 downregulated) in the angular process at 3 days post-BTX-A injection, and the calcium signaling pathway was unveiled through the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, TRPC1, Wnt5a, CaMKII, Ctnnb1, and RUNX2 expression were significantly downregulated at 1 and 3 days postinjection. CONCLUSIONS: Unilateral injection of BTX-A into the masseter muscle in adolescent rats induces mandibular asymmetry by suppressing the angular process growth on the injected side.
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Toxinas Botulínicas Tipo A , Ratas , Animales , Toxinas Botulínicas Tipo A/farmacología , Músculo Masetero , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Ratas Wistar , Estética DentalRESUMEN
Prostate cancer (PC) is one of the most common cancers in men and becoming the second leading cause of cancer fatalities. At present, the lack of effective strategies for prognosis of PC patients is still a problem to be solved. Therefore, it is significant to identify potential gene signatures for PC patients' prognosis. Here, we summarized 71 different prognostic gene signatures for PC and concluded 3 strategies for signature construction after extensive investigation. In addition, 14 genes frequently appeared in 71 different gene signatures, which enriched in mitotic and cell cycle. This review provides extensive understanding and integrated analysis of current prognostic signatures of PC, which may help researchers to construct gene signatures of PC and guide future clinical treatment.
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An iron-catalyzed efficient C-H amination for the construction of imidazole-fused-ring systems was developed under aerobic conditions. Compared to previous studies, this work exhibited green features. The reaction was conducted in the green solvent anisole, with water as the only byproduct. Four C(sp3)-H bonds were cleaved and three C-N bonds were formed in this transformation. Imidazo[1,5-a]pyridine-, imidazo[5,1-b]oxazole-, imidazo[5,1-b]thiazole-, imidazo[1,5-a]pyrazine-, and imidazo[1,5-a]imidazole-related N-heterocycles were obtained in acceptable-to-excellent yield.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Receptores Quiméricos de Antígenos , Humanos , Citomegalovirus , Receptores Quiméricos de Antígenos/genética , Herpesvirus Humano 4 , Viremia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lectina 2 Similar a Ig de Unión al Ácido SiálicoRESUMEN
Purpose: The current study assesses which are the main risk factors, clinical outcome and prognosis following the colonization of CRE in patients that underwent allo-HSCT. Patients and Methods: A total of 343 patients subjected to allo-HSCT in the period comprised between June 2021 and June 2022 were enrolled in this retrospective study. The CRE colonization was diagnosed by clinical history and routine microbial culture of perirectal swab. In this regard, a clinical prediction model was designed based on independent risk factors underlying the pre-transplantation CRE colonization using a backward stepwise logistic regression, followed by the evaluation of its discrimination and calibration efficacies, along with clinical usefulness. Furthermore, univariate and multivariate Cox regression analyses were then conducted to assess the risk factors for post-transplantation clinical outcomes. Results: Out of 343 patients enrolled in this study, 135 (39.3%) reported CRE colonization. The independent risk factor variables for CRE colonization were incorporated into the nomogram to build a prediction model, which showed an area under the curve of 0.767 (95% CI: 0.716-0.818), and well-fitted calibration curves (χ2 = 1.737, P = 0.9788). The patients with CRE colonization reported a significantly lower platelet engraftment rate with a higher risk of post-transplantation BSI when compared with the non-CRE colonization group (P = 0.02 and P < 0.001; respectively). The non-relapse mortality (NRM) value was higher in the CRE patients (P < 0.05), consistently with a survival probability that was thus significantly lower for the same timeframe (P < 0.05). Conclusion: A reliable clinical prediction model for pre-transplantation CRE colonization was developed that demonstrated that the CRE colonization negatively affects platelet engraftment and survival outcomes following allo-HSCT.
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Traditional AI-planning methods for task planning in robotics require a symbolically encoded domain description. While powerful in well-defined scenarios, as well as human-interpretable, setting this up requires a substantial effort. Different from this, most everyday planning tasks are solved by humans intuitively, using mental imagery of the different planning steps. Here, we suggest that the same approach can be used for robots too, in cases which require only limited execution accuracy. In the current study, we propose a novel sub-symbolic method called Simulated Mental Imagery for Planning (SiMIP), which consists of perception, simulated action, success checking, and re-planning performed on 'imagined' images. We show that it is possible to implement mental imagery-based planning in an algorithmically sound way by combining regular convolutional neural networks and generative adversarial networks. With this method, the robot acquires the capability to use the initially existing scene to generate action plans without symbolic domain descriptions, while at the same time, plans remain human-interpretable, different from deep reinforcement learning, which is an alternative sub-symbolic approach. We create a data set from real scenes for a packing problem of having to correctly place different objects into different target slots. This way efficiency and success rate of this algorithm could be quantified.
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Virus-induced gene silencing (VIGS) is a fast and efficient method for assaying gene function in plants. At present, the VIGS system mediated by Tobacco rattle virus (TRV) has been successfully practiced in some species such as cotton and tomato. However, little research of VIGS systems has been reported in woody plants, nor in Chinese jujube. In this study, the TRV-VIGS system of jujube was firstly investigated. The jujube seedlings were grown in a greenhouse with a 16 h light/8 h dark cycle at 23 °C. After the cotyledon was fully unfolded, Agrobacterium mixture containing pTRV1 and pTRV2-ZjCLA with OD600 = 1.5 was injected into cotyledon. After 15 days, the new leaves of jujube seedlings showed obvious photo-bleaching symptoms and significantly decreased expression of ZjCLA, indicating that the TRV-VIGS system had successfully functioned on jujube. Moreover, it found that two injections on jujube cotyledon could induce higher silencing efficiency than once injection. A similar silencing effect was then also verified in another gene, ZjPDS. These results indicate that the TRV-VIGS system in Chinese jujube has been successfully established and can be applied to evaluate gene function, providing a breakthrough in gene function verification methods.
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A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 µm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1ß. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.