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Competitive interactions have a vital role in the ecology of most animal species1-3 and powerfully influence the behaviour of groups4,5. To succeed, individuals must exert effort based on not only the resources available but also the social rank and behaviour of other group members2,6,7. The single-cellular mechanisms that precisely drive competitive interactions or the behaviour of social groups, however, remain poorly understood. Here we developed a naturalistic group paradigm in which large cohorts of mice competitively foraged for food as we wirelessly tracked neuronal activities across thousands of unique interactions. By following the collective behaviour of the groups, we found neurons in the anterior cingulate that adaptively represented the social rank of the animals in relation to others. Although social rank was closely behaviourally linked to success, these cells disambiguated the relative rank of the mice from their competitive behaviour, and incorporated information about the resources available, the environment, and past success of the mice to influence their decisions. Using multiclass models, we show how these neurons tracked other individuals within the group and accurately predicted upcoming success. Using neuromodulation techniques, we also show how the neurons conditionally influenced competitive effort-increasing the effort of the animals only when they were more dominant to their groupmates and decreasing it when they were subordinate-effects that were not observed in other frontal lobe areas. Together, these findings reveal cingulate neurons that serve to adaptively drive competitive interactions and a putative process that could intermediate the social and economic behaviour of groups.
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Conducta Competitiva , Ecología , Animales , Conducta Competitiva/fisiología , Alimentos , Giro del Cíngulo/fisiología , Ratones , Neuronas/fisiología , Conducta SocialRESUMEN
When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1-3, and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3-5. Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction.
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B cell development requires the ordered rearrangement of Ig genes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags. Igκ rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26 transformation-specific transcription factor Spi-C is activated in response to dsDNA double-stranded breaks in small pre-B cells to negatively regulate pre-BCR signaling and Igκ rearrangement. However, it is not clear if Spi-C regulates Igκ rearrangement through transcription or by controlling RAG expression. In this study, we investigated the mechanism of Spi-C negative regulation of Igκ L chain rearrangement. Using an inducible expression system in a pre-B cell line, we found that Spi-C negatively regulated Igκ rearrangement, Igκ transcript levels, and Rag1 transcript levels. We found that Igκ and Rag1 transcript levels were increased in small pre-B cells from Spic-/- mice. In contrast, Igκ and Rag1 transcript levels were activated by PU.1 and were decreased in small pre-B cells from PU.1-deficient mice. Using chromatin immunoprecipitation analysis, we identified an interaction site for PU.1 and Spi-C located in the Rag1 promoter region. These results suggest that Spi-C and PU.1 counterregulate Igκ transcription and Rag1 transcription to effect Igκ recombination in small pre-B cells.
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Cadenas kappa de Inmunoglobulina , Células Precursoras de Linfocitos B , Ratones , Animales , Células Precursoras de Linfocitos B/metabolismo , Cadenas kappa de Inmunoglobulina/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/genética , Recombinación GenéticaRESUMEN
The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.
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We have previously reported a failure of recovery of synaptic function in the CA1 region of acute hippocampal slices from mice with a conditional neuronal knockout (KO) of GLT-1 (EAAT2, Slc1A2) driven by synapsin-Cre (synGLT-1 KO). The failure of recovery of synaptic function is due to excitotoxic injury. We hypothesized that changes in mitochondrial metabolism contribute to the heightened vulnerability to excitotoxicity in the synGLT-1 KO mice. We found impaired flux of carbon from 13C-glucose into the tricarboxylic acid cycle in synGLT-1 KO cortical and hippocampal slices compared with wild-type (WT) slices. In addition, we found downregulation of the neuronal glucose transporter GLUT3 in both genotypes. Flux of carbon from [1,2-13C]acetate, thought to be astrocyte-specific, was increased in the synGLT-KO hippocampal slices but not cortical slices. Glycogen stores, predominantly localized to astrocytes, are rapidly depleted in slices after cutting, and are replenished during ex vivo incubation. In the synGLT-1 KO, replenishment of glycogen stores during ex vivo incubation was compromised. These results suggest both neuronal and astrocytic metabolic perturbations in the synGLT-1 KO slices. Supplementing incubation medium during recovery with 20 mM D-glucose normalized glycogen replenishment but had no effect on recovery of synaptic function. In contrast, 20 mM non-metabolizable L-glucose substantially improved recovery of synaptic function, suggesting that D-glucose metabolism contributes to the excitotoxic injury in the synGLT-1 KO slices. L-lactate substitution for D-glucose did not promote recovery of synaptic function, implicating mitochondrial metabolism. Consistent with this hypothesis, phosphorylation of pyruvate dehydrogenase, which decreases enzyme activity, was increased in WT slices during the recovery period, but not in synGLT-1 KO slices. Since metabolism of glucose by the mitochondrial electron transport chain is associated with superoxide production, we tested the effect of drugs that scavenge and prevent superoxide production. The superoxide dismutase/catalase mimic EUK-134 conferred complete protection and full recovery of synaptic function. A site-specific inhibitor of complex III superoxide production, S3QEL-2, was also protective, but inhibitors of NADPH oxidase were not. In summary, we find that the failure of recovery of synaptic function in hippocampal slices from the synGLT-1 KO mouse, previously shown to be due to excitotoxic injury, is caused by production of superoxide by mitochondrial metabolism.
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B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent type of cancer in young children and is associated with high levels of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was tested for its ability to alter disease progression in a mouse model of B-ALL. Mb1-CreΔPB mice have deletions in genes encoding PU.1 and Spi-B in B cells and develop B-ALL at 100% incidence. Treatment of Mb1-CreΔPB mice with NAC in drinking water significantly reduced the frequency of CD19+ pre-B-ALL cells infiltrating the thymus at 11 weeks of age. However, treatment with NAC did not reduce leukemia progression or increase survival by a median 16 weeks of age. NAC significantly altered gene expression in leukemias in treated mice. Mice treated with NAC had increased frequencies of activating mutations in genes encoding Janus kinases 1 and 3. In particular, frequencies of Jak3 R653H mutations were increased in mice treated with NAC compared with control drinking water. NAC opposed oxidization of PTEN protein ROS in cultured leukemia cells. These results show that NAC alters leukemia progression in this mouse model, ultimately selecting for leukemias with high Jak3 R653H mutation frequencies. SIGNIFICANCE STATEMENT: In a mouse model of precursor B-cell acute lymphoblastic leukemia associated with high levels of reactive oxygen species, treatment with N-acetylcysteine did not delay disease progression but instead selected for leukemic clones with activating R653H mutations in Janus kinase 3.
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Agua Potable , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Ratones , Animales , Preescolar , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Quinasas Janus , Tasa de Mutación , Especies Reactivas de Oxígeno/metabolismo , Células Precursoras de Linfocitos B/metabolismo , Janus Quinasa 1/genética , Janus Quinasa 1/metabolismo , Mutación , Janus Quinasa 3/genética , Janus Quinasa 3/metabolismo , Progresión de la EnfermedadRESUMEN
The correlation between net baryon number and electric charge, χ_{11}^{BQ}, can serve as a magnetometer of QCD. This is demonstrated by lattice QCD computations using the highly improved staggered quarks with physical pion mass of M_{π}=135 MeV on N_{τ}=8 and 12 lattices. We find that χ_{11}^{BQ} along the transition line starts to increase rapidly with magnetic field strength eBâ³2M_{π}^{2} and by a factor 2 at eB≃8M_{π}^{2}. Furthermore, the ratio of electric charge chemical potential to baryon chemical potential, µ_{Q}/µ_{B}, shows significant dependence on the magnetic field strength and varies from the ratio of electric charge to baryon number in the colliding nuclei in heavy ion collisions. These results can provide baselines for effective theory and model studies, and both χ_{11}^{BQ} and µ_{Q}/µ_{B} could be useful probes for the detection of magnetic fields in relativistic heavy ion collision experiments as compared with corresponding results from the hadron resonance gas model.
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The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6
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AIM: This study aimed to identify the risk factors for gingival invagination during orthodontic treatment after premolar extraction. MATERIALS AND METHODS: The medical records of 135 patients who had undergone interdental space closure after premolar extraction were collected, and cone beam computed tomography was performed to determine the presence of gingival invagination. The risk factors were examined using mixed-effects models and generalized propensity score weighting (GPSW) to develop a predictive model. RESULTS: Univariate analysis revealed that the extraction site, buccal bone thickness 4 mm apical to the cemento-enamel junction (MB1), mid-root buccal bone thickness (MB2) and vertical skeletal relationships were related to gingival invagination (p < .05). Furthermore, a subsequent multivariable mixed-effects model analysis indicated a significantly increased risk of gingival invagination at MB1 < 1 mm (p < .001; odds ratio [ORMB1≤0.5mm] = 29.304; 95% confidence interval [CI]: 8.986-93.807; OR0.5Asunto(s)
Diente Premolar
, Tomografía Computarizada de Haz Cónico
, Humanos
, Femenino
, Estudios Retrospectivos
, Masculino
, Factores de Riesgo
, Diente Premolar/diagnóstico por imagen
, Adulto
, Enfermedades de las Encías/etiología
, Adolescente
, Extracción Dental/efectos adversos
, Adulto Joven
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AIM: To explore the value of a radiomics model based on enhanced computed tomography (CT) in differentiating anterior mediastinal lymphoma (AML) and thymoma without myasthenia gravis (MG) and calcification. MATERIALS AND METHODS: The present study analysed patients who were diagnosed histologically with AML and thymoma in three independent institutions. All pre-treatment patients underwent enhanced CT. In the training group of patients from institutions 1 (the First Affiliated Hospital of Kunming Medical University) and 3 (the Yunnan Cancer Hospital), two radiologists independently analysed the enhanced CT images and performed manual segmentation of each tumour. Radiomics features were screened using interobserver interclass coefficient (ICC) analysis, feature correlation analysis, and L1 regularisation. The discriminative efficacy of the logistic regression model was evaluated using receiver operating characteristic (ROC) analysis. Validation group of patients from institution 2 (the Second Affiliated Hospital of Zhejiang University School of Medicine) was used to validate the proposed models. RESULTS: A total of 114 patients were enrolled in this study and 1,743 radiomics features were extracted from the enhanced CT images. After feature screening, the remaining 37 robust radiomics features were used to construct the model. In the training group, the AUC of the model was 0.987 (95% confidence interval [CI]: 0.976-0.999), the sensitivity, specificity, and accuracy were 0.912, 0.946, and 0.924, respectively. In the validation group, the AUC of the model was 0.798 (95% CI: 0.683-0.913), the sensitivity, specificity, and accuracy were 0.760, 0.700, and 0.743, respectively. CONCLUSION: The radiomics model created provided effective information to assist in the selection of clinical strategies, thus reducing unnecessary procedures in patients with AML and guiding direct surgery in patients with thymoma to avoid biopsy.
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Calcinosis , Leucemia Mieloide Aguda , Linfoma , Miastenia Gravis , Timoma , Neoplasias del Timo , Humanos , Timoma/diagnóstico por imagen , Mediastino , Radiómica , China , Neoplasias del Timo/diagnóstico por imagen , Linfoma/diagnóstico por imagen , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
AIMS: Alcoholic cardiomyopathy (ACM) is recognized as a type of non-ischemic dilated cardiomyopathy (DCM). To date, the clinical prognosis of ACM remains a topic of debate in previous studies and there are limited studies on its cardiac MRI characteristics. The aim of this study was to summarize the clinical and MRI features of ACM patients and to identify the predictors of adverse prognosis based on clinical characteristics and MRI imaging findings. MATERIALS AND METHODS: Adult patients who were clinically diagnosed with ACM and underwent enhanced CMR between September 2015 and August 2022 were retrospectively enrolled. The primary endpoints were major adverse cardiovascular events, including cardiac-related death, heart transplantation, hospitalization for heart failure and life-threatening ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, or ICD shock). The risk factors associated with these primary end points were identified using multivariable Cox analysis. RESULTS: A total of 62 ACM patients (50 ± 9 years, 62 men) were included. The majority of patients presented with symptoms of heart failure. Over a median follow-up period of 30.3 months (IQR 12.2-57.7 months), 24 patients reached the primary endpoints. For clinical variables, multivariable analysis showed that drinking duration (HR=1.05; 95%CI:1.01, 1.11; p=0.03) and persistent drinking (HR=3.71; 95%CI:1.46, 9.44; p=0.01) were associated with MACE. For CMR variables, late gadolinium enhancement (LGE) percent (HR = 1.09; 95% CI: 1.03, 1.14; p<0.001) stood out as an independent predictor for MACE. CONCLUSIONS: In ACM patients, persistent drinking and cardiac MRI-defined myocardial scar were associated with adverse outcomes such as cardiac death, heart transplantation, hospitalization for heart failure or life-threatening ventricular arrhythmias.
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Cardiomiopatía Alcohólica , Imagen por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Femenino , Cardiomiopatía Alcohólica/diagnóstico por imagen , Pronóstico , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Factores de Riesgo , Imagen por Resonancia Cinemagnética/métodos , Medios de Contraste , AdultoRESUMEN
AIM: To investigate the value of pre-chemotherapy spectral computed tomography (CT) parameters in predicting neoadjuvant chemotherapy (NAC) response in gastric cancer (GC). MATERIALS AND METHODS: Sixty patients with GC who received NAC and underwent spectral CT examination before chemotherapy were enrolled retrospectively and divided into a responsive group and a non-responsive group according to the postoperative pathological tumour regression grade. Clinical characteristics were collected. The iodine concentration (IC), water concentration (WC), and effective atomic number (Eff-Z) of the portal venous phases were measured before chemotherapy, and IC was normalised to that of the aorta to provide the normalised IC (NIC). An independent samples t-test, Mann-Whitney U-test, or chi-square test was used to analyse the differences between the two groups, and the receiver operating curve (ROC) was used to evaluate the predictive performance of different variables. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was lower in the responsive group than in the non-responsive group (p<0.05). IC, NIC, and Eff-Z values were significantly higher in the responsive group than in the non-responsive group (p<0.01). The areas under the ROC curves for the NLR, IC, NIC, and Eff-Z were 0.694, 0.688, 0.799, and 0.690, respectively. The combination of NIC, Eff-Z, and NLR values showed good diagnostic performance in predicting response to NAC in GC, with an area under the ROC curve of 0.857, 76.92% sensitivity, 80% accuracy, and 85.71% specificity. CONCLUSION: Spectral CT parameters may serve as non-invasive tools for predicting the response to NAC in patients with GC.
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Yodo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Terapia Neoadyuvante , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Curva ROCRESUMEN
AIM: To explore the value of preoperative computed tomography (CT) histogram features in predicting the expression status of Ki-67 in patients with solid pseudopapillary pancreatic tumours (SPTP). MATERIALS AND METHODS: This retrospective study analysed venous phase CT images of 39 patients with SPTP confirmed at surgery and histopathology and measured using the Ki-67 proliferation index from November 2015 to February 2022. According to the Ki-67 proliferation index, they were divided into high expression (Ki-67 ≥ 4%) and low expression (Ki-67 < 4%) groups. The histogram features of quantitative parameters were extracted using MaZda software, and the quantitative parameters of CT histograms were compared between groups. The receiver operating characteristic (ROC) curves of the patients were plotted according to the parameters, with statistically significant differences. The area under the curve (AUC), sensitivity, and specificity were calculated, and the effectiveness of the histogram parameters in predicting Ki-67 expression was analysed and evaluated. RESULTS: In total, 27 SPTP patients were enrolled, including 11 with high expression of Ki-67 and 16 with low expression. Comparative analysis of the Ki-67 high- and low-expression groups revealed a statistically significant in necrosis and variance (p<0.05). ROC curve analysis showed that the AUC of necrosis and variance predicting Ki-67 expression status were 0.753 and 0.841, the sensitivities were 81.8% and 81.3%, and the specificities were 68.7% and 81.8%, respectively. CONCLUSION: Preoperative CT histogram features help predict Ki-67 expression status in patients with SPTP.
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Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Humanos , Antígeno Ki-67/metabolismo , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Curva ROC , NecrosisRESUMEN
AIM: To develop and validate a non-invasive computed tomography (CT)-based radiomics model for predicting vasculogenic mimicry (VM) status in lung adenocarcinoma (LA). MATERIALS AND METHODS: Two hundred and three patients with LA were enrolled retrospectively and grouped into training and test groups with a ratio of 7:3. Uni- and multivariate logistic regression analyses were performed in the training cohort to screen the independent clinical and radiological factors for VM, and the clinical model was then established. A radiomics model was established based on the rad-scores through support vector machine (SVM). A radiomics nomogram model was subsequently constructed by combining the rad-score with clinical-radiological factors. The receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA) were conducted to evaluate the performance of the three models. RESULTS: Nine selected radiomics features were selected for the radiomics model and the maximum length and spiculation sign were constructed for the clinical model. The radiomics nomogram model integrating the maximum length, spiculation sign, and rad-score yielded the best AUC in both the training (AUC = 0.925) and test cohorts (AUC = 0.978), in comparison with the radiomics model (AUC = 0.907 and 0.964, in both the training and test cohorts) and the clinical model (AUC = 0.834 and 0.836 in both training and test cohorts). CONCLUSIONS: The CT-based radiomics nomogram model showed satisfying discriminating performance for preoperatively and non-invasively predicting VM expression status in LA patients.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Radiómica , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adenocarcinoma del Pulmón/diagnóstico por imagen , Nomogramas , Neoplasias Pulmonares/diagnóstico por imagenRESUMEN
OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ã(L-AEFNIC) - ã(L-AEFC) (r= 0.419; p< 0.0001), ã(O-AEF40KeV) - ã(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.
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Neoplasias Pulmonares , Mediastinitis , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Persona de Mediana Edad , Mediastinitis/diagnóstico por imagen , Mediastinitis/complicaciones , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Anciano , Esclerosis/diagnóstico por imagen , Esclerosis/complicaciones , Adulto , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen , Broncoscopía/métodosRESUMEN
BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. OBJECTIVE: This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. METHODS: We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. RESULTS: A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). CONCLUSION: SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.
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BACKGROUND: We aimed to develop a nomogram model of overall survival (OS) and cancer-specific survival (CSS) in patients with differentiated thyroid cancer with distant metastases, and to evaluate and validate the nomogram. Also, its prognostic value was compared with that of the 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8SS). METHODS: Patients with distant metastatic differentiated thyroid cancer (DMDTC) from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. A total of 906 patients were divided into a training set (n = 634) and validation set (n = 272). OS and CSS were selected as the primary end point and secondary end point. LASSO regression analysis and multivariate Cox regression analysis were applied to screen variables for constructing OS and CSS nomograms for survival probability at 3, 5, and 10 years. Nomograms were evaluated and validated using the consistency index (C-index), time-dependent receiver operator characteristic (ROC) curves, area under the ROC curve, calibration curves, and decision curve analysis (DCA). The predictive survival of the nomogram was compared with that of AJCC8SS. Kaplan-Meier curves and log-rank tests were used to evaluate the risk-stratification ability OS and CSS nomograms. RESULTS: CS and CSS nomograms included six independent predictors: age, marital status, type of surgical procedure, lymphadenectomy, radiotherapy, and T stage. The C-index for the OS nomogram was 0.7474 (95% CI = 0.7199-0.775), and that for the CSS nomogram was 0.7572 (0.7281-0.7862). The nomogram showed good agreement with the "ideal" calibration curve in the training set and validation sets. DCA confirmed that the survival probability predicted by the nomogram had high clinical predictive value. The nomogram could stratify patients more accurately, and showed more robust accuracy and predictive power, than AJCC8SS. CONCLUSIONS: We established and validated prognostic nomograms for patients with DMDTC, which had significant clinical value compared with AJCC8SS.
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Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Nomogramas , Programa de VERF , Neoplasias de la Tiroides/terapia , Pronóstico , Estadificación de NeoplasiasRESUMEN
BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.
RESUMEN
PURPOSE: Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (RNA-seq) to find diagnostic markers and therapeutic targets. METHODS: ScRNA-seq data were clustered and malignant cells were identified. Differentially expressed genes (DEGs) were identified in malignant cells of scRNA-seq and bulk RNA-seq, respectively. PTC LNM diagnostic model was constructed based on intersecting DEGs using glmnet package. Next, PTC samples from 66 patients were used to validate the two most significant genes in the diagnostic model, S100A2 and type 2 deiodinase (DIO2) by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC). Further, the inhibitory effect of DIO2 on PTC cells was verified by cell biology behavior, western blot, cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, and xenograft tumors. RESULTS: Heterogeneity of PTC LNM was demonstrated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. A total of 19 differential genes were used to construct the diagnostic model. S100A2 and DIO2 differ significantly at the RNA (p < 0.01) and protein level in LNM patient tissues (p < 0.001). And differed in PTC tissues with different pathologic typing (p < 0.001). Further, EdU (p < 0.001) and cell biology behavior revealed that PTC cells overexpressed DIO2 had reduced proliferative capacity. Cell cycle proteins were reduced and cells are more likely to be stuck in G2/M phase (p < 0.001). CONCLUSIONS: This study explored the heterogeneity of PTC LNM using scRNA-seq. By combining with bulk RNA-seq data, diagnostic markers were explored and the model was established. Clinical diagnostic efficacy of S100A2 and DIO2 was validated and the treatment potential of DIO2 was discovered.
Asunto(s)
Biomarcadores de Tumor , Metástasis Linfática , Análisis de la Célula Individual , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Metástasis Linfática/diagnóstico , Metástasis Linfática/genética , Análisis de la Célula Individual/métodos , Animales , Ratones , Análisis de Secuencia de ARN/métodos , Femenino , Masculino , Proteínas S100/genética , Proteínas S100/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/metabolismo , Yodotironina Deyodinasa Tipo II , Proliferación Celular , Persona de Mediana Edad , Perfilación de la Expresión Génica/métodos , Factores QuimiotácticosRESUMEN
Respiratory rate (RR) is an important indicator of the health and welfare status of dairy cows. In recent years, progress has been made in monitoring the RR of dairy cows using video data and learning methods. However, existing approaches often involve multiple processing modules, such as region of interest (ROI) detection and tracking, which can introduce errors that propagate through successive steps. The objective of this study was to develop an end-to-end computer vision method to predict RR of dairy cows continuously and automatically. The method leverages the capabilities of a state-of-the-art Transformer model, VideoMAE, which divides video frames into patches as input tokens, enabling the automated selection and featurization of relevant regions, such as a cow's abdomen, for predicting RR. The original encoder of VideoMAE was retained, and a classification head was added on top of it. Further, the weights of the first 11 layers of the pre-trained model were kept, while the weights of the final layer and classifier were fine-tuned using video data collected in a tie-stall barn from 6 dairy cows. Respiratory rates measured using a respiratory belt for individual cows were serving as the ground truth (GT). The evaluation of the developed model was conducted using multiple metrics, including mean absolute error (MAE) of 2.58 breaths per minute (bpm), root mean squared error (RMSE) of 3.52 bpm, root mean squared prediction error (RMSPE; as a proportion of observed mean) of 15.03%, and Pearson correlation (r) of 0.86. Compared with a conventional method involving multiple processing modules, the end-to-end approach performed better in terms of MAE, RMSE and RMSPE. These results suggest the potential to implement the developed computer vision method for an end-to-end solution, for monitoring RR of dairy cows automatically in a tie-stall setting. Future research on integrating this method with other behavioral detection and animal identification algorithms for animal monitoring in a free-stall dairy barn can be beneficial for a broader application.