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BACKGROUND: Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiovascular and cerebral events consisting of death, heart failure hospitalization, myocardial infarction, and stroke. METHODS: Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by 13N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women's Hospital (Boston, MA) from 2015 to 2021. In this post hoc observational study, biomarkers, echocardiographic parameters, and longitudinal clinical outcomes were compared by tertiles of subendocardial MFR (MFRsubendo). RESULTS: Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFRsubendo was 2.57 (interquartile range, 2.08-3.10), and lower MFRsubendo was associated with older age, diabetes, lower renal function, greater coronary calcium burden, and higher systolic blood pressure (P<0.05 for all). In cross-sectional multivariable regression analyses, the lowest tertile of MFRsubendo was associated with myocardial injury and with greater left ventricular wall thickness and volumes compared with the highest tertile. Relative to the highest tertile, low MFRsubendo was independently associated with an increased rate of major adverse cardiovascular and cerebral events (adjusted hazard ratio, 2.99 [95% CI, 1.39-6.44]; P=0.005) and heart failure hospitalization (adjusted hazard ratio, 2.76 [95% CI, 1.04-7.32; P=0.042) over 1.1 (interquartile range, 0.6-2.8) years median follow-up. CONCLUSIONS: Among patients with hypertension without flow-limiting coronary artery disease, impaired MFRsubendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.
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PURPOSE: Single-isocenter multi-target intracranial stereotactic radiotherapy (SIMT) is an effective treatment for brain metastases with complex treatment plans and delivery optimization necessitating rigorous quality assurance. This work aims to assess five methods for quality assurance of SIMT treatment plans in terms of their suitability and sensitivity to delivery errors. METHODS: Sun Nuclear ArcCHECK and SRS MapCHECK, GafChromic EBT Radiochromic Film, machine log files, and Varian Portal Dosimetry were all used to measure 15 variations of a single SIMT plan. Variations of the original plan were created with Python. They comprised various degrees of systematic MLC offsets per leaf up to 2 mm, random per-leaf variations with differing minimum and maximum magnitudes, simulated collimator, and dose miscalibrations (MU scaling). The erroneous plans were re-imported into Eclipse and plan-quality degradation was assessed by comparing each plan variation to the original clinical plan in terms of the percentage of clinical goals passing relative to the original plan. Each erroneous plan could be then ranked by the plan-quality degradation percentage following recalculation in the TPS so that the effects of each variation could be correlated with γ pass rates and detector suitability. RESULTS & CONCLUSIONS: It was found that 2%/1 mm is a good starting point for the ArcCHECK, Portal Dosimetry, and the SRS MapCHECK methods, respectively, and provides clinically relevant error detection sensitivity. Looser dose criteria of 5%/1 mm or 5%/1.5 mm are suitable for film dosimetry and log-file-based methods. The statistical methods explored can be expanded to other areas of patient-specific QA and detector assessment.
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Neoplasias Encefálicas , Garantia da Qualidade dos Cuidados de Saúde , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Encefálicas/radioterapia , Radiocirurgia/métodos , Radiocirurgia/instrumentação , Garantia da Qualidade dos Cuidados de Saúde/normas , Radioterapia de Intensidade Modulada/métodos , Aceleradores de Partículas/instrumentação , Radiometria/métodos , Radiometria/instrumentação , AlgoritmosRESUMO
Animal and human studies have demonstrated that intranasal oxytocin (OT) can penetrate the brain and induce cognitive, emotional, and behavioral changes, particularly in social functioning. Consequently, numerous investigations have explored the potential of OT as a treatment for anxiety and autism, conditions characterized by social deficits. Although both subclinical and clinical studies provide converging evidence of the therapeutic effects of OT in reducing anxiety levels and improving social symptoms in autism, results are not always consistent. Additionally, the pharmacological mechanism of OT requires further elucidation for its effective clinical application. Therefore, this review aims to examine the contentious findings concerning the effects of OT on anxiety and autism, offer interpretations of the inconsistent results from the perspectives of individual differences and varying approaches to OT administration, and shed light on the underlying mechanisms of OT. Ultimately, standardization of dosage, frequency of administration, formulation characteristics, and nasal spray devices is proposed as essential for future human studies and clinical applications of OT treatment.
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Administração Intranasal , Ansiedade , Transtorno Autístico , Ocitocina , Ocitocina/administração & dosagem , Ocitocina/uso terapêutico , Ocitocina/farmacologia , Humanos , Ansiedade/tratamento farmacológico , Transtorno Autístico/tratamento farmacológico , AnimaisRESUMO
The adult zebrafish (Danio rerio), which is genetically accessible, is being employed as a valuable vertebrate model to study human disorders such as cardiomyopathy. Intraperitoneal (IP) injection is an important method that delivers compounds to the body for either testing therapeutic effects or generating disease models such as doxorubicin-induced cardiomyopathy (DIC). Currently, there are two methods of IP injection. Both methods have limitations when handling toxic compounds such as doxorubicin, which result in side effects manifesting as severe damage to the body shape and fish death. While these shortcomings could be overcome by extensive investigator training, a new IP injection method that has minimal side effects is desirable. Here, a unique IP injection method that is able to handle toxic compounds is reported. Consistently reduced cardiac function can result without incurring significant fish death. The technique can be easily mastered by researchers who have minimal experience with adult zebrafish.
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Cardiomiopatias , Peixe-Zebra , Adulto , Animais , Humanos , Injeções Intraperitoneais , Injeções , DoxorrubicinaRESUMO
Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potency in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.
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Canabidiol , Camundongos , Animais , Masculino , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico , Dopamina/farmacologia , Camundongos Endogâmicos C57BL , Receptores de Dopamina D2/metabolismo , Núcleo Accumbens , Dor , Receptores de Dopamina D1/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Camundongos TransgênicosRESUMO
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.
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Fibrilação Atrial , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas de Transporte/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , Espécies Reativas de Oxigênio , Tiorredoxinas/genéticaRESUMO
Allelic heterogeneity (AH) has been noted in truncational TTN-associated (TTNtv-associated) dilated cardiomyopathy (DCM); i.e., mutations affecting A-band-encoding exons are pathogenic, but those affecting Z-disc-encoding exons are likely benign. The lack of an in vivo animal model that recapitulates AH hinders the deciphering of the underlying mechanism. Here, we explored zebrafish as a candidate vertebrate model by phenotyping a collection of zebrafish ttntv alleles. We noted that cardiac function and sarcomere structure were more severely disrupted in ttntv-A than in ttntv-Z homozygous embryos. Consistently, cardiomyopathy-like phenotypes were present in ttntv-A but not ttntv-Z adult heterozygous mutants. The phenotypes observed in ttntv-A alleles were recapitulated in null mutants with the full titin-encoding sequences removed. Defective autophagic flux, largely due to impaired autophagosome-lysosome fusion, was also noted only in ttntv-A but not in ttntv-Z models. Moreover, we found that genetic manipulation of ulk1a restored autophagy flux and rescued cardiac dysfunction in ttntv-A animals. Together, our findings presented adult zebrafish as an in vivo animal model for studying AH in TTNtv DCM, demonstrated TTN loss of function is sufficient to trigger ttntv DCM in zebrafish, and uncovered ulk1a as a potential therapeutic target gene for TTNtv DCM.
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Cardiomiopatias , Cardiomiopatia Dilatada , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Peixe-Zebra/genética , Mutação , Sarcômeros/genética , Sarcômeros/patologiaRESUMO
We study the dynamics of the end monomers of a real chain confined in a spherical cavity to search for a small target on the cavity surface using Langevin dynamics simulation. The results are compared and contrasted with those of a Rouse chain to understand the influence of excluded volume interactions on the search dynamics, as characterized by the first passage time (FPT). We analyze how the mean FPT depends on the cavity size Rb, the target size a, and the degree of confinement quantified by Rg/Rb, with Rg being the polymer radius of gyration in free space. As a basic finding, the equilibrium distribution of the end monomers of a real chain in a closed spherical cavity differs from that of a Rouse chain at a given Rg/Rb, which leads to the differences between the mean FPTs of real and Rouse chains. Fitting the survival probability S(t) by a multi-exponential form, we show that the S(t) of real chains exhibits multiple characteristic times at large Rg/Rb. Our simulation results indicate that the search dynamics of a real chain exhibit three characteristic regimes as a function of Rg/Rb, including the transition from the Markovian to non-Markovian process at Rg/Rb ≈ 0.39, along with two distinct regimes at 0.39 < Rg/Rb < 1.0 and Rg/Rb > 1.0, respectively, where S(t) exhibits a single characteristic time and multiple characteristic times.
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Unpredictable rainfall frequently results in excess moisture, which is detrimental to the landscape because it interferes with the genetic, morphological, and physiological processes of plants, even though the majority of urban landscapes frequently experience moisture shortages. A study was conducted to analyze the effects of a 36-day waterlogging phase and a subsequent 12-day recovery period on the morpho-physiological responses of 17 Crassulaceae species with the goal of identifying those which were more tolerant of the conditions. Results revealed that waterlogging stress has an impact on all morpho-physiological parameters. Sensitive materials (S7, Hylotelephium telephium 'Purple Emperor' and S15, S. sexangulare) showed severe ornamental quality damage, mortality, decreases in total dry biomass, root-shoot ratio, and chlorophyll content, as well as higher MDA concentrations. Lower reductions in these parameters, along with improved antioxidant enzyme activities and greater recovery capabilities after drainage, were observed in the most tolerant materials S2 (H. spectabile 'Brilliant'), S3 (H. spectabile 'Carl'), and S5 (H. telephium 'Autumn Joy'). Furthermore, with the exception of early death materials (S7 and S15), all materials showed varying intensities of adventitious root formation in response to waterlogging. The 17 species were divided into 4 clusters based on the comprehensive evaluation value. The first group included S1-S3, S5-S6, S8-S12, which were waterlogged tolerant with the highest values (0.63-0.82). S14 belongs to the intermediate waterlogging tolerant. S4, S13, S16, and S17 were clustered into the low waterlogging-tolerant group. S7 and S15 were the most susceptible to waterlogging. The survival and success of Crassulaceae species (especially, the first and second cluster), throughout this prolonged period of waterlogging (36 days) and recovery were attributed to a combination of physiological and morphological responses, indicating that they are an appealing species for the creation of rain gardens or obstructed drainage locations.
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Clorofila , Estações do Ano , BiomassaRESUMO
We utilized molecular dynamic simulation to investigate the glass formation of star polymer melts in which the topological complexity is varied by altering the number of star arms (f). Emphasis was placed on how the "confinement effect" of repulsive inter-arm interactions within star polymers influences the thermodynamics and dynamics of star polymer melts. All the characteristic temperatures of glass formation were found to progressively increase with increasing f, but unexpectedly the fragility parameter KVFT was found to decrease with increasing f. As previously observed, stars having more than 5 or 6 arms adopt an average particle-like structure that is more contracted relative to the linear polymer size having the same mass and exhibit a strong tendency for intermolecular and intramolecular segregation. We systematically analyzed how varying f alters collective particle motion, dynamic heterogeneity, the decoupling exponent ζ phenomenologically linking the slow ß- and α-relaxation times, and the thermodynamic scaling index γt. Consistent with our hypothesis that the segmental dynamics of many-arm star melts and thin supported polymer films should exhibit similar trends arising from the common feature of high local segmental confinement, we found that ζ increases considerably with increasing f, as found in supported polymer films with decreasing thickness. Furthermore, increasing f led to greatly enhanced elastic heterogeneity, and this phenomenon correlates strongly with changes in ζ and γt. Our observations should be helpful in building a more rational theoretical framework for understanding how molecular topology and geometrical confinement influence the dynamics of glass-forming materials more broadly.
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BACKGROUND: This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy. METHODS: 54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon's up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions. RESULTS: The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05). CONCLUSIONS: In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively. TRIAL REGISTRATION: ChiCTR2200066663, 13/12/2022.
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Colecistectomia Laparoscópica , Humanos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Estudos Prospectivos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Método Duplo-CegoRESUMO
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay.
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Opioid use disorder (OUD) is a critical problem in China and is accompanied by depression and deficits in cognitive control. In China, the most successful intervention for OUD is the community drug rehabilitation where methadone maintenance treatment (MMT) plays a key role. Even though methadone for the treatment of OUD can be helpful, it can cause severe somatic side-effects, which limit its effectivity. Even worse, it can have detrimental effects on cognitive control, which is crucial to regain control over drug intake. Here, we consider the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an addition to MMT for opioid withdrawal treatment. Compared to other non-invasive brain stimulation methods, atVNS also targets the locus coeruleus (LC) important for noradrenaline (NA) synthesis. NA is an essential neurotransmitter impacted in opioid withdrawal and also critically involved in cognitive control processes. Its ADD-ON to MMT might be a useful mean to improve mood and enhance cognitive control processes impacted in OUD. We discuss the translational advantages of atVNS in China such as the cultural acceptance of the modality of treatment similar to electroacupuncture. Additionally, the wearability of the ear electrode and at-home self-administration without intense medical supervision makes of atVNS a useful tool to enhance clinical and cognitive outcomes especially in everyday life situation. We discuss how atVNS can be integrated in tele-medical health approaches allowing that innovative treatments can widely be disseminated and continued even in situations of restricted medical access.
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Transtornos Relacionados ao Uso de Opioides , Estimulação do Nervo Vago , Humanos , Analgésicos Opioides/uso terapêutico , Estimulação do Nervo Vago/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , China , Metadona/uso terapêuticoRESUMO
Comorbidity has been frequently observed between generalized anxiety disorder (GAD) and major depressive disorder (MDD), however, common and distinguishable alterations in the topological organization of functional brain networks remain poorly understood. We sought to determine a robust and sensitive functional connectivity marker for diagnostic classification and symptom severity prediction. Multi-layered dynamic functional connectivity including whole brain, network-node and node-node layers via graph theory and gradient analyses were applied to functional MRI resting-state data obtained from 31 unmedicated GAD and 34 unmedicated MDD patients as well as 33 age and education matched healthy controls (HC). GAD and MDD symptoms were assessed using Penn State Worry Questionnaire and Beck Depression Inventory II, respectively. Three network measures including global properties (i.e., global efficiency, characteristic path length), regional nodal property (i.e., degree) and connectivity gradients were computed. Results showed that both patient groups exhibited abnormal dynamic cortico-subcortical topological organization compared to healthy controls, with MDD > GAD > HC in degree of randomization. Furthermore, our multi-layered dynamic functional connectivity network model reached 77% diagnostic accuracy between GAD and MDD and was highly predictive of symptom severity, respectively. Gradients of functional connectivity for superior frontal cortex-subcortical regions, middle temporal gyrus-subcortical regions and amygdala-cortical regions contributed more in this model compared to other gradients. We found shared and distinct cortico-subcortical connectivity features in dynamic functional brain networks between GAD and MDD, which together can promote the understanding of common and disorder-specific topological organization dysregulations and facilitate early neuroimaging-based diagnosis.
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In this work, the adsorption dynamics of mixed aqueous solutions of tetraethyleneglycol monoocthyl ether (C8E4) - dodecyltrimethylammonium bromide (DTAB) were studied using sessile bubble surface tensiometry. When C8E4 was added to the DTAB solution, the dynamic surface tension exhibited a unique oscillation decay pattern. In contrast, the addition of DTAB to the C8E4 solution resulted in a simple monotonic decay of the surface tension. The same trend was observed for mixtures of tetradecyltrimethylammonium bromide (TTAB) and DTAB. The occurrence of two distinguishable dynamic surface tension behaviors showed reasonable similarity with the theory of the adsorption kinetics of polymer solutions, where the surface tension oscillation was caused by the delayed desorption of polymers due to the conformational change at the solution surface. We compared the dynamic surface tension of binary surfactant systems and the polymer solution theory, and discussed the origin of surface tension oscillations based on the difference in the surface activity of the surfactants.
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BACKGROUND: Hepatic echinococcosis is a severe endemic disease in some underdeveloped rural areas worldwide. Qualified physicians are in short supply in such areas, resulting in low rates of accurate diagnosis of this condition. In this study, we aimed to develop and evaluate an artificial intelligence (AI) system for automated detection and subtyping of hepatic echinococcosis using plain CT images with the goal of providing interpretable assistance to radiologists and clinicians. METHODS: We developed EDAM, an echinococcosis diagnostic AI system, to provide accurate and generalisable CT analysis for distinguishing hepatic echinococcosis from hepatic cysts and normal controls (no liver lesions), as well as subtyping hepatic echinococcosis as alveolar or cystic echinococcosis. EDAM includes a slice-level prediction model for lesion classification and segmentation and a patient-level diagnostic model for patient classification. We collected a plain CT database (n=700: 395 cystic echinococcosis, 122 alveolar echinococcosis, 130 hepatic cysts, and 53 normal controls) for developing EDAM, and two additional independent cohorts (n=156) for external validation of its performance and generalisation ability. We compared the performance of EDAM with 52 experienced radiologists in diagnosing and subtyping hepatic echinococcosis. FINDINGS: EDAM showed reliable performance in patient-level diagnosis on both the internal testing data (overall area under the receiver operating characteristic curve [AUC]: 0·974 [95% CI 0·936-0·994]; accuracy: 0·952 [0·939-0·965] for cystic echinococcosis, 0·981 [0·973-0·989] for alveolar echinococcosis; sensitivity: 0·966 [0·951-0·979] for cystic echinococcosis, 0·944 [0·908-0·970] for alveolar echinococcosis) and the external testing set (overall AUC: 0·953 [95% CI 0·840-0·973]; accuracy: 0·929 [0·915-0·947] for cystic echinococcosis, 0·936 [0·919-0·950] for alveolar echinococcosis; sensitivity: 0·913 [0·879-0·944] for cystic echinococcosis, 0·868 [0·841-0·897] for alveolar echinococcosis). The sensitivity of EDAM was robust across images from different CT manufacturers. EDAM outperformed most of the enrolled radiologists in detecting both alveolar echinococcosis and cystic echinococcosis. INTERPRETATION: EDAM is a clinically applicable AI system that can provide patient-level diagnoses with interpretable results. The accuracy and generalisation ability of EDAM demonstrates its potential for clinical use, especially in underdeveloped areas. FUNDING: Project of Qinghai Provincial Department of Science and Technology of China, National Natural Science Foundation of China, and Tsinghua-Fuzhou Institute of Data Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Cistos , Aprendizado Profundo , Equinococose Hepática , Equinococose , Humanos , Equinococose Hepática/diagnóstico por imagem , Estudos Retrospectivos , Inteligência Artificial , Tomografia Computadorizada por Raios XRESUMO
Today, most humanoid mechanical fingers use an underactuated mechanism driven by linkages or tendons, with only a single and fixed grasping trajectory. This paper proposes a new multi-mode humanoid finger mechanism based on linkage and tendon fusion transmission, which is embedded with an adjustable-length tendon mechanism to achieve three types of grasping mode. The structural parameters of the mechanism are optimized according to the kinematic and static models. Furthermore, a discussion was conducted on how to set the speed ratio of the linkage driving motor and the tendon driving motor to adjust the length and tension of the tendon, in order to achieve the switching of the shape-adaptive, coupled-adaptive, and variable coupling-adaptive grasping modes. Finally, the multi-mode functionality of the proposed finger mechanism was verified through multiple grasping experiments.
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Hepatocellular carcinoma (HCC) poses a significant threat to human health and medical care. Its dynamic microenvironment and stages of development will influence the treatment strategies in clinics. Reconstructing tumor-microvascular interactions in different stages of the microenvironment is an urgent need forin vitrotumor pathology research and drug screening. However, the absence of tumor aggregates with paracancerous microvascular and staged tumor-endothelium interactions leads to bias in the antitumor drug responses. Herein, a spheroid-on-demand manipulation strategy was developed to construct staged endothelialized HCC models for drug screening. Pre-assembled HepG2 spheroids were directly printed by alternating viscous and inertial force jetting with high cell viability and integrity. A semi-open microfluidic chip was also designed to form a microvascular connections with high density, narrow diameter, and curved morphologies. According to the single or multiple lesions in stages â or â HCC, endothelialized HCC models from micrometer to millimeter scale with dense tumor cell aggregation and paracancerous endothelial distribution were successively constructed. A migrating stage â HCC model was further constructed under TGF-ßtreatment, where the spheroids exhibited a more mesenchymal phenotype with a loose cell connection and spheroid dispersion. Finally, the stage â HCC model showed stronger drug resistance compared to the stage â model, while the stage III showed a more rapid response. The corresponding work provides a widely applicable method for the reproduction of tumor-microvascular interactions at different stages and holds great promise for the study of tumor migration, tumor-stromal cell interactions, and the development of anti-tumor therapeutic strategies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Esferoides Celulares/patologia , Impressão Tridimensional , Microambiente TumoralRESUMO
BACKGROUND AND AIMS: Coronary small vessel disease (CSVD) is often associated with significant percutaneous coronary intervention (PCI) related complications, complex lesions, complex PCI, and poor long-term prognosis. We designed this retrospective study to clarify the characteristics, risk factors, and prognostic analyses of CSVD in Chinese populations. METHODS: A total of 986 patients who underwent coronary angiography and stent implantation at the First Affiliated Hospital of Zhejiang University School of Medicine were evaluated. Patients were grouped into CSVD or non-small vessel disease (non-CSVD) according to stent diameter. Clinical data, coronary angiography, and long-term follow-up were recorded. Multivariate logistic regression, the Kaplan-Meier method, Log-rank Test, and Cox regression model were used for statistical analysis. RESULTS: Alcohol consumption (OR = 0.420, 95% CI: 0.299-0.588, P < 0.001) was implicated as a negative CSVD correlation factor. CSVD was more likely to be associated with multi-vessel lesions (79.2% vs. 49.4%, P < 0.001), bifurcation lesions (24.0% vs. 12.4%, P < 0.001), chronic total obstruction lesions (29.5% vs. 9.4%, P < 0.001), and long lesions (55.2% vs. 35.7%, P < 0.001), which reduced the efficacy of revascularization (70.1% vs. 85.1%, P < 0.001). In the follow-ups, cardiac death (2.3% vs. 0.4%, P = 0.008), stroke (1.9% vs. 0.3%, P = 0.007), target lesion revascularization (5.8% vs. 2.9%, P = 0.029), target vessel revascularization (6.8% vs. 3.4%, P = 0.016), and non-target vessel revascularization (7.8% vs. 4.0%, P = 0.012) were all substantially higher in CSVD patients. Troponin I level (OR = 1.008, 95% CI: 1.004-1.012, P < 0.001), complete revascularization (OR = 0.292, 95% CI: 0.160-0.531, P < 0.001), and aspirin administration (OR = 0.041, 95% CI: 0.013-0.131, P < 0.001) were independent predictors of MACE events of all patients. CONCLUSION: Compared to non-CSVD, CSVD was associated with more complex lesions, had worse revascularization efficacy, and a poorer prognosis.