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Smart polymer materials that are nonliving yet exhibit complex "life-like" or biomimetic behaviors have been the focus of intensive research over the past decades, in the quest to broaden our understanding of how living systems function under nonequilibrium conditions. Identification of how chemical and mechanical coupling can generate resonance and entrainment with other cells or external environment is an important research question. We prepared Belousov-Zhabotinsky (BZ) self-oscillating hydrogels which convert chemical energy to mechanical oscillation. By cyclically applying external mechanical stimulation to the BZ hydrogels, we found that when the oscillation of a gel sample entered into harmonic resonance with the applied oscillation during stimulation, the system kept a "memory" of the resonant oscillation period and maintained it post stimulation, demonstrating an entrainment effect. More surprisingly, by systematically varying the cycle length of the external stimulation, we revealed the discrete nature of the stimulation-induced resonance and entrainment behaviors in chemical oscillations of BZ hydrogels, i.e., the hydrogels slow down their oscillation periods to the harmonics of the cycle length of the external mechanical stimulation. Our theoretical model calculations suggest the important roles of the delayed mechanical response caused by reactant diffusion and solvent migration in affecting the chemomechanical coupling in active hydrogels and consequently synchronizing their chemical oscillations with external mechanical oscillations.
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The rapid emergence of SARS-CoV-2 variants of concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as to inform the development of vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents of breakthrough infection with relatively high neutralizing titers against all tested viruses. Among 50 spike-specific monoclonal antibodies (mAbs) cloned from their B cells, the top 6 neutralizing mAbs (KXD01-06) belong to previously defined IGHV3-53/3-66 public antibodies. Although most antibodies in this class are dramatically escaped by VOCs, KXD01-06 all exhibit broad neutralizing capacity, particularly KXD01-03, which neutralize SARS-CoV-2 from prototype to the emerging EG.5.1 and FL.1.5.1. Deep mutational scanning reveals that KXD01-06 can be escaped by current and prospective variants with mutations on D420, Y421, L455, F456, N460, A475 and N487. Genetic and functional analysis further indicates that the extent of somatic hypermutation is critical for the breadth of KXD01-06 and other IGHV3-53/3-66 public antibodies. Overall, the prevalence of broadly neutralizing IGHV3-53/3-66 public antibodies in these two convalescents provides rationale for novel vaccines based on this class of antibodies. Meanwhile, KXD01-06 can be developed as candidates of therapeutics against SARS-CoV-2 through further affinity maturation.
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COVID-19 , Vacinas , Humanos , SARS-CoV-2/genética , Infecções Irruptivas , Estudos Prospectivos , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Anticorpos Antivirais , Anticorpos Neutralizantes , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome-sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland.
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Astrocitoma , Glioma , Humanos , Fosfatidilinositol 3-Quinases , Mutação , Glioma/genética , Medula Espinal/patologia , Proteínas de Ligação a RNA/genéticaRESUMO
BACKGROUND: Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. METHODS: This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. RESULTS: A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. CONCLUSIONS: Our multi-omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.
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Biomarcadores , Microbioma Gastrointestinal , Síndrome Metabólica , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/microbiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Antipsicóticos/uso terapêutico , RNA Ribossômico 16S/genéticaRESUMO
This study proposes a numerical approach for simulating bone remodeling in lumbar interbody fusion (LIF). It employs a topology optimization method to drive the remodeling process and uses a pixel function to describe the structural topology and bone density distribution. Unlike traditional approaches based on strain energy density or compliance, this study adopts von Mises stress to guide the remodeling of LIF. A novel pixel interpolation scheme associated with stress criteria is applied to the physical properties of the bone, directly addressing the stress shielding effect caused by the implanted cage, which significantly influences the bone remodeling outcome in LIF. Additionally, a boundary inverse approach is utilized to reconstruct a simplified analysis model. To reduce computational cost while maintaining high structural resolution and accuracy, the Scaled Boundary Finite Element Method (SBFEM) is introduced. The proposed numerical approach successfully generates results that closely resemble human lumbar interbody fusion.
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As one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection.
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Metabolismo dos Lipídeos , Olanzapina , Aumento de Peso , Animais , Feminino , Masculino , Camundongos , Metabolismo dos Lipídeos/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Lipidômica/métodos , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fatores Sexuais , Benzodiazepinas/farmacologia , Espectrometria de Massas/métodos , Dislipidemias/induzido quimicamente , Dislipidemias/metabolismo , Antipsicóticos , Lipídeos/sangue , Lipídeos/químicaRESUMO
Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.
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Necroptose , Proteínas Quinases , Camundongos , Animais , Humanos , Proteínas Quinases/metabolismo , Reposicionamento de Medicamentos , Apoptose , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
OBJECTIVE: Dural ossification (DO) is common in patients with ossification of the posterior longitudinal ligament (OPLL). The existence of DO makes surgery challenging and increases the risk of complications. The aim of this study was to investigate the incidence, distribution and radiological characteristics of DO associated with OPLL. METHODS: From January 2017 to January 2019, 55 patients with cervical OPLL were treated in our single center using an anterior cervical approach microsurgery. Preoperative CT images of decompressed segments were evaluated to identify imaging signs of DO. The 'double-layer sign' (DLS), 'parenthese sign' (PS) and 'hook sign' (HS) were considered to be characteristic imaging findings of DO in OPLL. Two kinds of confusing signs (false double-layer) were identified. RESULTS: Nineteen segments from 15 patients with OPLL had DO related to OPLL. The incidence of DO in OPLL segments was 30.16% (19/63), and the incidence of DO in patients with OPLL was 27.27% (15/55). DO occurred at the intervertebral space level in 14 cases and at the posterior level of the vertebral body in 5 cases. The sensitivity and specificity of imaging diagnosis were 89.47% (17/19) and 81.82% (36/44), respectively. The positive predictive value was relatively low, 68.00% (17/25), due to the false-positive double-layer sign. The negative predictive value was 94.74% (36/38). CONCLUSION: DO was relatively common in cervical OPLL. DLS might be misdiagnosed. PS and HS can vividly and intuitively describe the imaging features of DO and have high diagnostic accuracy.
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Ligamentos Longitudinais , Ossificação do Ligamento Longitudinal Posterior , Humanos , Ligamentos Longitudinais/cirurgia , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgiaRESUMO
Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. In this study we investigated the antitumor activity of osimertinib, an FDA-approved epidermal growth factor receptor (EGFR) inhibitor, against patient-derived primary GBM cells. Using high-throughput screening approach, we screened the entire panel of FDA-approved drugs against primary cancer cells derived from glioblastoma patients, found that osimertinib (3 µM) suppressed the proliferation of a subset (10/22) of EGFR-negative GBM cells (>50% growth inhibition). We detected the gene expression difference between osimertinib-sensitive and -resistant cells, found that osimertinib-sensitive GBM cells displayed activated MAPK-signaling pathway. We further showed that osimertinib potently inhibited the MNK kinase activities with IC50 values of 324 nM and 48.6 nM, respectively, against MNK1 and MNK2 kinases; osimertinib (0.3-3 µM) dose-dependently suppressed the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). In GBM patient-derived xenografts mice, oral administration of osimertinib (40 mg· kg-1 ·d-1, for 18 days) significantly suppressed the tumor growth (TGI = 74.5%) and inhibited eIF4E phosphorylation in tumor cells. Given the fact that osimertinib could cross the blood-brain barrier and its toxicity was well tolerated in patients, our results suggest that osimertinib could be a new and effective drug candidate for the EGFR-negative GBM patients.
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Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Criança , Receptores ErbB/deficiência , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Masculino , Camundongos , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto JovemRESUMO
BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.
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Depressão , Saúde Mental , China , Grupos Focais , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The existing classification in Chiari I malformation (CM-I) has limited significance for the selection of surgical methods. OBJECTIVE: The purpose of this study was to investigate the surgery of CM-I with syringomyelia based on the high-resolution MR imaging (HRMRI) findings. METHODS: Data from 115 patients were collected and retrospectively analyzed. For those with syringomyelia up to the level of C1, HRMRI was performed and according to the communication status between the fourth ventricle and the syringomyelia, patients can be divided into four types, namely Type A: classic communicating; Type B: partial communicating; Type C: non-communicating; Type D: atrophic. All operations were performed with Foramen magnum and Magendie dredging (FMMD), and all intradural factors that may have induced the obstruction of CSF circulation were recorded. The efficiency of operation on syringomyelia was evaluated by mJOA, imaging findings, and complications in the follow-up periods. RESULTS: The postoperative follow-up period was from 12 to 24 months, with an average of 14.3 months. At 1 year, the mJOA of 115 patients was significantly higher than that before the operations (before surgery 12.1 ± 2.3 vs. after surgery 14. 2 ± 1.4, P < 0.05). In addition, postoperative re-examination showed that the size of the syringomyelia was reduced or completely resolved in patients of Type A, 100% (2/2); Type B, 81% (9/11); Type C, 84% (81/97); and Type D, 20% (1/5). CONCLUSIONS: According to our new classification based on HRMRI, FMMD is the key to surgical treatment, especially for Type A and Type B patients.
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Malformação de Arnold-Chiari , Siringomielia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Forame Magno , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Siringomielia/diagnóstico por imagem , Siringomielia/cirurgia , Resultado do TratamentoRESUMO
Acute myeloid leukemia (AML) is reported to be vulnerable to transcription disruption due to transcriptional addiction. Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, has attracted extensive attention as a drug target. Although several inhibitors, such as alvocidib and dinaciclib, have shown potent therapeutic effects in clinical trials on AML, the lack of high selectivity for CDK9 and other CDKs has limited their optimal clinical efficacy. Therefore, developing highly selective CDK9 inhibitors is still imperative for the efficacy and safety profile in treating AML. Here, we report a novel highly selective CDK9 inhibitor, JSH-009, which exhibited high potency against CDK9 and displayed great selectivity over 468 kinases/mutants. It also demonstrates impressive in vitro and in vivo antileukemic efficacy in preclinical models of AML, which makes JSH-009 a useful pharmacological tool for elucidating CDK9-mediated transcription and a novel therapeutic candidate for AML.
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Antineoplásicos/uso terapêutico , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Inibidores de Proteínas Quinases/farmacologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: Primary spinal cord glioblastoma (GBM) is a rare and devastating disease. Little attention was ever paid to this rare disease. As a result, the standard treatment protocol and prognostic factors of primary spinal cord GBM were not well established. The aim of this study was to determine the predictors associated with survival in patients with primary spinal cord GBM. METHODS: A total of 122 patients with primary spinal cord GBM from Surveillance, Epidemiology, and End Results database and our institution were included in this retrospective analysis. Information about age, sex, race, tumor invasion, extent of resection, radiation, chemotherapy and year of diagnosis was collected. Univariate and multivariate accelerated failure time (AFT) regression model was performed to identify prognostic factors. RESULTS: Of the 122 patients, 102 (83.6%) expired at the time of data collection. Overall survival at 1 year, 2 years, 3 years and 5 years was 48.4%, 22.8%, 17.1% and 8.4%, respectively, and median survival time was 12 months. Only radiation was found to be associated with survival in the AFT regression model (time ratio 1.94, 95% CI 1.01-3.72, p < 0.05). Radiotherapy could improve survival slightly; patients who received RT survived approximately two times as long as patients who did not receive RT, but the advantage was short term. CONCLUSION: The survival of primary spinal cord GBM is poor in the current treatment strategy. Radiotherapy was associated with better survival, but the advantage was short term.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias da Medula Espinal , Bases de Dados Factuais , Glioblastoma/terapia , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias da Medula Espinal/terapiaRESUMO
Have you ever found it difficult to read something because you lack knowledge on the topic? We investigated this phenomenon with a sample of 3,534 high school students who took a background-knowledge test before working on a reading-comprehension test on the topic of ecology. Broken-line regression revealed a knowledge threshold: Below the threshold, the relationship between comprehension and knowledge was weak (ß = 0.18), but above the threshold, a strong and positive relation emerged (ß = 0.81). Further analyses indicated that certain topically relevant words (e.g., ecosystem, habitat) were more important to know than others when predicting the threshold, and these keywords could be identified using natural-language-processing techniques. Collectively, these results may help identify who is likely to have a problem comprehending information on a specific topic and, to some extent, what knowledge is likely required to comprehend information on that topic.
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Compreensão/fisiologia , Psicolinguística , Leitura , Adolescente , Feminino , Humanos , Conhecimento , MasculinoRESUMO
The dynamics of an entangled polymer melt confined in a channel by parallel plates is investigated by Molecular Dynamics (MD) simulations of a detailed, multi-chain model. A primitive path analysis predicts that the density of entanglements remains approximately constant throughout the gap and drops to lower values only in the immediate vicinity of the surface. Based on these observations, we propose a coarse-grained, single-chain slip-spring model with a uniform density of slip-spring anchors and slip-links. The slip-spring model is compared to the Kremer-Grest MD bead-spring model via equilibrium correlation functions of chain orientations. Reasonably good agreement between the single-chain model and the detailed multi-chain model is obtained for chain relaxation dynamics, both away from the surface and for chains whose center of mass positions are at a distance from the surface that is less than the bulk chain radius of gyration, without introducing any additional model parameters. Our results suggest that there is no considerable drop in topological interactions for chains in the vicinity of a single flat surface. We infer from the slip-spring model that the experimental plateau modulus of a confined polymer melt may be different to a corresponding unconfined system even if there is no drop in topological interactions for the confined case.
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The treatment strategies of depressive disorder include pharmacological treatment, psychotherapy, and physical therapy (electroconvulsive therapy [ECT], transcranial magnetic stimulation [TMS], etc.). The updated CANMAT guidelines recommended the most second-generation antidepressants as first-line treatments for patients with a major depressive disorder (MDD) of moderate or greater severity. Before antidepressant treatment, comprehensive assessment and safety monitoring are necessary. The application of measurement-based care in the diagnosis and treatment of depression would better ensure that enough dosage and response of antidepressant is achieved at each key point, and the final outcome of disease is improved. It is recommended that antidepressant is used with monotherapy in patients with depression. Antidepressants of different types and different mechanisms could be combined to improve the efficacy for patients with treatment-resistant depression (TRD). To prevent the relapse and recurrence of disease, the long-term treatment comprised of acute treatment, consolidation treatment, and maintenance treatment must be considered for all patients.
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Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Eletroconvulsoterapia , Humanos , Psicoterapia , Estimulação Magnética Transcraniana , Resultado do TratamentoRESUMO
The advances in the Internet and related technologies may lead to changes in professional roles of psychiatrists and psychotherapists. The application of artificial intelligence (AI) and electronic measurement-based care (eMBC) in the treatment of depressive disorder has addressed more interest. AI could play a role in population health management and patient administration as well as assist physicians to make a decision in the real-world clinical practice. The eMBC strengthens MBC through web/mobile devices and telephone consulting services, to monitor disease progression, and customizes the MBC interface in electronic medical record systems (EMRs).
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Inteligência Artificial , Transtorno Depressivo/terapia , Internet , Tomada de Decisão Clínica , Registros Eletrônicos de Saúde , HumanosRESUMO
The study of dynamics and rheology of well-entangled branched polymers remains a challenge for computer simulations due to the exponentially growing terminal relaxation times of these polymers with increasing molecular weights. We present an efficient simulation algorithm for studying the arm retraction dynamics of entangled star polymers by combining the coarse-grained slip-spring (SS) model with the forward flux sampling (FFS) method. This algorithm is first applied to simulate symmetric star polymers in the absence of constraint release (CR). The reaction coordinate for the FFS method is determined by finding good agreement of the simulation results on the terminal relaxation times of mildly entangled stars with those obtained from direct shooting SS model simulations with the relative difference between them less than 5%. The FFS simulations are then carried out for strongly entangled stars with arm lengths up to 16 entanglements that are far beyond the accessibility of brute force simulations in the non-CR condition. Apart from the terminal relaxation times, the same method can also be applied to generate the relaxation spectra of all entanglements along the arms which are desired for the development of quantitative theories of entangled branched polymers. Furthermore, we propose a numerical route to construct the experimentally measurable relaxation correlation functions by effectively linking the data stored at each interface during the FFS runs. The obtained star arm end-to-end vector relaxation functions Φ(t) and the stress relaxation function G(t) are found to be in reasonably good agreement with standard SS simulation results in the terminal regime. Finally, we demonstrate that this simulation method can be conveniently extended to study the arm-retraction problem in entangled star polymer melts with CR by modifying the definition of the reaction coordinate, while the computational efficiency will depend on the particular slip-spring or slip-link model employed.
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OBJECTIVE: It is difficult to completely and safely remove a tumor that is located in the subaxial cervical spine by using the posterior approach because of the anatomical characteristics. Previous reports regarding the total removal of subaxial schwannomas using the one-stage posterior approach are still limited. This study was to evaluate the feasibility and efficacy of treating the dumbbell-shaped schwannomas in the subaxial cervical spine using the one-stage posterior approach. METHODS: Patients with dumbbell-shaped schwannomas in the subaxial cervical spine were treated using the one-stage posterior approach. Surgical profile, clinical outcomes, MRI and X-ray images, and complications were investigated. Japanese Orthopaedic Association (JOA) score and McCormick functional schema score were obtained. RESULTS: The average follow-up was 21.5 ± 5.1 months, with a range of 12-31 months. Twenty-six patients were enrolled in the study. Total resection was achieved in all patients using the one-stage posterior approach with hemi- or laminectomy and facetectomy. All cases underwent lateral mass screw fixation and fusion. JOA improved significantly (p < 0.01). The McCormick score improved significantly (p < 0.05) after the surgery. No mortality, morbidity, or tumor recurrence was observed during the follow-up period. CONCLUSION: Our technique was feasible and effective for the treatment of dumbbell schwannomas in the subaxial cervical spine. The tumor could be totally removed in most cases safely.
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Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais , Feminino , Humanos , Laminectomia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The purpose of this study focuses on the changes of the syrinx volume after posterior reduction and fixation of the basilar invagination (BI) and atlantoaxial dislocation (AAD) with syringomyelia. METHODS: We retrospectively analyzed the clinical outcome and syrinx volume changes in 71 patients with BI, AAD and syringomyelia treated with the posterior reduction and fixation technique. RESULTS: Clinical improvement was observed in 64 (90.1 %) patients postoperatively; 5 (7.0 %) were stable and 2 (2.8 %) were clinically aggravated. The postoperative Atlantodental interval became normal in 61 patients (86.0 %); showed reduction that was greater than 50 % but not complete in 5 patients (7.0 %); and reduction which was less than 50 % in 5 patients (7.0 %). The size of the syrinx was reduced postoperatively in 66 patients (93.0 %) while no change in the remaining 5 patients (7.0 %). CONCLUSIONS: Posterior reduction and fixation of the AAD and BI can effectively enlarge the foramen magnum, improve the cerebrospinal fluid circulation and consequently reduce the volume of the syrinx.