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1.
J Transl Med ; 22(1): 53, 2024 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218903

RESUMO

BACKGROUND: Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells. METHODS: To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson's disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector. RESULTS: This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson's disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals. CONCLUSIONS: Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.


Assuntos
Doença de Parkinson , Animais , Doença de Parkinson/genética , Doença de Parkinson/terapia , Leucócitos Mononucleares , Encéfalo/metabolismo , Terapia Genética/métodos , Transgenes , Vetores Genéticos , Dependovirus/genética
2.
Breast Cancer Res Treat ; 202(2): 275-286, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37542632

RESUMO

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos Retrospectivos , Prognóstico , Mama/patologia , Receptor ErbB-2/metabolismo , Período Pós-Parto , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo
3.
Sensors (Basel) ; 23(10)2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430539

RESUMO

With the development of artificial intelligence technology, systems that can actively adapt to their surroundings and cooperate with other systems have become increasingly important. One of the most important factors to consider during the process of cooperation among systems is trust. Trust is a social concept that assumes that cooperation with an object will produce positive results in the direction we intend. Our objectives are to propose a method for defining trust during the requirements engineering phase in the process of developing self-adaptive systems and to define the trust evidence models required to evaluate the defined trust at runtime. To achieve this objective, we propose in this study a provenance-based trust-aware requirement engineering framework for self-adaptive systems. The framework helps system engineers derive the user's requirements as a trust-aware goal model through analysis of the trust concept in the requirements engineering process. We also propose a provenance-based trust evidence model to evaluate trust and provide a method for defining this model for the target domain. Through the proposed framework, a system engineer can treat trust as a factor emerging from the requirements engineering phase for the self-adaptive system and understand the factors affecting trust using the standardized format.

4.
Sensors (Basel) ; 23(21)2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37960682

RESUMO

Images captured during marine engineering operations suffer from color distortion and low contrast. Underwater image enhancement helps to alleviate these problems. Many deep learning models can infer multi-source data, where images with different perspectives exist from multiple sources. To this end, we propose a multichannel deep convolutional neural network (MDCNN) linked to a VGG that can target multi-source (multi-domain) underwater image enhancement. The designed MDCNN feeds data from different domains into separate channels and implements parameters by linking VGGs, which improves the domain adaptation of the model. In addition, to optimize performance, multi-domain image perception loss functions, multilabel soft edge loss for specific image enhancement tasks, pixel-level loss, and external monitoring loss for edge sharpness preprocessing are proposed. These loss functions are set to effectively enhance the structural and textural similarity of underwater images. A series of qualitative and quantitative experiments demonstrate that our model is superior to the state-of-the-art Shallow UWnet in terms of UIQM, and the performance evaluation conducted on different datasets increased by 0.11 on average.

5.
Requir Eng ; 28(2): 213-227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36105860

RESUMO

As software engineering (SE) practitioners, we can help society by using our communities of experts to address a software need of a socially conscious organization. Doing so can benefit society in the locale of a SE conference and provide access to international experts for local organizations. Furthermore, established SE researchers as well as practitioners and students have the opportunity for a unique learning experience. While the SE community has already realized the importance of addressing human values and promoting social good objectives in software development, we are unaware of previous attempts to leverage SE conferences for this activity. Conferences present an opportunity to enjoy the assembly of SE practitioners, researchers, and students for the purpose of a philanthropic endeavor. Over the past four years of running a "Requirements Engineering for Social Good" event called RE Cares, co-located with the International Conference on Requirements Engineering, we worked with the stakeholders local to the conference venue. We selected stakeholders who would not necessarily have ready access to requirements engineering, software design, and development expertise otherwise, to build software targeting "good causes." In the last two years, this event was altered to adapt to the constraints induced by COVID-19, moving to a hybrid mode and changing many of its practices accordingly. This paper summarizes and generalizes our experiences, discussing our lessons learned in the context of the pandemic and beyond and providing a framework for conducting similar social contribution in any SE conferences in general.

6.
Sensors (Basel) ; 22(10)2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35632312

RESUMO

Current blockchain-based cloud (BBC) systems have several security vulnerabilities regarding smart contracts (SC), and several attacks have been reported recently. The SC development lacks standard design processes that follow software lifecycle principles to model secure SC. Secondly, the security mechanisms in the SC are not constantly evolved to resist evolving adversary attacks. BBC systems lack self-adaptive security capability to make spontaneous decisions when adversarial attacks are encountered. To build a self-adaptive secure BBC system that follows standard software development lifecycle principles to model secure SC, we propose the so-called self-adaptive security RE_BBC framework. The framework would utilize the MAPE-BBC adaptation loop to make decisions internally based on the threat models, goal models, and service level agreement (SLA) SC security specifications. The framework identifies vulnerabilities and threats and takes precautionary measures using self-adaptive SC agents. We validated the proposed methodology theoretically and empirically, and statistically proved the research questions and hypothesis using the t-test and Mann-Whitney U test. Subsequently, we compare our proposed approach with the Security Quality Requirements Engineering approach (SQUARE). The feasibility results and the replicated study results indicate that the proposed approach outperformed the SQUARE approach in terms of artifacts quality, self-adaptive security evaluation quality, efficiency in response time, complexity, and usefulness of the proposed approach for the Healthcare Data Management (HDM) system. SC security developers can immensely benefit from our proposed methodology. They need not reengineer SC from scratch; depending on their security needs and plan, the contract can be adapted to execute a new plan.


Assuntos
Blockchain , Segurança Computacional , Atenção à Saúde , Software
7.
J Foot Ankle Surg ; 60(6): 1110-1116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34130930

RESUMO

The purpose of this study was to investigate the suitability of bioabsorbable materials for fixation of extended distal chevron osteotomy and Akin osteotomy for the treatment of moderate to severe hallux valgus. We performed a retrospective analysis of extended distal chevron osteotomy and Akin osteotomy for the treatment of moderate to severe hallux valgus (33 patients, 42 feet). Fixation of extended distal chevron osteotomy and Akin osteotomy was performed using poly-l-lactic acid pins and polylactic acid/polyglycolic acid copolymer sutures, respectively. The radiological outcomes were evaluated based on the preoperative and 3-year follow-up intermetatarsal angle, hallux valgus angle, and hallux interphalangeal angle. The clinical results were assessed according to 3-year follow-up Manchester-Oxford Foot Questionnaire scores, patient satisfaction, and postoperative complications. All radiological and clinical results were compared with those of a control group treated with metallic implants. The mean 3-year follow-up intermetatarsal angle, hallux valgus angle, and hallux interphalangeal angle were significantly corrected from the preoperative values (all p < .001). The mean 3-year follow-up Manchester-Oxford Foot Questionnaire scores score was significantly improved from the preoperative values (p < .001). Regarding patient satisfaction, 88.1% of the patients reported good to excellent results. A total of seven complications were reported. All radiological and clinical results were comparable with those of control group treated with metallic implant. Based on these results, we recommend using bioabsorbable materials as another reliable device for fixation of extended distal chevron osteotomy and Akin osteotomy even for the treatment of moderate to severe hallux valgus.


Assuntos
Hallux Valgus , Implantes Absorvíveis , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Osteotomia , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
8.
Foot Ankle Surg ; 27(2): 217-223, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32402519

RESUMO

BACKGROUND: We used axial loading computed tomography (AL CT) to evaluate preoperative and postoperative talocrural joints of patients who underwent supramalleolar osteotomy (SMO) to treat varus ankle osteoarthritis. METHODS: We performed retrospective analyses of 16 patients (18 feet) who underwent SMO including fibular osteotomy. Radiographic assessment was performed with weightbearing radiographs and AL CT. Clinical outcomes were assessed based on American Orthopedic Foot & Ankle Society (AOFAS) scale, visual analog scale (VAS) for pain, and Foot and Ankle Ability Measure (FAAM). RESULTS: The mean 2-year follow-up tibial-ankle surface angle, talar tilt angle, Takakura stage, and tibial-lateral surface angle were all significantly different relative to preoperative parameters (P<.05). The mean 6-month follow-up talus rotation ratio was significantly corrected compared to the preoperative value (P=.001). The mean 2-year follow-up AOFAS, VAS at gait, and FAAM scores were all significantly improved relative to preoperative measurements (P=.001). CONCLUSIONS: Abnormal internal rotation of the talus in mild to moderate varus ankle osteoarthritis found on AL CT was significantly corrected after SMO. LEVEL OF EVIDENCE: Therapeutic Level IV.


Assuntos
Articulação do Tornozelo , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Osteotomia , Amplitude de Movimento Articular/fisiologia , Tálus/fisiopatologia , Adulto , Idoso , Tornozelo , Feminino , Fíbula/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Estudos Retrospectivos , Tálus/diagnóstico por imagem , Tálus/cirurgia , Tíbia/cirurgia , Tomografia Computadorizada por Raios X , Suporte de Carga , Adulto Jovem
10.
Int J Med Sci ; 16(11): 1525-1533, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673245

RESUMO

Radiotherapy, although used worldwide for the treatment of head, neck, and oral cancers, causes acute complications, including effects on vasculature and immune response due to cellular stress. Thus, the ability to diagnose side-effects and monitor vascular response in real-time during radiotherapy would be highly beneficial for clinical and research applications. In this study, recently-developed fluorescence micro-endoscopic technology provides non-invasive, high-resolution, real-time imaging at the cellular level. Moreover, with the application of high-resolution imaging technologies and micro-endoscopy, which enable improved monitoring of adverse effects in GFP-expressing mouse models, changes in the oral vasculature and lymphatic vessels are quantified in real time for 10 days following a mild localized single fractionation, 10 Gy radiotherapy treatments. Fluorescence micro-endoscopy enables quantification of the cardiovascular recovery and immune response, which shows short-term reduction in mean blood flow velocity, in lymph flow, and in transient immune infiltration even after this mild radiation dose, in addition to long-term reduction in blood vessel capacity. The data provided may serve as a reference for the expected cellular-level physiological, cardiovascular, and immune changes in animal disease models after radiotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Animais , Fracionamento da Dose de Radiação , Endoscopia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Vasos Linfáticos/patologia , Vasos Linfáticos/efeitos da radiação , Camundongos , Boca/irrigação sanguínea , Boca/diagnóstico por imagem , Boca/patologia , Boca/efeitos da radiação , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Lesões por Radiação/patologia
11.
Acta Med Okayama ; 72(6): 583-589, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30573913

RESUMO

We retrospectively evaluated the altered biomechanics of the talus in 15 adult patients (7 males, 8 females) with chronic lateral ankle instability when the ankle joint moved actively from full dorsiflexion to full plantarflexion under a non-weight bearing condition. CT images were taken for the unstable ankle and the contralateral normal (control) ankle. Three-dimensional surface models of both ankle joints were reconstructed from the CT data, and we used a computer simulation program to compare both ankle motions of inversion/eversion in the coronal plane, plantarflexion/dorsiflexion in the sagittal plane, and internal rotation/external rotation in the axial plane. This evaluation method provides in vivo, dynamic, and 3D results of ankle motion. In the ankles with chronic lateral instability and the controls, the average talar rotational movement of inversion (+)/eversion (-) was 19.0° and 15.5° and the internal rotation (+)/external rotation (-) was 30.4° and 20.7°, respectively. Paired t-tests revealed significant differences in the amount of inversion (+)/eversion (-) (p=0.012) and internal rotation (+)/external rotation (-) (p<0.001) between unstable and normal ankle joints. The difference of mean rotational movement in internal rotation (9.7°) was greater than that of inversion (3.5°). Rotational instability should be considered when evaluating chronic lateral ankle instability.


Assuntos
Articulação do Tornozelo/patologia , Instabilidade Articular/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Articulação do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Radiology ; 284(1): 45-54, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28253106

RESUMO

Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease-free survival. Conclusion Higher values of CAD-measured peak enhancement and washout component at preoperative MR imaging were significantly associated with poorer disease-free survival of patients with primary operable breast cancer. © RSNA, 2017.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Diagnóstico por Computador , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Meios de Contraste , Intervalo Livre de Doença , Feminino , Humanos , Cinética , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Compostos Organometálicos , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Breast Cancer Res Treat ; 157(1): 31-40, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27091644

RESUMO

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/anatomia & histologia , Imagem de Difusão por Ressonância Magnética/métodos , Menopausa/fisiologia , Ciclo Menstrual/fisiologia , Adulto , Idoso , Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos
14.
ScientificWorldJournal ; 2014: 382797, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25250374

RESUMO

In mobile cloud computing environment, the cooperation of distributed computing objects is one of the most important requirements for providing successful cloud services. To satisfy this requirement, all the members, who are employed in the cooperation group, need to share the knowledge for mutual understanding. Even if ontology can be the right tool for this goal, there are several issues to make a right ontology. As the cost and complexity of managing knowledge increase according to the scale of the knowledge, reducing the size of ontology is one of the critical issues. In this paper, we propose a method of extracting ontology module to increase the utility of knowledge. For the given signature, this method extracts the ontology module, which is semantically self-contained to fulfill the needs of the service, by considering the syntactic structure and semantic relation of concepts. By employing this module, instead of the original ontology, the cooperation of computing objects can be performed with less computing load and complexity. In particular, when multiple external ontologies need to be combined for more complex services, this method can be used to optimize the size of shared knowledge.


Assuntos
Sistemas Computacionais , Disseminação de Informação/métodos , Armazenamento e Recuperação da Informação/métodos , Bases de Conhecimento , Algoritmos , Biologia Computacional/métodos , Humanos
15.
Trauma Surg Acute Care Open ; 9(1): e001271, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298819

RESUMO

Background: Fibrinogen concentrate (FC) can be administered during massive transfusions to manage trauma-induced coagulopathy. However, its effectiveness in survival remains inconclusive due to scarce high-level evidence. This study aimed to investigate the hemostatic effects of FC regarding mortality in massive hemorrhage caused by trauma. Methods: This retrospective study analyzed 839 patients who received massive transfusions (red blood cells (RBCs) ≥5 units in 4 hours or ≥10 units in 24 hours) at a level I trauma center between 2015 and 2022. Patients who were transferred to other hospitals or were deceased upon arrival, suffered or died from severe brain injury, and were aged 15 years or less were excluded (n=334). 1:2 propensity score matching was performed to compare the 'FC (+)' group who had received FC in 24 hours (n=68) with those who had not ('FC (-)', n=437). The primary outcome was mortality, and the secondary outcomes included transfusion volume. Results: The variables for matching included vital signs, injury characteristics, prehospital time, implementation of resuscitative endovascular balloon occlusion of the aorta, and blood gas analysis results. The administration of FC did not significantly reduce or predict mortality (in-hospital, 24 hours, 48 hours, or 7 days). The FC (-) group received more units of RBC (25.69 units vs. 16.71 units, p<0.001, standardized mean difference [SMD] 0.595), fresh frozen plasma (16.79 units vs. 12.91 units, p=0.023, SMD 0.321), and platelets (8.76 units vs. 5.46 units, p=0.002, SMD 0.446) than the FC (+) group. Conclusion: The use of FC did not show survival benefits but reduced transfusion requirements in traumatic massive hemorrhages, highlighting a need for future investigations. In the future, individualized goal-directed transfusion with FC may play a significant role in treating massive bleeding. Level of evidence: IV, retrospective study having more than one negative criterion.

16.
Acta Neuropathol Commun ; 12(1): 5, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172953

RESUMO

BACKGROUND: Parthanatos represents a critical molecular aspect of Parkinson's disease, wherein AIMP2 aberrantly activates PARP-1 through direct physical interaction. Although AIMP2 ought to be a therapeutic target for the disease, regrettably, it is deemed undruggable due to its non-enzymatic nature and predominant localization within the tRNA synthetase multi-complex. Instead, AIMP2 possesses an antagonistic splice variant, designated DX2, which counteracts AIMP2-induced apoptosis in the p53 or inflammatory pathway. Consequently, we examined whether DX2 competes with AIMP2 for PARP-1 activation and is therapeutically effective in Parkinson's disease. METHODS: The binding affinity of AIMP2 and DX2 to PARP-1 was contrasted through immunoprecipitation. The efficacy of DX2 in neuronal cell death was assessed under 6-OHDA and H2O2 in vitro conditions. Additionally, endosomal and exosomal activity of synaptic vesicles was gauged in AIMP2 or DX2 overexpressed hippocampal primary neurons utilizing optical live imaging with VAMP-vGlut1 probes. To ascertain the role of DX2 in vivo, rotenone-induced behavioral alterations were compared between wild-type and DX2 transgenic animals. A DX2-encoding self-complementary adeno-associated virus (scAAV) was intracranially injected into 6-OHDA induced in vivo animal models, and their mobility was examined. Subsequently, the isolated brain tissues were analyzed. RESULTS: DX2 translocates into the nucleus upon ROS stress more rapidly than AIMP2. The binding affinity of DX2 to PARP-1 appeared to be more robust compared to that of AIMP2, resulting in the inhibition of PARP-1 induced neuronal cell death. DX2 transgenic animals exhibited neuroprotective behavior in rotenone-induced neuronal damage conditions. Following a single intracranial injection of AAV-DX2, both behavior and mobility were consistently ameliorated in neurodegenerative animal models induced by 6-OHDA. CONCLUSION: AIMP2 and DX2 are proposed to engage in bidirectional regulation of parthanatos. They physically interact with PARP-1. Notably, DX2's cell survival properties manifest exclusively in the context of abnormal AIMP2 accumulation, devoid of any tumorigenic effects. This suggests that DX2 could represent a distinctive therapeutic target for addressing Parkinson's disease in patients.


Assuntos
Doença de Parkinson , Parthanatos , Animais , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases , Proteínas Nucleares/metabolismo , Peróxido de Hidrogênio , Oxidopamina , Doença de Parkinson/genética , Doença de Parkinson/terapia , Rotenona , Linhagem Celular Tumoral
17.
Adv Mater ; 36(41): e2406179, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39003621

RESUMO

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.

18.
Sensors (Basel) ; 13(10): 13099-122, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24084108

RESUMO

Smartphone-based activity recognition (SP-AR) recognizes users' activities using the embedded accelerometer sensor. Only a small number of previous works can be classified as online systems, i.e., the whole process (pre-processing, feature extraction, and classification) is performed on the device. Most of these online systems use either a high sampling rate (SR) or long data-window (DW) to achieve high accuracy, resulting in short battery life or delayed system response, respectively. This paper introduces a real-time/online SP-AR system that solves this problem. Exploratory data analysis was performed on acceleration signals of 6 activities, collected from 30 subjects, to show that these signals are generated by an autoregressive (AR) process, and an accurate AR-model in this case can be built using a low SR (20 Hz) and a small DW (3 s). The high within class variance resulting from placing the phone at different positions was reduced using kernel discriminant analysis to achieve position-independent recognition. Neural networks were used as classifiers. Unlike previous works, true subject-independent evaluation was performed, where 10 new subjects evaluated the system at their homes for 1 week. The results show that our features outperformed three commonly used features by 40% in terms of accuracy for the given SR and DW.


Assuntos
Acelerometria/instrumentação , Actigrafia/instrumentação , Algoritmos , Telefone Celular , Computadores de Mão , Monitorização Ambulatorial/instrumentação , Reconhecimento Automatizado de Padrão/métodos , Acelerometria/métodos , Actigrafia/métodos , Sistemas Computacionais , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Miniaturização , Monitorização Ambulatorial/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transdutores
19.
J Phys Ther Sci ; 25(5): 635-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-24259819

RESUMO

[Purpose] The purpose of this study was to investigate the effects of visual feedback training (VFT) in the sitting position on sitting balance ability and visual perception of chronic stroke patients. [Subjects] Twenty-two hospitalized subjects who had experienced a stroke more than six months earlier were included in this study. [Methods] Subjects in both the experimental group (n=12) and the control group (n=10) participated in a conventional rehabilitation program involving a 60-minute session five days per week for a period of four weeks. Subjects in the experimental group additionally practiced VFT 30-minute sessions, five days per week, for a period of four weeks. [Results] After the intervention, the experimental group showed significantly improved static sitting balance ability (left∙right, anterior∙posterior moment, and velocity moment), and dynamic sitting balance ability (anterior∙lateral moment). In visual perception tests, motor free visual perception test (MVPT) scores showed a significant increase of approximately 17% in the experimental group after the intervention. [Conclusion] The results of this study demonstrate the effectiveness of VFT in enhancing body function, as evidenced by improved sitting balance and visual perception of chronic stroke patients.

20.
J Chest Surg ; 56(2): 108-116, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36710580

RESUMO

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has recently gained popularity as an adjunct to resuscitation of patients with traumatic shock. However, the effectiveness of REBOA is still debated because of inconsistent indications across centers and the lack of medical records. The purpose of this study was to investigate the effectiveness and feasibility of REBOA by analyzing clinical results from a single center. Methods: This study included 96 patients who underwent REBOA between August 2016 and September 2021 at a regional trauma center according to the center's treatment algorithm for traumatic shock. Medical records, including the time of the decision to conduct the REBOA procedure, time of operation, type of aortic occlusion, and clinical outcomes, were collected prospectively and analyzed retrospectively. Patients were classified by REBOA protocol (group 1, 2, or 3) and survival status (survivor or non-survivor) for analysis. Results: The overall success rate of the procedure was 97.9%, and the survival rate was 32.6%. In survivors, blood pressure was higher than in non-survivors both before the REBOA procedure (p=0.002) and after aortic occlusion (p=0.03). The total aortic occlusion time was significantly shorter (p=0.001) and the proportion of partial aortic occlusion was significantly higher (p=0.014) among the survivors. The non-survivors had more acidosis (p<0.001) and higher lactate concentrations (p<0.001) than the survivors. Conclusion: REBOA may be a feasible bridge therapy for resuscitation of patients with traumatic shock. Prompt and accurate decision-making to perform REBOA followed by damage control surgery could improve survival rates and clinical outcomes.

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