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1.
J Chin Med Assoc ; 87(7): 714-721, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829990

ABSTRACT

BACKGROUND: Changing the course duration or timing of subjects in learning pathways would influence medical students' learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts. METHODS: This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset. RESULTS: We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway. CONCLUSION: An approach to finding a promising learning pathway facilitating students' learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.


Subject(s)
Cognition , Learning , Humans , Cohort Studies , Students, Medical/psychology , Curriculum , Female , Male
2.
Stat Med ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845095

ABSTRACT

The US FDA's Project Optimus initiative that emphasizes dose optimization prior to marketing approval represents a pivotal shift in oncology drug development. It has a ripple effect for rethinking what changes may be made to conventional pivotal trial designs to incorporate a dose optimization component. Aligned with this initiative, we propose a novel seamless phase II/III design with dose optimization (SDDO framework). The proposed design starts with dose optimization in a randomized setting, leading to an interim analysis focused on optimal dose selection, trial continuation decisions, and sample size re-estimation (SSR). Based on the decision at interim analysis, patient enrollment continues for both the selected dose arm and control arm, and the significance of treatment effects will be determined at final analysis. The SDDO framework offers increased flexibility and cost-efficiency through sample size adjustment, while stringently controlling the Type I error. This proposed design also facilitates both accelerated approval (AA) and regular approval in a "one-trial" approach. Extensive simulation studies confirm that our design reliably identifies the optimal dosage and makes preferable decisions with a reduced sample size while retaining statistical power.

3.
Proc Natl Acad Sci U S A ; 121(27): e2402587121, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38923994

ABSTRACT

Morphogenesis is one of the most marvelous natural phenomena. The morphological characteristics of biological organs develop through growth, which is often triggered by mechanical force. In this study, we propose a bioinspired strategy for hydrogel morphogenesis through force-controlled chemical reaction and growth under isothermal conditions. We adopted a double network (DN) hydrogel with sacrificial bonds. Applying mechanical force to the gel caused deformation and sacrificial bond rupture. By supplying monomers to the gel, the radicals generated by the bond rupture triggered the formation of a new network inside the deformed gel. This new network conferred plasticity to the elastic gel, allowing it to maintain its deformed shape, along with increased volume and strength. We demonstrated that sheet-shaped DN hydrogels rapidly adopted various three-dimensional shapes at ambient temperature when subjected to forces such as drawing and blowing. This mechanism enables morphogenesis of elastic hydrogels and will promote the application of these materials in biomedical fields and soft machines.

4.
Sci Adv ; 10(20): eadl4387, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38748786

ABSTRACT

4D printing enables 3D printed structures to change shape over "time" in response to environmental stimulus. Because of relatively high modulus, shape memory polymers (SMPs) have been widely used for 4D printing. However, most SMPs for 4D printing are thermosets, which only have one permanent shape. Despite the efforts that implement covalent adaptable networks (CANs) into SMPs to achieve shape reconfigurability, weak thermomechanical properties of the current CAN-SMPs exclude them from practical applications. Here, we report reconfigurable 4D printing via mechanically robust CAN-SMPs (MRC-SMPs), which have high deformability at both programming and reconfiguration temperatures (>1400%), high Tg (75°C), and high room temperature modulus (1.06 GPa). The high printability for DLP high-resolution 3D printing allows MRC-SMPs to create highly complex SMP 3D structures that can be reconfigured multiple times under large deformation. The demonstrations show that the reconfigurable 4D printing allows one printed SMP structure to fulfill multiple tasks.

5.
Inquiry ; 61: 469580241237095, 2024.
Article in English | MEDLINE | ID: mdl-38712799

ABSTRACT

Improving the residents' health is an important strategy for addressing the declining population dividend in China under the new development paradigm. Based on the panel data of 290 prefecture-level cities in China from 2010 to 2021, this paper uses environmental tax as a quasi-natural experiment, and adopts a DID model to explore the impact of market-based environmental regulation on the residents' health. The results show that the implementation of environmental tax can significantly reduce the population mortality rate, indicating an enhancement in residents' health outcomes. Mechanism analysis shows that environmental tax mainly relies on air quality to improve the residents' health. Also, the heath effect of environmental tax will be effective with the increase of income, and it's stronger in administrative border areas. Heterogeneity analysis shows that the effect of environmental tax on residents' health in western regions and resource-based cities is significantly stronger than those in central and eastern regions and non-resource-based cities. This paper provides new evidence for a comprehensive understanding of the impact of market-based environmental regulations on residents' well-being, offering insights for the implementation of green development strategies.


Subject(s)
Taxes , Humans , China , Health Status , Air Pollution/prevention & control , Cities
6.
J Chin Med Assoc ; 87(6): 609-614, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38648194

ABSTRACT

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data preprocessing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and 10 subjects from the basic medical science stage with an area under the ROC curve (AUC) >0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry, and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.


Subject(s)
Clinical Clerkship , Machine Learning , Humans , Cohort Studies , Students, Medical , Male , Female
7.
Front Immunol ; 15: 1367265, 2024.
Article in English | MEDLINE | ID: mdl-38550589

ABSTRACT

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.


Subject(s)
Hepatitis B, Chronic , Humans , Male , Female , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/pathology , Alanine Transaminase , Retrospective Studies , DNA, Viral , Antiviral Agents/therapeutic use
8.
Clin Imaging ; 108: 110112, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38457906

ABSTRACT

PURPOSE: To illustrate MRI findings in patients with femoral neuropathy following anterior approach total hip arthroplasty (THA). METHODS: This was a retrospective review of patients who underwent MRI for femoral neuropathy following anterior approach THA between January 1, 2010, and July 1, 2022. Included patients had no preexisting neurologic condition. Clinical and diagnostic data were collected. MRIs were reviewed in consensus by 2 musculoskeletal radiologists. RESULTS: A total of 115 patient records were reviewed, 17 of which were included in the final analysis (mean age 64 years; 11 females). Study subjects presented with weakness with hip flexion and knee extension and pain and numbness in the femoral nerve distribution. In 7 subjects, the femoral nerve appeared normal. In 5 subjects, the femoral nerve was hyperintense on fluid-sensitive fat-suppressed imaging. In 4 patients, mass effect on the femoral nerve by either ill-defined soft tissue edema (n = 2), seroma (n = 1), or heterotopic ossification (n = 1) was detected. Only 1 patient had a nerve transection. Patients were imaged at a median time of 8 months (range: 1 day to 11 years) following arthroplasty placement. Clinical follow-up was available in 8 patients, of whom half had complete symptomatic resolution and half had partial improvement at a mean follow-up time of 39.3 months (SD 51.1). Of these 8, 1 underwent revision arthroplasty, 1 had removal of hardware, and another had excision of heterotopic ossification. CONCLUSION: MRI provides a means to directly evaluate the femoral nerve following anterior approach THA in both the immediate and chronic postoperative periods.


Subject(s)
Arthroplasty, Replacement, Hip , Femoral Neuropathy , Ossification, Heterotopic , Female , Humans , Middle Aged , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Femoral Neuropathy/diagnostic imaging , Femoral Neuropathy/etiology , Femoral Nerve/diagnostic imaging , Femoral Nerve/injuries , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Magnetic Resonance Imaging , Retrospective Studies , Treatment Outcome
9.
Perfusion ; : 2676591241238871, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38458155

ABSTRACT

OBJECTIVES: Hybrid coronary revascularization (HCR) involves the use of minimally invasive direct coronary artery bypass grafting (CABG) to treat the left anterior descending artery (LAD), and percutaneous coronary intervention to treat non-LAD vessels. We reported the results of a comparative analysis between HCR and off-pump CABG via sternotomy (OPCABG). METHODS: Data were retrospectively collated from patients who underwent HCR or OPCABG for multivessel coronary artery disease between 2011 and 2022. Propensity score-based matching was performed to reduce the selection bias. The Comparisons of cardiac-related death, major adverse cardiac and cerebrovascular events (MACCE), and repeat revascularization were performed by Kaplan-Meier analysis or the Fine-Gray test. RESULTS: After matching, the baseline characteristics were well-balanced between the two groups with 91 patients per group. There was no significant difference in operative mortality rate (1.1% for HCR vs2.2% for OPCABG, p = 1.000). However, patients undergoing HCR required a significantly lower rate of blood product transfusions (p < .001) and experienced significantly fewer pulmonary complications than OPCABG patients (p < .001). At 10 years, the incidences of cardiac-related death, MACCE and repeat revascularization did not differ significantly between the two groups (9.5% vs11.5%, p = .277; 4.7% vs12.3%, p = .361; 1.2% vs2.5%, p = .914, respectively). CONCLUSIONS: For patients with multi-vessel lesions, HCR was comparable to OPCABG in long-term outcomes such as cardiac-related death, MACCE, and the durability of grafts. Additionally, HCR was better than OPCABG in perioperative outcomes. HCR may be an alternative therapy for OPCABG in patients with multi-vessel coronary artery disease.

10.
Opt Lett ; 49(6): 1607-1610, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489462

ABSTRACT

We numerically establish the controllable conversion between Laguerre-Gaussian and Hermite-Gaussian solitons in nonlinear media featuring parabolic and cross-phase potential wells. The parabolic potential maintains the stability of Laguerre-Gaussian and Hermite-Gaussian beams, while the actual conversion between the two modes is facilitated by the cross-phase potential, which induces an additional phase shift. By flexibly engineering the range of the cross-phase potential well, various higher-mode solitons can be generated at desired distances. Beams carrying orbital angular momentum can also be efficiently controlled by this method. In addition, other types of beams, such as sine complex-various-function Gaussian and hypergeometric-Gaussian vortex beams, can be periodically transformed and manipulated in a similar manner. Our approach allows the intricate internal relationships between different modes of beams to be conveniently revealed.

11.
BMC Cardiovasc Disord ; 24(1): 182, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532333

ABSTRACT

OBJECTIVE: To evaluate the early and mid-term outcomes of open repair in patients with thoracoabdominal aortic aneurysm (TAAA) after thoracic endovascular aortic repair (TEVAR). METHODS: This was a retrospective single center study. Data were retrospectively collected and analyzed for consecutive patients undergoing open TAAA repair (TAAAR) after TEVAR from November 2016 to June 2021. Indications for TAAAR included aneurysm progression due to endoleak, persisted false lumen perfusion, proximal/distal disease progression, and aorta rupture. The risk factor of operative mortality was analyzed by multivariable logistic regression model and the survival was evaluated by Kaplan-Meier. RESULTS: Sixty-three patients who met the inclusion criteria for the study were identified. The mean age at TAAAR was 41 ± 12 years and 43 (68.3%) were male. Marfan syndrome (MFS) was presented in 39 patients (61.9%). 60 (95.2%) patients presented with post-dissection aneurysm and 3 (4.8%) patients with degenerative aneurysm. The extent of TAAA was Crawford I in 9 (14.3%), II in 22 (34.9%), III in 23 (36.5%), and IV in 9 (14.3%). Emergent TAAAR was done in 10 (15.9%) patients, and deep hypothermic circulatory arrest was used in 22 (34.6%). Endograft was explanted in 31 (49.2%). Operative mortality was 11 (17.5%). Stroke, paraplegia, and acute kidney failure occurred in 5 (7.9%), 7 (11.1%), and 6 (9.5%) patients, respectively. Pulmonary complications occurred in 19 (30.2%) patients. The estimated survival was 74.8 ± 4.9% at 5 years. Late reoperations were performed in 2 patients at 2.5 years and 1.3 years, respectively. CONCLUSIONS: In this series of TAAA after TEVAR, TAAAR was related with a high risk of operative mortality and morbidity and the midterm outcomes represented a durable treatment and were respectable.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Aneurysm, Thoracoabdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Male , Female , Endovascular Aneurysm Repair , Blood Vessel Prosthesis/adverse effects , Retrospective Studies , Blood Vessel Prosthesis Implantation/adverse effects , Treatment Outcome , Aortic Aneurysm, Thoracic/surgery , Risk Factors , Endovascular Procedures/adverse effects , Postoperative Complications
12.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38256911

ABSTRACT

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

13.
Br J Radiol ; 97(1153): 274-282, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263841

ABSTRACT

OBJECTIVES: To validate the feasibility of intravoxel incoherent motion imaging (IVIM) for monitoring renal injury and uric acid-lowering efficacy in a rat model of hyperuricaemia. METHODS: A total of 92 rats were analysed and categorized into 4 groups: control (CON), hyperuricaemia (HUA), allopurinol intervention (ALL), and combined intervention (COM). Eight rats were randomly selected from each group and underwent IVIM scanning on days 0, 1, 3, 5, 7, and 9. Quantitative magnetic resonance values (D, D*, and f values) measured from the different renal anatomical regions. Quantitative histopathological analysis was performed to assess renal tubular injury using neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis using alpha-smooth-muscle-actin (α-SMA). Pearson's correlation analysis was used to determine the correlation between IVIM-derived parameters and the expression of NGAL and α-SMA. RESULTS: The D values of the HUA, ALL, and COM groups generally showed a downward trend over time, and this fluctuation was most significant in the HUA group. The D values showed significant intergroup differences at each point, whereas only a few discrepancies were found in the D* and f values. In addition, the renal D value was negatively correlated with the positive staining rates for NGAL and α-SMA (P < .05), except for the lack of correlation between Dos and α-SMA (P > .05). CONCLUSION: IVIM could be a noninvasive and potential assessment modality for the evaluation of renal injury induced by hyperuricaemia and its prognostic efficacy. ADVANCES IN KNOWLEDGE: IVIM could be a surrogate manner in monitoring renal damage induced by hyperuricaemia and its treatment evaluation.


Subject(s)
Hyperuricemia , Animals , Rats , Lipocalin-2 , Uric Acid , Kidney , Diagnostic Imaging
14.
Skeletal Radiol ; 53(5): 863-869, 2024 May.
Article in English | MEDLINE | ID: mdl-37930380

ABSTRACT

OBJECTIVE: To determine if diagnostic ultrasound can reliably distinguish between synovial patterns of prosthetic joint infection and polymeric wear in total knee replacements. METHODS AND METHODS: This retrospective study was approved by our hospital IRB. Using the radiology report database, MR examinations performed within a week of diagnostic ultrasound and/or ultrasound-guided aspiration were identified. This yielded (1) 24 cases with MR and ultrasound comparisons; (2) 44 cases with MR, ultrasound, and aspiration comparisons; and (3) 92 cases with ultrasound and aspiration comparisons. The MR studies were reviewed by a musculoskeletal radiologist. The ultrasound studies were each reviewed by 2 other musculoskeletal radiologists. Each study was graded for synovial pattern indicating infection, polymeric wear, or normal/nonspecific. Agreement between the MR grader and the ultrasound graders as well as ultrasound inter-rater agreement were assessed using k statistics. Sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound were calculated. RESULTS: Agreement between ultrasound and MR imaging was fair to moderate: k of 0.27 (95% CI: 0.04, 0.50) and 0.44 (95% CI: 0.23, 0.65) for ultrasound raters 1 and 2, respectively. Inter-rater agreement between ultrasound graders 1 and 2 was moderate, with k of 0.56 (95% CI: 0.42, 0.70). Ultrasound sensitivities for infection were 0.13 and 0.09, while specificities were 0.94 and 0.98. Ultrasound sensitivities for polymeric wear were 0.38 and 0.62 with specificities of 0.90 and 0.76. CONCLUSION: Ultrasound does not perform well in distinguishing patterns of synovitis either compared to MRI or a reference standard of aspiration/clinical follow-up.


Subject(s)
Knee Joint , Synovitis , Humans , Retrospective Studies , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging/methods , Ultrasonography , Sensitivity and Specificity
15.
Public Health Nurs ; 41(2): 200-208, 2024.
Article in English | MEDLINE | ID: mdl-38037451

ABSTRACT

OBJECTIVES: To explore the risk factors of social isolation in older adults by meta-analysis. METHODS: We examined articles that had been published on the China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service platform, VIP Periodical Chinese Journal Service platform, Medical Literature database, PubMed, Embase database, Chinese BioMedical Literature database (CBM), and the Cochrane Library. RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 13 pieces of literature comprising 47,288 patients were included, including five in Chinese and eight in English. According to our review, the common risk factors reported were age, sex, education level, marital status, self-rated health status, depression, social support, cognitive function, and basic diseases. Gender (female), education level (lower education level), marital status (divorced), self-rated health status (poor), depression, lack of social support, inadequate cognitive function, and underlying disorders were the key risk factors for social isolation in older adults. CONCLUSIONS: To reduce social isolation in older adults, paying more attention to the aging population with poor marital statuses, low education levels, poor health statuses, depression, poor cognitive function, and other underlying diseases is necessary. It is essential to encourage patients and their family members to participate in social activities and build a multi-social support system to reduce social isolation in older adults.


Subject(s)
Health Status , Social Isolation , Aged , Humans , China/epidemiology , Risk Factors
16.
Front Immunol ; 14: 1280759, 2023.
Article in English | MEDLINE | ID: mdl-38045698

ABSTRACT

Objective: This paper observes the efficacy of chemotherapy combined with CD19 and CD20 monoclonal antibodies in clearing minimal residual disease (MRD) and bridging transplantation for refractory acute B-lymphoblastic leukemia (B-ALL) in children and reviews the literature. Methods: A 4-year-old boy diagnosed with B-ALL in our hospital was treated with the SCCLG-ALL-2016 protocol. MRD and gene quantification decreased after induction but remained persistently positive, with poor efficacy. After this patient received three cycles of consolidation chemotherapy combined with blinatumomab and rituximab, MRD and fusion gene quantification became negative, and he received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: During the use of monoclonal antibodies, neurotoxicity, CRS, or other side effects did not occur. Before transplantation, MRD became negative, and the bone marrow had been in complete remission since transplantation (13 months). Conclusion: Chemotherapy combined with blinatumomab for refractory B-ALL in children can bring a better remission rate for patients and is a means of bridging transplantation. Nevertheless, sequential CD20 monoclonal antibody therapy is the first report , and no adverse effects were observed in our case. It is well tolerated and can be used as one of the treatments for refractory B-ALL.


Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child, Preschool , Humans , Male , Antibodies, Monoclonal/therapeutic use , Bone Marrow , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
17.
Neoplasma ; 70(4): 526-533, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37789783

ABSTRACT

The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy.


Subject(s)
Gastrointestinal Stromal Tumors , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/genetics , Imatinib Mesylate/pharmacology , Cell Line, Tumor , Autophagy/genetics , Hypoxia/genetics , Cell Proliferation/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics
18.
J Immunother ; 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37904601

ABSTRACT

Immune checkpoint inhibitors (ICI) have gained approval as a treatment for a wide array of cancers. Their mechanism of action prevents the inactivation of cytotoxic T-cells, allowing for its cytotoxic response. However, the upregulation of the immune system by ICI also leads to many undesired adverse events known as immune-related adverse events (irAEs), ranging from dermatologic manifestations, such as rashes, to inflammation of mucous membranes, to hematologic toxicities. Here, we report a case of ICI-induced pure white cell aplasia, secondary to the agent durvalumab, which responded to treatment with filgrastim, prednisone, and cyclosporine. ICI-neutropenia accounts for 0.6% of all irAEs or 17% of hematologic irAEs. Given the rarity of hematologic irAEs, the available treatment guidelines are based on expert consensus. As ICI becomes more widely used, we can expect an increase in the prevalence of rare irAEs as well. This case report aims to present a rare side effect of ICI and demonstrate its response to immunosuppressive therapy while providing guidance for future clinicians and further elucidating the mechanism behind these irAEs.

19.
Biologicals ; 84: 101717, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37801802

ABSTRACT

O'nyong-nyong fever is a mosquito-borne tropical viral disease while few molecular diagnostic tools have been established for its surveillance until now. In the current study, a single-step, dual-color real-time reverse transcription polymerase chain reaction (RT-PCR) assay which contained both external quality control (EQC) and internal quality control (IQC) prepared by armored RNA technique was developed and evaluated for the detection of o'nyong-nyong virus (ONNV). Results showed that the assay was established successfully without cross-reaction with genetically related or symptom-alike diseases, which showed high specificity of the assay. The coefficient of variation of the assay was 0.97%, far less than 5%, indicating good repeatability of the assay. The lower limit of detection of the assay could reach as low as 100 copies of genome equivalent. During evaluation, the assay could correctly detect ONNV from spiked human serum samples and Anopheles species mosquito samples, while no ONNV positive was observed either from serum samples of patients with acute febrile illness or from local Anopheles species mosquitoes, suggesting no ONNV had been transmitted locally. In conclusion, the assay could potentially provide a valuable platform for ONNV molecular detection, which may improve the preparedness for future o'nyong-nyong fever outbreaks.


Subject(s)
Anopheles , O'nyong-nyong Virus , Animals , Humans , O'nyong-nyong Virus/genetics , Reverse Transcriptase Polymerase Chain Reaction , Anopheles/genetics , Real-Time Polymerase Chain Reaction , Cross Reactions
20.
IEEE Trans Pattern Anal Mach Intell ; 45(12): 14465-14480, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37713217

ABSTRACT

During image editing, existing deep generative models tend to re-synthesize the entire output from scratch, including the unedited regions. This leads to a significant waste of computation, especially for minor editing operations. In this work, we present Spatially Sparse Inference (SSI), a general-purpose technique that selectively performs computation for edited regions and accelerates various generative models, including both conditional GANs and diffusion models. Our key observation is that users prone to gradually edit the input image. This motivates us to cache and reuse the feature maps of the original image. Given an edited image, we sparsely apply the convolutional filters to the edited regions while reusing the cached features for the unedited areas. Based on our algorithm, we further propose Sparse Incremental Generative Engine (SIGE) to convert the computation reduction to latency reduction on off-the-shelf hardware. With about 1%-area edits, SIGE accelerates DDPM by 3.0× on NVIDIA RTX 3090 and 4.6× on Apple M1 Pro GPU, Stable Diffusion by 7.2× on 3090, and GauGAN by 5.6× on 3090 and 5.2× on M1 Pro GPU. Compared to our conference paper, we enhance SIGE to accommodate attention layers and apply it to Stable Diffusion. Additionally, we offer support for Apple M1 Pro GPU and include more results to substantiate the efficacy of our method.

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