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BACKGROUND: Participatory approaches have become a widely applied research approach. Despite their popularity, there are many challenges associated with the evaluation of participatory projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of our evaluation were to explore the main benefits and challenges of implementing and participating in a participatory study and to describe study impacts. METHODS: We conducted two meetings with leaders and members of the participating groups followed by in-depth interviews with 10 participants. We then held a dissemination meeting with over 70 participants, including the representatives of each group, researchers from non-governmental organizations (community-based, national and international), and govenrment officials from the Vietnam Ministry of Health and the Department of Health of HCMC. RESULTS: Results include four categories where we describe first the participatory impacts, followed by the collaborative impacts. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. CONCLUSION: In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view.
Participatory approaches in research aim to include participants in an array of aspects of the study, including developing research questions, collecting data, conducting analysis, etc. It has become a more popular method, however there are still challenges surrounding the evaluation of these projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of the evaluation were to discuss and explore the main benefits and challenges with those who participated, as well as assess study impacts. To conduct the evaluation, we conducted two meetings with leaders and members of the participating groups followed by interviews with 10 people who were involved. The evaluation results included four categories including impacts for members as well as wider impacts in the community. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view.
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Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.
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Trasplante de Microbiota Fecal , Lactobacillus , Humanos , Trasplante de Microbiota Fecal/métodos , Adulto , Adolescente , Femenino , Masculino , Adulto Joven , Método Doble Ciego , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/microbiología , Microbioma Gastrointestinal , Proyectos Piloto , Heces/microbiología , Resultado del Tratamiento , Enfermedad de Crohn/terapia , Enfermedad de Crohn/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Colitis Ulcerosa/terapia , Colitis Ulcerosa/microbiologíaRESUMEN
This was a cross-sectional study on the availability of laboratory infrastructure and capacity for the diagnosis of invasive fungal diseases in 24 public hospitals in Vietnam in 2023. Among the hospitals surveyed, 66.7% (14/21) had specialised personnel assigned for mycology testing, and 95.8% (23/24) had a separate microbiology laboratory space. Microscopy and culture methods are available in nearly all laboratories for isolate identification. Antifungal susceptibility testing is only performed for yeasts in 16/24 (66.7%) laboratories. Non-culture methods are hardly used in laboratories. Strengthening local laboratory capacities is essential to meeting health needs in these endemic regions.
There was a need for investment in fungal diagnostics to improve health services in the settings with burden of endemic fungal infections.
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BACKGROUND: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. METHODS: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. FINDINGS: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. CONCLUSIONS: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. FUNDING: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.
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There have been many studies on the adverse effects of coronavirus disease 2019 (COVID-19) vaccines but the urinary incontinence after COVID-19 vaccination is rare. Here, we report an 8-year-old boy presented to outpatient department, Thai Binh University of Medicine Hospital, Thai Binh, Vietnam with complaints of urinary incontinence for the past 2 weeks, following the first dose of the messenger RNA vaccine. He had no other abnormalities in clinical and laboratory exams. This clinical situation suggested vaccine side effects. No specific treatment was administered upon diagnosis without toilet and bladder training. Subsequent monitoring revealed a gradual reduction in symptoms over 2 months, with complete recovery achieved at the 14th week from the onset of symptoms, without necessitating any medical intervention. This case highlights the need for thorough evaluation and assessment of potential adverse effects following vaccination, including uncommon presentations.
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BACKGROUND: The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not on normal hematopoietic stem cells (HSCs), providing an opportunity to target and eliminate the disease, while sparing normal hematopoiesis. Herein, we report the activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML. METHODS: Antibodies to IL1RAP were isolated from CD138+ B cells collected from the immunized mice by optoelectric positioning and single cell sequencing. Individual mouse monoclonal antibodies (mAbs) were produced and characterized, from which we generated BIF002, an anti-human IL1RAP/CD3 TCE using Fab arm exchange. Mutations in human IgG1 Fc were introduced to reduce FcγR binding. The antileukemic activity of BIF002 was characterized in vitro and in vivo using multiple cell lines and patient derived AML samples. RESULTS: IL1RAP was found to be highly expressed on most human AML cell lines and primary blasts, including CD34+ LSC-enriched subpopulation from patients with both de novo and relapsed/refractory (R/R) leukemia, but not on normal HSCs. In co-culture of T cells from healthy donors and IL1RAPhigh AML cell lines and primary blasts, BIF002 induced dose- and effector-to-target (E:T) ratio-dependent T cell activation and leukemic cell lysis at subnanomolar concentrations. BIF002 administered intravenously along with human T cells led to depletion of leukemic cells, and significantly prolonged survival of IL1RAPhigh MOLM13 or AML patient-derived xenografts with no off-target side effects, compared to controls. Of note, BiF002 effectively redirects T cells to eliminate LSCs, as evidenced by the absence of disease initiation in secondary recipients of bone marrow (BM) from BIF002+T cells-treated donors (median survival not reached; all survived > 200 days) compared with recipients of BM from vehicle- (median survival: 26 days; p = 0.0004) or isotype control antibody+T cells-treated donors (26 days; p = 0.0002). CONCLUSIONS: The novel anti-IL1RAP/CD3 TCE, BIF002, eradicates LSCs and significantly prolongs survival of AML xenografts, representing a promising, novel treatment for AML.
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Proteína Accesoria del Receptor de Interleucina-1 , Leucemia Mieloide Aguda , Células Madre Neoplásicas , Linfocitos T , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/tratamiento farmacológico , Humanos , Animales , Ratones , Proteína Accesoria del Receptor de Interleucina-1/inmunología , Linfocitos T/inmunología , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Ratones Endogámicos NODRESUMEN
We disclose the synthesis of 3-arylquinoxalin-2-ones from o-phenylenediamines and readily available arylacetates. The method harnesses the selective oxidative property of elemental sulfur in the presence of amine base catalyst and DMSO. The reactions are operationally simple and tolerate a wide range of functional groups.
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Video-based remote photoplethysmography (rPPG) has emerged as a promising technology for non-contact vital sign monitoring, especially under controlled conditions. However, the accurate measurement of vital signs in real-world scenarios faces several challenges, including artifacts induced by videocodecs, low-light noise, degradation, low dynamic range, occlusions, and hardware and network constraints. In this article, a systematic and comprehensive investigation of these issues is conducted, measuring their detrimental effects on the quality of rPPG measurements. Additionally, practical strategies are proposed for mitigating these challenges to improve the dependability and resilience of video-based rPPG systems. Methods for effective biosignal recovery in the presence of network limitations are detailed, along with denoising and inpainting techniques aimed at preserving video frame integrity. Compared to previous studies, this paper addresses a broader range of variables and demonstrates improved accuracy across various rPPG methods, emphasizing generalizability for practical applications in diverse scenarios with varying data quality. Extensive evaluations and direct comparisons demonstrate the effectiveness of these approaches in enhancing rPPG measurements under challenging environments, contributing to the development of more reliable and effective remote vital sign monitoring technologies.
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Artefactos , Fotopletismografía , Grabación en Video , Humanos , Fotopletismografía/métodos , Procesamiento de Señales Asistido por Computador , Masculino , Femenino , Adulto , Monitoreo Fisiológico/métodosRESUMEN
We report on the antileukemic activity of homoharringtonine (HHT) in T-ALL. We showed that HHT inhibited NOTCH/MYC pathway and induced a significantly longer survival in T-ALL mouse and patient-derived xenograft models, therefore supporting HHT as a promising agent for T-ALL.
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Non-traditional security (NTS) threats have a vast and profound impact on many aspects of economic, political, social, and many other areas, especially supply chain finance (SCF), particularly in countries like Vietnam, which potentially affects the economic efficiency of businesses' supply chain financial, thereby affecting the general economy of the country and the world. In order to prevent and minimize the negative impacts caused by NTS threats to SCF, this study was conducted to identify NTS threats affecting SCF in Vietnam, at the same time calculate the weight of the impact level and find out the cause and effect relationship between them. Solution strategies are also proposed and ranked, thereby serving as a reference basis for relevant parties to choose appropriate response solutions. Due to the multi-criteria nature of NTS threats, the multiple criteria decision-making (MCDM) method is used in combination with the Z-number concept and Fuzzy set theory to approach the problem of certainty and increase the accuracy of study. The NTS threats are first identified through a literature review and then validated for suitability using the DELPHI technique (DELPHI). Suitable threats will be determined by relationship, weighted by Decision Making Trial And Evaluation Laboratory (DEMATEL) method. Proposed strategies are ranked using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method. The results indicate that there are 19 NTS factors affecting SCF in Vietnam, and the global economic downturn, pandemic and health crisis, financial crisis and cybersecurity risk are the four root cause factors with the most decisive influence. Businesses and concerns need to prioritize addressing these four threats because they not only have a strong impact but also entail many other threats. The two strategies considered to be the most effective are a sustainable practice and a risk-hedging strategy. Businesses, governments, and stakeholders also should pay attention to the macroeconomic environment, technology, and environment and build sustainable businesses, regularly monitoring economic fluctuations and creating plans to prevent risks.
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Accurate medical image segmentation is critical for disease quantification and treatment evaluation. While traditional U-Net architectures and their transformer-integrated variants excel in automated segmentation tasks. Existing models also struggle with parameter efficiency and computational complexity, often due to the extensive use of Transformers. However, they lack the ability to harness the image's intrinsic position and channel features. Research employing Dual Attention mechanisms of position and channel have not been specifically optimized for the high-detail demands of medical images. To address these issues, this study proposes a novel deep medical image segmentation framework, called DA-TransUNet, aiming to integrate the Transformer and dual attention block (DA-Block) into the traditional U-shaped architecture. Also, DA-TransUNet tailored for the high-detail requirements of medical images, optimizes the intermittent channels of Dual Attention (DA) and employs DA in each skip-connection to effectively filter out irrelevant information. This integration significantly enhances the model's capability to extract features, thereby improving the performance of medical image segmentation. DA-TransUNet is validated in medical image segmentation tasks, consistently outperforming state-of-the-art techniques across 5 datasets. In summary, DA-TransUNet has made significant strides in medical image segmentation, offering new insights into existing techniques. It strengthens model performance from the perspective of image features, thereby advancing the development of high-precision automated medical image diagnosis. The codes and parameters of our model will be publicly available at https://github.com/SUN-1024/DA-TransUnet.
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Linear gold complexes of the "carbene-metal-amide" (CMA) type are prepared with a rigid benzoguanidine amide donor and various carbene ligands. These complexes emit in the deep-blue range at 424 and 466 nm with 100% quantum yields in all media. The deep-blue thermally activates delayed fluorescence originates from a charge transfer state with an excited state lifetime as low as 213 ns, resulting in fast radiative rates of 4.7 × 106 s-1. The high thermal and photo-stability of these carbene-metal-amide (CMA) materials enabled the authors to fabricate highly energy-efficient organic light-emitting diodes (OLED) in host-guest architectures. Deep-blue OLED devices with electroluminescence at 416 and 457 nm with practical external quantum efficiencies of up to 23% at 100 cd m-2 with excellent color coordinates CIE (x; y) = 0.16; 0.07 and 0.17; 0.18 are reported. The operating stability of these OLEDs is the longest reported to date (LT50 = 1 h) for deep-blue CMA emitters, indicating a high promise for further development of blue OLED devices. These findings inform the molecular design strategy and correlation between delayed luminescence with high radiative rates and CMA OLED device operating stability.
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Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9â ±â 0.1 versus 0.8â ±â 0.1 (Pâ <â .001), while ScysC concentration did not show this difference. The mGFR in the age groupsâ <â 40, 40 to 59, andâ ≥â 60: 105.0â ±â 9.9, 94.8â ±â 8.6, and 93.4â ±â 10.6, respectively (Pâ <â .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFRâ =â -1.6, Râ =â 0.68, Pâ <â .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.
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Creatinina , Cistatina C , Tasa de Filtración Glomerular , Humanos , Cistatina C/sangre , Femenino , Masculino , Creatinina/sangre , Persona de Mediana Edad , Adulto , Estudios Transversales , Vietnam , Pentetato de Tecnecio Tc 99m , Anciano , Biomarcadores/sangre , Radiofármacos , Pueblos del Sudeste AsiáticoRESUMEN
BACKGROUND: Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. METHODS: We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. FINDINGS: M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. INTERPRETATION: Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that M tuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. FUNDING: National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.
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Antituberculosos , Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Vietnam/epidemiología , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Estudio de Asociación del Genoma Completo , Resultado del Tratamiento , Fenotipo , Filogenia , Mutación , Fenómica , Genotipo , Femenino , Adulto , MasculinoRESUMEN
The increasing incidence of urothelial carcinoma, coupled with advancements in its therapeutic landscape, has resulted in improved survival rates for patients. This, in turn, has led to a growing population of patients requiring specialized oncological care, with Enfortumab vedotin (EV) emerging as a pivotal treatment for metastatic urothelial carcinoma. While EV is associated with hyperglycemia, ketoacidosis is exceedingly rare. To the best of our knowledge, the link between EV and hemophagocytic lymphohistiocytosis (HLH) has not yet been explored. A 56-year-old patient diagnosed with metastatic urothelial carcinoma underwent EV treatment as a third-line treatment after progression following treatment with cisplatin/gemcitabine and pembrolizumab. Notably, after receiving two doses of EV, the patient exhibited refractory insulin resistance, leading to ketoacidosis. Subsequently, HLH emerged, necessitating a treatment regimen involving dexamethasone and etoposide. Despite intensive efforts, the patient experienced septic shock, resulting in death. The present case report highlights refractory insulin resistance and ketoacidosis, followed by reactive HLH, in the context of EV therapy. The limited literature on these complications demonstrates the need for further research to improve the understanding of the underlying mechanisms. With growing evidence of the efficacy of EV and evolving survival rates in urothelial carcinoma, healthcare professionals must remain vigilant for potential adverse effects, ensuring early recognition and optimal patient care.
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Terpenes in essential oils (EOs) have recently received significant attention due to their potential to improve brain and whole-body health. A deeper understanding of the terpene composition of edible EOs is important for fully exploring their possible applications. In our study, we employed a comprehensive study using four different methods to analyze EO samples, including GC-MS with solid phase microextraction (SPME), liquid injection (LI), derivatization to trimethylsilyl ethers (TMSE), and LC-MS. Our findings revealed that relying on a single analytical method may be insufficient for detecting all terpenes in EOs. Despite identifying a total of 156 terpenes in the samples, only 58 were detectable across all 4 methods. To obtain a more accurate terpene profile of EOs, we advocate for the combined use of LI-GC and TMSE-GC. The terpenes detected by these two methods are complementary, enabling the detection of all terpenes with high VIP in the samples.
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Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles , Microextracción en Fase Sólida , Terpenos , Aceites Volátiles/química , Terpenos/análisis , Terpenos/química , Microextracción en Fase Sólida/métodos , Cromatografía Liquida/métodos , Aceites de Plantas/químicaRESUMEN
Plants use chemistry to overcome diverse challenges. A particularly striking chemical trait that some plants possess is the ability to synthesize massive amounts of epicuticular wax that accumulates on the plant's surfaces as a white coating visible to the naked eye. The ability to synthesize basic wax molecules appears to be shared among virtually all land plants, and our knowledge of ubiquitous wax compound synthesis is reasonably advanced. However, the ability to synthesize thick layers of visible epicuticular crystals ("wax blooms") is restricted to specific lineages, and our knowledge of how wax blooms differ from ubiquitous wax layers is less developed. Here, we recruited the help of citizen scientists and middle school students to survey the wax bloom chemistry of 78 species spanning dicot, monocot, and gymnosperm lineages. Using gas chromatography-mass spectrometry, we found that the major wax classes reported from bulk wax mixtures can be present in wax bloom crystals, with fatty acids, fatty alcohols, and alkanes being present in many species' bloom crystals. In contrast, other compounds including aldehydes, ketones, secondary alcohols, and triterpenoids were present in only a few species' wax bloom crystals. By mapping the 78 wax bloom chemical profiles onto a phylogeny and using phylogenetic comparative analyses, we found that secondary alcohol and triterpenoid-rich wax blooms were present in lineage-specific patterns that would not be expected to arise by chance. That finding is consistent with reports that secondary alcohol biosynthesis enzymes are found only in certain lineages but was a surprise for triterpenoids, which are intracellular components in virtually all plant lineages. Thus, our data suggest that a lineage-specific mechanism other than biosynthesis exists that enables select species to generate triterpenoid-rich surface wax crystals. Overall, our study outlines a general mode in which research scientists can collaborate with citizen scientists as well as middle and high school classrooms not only to enhance data collection and generate testable hypotheses but also to directly involve classrooms in the scientific process and inspire future STEM workers.
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PURPOSE: The factors related to pericoronitis severity are unclear, and this study aimed to address this knowledge gap. MATERIALS AND METHODS: In total, 113 patients with pericoronitis were included, and their demographic, clinical, and radiographic characteristics were recorded. The Patient-Clinician Pericoronitis Classification was used to score and categorize the severity of pericoronitis. Statistical analysis was conducted to examine the participants' characteristics, validity of the Patient-Clinician Pericoronitis Classification, and risk factors associated with the severity of pericoronitis. RESULTS: The demographic, clinical, and radiographic characteristics of males and females were similar, except for Winter's classification, pain, and intraoral swelling. The constructive validity of the Patient-Clinician Pericoronitis Classification was confirmed with three latent factors, including infection level, patient discomfort, and social interference. Ordinal logistic multivariate regression analysis revealed that upper respiratory tract infection was the sole risk factor associated with pericoronitis severity in males (odds ratio = 4.838). In females, pericoronitis on the right side (odds ratio = 2.486), distal radiolucency (odds ratio = 5.203), and menstruation (odds ratio = 3.416) were significant risk factors. CONCLUSION: This study demonstrated the constructive validity of the Patient-Clinician Pericoronitis Classification. Among females, pericoronitis in mandibular third molars on the right side with radiolucency in menstruating individuals was more severe. In males, upper respiratory tract infection was the sole risk factor associated with pericoronitis severity. CLINICAL RELEVANCE: Individuals with risk factors should be aware of severe pericoronitis in the coming future.
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Tercer Molar , Pericoronitis , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Factores de Riesgo , Tercer Molar/diagnóstico por imagen , Pericoronitis/complicaciones , Adulto , Adolescente , Mandíbula/diagnóstico por imagenRESUMEN
The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction.
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Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular level of methionine in AML cells. Based on these findings, we hypothesized that combining 8CA or 8AA with VEN can efficiently target the Methionine-MAT2A-S-adenosyl-methionine (SAM) axis in AML. Our results demonstrate that VEN and 8CA/8AA synergistically decrease the SAM biosynthesis and effectively target AML cells both in vivo and in vitro. These findings suggest the promising potential of combining 8CA/8AA and VEN for AML treatment by inhibiting Methionine-MAT2A-SAM axis and provide a strong rationale for our recently activated clinical trial.