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1.
Chem Biodivers ; : e202400379, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743034

RESUMO

Robusta coffee blossom honey stands as a key regional product in Dak Lak province, Vietnam. Despite its significance, there exists a dearth of scientific data for assessing its quality. This study aims to fill this gap by characterizing the physicochemical properties and biological activities of coffee blossom honeys from three distinct sub-regions within Dak Lak province, Vietnam. These activities include ferric reducing power (FRP), DPPH and ABTS radical scavenging, as well as tyrosinase inhibitory activities. Moreover, the study compares these honey samples with other popular varieties in Vietnam, such as Lychee and Longan honeys. The physicochemical parameters of the honey samples meet the standards set by Codex Alimentarius 2001. Through UPLC analysis, eleven compounds were identified, with caffeine serving as a marker for coffee honey. Furthermore, by employing multiple factor analysis (MFA), it was observed that certain physicochemical properties correlate positively with tyrosinase inhibitory, DPPH, ABTS free radicals scavenging activities, and FRP. Notably, tyrosinase inhibitory activity exhibited a positive correlation with antioxidant activity. These findings underscore the high quality of Coffea robusta honey, showcasing its potent antioxidant and tyrosinase inhibitory activities.

2.
Arthrosc Tech ; 13(4): 102920, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690332

RESUMO

The idea of using quadriceps tendon autograft (QT) anterior cruciate ligament reconstruction first came into being in the 1990s; it was, however, not widely recognized and has resurfaced only in recent times. Because sufficient technological supports have not been developed to enable an optimal artificial graft, autologous grafts are still the most dependable option. The major reason for choosing QT instead of hamstring or patellar tendon to get autologous grafts is that it seems to cause the fewest donor site problems. Two commonly applied ways of using the quadriceps are partial and full thickness; another option is superficial. Our technique for harvesting the superficial part of the QT, which starts proximal to the fused point of the 3 layers, is aimed at circumventing premature cutting of the graft.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38573425

RESUMO

Academic medicine, and medicine in general, are less diverse than the general patient population. Family Medicine, while still lagging behind the general population, has the most diversity in leadership and in the specialty in general, and continues to lead in this effort, with 16.7% of chairs identifying as underrepresented in medicine. Historical and current systematic marginalization of Black or African American, Latina/e/o/x, Hispanic or of Spanish Origin (LHS), American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and Southeast Asian individuals has created severe underrepresentation within health sciences professions. Over the last 30 years, the percentage of faculty from these groups has increased from 7 to 9% in allopathic academic medicine, with similar increases in Osteopathic Medicine, Dentistry, and Pharmacy, but all lag behind age-adjusted population means. Traditionally, diversity efforts have focused on increasing pathway programs to address this widening disparity. While pathway programs are a good start, they are only a portion of what is needed to create lasting change in the diversity of the medical profession as well as the career trajectory and success of underrepresented in medicine (URiM) health professionals toward self-actualization and positions of leadership. This article elucidates all parts of an ecosystem necessary to ensure that equity, diversity, and inclusion outcomes can improve.

4.
Int J Biol Macromol ; 269(Pt 2): 131924, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38688335

RESUMO

The objectives of this study were to purify 42 kDa chitinase derived from Trichoderma asperellum SH16 produced in Nicotiana benthamiana by a polyethylene glycol (PEG)/salt aqueous two-phase system (ATPS). The specific activities of the crude chitinase and the partially purified chitinase from N. benthamiana were about 251 unit/mg and 386 unit/mg, respectively. The study found the 300 g/L PEG 6000 + 200 g/L potassium phosphate (PP) and 300 g/L PEG 6000 + 150 g/L sodium phosphate (SP) systems had the highest partitioning efficiency for each salt in primary extraction. However, among the two types of salt, PP displayed higher efficiency than SP, with a partitioning coefficient K of 4.85 vs. 3.89, a volume ratio V of 2.94 vs. 2.68, and a partitioning yield Y of approximately 95 % vs. 83 %. After back extraction, the enzymatic activity of purified chitinase was up to 834 unit/mg (PP) and 492 unit/mg (SP). The purification factors reached 3.32 (PP) and 1.96 (SP), with recovery yields of about 59 % and 61 %, respectively. SDS-PAGE and zymogram analysis showed that the recombinant chitinase was significantly purified by using ATPS. The purified enzyme exhibited high chitinolytic activity, with the hydrolysis zone's diameter being around 2.5 cm-3 cm. It also dramatically reduced the growth of Sclerotium rolfsii; the colony diameter after treatment with 60 unit of enzyme for 104 spores was only about 1 cm, compared to 3.5 cm in the control. The antifungal effect of chitinase suggests that this enzyme has great potential for applications in agricultural production as well as postharvest fruit and vegetable preservation.

6.
RSC Adv ; 14(18): 12954-12965, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38650687

RESUMO

This study attempted to improve the photocatalytic activity of zinc oxide (ZnO) semiconductors in the visible light region by introducing the co-doping of carbon (C) and tantalum (Ta) to ZnO (ZTC) using a simple hydrothermal method with the respective precursors. The obtained uniform ZTC nanoparticles with an average crystal size of 29.30 nm (according to Scherrer's equation) revealed a redshift with a decrease in bandgap (Eg) from 3.04 eV to 2.88 eV, allowing the obtained photocatalyst to absorb the energy of the visible light for photocatalysis. Furthermore, the Zn 2p and Ta 4f core level spectra confirmed the presence of Zn2+ and Ta5+ in the ZTC sample. In addition, the infrared spectra identified hydrogen-related defects (HRDs), while the O 1s spectra indicated the existence of oxygen vacancies (VO). Electrochemical tests revealed improvement in the electron conductivity and charge separation of the obtained materials. To follow, the photocatalytic performance assessment was conducted by varying the C/Zn2+ ratios (5, 10, and 15 mol%) in ZTC samples, the initial RhB concentration (7, 15, and 30 ppm), and the pH of the RhB solution (3.0-10.0). The photodegradation on ZTC samples showed the most effectiveness for a 7 ppm RhB solution with a C/Zn2+ ratio of 10 mol% in the slightly alkaline medium (pH 9.0). Additionally, ZTC also exhibited commendable durability after being reused several times. The nature of RhB photodegradation was proposed and discussed via a mechanism at the end of this work.

7.
medRxiv ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38585957

RESUMO

Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients. Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset. Main Outcome Measures: Quantitative FAF imaging features including area in mm 2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM , ABCC6 , ABCA4 , RDH12 , and RPE65 , with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm 2 . The five genes with the largest hyper-AF areas were BEST1 , CDH23 , RDH12 , MYO7A , and NR2E3 , with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm 2 respectively. The five genes with largest ring areas were CDH23 , NR2E3 , CRX , EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm 2 . Vessel density was found to be highest in EFEMP1 , BEST1 , TIMP3 , RS1 , and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes ( RPGR, USH2A, RHO, EYS ) found EYS to be the fastest progressor at -0.18 mm 2 /year. Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

8.
Sci Rep ; 14(1): 7241, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538725

RESUMO

Four isolates of the opportunistic pathogen Elizabethkingia anophelis were identified for the first time in a Vietnamese hospital and underwent antimicrobial susceptibility testing and genomic characterization by whole-genome sequencing. Complete, fully circularized genome sequences were obtained for all four isolates. Average Nucleotide Identity analysis and single nucleotide polymorphism phylogenetic analysis on the core genome showed that three of the four isolates were genetically distinct, ruling out the hypothesis of a single strain emergence. Antibiotic susceptibility testing highlighted multi-resistant phenotypes against most antimicrobial families, including beta-lactams, carbapenems, aminoglycosides, quinolones, macrolides, amphenicols, rifamycins and glycopeptides. Additionally, in silico genomic analysis was used to correlate the phenotypic susceptibility to putative resistance determinants, including resistance genes, point mutations and multidrug efflux pumps. Nine different resistance genes were located inside a single resistance pocket predicted to be a putative Integrative and Conjugative Element (ICE). This novel ICE was shared by three isolates from two different lineages and displayed similarity with ICEs previously reported in various Elizabethkingia and Chryseobacterium species. The role of such ICEs in pathogenicity, genome plasticity and antimicrobial resistance gene spread within the Flavobacteriaceae family needs to be further elucidated.


Assuntos
Flavobacteriaceae , Genoma Bacteriano , Vietnã , Filogenia , Antibacterianos/farmacologia
9.
Sci Data ; 11(1): 321, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548727

RESUMO

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.


Assuntos
Broncoscopia , Neoplasias Pulmonares , Humanos , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico por imagem , Tórax/diagnóstico por imagem , Pontos de Referência Anatômicos/diagnóstico por imagem
10.
Micromachines (Basel) ; 15(3)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38542631

RESUMO

Recently, triboelectric nanogenerators (TENGs) have emerged as having an important role in the next wave of technology due to their large potential applications in energy harvesting and smart sensing. Recognizing this, a device based on TENGs, which can solve some of the problems in the liquid flow measurement process, was considered. In this paper, a new method to measure the liquid flow rate through a pipe which is based on the triboelectric effect is reported. A single-electrode flowing liquid-based TENG (FL-TENG) was developed, comprising a silicon pipe and an electrode coated with a polyvinylidene fluoride (PVDF) membrane. The measured electrical responses show that the FL-TENG can generate a peak open-circuit voltage and peak short-circuit current of 2.6 V and 0.3 µA when DI water is passed through an 8 mm cell FL-TENG at a flow rate of 130 mL/min and reach their maximum values of 17.8 V-1.57 µA at a flow rate of 1170 mL/min, respectively. Importantly, the FL-TENG demonstrates a robust linear correlation between its electrical output and the flow rate, with the correlation coefficient R2 ranging from 0.943 to 0.996. Additionally, this study explores the potential of the FL-TENG to serve as a self-powered sensor power supply in future applications, emphasizing its adaptability as both a flow rate sensor and an energy harvesting device.

11.
Malar J ; 23(1): 64, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429807

RESUMO

Malaria remains a global health challenge, disproportionately affecting vulnerable communities. Despite substantial progress, the emergence of anti-malarial drug resistance poses a constant threat. The Greater Mekong Subregion (GMS), which includes Cambodia, China's Yunnan province, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam has been the epicentre for the emergence of resistance to successive generations of anti-malarial therapies. From the perspective of the World Health Organization (WHO), this article considers the collaborative efforts in the GMS, to contain Plasmodium falciparum artemisinin partial resistance and multi-drug resistance and to advance malaria elimination. The emergence of artemisinin partial resistance in the GMS necessitated urgent action and regional collaboration resulting in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015-2030), advocating for accelerated malaria elimination interventions tailored to country needs, co-ordinated and supported by the WHO Mekong malaria elimination programme. The strategy has delivered substantial reductions in malaria across all GMS countries, with a 77% reduction in malaria cases and a 97% reduction in malaria deaths across the GMS between 2012 and 2022. Notably, China was certified malaria-free by WHO in 2021. Countries' ownership and accountability have been pivotal, with each GMS country outlining its priorities in strategic and annual work plans. The development of strong networks for anti-malarial drug resistance surveillance and epidemiological surveillance was essential. Harmonization of policies and guidelines enhanced collaboration, ensuring that activities were driven by evidence. Challenges persist, particularly in Myanmar, where security concerns have limited recent progress, though an intensification and acceleration plan aims to regain momentum. Barriers to implementation can slow progress and continuing innovation is needed. Accessing mobile and migrant populations is key to addressing remaining transmission foci, requiring effective cross-border collaboration. In conclusion, the GMS has made significant progress towards malaria elimination, particularly in the east where several countries are close to P. falciparum elimination. New and persisting challenges require sustained efforts and continued close collaboration. The GMS countries have repeatedly risen to every obstacle presented, and now is the time to re-double efforts and achieve the 2030 goal of malaria elimination for the region.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/epidemiologia , Malária/prevenção & controle , Malária/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/tratamento farmacológico , Organização Mundial da Saúde , Sudeste Asiático
12.
Mol Cancer ; 23(1): 56, 2024 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491381

RESUMO

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.


Assuntos
Anidrases Carbônicas , Carcinoma de Células Renais , Neoplasias Renais , Receptores de Antígenos Quiméricos , Animais , Camundongos , Humanos , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/patologia , Receptores de Antígenos Quiméricos/genética , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/uso terapêutico , Antígenos de Neoplasias , Anticorpos , Linfócitos T/metabolismo
13.
J Anal Methods Chem ; 2024: 1329212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505133

RESUMO

Sausage is a convenient food that is widely consumed in the world and in Vietnam. Due to the rapid development of this product, the authenticity of many famous brands has faded by the rise of adulteration. Therefore, in this study, principal component analysis (PCA) was combined with chemical analysis to identify 6 sausage brands. Sausage samples were dried and then ground to a fine powder for both instrumental analyses of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and inductively coupled plasma-mass spectrometry (ICP-MS). Dried measurements of ATR-FTIR was performed directly on the ZnSe crystal, while elemental data were obtained through microwave digestion before the ICP-MS analysis. Principal component analysis (PCA) within the framework software of XLSTAT and STATISTICA 12 was performed on the spectroscopy and elemental dataset of sausage samples. PCA visualized the distinction of 6 sausage brands on both datasets of ATR-FTIR and ICP-MS. The classification on the spectroscopy profile showed that although more than 90% variation of the dataset was explained on the first two PCs, the difference between several brands was not detected as the distribution of data overlapped with one another. The PCA observation of the elemental composition on PC1 and PC3 has separated the sausage brands into 6 distinctive groups. Besides, several key elements contributed to the brands' identification have been detected, and the most distinctive elements are Na, K, Ca, and Ba. PCA visualization showed the feasibility of the classification of sausage samples from different brands when combined with the results of FT-IR and ICP-MS methods. The experiment was able to differentiate the sausages from the 5 brands using multivariate statistics.

14.
J Hypertens ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38509747

RESUMO

Hypertension remains the leading modifiable risk factor for cardiovascular disease worldwide. Over the past 30 years, the prevalence of hypertension has been increasing in East and Southeast Asia to a greater extent as compared with other Western countries. Asians with hypertension have unique characteristics. This can be attributed to increased impact of obesity on Asians with hypertension, excessive salt intake and increased salt sensitivity, loss of diurnal rhythm in blood pressure and primary aldosteronism. The impact of hypertension on cardiovascular (particularly strokes) and chronic kidney disease is greater in Asians. These unique characteristics underpinned by the diverse socioeconomic backgrounds pose its own challenges in the diagnosis and management of hypertension in Asia.

15.
Infect Dis Poverty ; 13(1): 27, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528604

RESUMO

BACKGROUND: In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private sector. METHODS: Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate regression. RESULTS: The pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578; P = 0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313; P = 0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164; P < 0.001). This resulted in no significant difference in catastrophic costs between the two cohorts (Private: 55% vs NTP: 52%; P = 0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio (aOR = 13.71; 95% confidence interval (CI): 1.36-138.14; P = 0.026], unemployment during treatment (aOR = 10.86; 95% CI: 2.64-44.60; P < 0.001) and experiencing TB-related stigma (aOR = 37.90; 95% CI: 1.72-831.73; P = 0.021). CONCLUSIONS: Persons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the public or private sector. Patient costs could be reduced through expanded insurance reimbursement to minimize direct medical costs in the private sector, use of remote monitoring and multi-week/month dosing strategies to avert economic costs in the public sector and greater access to social protection mechanism in general.


Assuntos
Setor de Assistência à Saúde , Tuberculose , Humanos , Vietnã/epidemiologia , Tuberculose/tratamento farmacológico , Custos de Cuidados de Saúde , Renda
16.
Transfus Apher Sci ; 63(2): 103878, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38388334

RESUMO

BACKGROUND: In Vietnam, a lack of evidence about the unexpected antibodies hinders the capabilities to prepare the necessary resources and personnel for treating patients with blood disorders. This study aimed to measure the rates of different unexpected antibodies in patients having blood orders in Vietnam. STUDY DESIGN AND METHODS: A cross-sectional study was conducted at the National Institute of Hematology - Blood Transfusion, Vietnam on 5608 patients with blood disorders. Information was obtained from the medical records, blood transfusion forms, screening test forms. RESULTS: The prevalence rate of unexpected antibodies in patients with haematological disorders was 9.3%. The most prevalent occurrence was the presence of an atypical antibody type, accounting for 61% of patients. The co-occurrence of this atypical antibody type and other types of antibodies was also observed, with the respective occurrence rates of 23.9%, 10.1%, 3.8%, and 1.2% for the combination of two, three, four, and five unexpected antibody types. The presence of one type of unexpected antibody was predominant, namely anti-E, accounting for the highest proportion (32.9%), followed by anti-Mia (18.4%). Among the 125 patients, the most frequently observed combination of abnormal antibodies was anti-E with anti-c (14.3%) and anti-E with anti-Mia (3.4%). Among the cohort of 53 patients exhibiting three types of unexpected antibodies, the most prevalent combination observed was anti-c, anti-E, and anti-Mia (5.7%). CONCLUSION: This study revealed a prevalence rate of 9.3% in the presence of unexpected antibodies in patients with blood disorders. The occurrence of individual unexpected antibodies surpasses that of coordinated antibodies.


Assuntos
Antígenos de Grupos Sanguíneos , Doenças Hematológicas , Humanos , Vietnã/epidemiologia , Estudos Transversais , Anticorpos , Transfusão de Sangue , Isoanticorpos
17.
Clin Cancer Res ; 30(9): 1889-1905, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38381406

RESUMO

PURPOSE: Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine-resistant ER+ breast cancer models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ breast cancer. Nonetheless, the precise mechanisms responsible for the activity of CDK7i in ER+ breast cancer remain elusive. Herein, we sought to unravel these mechanisms. EXPERIMENTAL DESIGN: We conducted multi-omic analyses in ER+ breast cancer models in vitro and in vivo, including models with different genetic backgrounds. We also performed genome-wide CRISPR/Cas9 knockout screens to identify potential therapeutic vulnerabilities in CDK4/6i-resistant models. RESULTS: We found that the on-target antitumor effects of CDK7 inhibition in ER+ breast cancer are in part p53 dependent, and involve cell cycle inhibition and suppression of c-Myc. Moreover, CDK7 inhibition exhibited cytotoxic effects, distinctive from the cytostatic nature of ET and CDK4/6i. CDK7 inhibition resulted in suppression of ER phosphorylation at S118; however, long-term CDK7 inhibition resulted in increased ER signaling, supporting the combination of ET with a CDK7i. Finally, genome-wide CRISPR/Cas9 knockout screens identified CDK7 and MYC signaling as putative vulnerabilities in CDK4/6i resistance, and CDK7 inhibition effectively inhibited CDK4/6i-resistant models. CONCLUSIONS: Taken together, these findings support the clinical investigation of selective CDK7 inhibition combined with ET to overcome treatment resistance in ER+ breast cancer. In addition, our study highlights the potential of increased c-Myc activity and intact p53 as predictors of sensitivity to CDK7i-based treatments.


Assuntos
Apoptose , Neoplasias da Mama , Ciclo Celular , Quinase Ativadora de Quinase Dependente de Ciclina , Quinases Ciclina-Dependentes , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-myc , Receptores de Estrogênio , Transdução de Sinais , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Apoptose/efeitos dos fármacos , Animais , Camundongos , Receptores de Estrogênio/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/genética , Sistemas CRISPR-Cas
18.
Ther Clin Risk Manag ; 20: 75-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351953

RESUMO

Objective: Chyle leak (CL) after head and neck surgery is a rare but well-known complication. In patients with high-output leakage, the treatment can be complicated. This study aims to report on a recent innovation in lymphatic intervention for treating such patients. Materials and Methods: A retrospective review of 36 patients with chyle leak after neck surgery for thyroid cancer was conducted to assess the efficacy of percutaneous lymphatic embolization and thoracic duct (TD) disruption. Results: Antegrade catheterization of the thoracic duct was achieved in 31 of 36 patients (86.1%). Therefore, embolization of the thoracic duct and thoracic duct branches was performed in 26 and 5 patients, respectively. In 5 cases of unsuccessful antegrade catheterization into the thoracic duct, transcervical access embolization was performed in 2 patients, and TD disruption (TDD) was performed in 3 patients. The pooled overall technical success rate of lymphatic embolization was 33/36 patients (91.7%). One patient who underwent thoracic duct embolization (TDE) with technical success (1/33 patients) but clinical failure had additional treatment directly sclerosing the TD under computed tomography scan. Cervical fluid collection sclerotherapy was done in 7 patients as an additional treatment. Resolution of the chyle leak after procedures was observed in all patients (100%). The mean time to resolution was 3 days (1-7 days). There was no complication intra and after procedures. Conclusion: TDE, selective TD branches embolization and TDD are safe and effective minimally invasive treatments for CL post-surgery for thyroid carcinoma. Sclerosing cervical fluid collection contributes to clinical success.

19.
J Pharm Anal ; 14(1): 16-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352944

RESUMO

The spread of tuberculosis (TB), especially multidrug-resistant TB and extensively drug-resistant TB, has strongly motivated the research and development of new anti-TB drugs. New strategies to facilitate drug combinations, including pharmacokinetics-guided dose optimization and toxicology studies of first- and second-line anti-TB drugs have also been introduced and recommended. Liquid chromatography-mass spectrometry (LC-MS) has arguably become the gold standard in the analysis of both endo- and exo-genous compounds. This technique has been applied successfully not only for therapeutic drug monitoring (TDM) but also for pharmacometabolomics analysis. TDM improves the effectiveness of treatment, reduces adverse drug reactions, and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window. Based on TDM, the dose would be optimized individually to achieve favorable outcomes. Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs, aiding in the discovery of potential biomarkers for TB diagnostics, treatment monitoring, and outcome evaluation. This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades. Besides, we discussed the advantages and disadvantages of this technique in practical use. The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted. Lastly, we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies (pharmacometrics, drug and vaccine developments, machine learning/artificial intelligence, among others) to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

20.
Data Brief ; 53: 110087, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38328300

RESUMO

Paenibacillus tyrfis YSS-72.2.G2 is a soil chitinolytic bacterium newly isolated from Yok Don National Park of Vietnam. Our previous results demonstrated that this bacterium was a strong chitinase producer, possessed plant growth promotion, and had high activity against phytopathogenic fungi. However, the genome sequence of this strain is unknown. This work aimed to establish data on the genome sequence of P. tyrfis YSS-72.2.G2 and its chitinase system for further assessments regarding biocontrol mechanisms and plant growth promotion. The P. tyrfis YSS-72.2.G2 genome is 7,756,121 bp in size and 53.4 % G+C. It harbors 6,948 protein-coding genes, 5 rRNA genes, 82 tRNA genes, 4 ncRNA genes, 99 pseudo genes, and 5 CRISPR arrays. Genes involved in heavy metal resistance (5 genes), iron acquisition (5 genes), and IAA biosynthesis (5 genes) were predicted in the genome. There were 234 carbohydrate-active enzymes found in this genome; among them, 13 enzymes possibly possess activity against phytopathogens. Chitin-degrading system of YSS-72.2.G2 contains 15 chitinolytic enzymes. In addition, 28 gene clusters coding for antimicrobial metabolites were identified, of these, 14 show no sequence similarities to the known clusters. The raw sequences were submitted to the Sequence Read Archive on the National Center for Biotechnology Information with accession number PRJNA946889. The genome sequence of P. tyrfis YSS-72.2.G2 has been deposited in the DDBJ/GenBank/EMBL database under accession number NZ_BSDJ00000000. Data provide insight into the genomic information of strain YSS-72.2.G2. This is the first work reporting data on the genome sequence of P. tyrfis isolated from Vietnam.

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