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BACKGROUND: Statistical Process Control (SPC) tools providing feedback to surgical teams can improve patient outcomes over time. However, the quality of routinely available hospital data used to build these tools does not permit full capture of the influence of patient case-mix. We aimed to demonstrate the value of considering time-related variables in addition to patient case-mix for detection of special cause variations when monitoring surgical outcomes with control charts. METHODS: A retrospective analysis from the French nationwide hospital database of 151,588 patients aged 18 and older admitted for colorectal surgery between January 1st, 2014, and December 31st, 2018. GEE multilevel logistic regression models were fitted from the training dataset to predict surgical outcomes (in-patient mortality, intensive care stay and reoperation within 30-day of procedure) and applied on the testing dataset to build control charts. Surgical outcomes were adjusted on patient case-mix only for the classical chart, and additionally on secular (yearly) and seasonal (quarterly) trends for the enhanced control chart. The detection of special cause variations was compared between those charts using the Cohen's Kappa agreement statistic, as well as sensitivity and positive predictive value with the enhanced chart as the reference. RESULTS: Within the 5-years monitoring period, 18.9% (28/148) of hospitals detected at least one special cause variation using the classical chart and 19.6% (29/148) using the enhanced chart. 59 special cause variations were detected overall, among which 19 (32.2%) discordances were observed between classical and enhanced charts. The observed Kappa agreement between those charts was 0.89 (95% Confidence Interval [95% CI], 0.78 to 1.00) for detecting mortality variations, 0.83 (95% CI, 0.70 to 0.96) for intensive care stay and 0.67 (95% CI, 0.46 to 0.87) for reoperation. Depending on surgical outcomes, the sensitivity of classical versus enhanced charts in detecting special causes variations ranged from 0.75 to 0.89 and the positive predictive value from 0.60 to 0.89. CONCLUSION: Seasonal and secular trends can be controlled as potential confounders to improve signal detection in surgical outcomes monitoring over time.
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Mortalidade Hospitalar , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , França , Reoperação/estatística & dados numéricos , Adulto , Idoso de 80 Anos ou mais , Tempo de Internação , Bases de Dados Factuais , Resultado do TratamentoRESUMO
The tumor microenvironment (TME), composed of and influenced by a heterogeneous set of cancer cells and an extracellular matrix, plays a crucial role in cancer progression. The biophysical aspects of the TME (namely, its architecture and mechanics) regulate interactions and spatial distributions of cancer cells and immune cells. In this review, we discuss the factors of the TME-notably, the extracellular matrix, as well as tumor and stromal cells-that contribute to a pro-tumor, immunosuppressive response. We then discuss the ways in which cells of the innate and adaptive immune systems respond to tumors from both biochemical and biophysical perspectives, with increased focus on CD8+ and CD4+ T cells. Building upon this information, we turn to immune-based antitumor interventions-specifically, recent biophysical breakthroughs aimed at improving CAR-T cell therapy.
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Background: Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves. Methods: We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis. Results: The results showed that using 10% (NH4)2SO4 and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively.Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 µg/mL on both C. acnes and S. epidermidis. This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 µg/mL on C. acnes and S. epidermidis, respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 µg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 µg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 µg/mL). Conclusion: To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne.
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Essential Tremor (ET) is the most frequent movement disorder in adults. Upper-limb exoskeletons are a promising solution to alleviate ET symptoms. We propose a novel wrist exoskeleton for tremor damping. The TuMove exoskeleton is light-weight, portable, easy to use, and designed for ADLs and activities requiring hand dexterity. We validated the effectiveness of our exoskeleton by inducing forearm tremors using TENS on 5 healthy subjects. Our results show that wrist ranges are generally kept in most of the ROM needed in ADLs. The damping system reduced more than 30% of the tremor's angular velocity during drinking and pouring tasks. Furthermore, the completion time of the Archimedes spiral was decreased by 2.76 seconds (13.0%) and for the 9-Hole-Peg-Test by 2.77 seconds (11.8 %), indicating a performance improvement in dexterity tasks.
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Tremor Essencial , Exoesqueleto Energizado , Estimulação Elétrica Nervosa Transcutânea , Adulto , Humanos , Punho , Tremor , Atividades Cotidianas , Extremidade SuperiorRESUMO
BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused a serious global communicable disease burden. Although COVID-19 and its policy responses have significantly influenced older adults, the impact of COVID-19 on depression in the older population is not fully understood. We aimed to investigate whether a history of COVID-19 infection and a decline in outdoor activities during the COVID-19 pandemic were associated with depression among older adults in Vietnam. METHODS: This multicenter cross-sectional study was conducted on 1,004 outpatients (aged ≥60 years; mean age 70.8 ± 7.3 years; men, 33.0%) visiting three hospitals for a comprehensive geriatric assessment between November 2021 and July 2022. Depression over the past week was evaluated using the 15-item Geriatric Depression Scale. History of COVID-19 infection and decline in outdoor activities were included as binary variables. We adjusted these two factors with sociodemographic and geriatric variables and comorbidities using a logistic regression analysis in separate models. RESULTS: A total of 156 participants (15.5%) experienced depression. The proportion of mild, moderate, and severe depressive symptoms was 14.1%, 44.9%, and 41.0%, respectively. In the multivariate model, decline in outdoor activities (odds ratio [OR] 17.2, 95% confidence interval [CI] 9.15-32.2, p <0.001) and history of COVID-19 infection (OR 2.22, 95% CI 1.28-3.84, p = 0.004) were associated with depression. Additionally, we found that age ≥ 75 years, female sex, being underweight, limitations in functional status, poor sleep quality, and stroke were associated with depression. Of the associated factors, decline in outdoor activities had a moderate strength of association with depression (r = 0.419), while each of the remaining factors had a weak strength of association. CONCLUSIONS: COVID-19 had a direct and indirect impact on depression in older adults, reflecting an association between both a history of COVID-19 infection and a decline in outdoor activities during the COVID-19 pandemic and depression in the older population.
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COVID-19 , Depressão , Masculino , Idoso , Humanos , Feminino , Pessoa de Meia-Idade , Depressão/diagnóstico , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Vietnã/epidemiologiaRESUMO
Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.
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Antineoplásicos , Carcinoma , Humanos , Indazóis/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Triptofano , Indolamina-Pirrol 2,3,-Dioxigenase , Inibidores Enzimáticos/químicaRESUMO
Objective: To evaluate the prevalence of post-traumatic stress disorder (PTSD) and other psychological disturbances in the Vietnamese healthcare workers (HCWs) at COVID-19 field hospitals. Methods: A cross-sectional study was conducted using the Impact of Event Scale-Revised (IES-R) to measure PTSD and the Depression Anxiety Stress scale (DASS) to measure other psychological disturbances. The anxiety about COVID-19 was evaluated by the fear of COVID-19 (FOC) scale. A self-developed questionnaire was used to assess work conditions and HCW's major concerns and preparedness. Ordinal logistic regression was used to identify factors associated with the severity of PTSD. A structural modeling equation (SEM) model was fitted to examine the correlation between PTSD and other psychological disturbances. Results: A total of 542 HCWs participated in this study. The prevalence of PTSD was 21.2%, most cases were mild. In the ordinal logistic regression analysis, a history of mental illness, poor preparedness, working in a condition with poor resources, a greater number of concerns, and greater fear of COVID-19 were independently associated with higher severity of PTSD. The prevalence of depression, anxiety, and stress was 46.8%, 38.3%, and 60.2, respectively. In the SEM model, PTSD and psychological disturbances had a strong correlation (standardized covariance 0.86). Conclusion: The prevalence of PTSD and other psychological disturbances was alarmingly high among HCWs who worked at COVID-19 field hospitals. The reported associated factors can be useful for policymakers and health authorities in the preparation for future pandemics.
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Objectives: This study aimed to determine the antibiotic-resistant profile and to identify molecular characterization of some virulence genes of Klebsiella spp. isolated from mastitis samples in Vietnam. Materials and Method: A total of 468 samples from clinical mastitis cases were collected and submitted to the Laboratory. All samples were cultured, and Klebsiella spp. was identified through biochemical reactions and confirmed by Polymerase chain reaction (PCR). Antimicrobial resistance was tested by disk diffusion method, and virulence and resistance genes were tested by PCR. Results: An antibiogram study showed that a high proportion of isolates are multidrug-resistant (94%). All isolates were resistant to lincomycin and sulfamethoxazole, followed by ampicillin (94%), sulphonamide (66%), amoxicillin (56%), streptomycin (52%), polymyxin B (28%), colistin sulfate (12%), tetracycline (6%), ciprofloxacin (4%), florfenicol (4%), enrofloxacin (4%), piperacillin (2%), trimethoprim (2%), nalidixic acid (2%), imipenem (2%), and sulfamethoxazole/trimethoprim (2%). In contrast, all isolates showed sensitivity to gentamicin and ceftiofur. The appearance of an efflux pump system, extended-spectrum beta-lactamase (ESBL), tetracycline, and sulphonamides-resistant genes was reconfirmed using different specific primers. Capsular serotype K1 and virulence genes magA, fimH, and entB, responsible for hypermucoviscosity production, adherence, and enterobactin production, were confirmed in isolates. Multidrug resistance and virulence potential in Klebsiella spp. are changing this mastitis pathogen into a superbug and making its management harder. Conclusions: Klebsiella spp. associated with bovine mastitis in Nghe An province were mostly multidrug-resistant and carried virulence genes including fimH, entB, and antimicrobials resistant genes (bla SHV, acrAKp, tetA, etc.), but these isolates were not ESBL producers.
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Purpose: Detection of antenatal common mental disorders in low-resource settings like Vietnam is important and requires a reliable, valid and practical screening tool. Currently, there is no such tool validated for use among pregnant women in Vietnam. This study aims to assess the validity of the Vietnamese version of the 20-item Self Reporting Questionnaire (SRQ-20) by evaluating its reliability, factorial structure, and performance in detecting common mental disorder (CMD) symptoms, thereby identifying the optimum cut-off score for CMD screening among pregnant women in Vietnam. Participants and Methods: A total of 210 pregnant women from four rural communes participated in a face-to-face interview using the Vietnamese version of the SRQ-20, followed by a clinical diagnostic interview based on ICD-10 diagnostic criteria of CMDs. The reliability of the SRQ-20 was assessed by calculating the scale's Cronbach's alpha to measure internal consistency. Factor analyses were undertaken to examine the factor structure of the instrument. The Receiver Operating Characteristic (ROC) curve analysis was performed to assess the performance of the SRQ-20 against the clinical diagnosis and to identify the optimum cut-off score. Results: Internal consistency was good, with a Cronbach's alpha of 0.87. Factor analyses resulted in a 4-factor solution. The area under the ROC curve (AUC) for detection of CMDs was 0.90. The optimum cut-off score of the SRQ-20 for detection of CMD symptoms among Vietnamese pregnant women was 5/6. Conclusion: The Vietnamese version of the SRQ-20 has the capacity to detect CMDs among pregnant women effectively and is recommended for use as a screening tool for CMDs in antenatal care settings in Vietnam.
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Vocal fatigue is a measurable form of performance fatigue resulting from overuse of the voice and is characterized by negative vocal adaptation. Vocal dose refers to cumulative exposure of the vocal fold tissue to vibration. Professionals with high vocal demands, such as singers and teachers, are especially prone to vocal fatigue. Failure to adjust habits can lead to compensatory lapses in vocal technique and an increased risk of vocal fold injury. Quantifying and recording vocal dose to inform individuals about potential overuse is an important step toward mitigating vocal fatigue. Previous work establishes vocal dosimetry methods, that is, processes to quantify vocal fold vibration dose but with bulky, wired devices that are not amenable to continuous use during natural daily activities; these previously reported systems also provide limited mechanisms for real-time user feedback. This study introduces a soft, wireless, skin-conformal technology that gently mounts on the upper chest to capture vibratory responses associated with vocalization in a manner that is immune to ambient noises. Pairing with a separate, wirelessly linked device supports haptic feedback to the user based on quantitative thresholds in vocal usage. A machine learning-based approach enables precise vocal dosimetry from the recorded data, to support personalized, real-time quantitation and feedback. These systems have strong potential to guide healthy behaviors in vocal use.
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Canto , Distúrbios da Voz , Voz , Humanos , Retroalimentação , Distúrbios da Voz/etiologia , Voz/fisiologia , Prega Vocal/fisiologiaRESUMO
OBJECTIVES: The control chart is a graphical tool for data interpretation that detects aberrant variations in specific metrics, ideally leading to the identification of special causes that can be resolved. A clear assessment of control chart utilization and its potential impact in surgery is required to justify recommendations for its dissemination. This review aims to describe how performance monitoring using control charts was used over time in surgery. METHODS: A systematic search of PubMed regarding statistical process control in surgery from its inception until December 2019 was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Information extracted from selected publications included study aim and population setting, monitored indicators, control charts methodological parameters, and implementation strategy. RESULTS: One hundred thirteen studies met the selection criteria with a median of 1916 monitored patients. Overall, 57.5% of studies focused on control chart methodology, 24.8% aimed at evaluating performance changes using control charts retrospectively, and 17.7% implemented control charts for continuous quality improvement prospectively. Although there was a great diversity of used indicators and charting tools, the evaluation of patient safety (72.6%) or efficiency (15.9%) metrics based on Shewhart control chart (33.6%) or cumulative sum chart (54.9%) were common. To foster control charts implementation, 14 studies promoted their periodic review, but only three assessed their impact on patient outcomes. CONCLUSIONS: The scientific literature supports the feasibility and utility of control chart to improve patient safety in multiple surgical settings. Additional studies are necessary to reveal the optimal manner in which to implement this affordable tool in surgical practice.
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Melhoria de Qualidade , Procedimentos Cirúrgicos Operatórios , Humanos , Estudos Retrospectivos , Segurança do PacienteRESUMO
We report on a process to record the presence and the location of osteocyte nuclei using two nucleic staining dyes, Diamond™ Nucleic Acids Dye (DD) and DAPI (4',6-diamidino-2-phenylindole). Knowledge of the presence and number of osteocytes is key to any success in subsequent DNA profiling. Osteocytes are most numerous cells and thus the main source of DNA in bone samples, which can be preserved for histological analyses. Archived samples are either fixed in formalin or preserved in ethanol prior to embedding in resin. These resin-embedded samples are potentially used as ante mortem reference samples. Cases of a missing person investigation are one example where this type of preserved reference material may be of value. When resin is required for sample preservation it represents a problem for subsequent DNA profiling, if needed as a reference sample in human identification. It is essential therefore to remove the resin prior to DNA analyses as resin is a known inhibitor of DNA profiling. Current methods of resin removal are lengthy and require toxic chemicals. This report describes a simplified process to remove resin and visualise the location of nucleated osteocytes. Eight sections of bone samples at 5-µm thickness were stained with DD and DAPI. A further three samples were processed using a formalin-fixed method and three additional samples treated following an ethanol-preserved method (11 samples for both the formalin-fixed and 11 for the ethanol-preserved with eight in common). The location and number of nuclei could be recorded clearly due to the fluorescence created by the dye binding to DNA. The number of stained nuclei correlated with the mass of DNA isolated from the sections (r = 0.873, p = 1.21 × 10-10). A significant difference between the degradation indices of two groups (p = 8.505 × 10-5) showed that ethanol preservation is a preferred method to yield DNA of the quality needed for subsequent short tandem repeats (STR) profiling. Ten of the 11 samples isolated using the ethanol-preserved process recorded a complete STR profile (30/30 alleles), whereas eight of the formalin-fixed samples generated full profiles, and only one of the 11 samples amplified less than 23 alleles. Both the ethanol-preserved and formalin-fixed methods are an improvement on current methods by removing the need for strong solutes in resin removal, and the method leads to STR profiles from resin-embedded bone samples within 24 h.
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DNA , Osteócitos , Humanos , Osteócitos/química , DNA/análise , Formaldeído , Osso e Ossos , Corantes , Etanol , Impressões Digitais de DNA/métodos , Repetições de MicrossatélitesRESUMO
Klebsiella pneumoniae, a member of the family Enterobacteriaceae, is a rod-shaped, Gram-negative bacterium, mainly found in the hospital environment and medical tools. It is the leading cause of nosocomial infection, characterized by bloodstream infection, wound site infection, urinary tract infection, and sepsis, mostly in older adults, newborn infants, and immunocompromised patients. This present study demonstrated a novel diagnostic method for K. pneumoniae detection based on the gold nanozyme activity for the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. The nanozyme activity of AuNPs with staining enhancement was statistically three times higher than that of the bare AuNPs in solid absorption at 650 nm. Nano-ELISA with staining enhancement could detect as low as 102 CFUs/mL of K. pneumoniae concentration, as the cutoff value was determined to be 0.158, which boosted the sensitivity of the immunoreactions by up to 100-fold. The detection limit of our assays was 26.023 CFUs/mL, and the limit of quantification was 78.857 CFUs/mL. There was no cross-reaction against other bacteria, which proved the immunoassays' remarkable specificity for recognizing K. pneumoniae. Taken together, we successfully developed and optimized the highly sensitive and decently specific nano-ELISA strategy that might be applicable for detecting various other bacterial pathogens.
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Background: Quantifying grit with the Short Grit Scale (Grit-S) has shown ability to predict success in various academic and professional domains. Grit has yet to be analyzed in patients with cancer. Methods: This study is a longitudinal analysis of prospectively distributed Grit-S surveys to patients undergoing radical or partial nephrectomy. Patients who completed a preoperative Grit-S survey with confirmed renal cell carcinoma (RCC) were included in the analysis. The relationship between preoperative grit scores and overall survival (OS) was determined using Cox proportional-hazard models and Kaplan-Meier analysis. Results: A total of 323 patients with RCC that completed the Grit-S survey prior to nephrectomy were included in the study. Median Grit score was 3.9. Most patients were male (67.5%), White (69.3%), and greater than 60 years old (57.0%) with a median age of 62 at the time of surgery. Patients scoring above or below the median grit score had similar baseline characteristics. As a binary variable, lower preoperative grit was significantly associated with shorter OS [hazard ratio (HR) =2.02, 95% confidence interval (CI): 1.12-3.63, P=0.019] on multivariable analysis. Unit changes in grit were not significantly associated with OS (HR =0.77, 95% CI: 0.53-1.14, P=0.193). Conclusions: Lower grit scores may predict decreased OS in RCC patients undergoing nephrectomy. The Grit-S survey may have utility in preoperative evaluation. Further research assessing grit in other malignancies and how to psychologically optimize patients prior to surgery are needed.
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Recently reported winged microelectronic systems offer passive flight mechanisms as a dispersal strategy for purposes in environmental monitoring, population surveillance, pathogen tracking, and other applications. Initial studies indicate potential for technologies of this type, but advances in structural and responsive materials and in aerodynamically optimized geometries are necessary to improve the functionality and expand the modes of operation. Here, we introduce environmentally degradable materials as the basis of 3D fliers that allow remote, colorimetric assessments of multiple environmental parameters-pH, heavy metal concentrations, and ultraviolet exposure, along with humidity levels and temperature. Experimental and theoretical investigations of the aerodynamics of these systems reveal design considerations that include not only the geometries of the structures but also their mass distributions across a range of bioinspired designs. Preliminary field studies that rely on drones for deployment and for remote colorimetric analysis by machine learning interpretation of digital images illustrate scenarios for practical use.
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α-Alkylation of a ß-keto ester is a frequently used reaction for carbon-carbon bond formation. However, extension to a stereoselective reaction remains a significant challenge, because the product easily racemizes under acidic or basic conditions. Here, we report a hybrid system consisting of Pd and Ru complexes that catalyzes the asymmetric dehydrative condensation between cinnamyl-type allylic alcohols and ß-keto esters. α-Non-substituted ß-keto ester can be allylated to afford an α-mono-substituted product with high regio-, diastereo-, and enantioselectivity. No epimerization occurs owing to the nearly neutral conditions, which is achieved by a rapid proton transfer from Pd-enolate formation to Ru π-allyl complex formation. Four diastereomers can be synthesized on demand by changing the stereochemistry of the Pd or Ru complex. Eight stereoisomers with three adjacent stereogenic centers can be synthesized by employing diastereoselective reduction of the ketone in the products. The formal synthesis of (+)-pancratistatin demonstrates the utility of the reaction.
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Ésteres , Prótons , Carbono , Catálise , Ésteres/química , Cetonas , EstereoisomerismoRESUMO
Complex breast cancer cases that need further multidisciplinary tumor board (MTB) discussions should have priority in the organization of MTBs. In order to optimize MTB workflow, we attempted to predict complex cases defined as non-compliant cases despite the use of the decision support system OncoDoc, through the implementation of machine learning procedures and algorithms (Decision Trees, Random Forests, and XGBoost). F1-score after cross-validation, sampling implementation, with or without feature selection, did not exceed 40%.
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Neoplasias da Mama , Algoritmos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Tomada de Decisões , Feminino , Humanos , Aprendizado de Máquina , Cooperação do PacienteRESUMO
During the COVID-19 pandemic, many countries implemented international travel restrictions that aimed to contain viral spread while still allowing necessary cross-border travel for social and economic reasons. The relative effectiveness of these approaches for controlling the pandemic has gone largely unstudied. Here we developed a flexible network meta-population model to compare the effectiveness of international travel policies, with a focus on evaluating the benefit of policy coordination. Because country-level epidemiological parameters are unknown, they need to be estimated from data; we accomplished this using approximate Bayesian computation, given the nature of our complex stochastic disease transmission model. Based on simulation and theoretical insights we find that, under our proposed policy, international airline travel may resume up to 58% of the pre-pandemic level with pandemic control comparable to that of a complete shutdown of all airline travel. Our results demonstrate that global coordination is necessary to allow for maximum travel with minimum effect on viral spread.
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COVID-19 , Influenza Humana , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Influenza Humana/epidemiologia , Pandemias/prevenção & controle , ViagemRESUMO
Bone cells are a suitable substrate for DNA analysis if required to identify the person from whom a sample was taken. Osteocytes, the most abundant cell type in bone, are embedded within mineralized bone matrix. To release DNA from osteocytes for subsequent analyses, either demineralization of the mineral matrix or an overnight incubation is routinely carried out. In this study, we report on a simplified and rapid approach to analyze preserved bone samples that omits this lengthy decalcification process. Nine tibial bone samples were processed to release matrix-free bone cells after fragmentation without the use of liquid nitrogen. Cell morphology was assessed by microscopy at 220× magnification following staining with Diamond™ Nucleic Acid Dye. Based on the presence of stained nuclei, samples were processed either using a DNA extraction process or by a semi-direct PCR process. The analysis of the quantity and quality of DNA isolated by both methods was carried out by real-time PCR and STR profiling to assess inhibition of PCR and DNA degradation. All samples resulted in informative STR profiles with minimal indication of inhibitors. These results demonstrate a potential approach of STR profiling from matrix-free bone cells within 8 hours without decalcification and DNA extraction.
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Impressões Digitais de DNA , Osteócitos , DNA/genética , Impressões Digitais de DNA/métodos , Humanos , Repetições de Microssatélites , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Tenatoprazole, a newly developed proton pump inhibitor candidate, was developed as an acid inhibitor for gastric acid hypersecretion disorders such as gastric ulcer and reflux esophagitis. It is known that tenatoprazole is metabolized to three major metabolites of 5'-hydroxy tenatoprazole, tenatoprazole sulfide, and tenatoprazole sulfone in human liver, primarily catalyzed by CYPs 2C19 and 3A4. While CYP2C19 prefers the hydroxylation of tenatoprazole at C-5' position, CYP3A4 is mainly involved in sulfoxidation reaction to make tenatoprazole sulfone. Tenatoprazole sulfide is a major human metabolite of tenatoprazole and is formed spontaneously and non-enzymatically from tenatoprazole. However, its metabolic fate in the human liver is not fully known. Furthermore, no systematic metabolic study has been performed to study tenatoprazole or tenatoprazole sulfide. Here, we studied the functions of human cytochromes P450 in the metabolic pathway of tenatoprazole and tenatoprazole sulfide by using recombinant human P450s and human liver microsomes. Both CYP 2C19 and CYP3A4 showed distinct regioselective and stereospecific monooxygenation activities toward tenatoprazole and tenatoprazole sulfide. Furthermore, a new major metabolite of tenatoprazole sulfide was found, 1'-N-oxy-5'-hydroxytenatoprzole sulfide, which has never been reported. In conclusion, the metabolic fates of tenatoprazole and tenatoprazole sulfide should be considered in the clinical use of tenatoprazole.