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Encoding logical qubits in bosonic modes provides a potentially hardware-efficient implementation of fault-tolerant quantum information processing. Here, we demonstrate high-fidelity and deterministic preparation of highly nonclassical bosonic states in the mechanical motion of a trapped ion. Our approach implements error-suppressing pulses through optimized dynamical modulation of laser-driven spin-motion interactions to generate the target state in a single step. We demonstrate logical fidelities for the Gottesman-Kitaev-Preskill state as high as F[over ¯]=0.940(8), a distance-3 binomial state with an average fidelity of F=0.807(7), and a 12.91(5) dB squeezed vacuum state.
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Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality. Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders, which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries. Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases. In this review, we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations, epidemiology, and aberrant cellular composition involving the biliary ductules, cholangiocytes, immune system, fibroblasts, and the microbiome. We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies. This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.
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It has been proposed that, when processing a stream of events, humans divide their experiences in terms of inferred latent causes (LCs) to support context-dependent learning. However, when shared structure is present across contexts, it is still unclear how the "splitting" of LCs and learning of shared structure can be simultaneously achieved. Here, we present the Latent Cause Network (LCNet), a neural network model of LC inference. Through learning, it naturally stores structure that is shared across tasks in the network weights. Additionally, it represents context-specific structure using a context module, controlled by a Bayesian nonparametric inference algorithm, which assigns a unique context vector for each inferred LC. Across three simulations, we found that LCNet could (1) extract shared structure across LCs in a function learning task while avoiding catastrophic interference, (2) capture human data on curriculum effects in schema learning, and (3) infer the underlying event structure when processing naturalistic videos of daily events. Overall, these results demonstrate a computationally feasible approach to reconciling shared structure and context-specific structure in a model of LCs that is scalable from laboratory experiment settings to naturalistic settings.
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Algoritmos , Teorema de Bayes , Redes Neurais de Computação , Humanos , AprendizagemRESUMO
OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.
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Gastrectomia , Hidrocortisona , Laparoscopia , Redução de Peso , Humanos , Estudos Prospectivos , Feminino , Hidrocortisona/metabolismo , Hidrocortisona/sangue , Masculino , Adulto , Pessoa de Meia-Idade , Cirurgia Bariátrica , Povo Asiático , Resultado do Tratamento , Estudos de Coortes , Obesidade/cirurgiaRESUMO
OBJECTIVE: Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with ß-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca2+]I activity and insulin secretion. METHODS: Metabolic profiling was conducted on Gcgrß-cell-/- and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for ß-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in ß-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. RESULTS: Gcgrß-cell-/- mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrß-cell-/- 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrß-cell-/- islets showed profound loss of pan-islet [Ca2+]I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated [Ca2+]I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8). CONCLUSION: These data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised [Ca2+]I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.
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Diabetes Mellitus Tipo 2 , Glucagon , Glucose , Homeostase , Secreção de Insulina , Células Secretoras de Insulina , Receptores de Glucagon , Transdução de Sinais , Animais , Glucagon/metabolismo , Camundongos , Células Secretoras de Insulina/metabolismo , Glucose/metabolismo , Receptores de Glucagon/metabolismo , Receptores de Glucagon/genética , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Masculino , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dieta Hiperlipídica , Glicemia/metabolismo , FemininoRESUMO
BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.
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COVID-19 , Caracteres Sexuais , Adulto , Feminino , Masculino , Humanos , Análise de Classes Latentes , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Análise por Conglomerados , Estilo de VidaRESUMO
Introduction: Adequate guidelines for treatment of people over 65 years, suffering traumatic thoracolumbar spine fractures without neurologic deficit, are currently lacking. Research question: The aim of this study was to systematically review the available literature regarding the outcome of conservative and surgical treatment of thoracolumbar spinal trauma in elderly patients. Material and methods: A systematic review according the PRISMA guidelines was performed. Pubmed, Web of Science, EMBASE and the Cochrane Central register were searched until June 2021. Risk of bias of the included studies was evaluated. Clinical and radiological results, as well as complications of conservative or surgical treatment were reviewed. Results: Six articles were included (one prospective randomized trial, two prospective and three retrospective cohort studies). In these studies conflicting results were observed with regard to pain, radiological results and complications following both conservative and surgical treatment strategies for thoracolumbar spine fractures in elderly. Discussion and conclusion: Treatment of thoracolumbar fractures in elderly should focus on early mobilization to reduce complications and hospital stay. This may improve functional outcome and prevent worsening of frailty in this vulnerable group of patients. To elucidate the optimal treatment for elderly patient with thoracolumbar fractures, future research should focus on patient specific treatment rather than the mere difference between outcome of surgical and conservative treatment.
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OBJECTIVE: To investigate the effects of sodium fluoride on the ameloblast and reveal the mechanism of dental fluorosis. MATERIALS AND METHODS: Mouse ameloblast-like cell line (ALC) cells were treated with various concentrations of NaF, and subjected to Incucyte, fluorescence immunoassay, transmission electron microscopy, reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot for autophagy examination, alkaline phosphatase and alizarin red staining for mineralization after osteogenic induction. RESULTS: NaF exerts a dose-dependent inhibitory effect on ALC cell growth. TEM and fluorescence immunoassay showed that 1.5 mM or higher concentrations of NaF could induce a fusion of lysosome and mitochondria, finally increasing the number of autophagosome. RT-qPCR and western blot showed that the upregulation of autophagy related gene 13 (ATG13), downregulation of phosphorylated Unc-51-like kinase 1 (p-ULK1) were found in NaF-induced autophagy of ALC cells. The knockdown of ATG13 could rescue it as well as the expression of p-ULK1 and LC3B. Besides, alizarin red staining showed that fluoride under these concentrations could promote the mineralization of ALC. CONCLUSIONS: The data show that fluoride in higher concentration can induce autophagy via the p-ULk1/ATG13/LC3B pathway of ALCs than lower ones promote mineralization in vitro, which provides insight into the function of NaF in the autophagy and mineralization of ameloblast.
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The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.
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Osteoporose , Fraturas da Coluna Vertebral , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos de Coortes , Prevalência , Incidência , Vietnã , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Densidade Óssea , Absorciometria de Fóton/métodos , Fatores de Risco , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesõesRESUMO
INTRODUCTION: Maternal medicine is important and complex. It focuses on the care of mothers with comorbidities or medical disorders during pregnancy. To date, there are limited tools to assess clinicians' knowledge, attitude and practice (KAP) in this field. MATERIALS AND METHODS: This study aims to develop and validate a questionnaire measuring the KAP of clinicians towards maternal medicine. Literature reviews, item generation and multiple experts' reviews were conducted during the questionnaire development phase. Convenient sampling was undertaken for this cross-sectional survey. A total of 168 clinicians from one tertiary hospital and three health clinics participated in thepilot testing using the modified questionnaire. In addition, test-retest was performed on 30 participants to examine its reliability, whilst exploratory factor analysis (EFA) was undertaken to determine its construct validity. RESULTS: This finalised questionnaire contained 36 items with excellent content validity. Pertaining to test-retest reliability, all knowledge domain items showed Kappa values > 0.20, except item K29; attitude domain items overall Cronbach's alpha was 0.787 with corrected item-total correlation > 0.300 and lastly, all items in practice domain achieved intra-class correlation index > 0.700, except P2.5. EFA supported four factor structures, but six items were removed due to the following reasons: cross loading, negative or poor loading factor (< 0.3). CONCLUSION: Overall, this instrument has an acceptable psychometric property, content validity, internal reliability and construct validity. It is hope that this questionnaire would be validated in other populations and be used in future research to enrich our understanding of clinicians' KAP towards maternal medicine.
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Conhecimentos, Atitudes e Prática em Saúde , Mães , Feminino , Gravidez , Humanos , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Candida tropicalis is a globally distributed yeast that has been popping up in the medical literature lately, albeit for unenviable reasons. C. tropicalis is associated with substantial morbidity, mortality as well as drug resistance. The aims of this study were to ascertain the antifungal susceptibility profile and the biofilm-producing capability of this notorious yeast in our centre. METHODS: C. tropicalis isolates from sterile specimens were collected over a 12-month period. Conclusive identification was achieved biochemically with the ID 32 C kit. Susceptibility to nine antifungal agents was carried out using the colourimetric broth microdilution kit Sensititre YeastOne YO10. Biofilm-producing capability was evaluated by quantifying biomass formation spectrophotometrically following staining with crystal violet. RESULTS: Twenty-four non-repetitive isolates of C. tropicalis were collected. The resistance rates to the triazole agents were 29.2% for fluconazole, 16.7% for itraconazole, 20.8% for voriconazole and 8.3% for posaconazole-the pan-azole resistance rate was identical to that of posaconazole. No resistance was recorded for amphotericin B, flucysosine or any of the echinocandins tested. A total of 16/24 (66.7%) isolates were categorized as high biomass producers and 8/24 (33.3%) were moderate biomass producers. None of our isolates were low biomass producers. CONCLUSION: The C. tropicalis isolates from our centre were resistant only to triazole agents, with the highest resistance rate being recorded for fluconazole and the lowest for posaconazole. While this is not by itself alarming, the fact that our isolates were prolific biofilm producers means that even azole-susceptible isolates can be paradoxically refractory to antifungal therapy.
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Antifúngicos , Fluconazol , Humanos , Antifúngicos/farmacologia , Fluconazol/farmacologia , Candida tropicalis , Candida , Testes de Sensibilidade Microbiana , Triazóis , Azóis , BiofilmesRESUMO
Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .
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Infecções por HIV , HIV-1 , Receptor Toll-Like 9 , Feminino , Humanos , Masculino , Adjuvantes Imunológicos , Anticorpos Neutralizantes , Anticorpos Amplamente Neutralizantes/uso terapêutico , Anticorpos Anti-HIV/uso terapêutico , Receptor Toll-Like 9/antagonistas & inibidores , Receptor Toll-Like 9/imunologiaRESUMO
Compared to the myriad of known triggers for rhinitis and asthma, environmental exposure research for atopic dermatitis (AD) is not well established. We recently reported that an untargeted search of U.S. Environmental Protection Agency (EPA) databases versus AD rates by United States (U.S.) postal codes revealed that isocyanates, such as toluene diisocyanate (TDI), are the pollutant class with the strongest spatiotemporal and epidemiologic association with AD. We further demonstrated that (di)isocyanates disrupt ceramide-family lipid production in commensal bacteria and activate the thermo-itch host receptor TRPA1. In this report, we reanalyzed regions of the U.S. with low levels of diisocyanate pollution to assess if a different chemical class may contribute. We identified antimony compounds as the top associated pollutant in such regions. Exposure to antimony compounds would be expected from brake dust in high-traffic areas, smelting plants, bottled water, and dust from aerosolized soil. Like TDI, antimony inhibited ceramide-family lipid production in Roseomonas mucosa and activated TRPA1 in human neurons. While further epidemiologic research will be needed to directly evaluate antimony exposure with surrounding AD prevalence and severity, these data suggest that compounds which are epidemiologically associated with AD, inhibit commensal lipid production, and activate TRPA1 may be causally related to AD pathogenesis.
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Conical intersections are ubiquitous in chemistry and physics, often governing processes such as light harvesting, vision, photocatalysis and chemical reactivity. They act as funnels between electronic states of molecules, allowing rapid and efficient relaxation during chemical dynamics. In addition, when a reaction path encircles a conical intersection, the molecular wavefunction experiences a geometric phase, which can affect the outcome of the reaction through quantum-mechanical interference. Past experiments have measured indirect signatures of geometric phases in scattering patterns and spectroscopic observables, but there has been no direct observation of the underlying wavepacket interference. Here we experimentally observe geometric-phase interference in the dynamics of a wavepacket travelling around an engineered conical intersection in a programmable trapped-ion quantum simulator. To achieve this, we develop a technique to reconstruct the two-dimensional wavepacket densities of a trapped ion. Experiments agree with the theoretical model, demonstrating the ability of analogue quantum simulators-such as those realized using trapped ions-to accurately describe nuclear quantum effects.
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OBJECTIVE: To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. METHODS: A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. RESULTS: Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05). CONCLUSION: Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
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Glomerulonefrite Membranosa , Testes Farmacogenômicos , Humanos , Autoanticorpos , Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/diagnóstico , Homozigoto , Imunossupressores/uso terapêutico , Receptores da Fosfolipase A2 , Deleção de Sequência , Albumina Sérica , Tacrolimo/uso terapêuticoRESUMO
INTRODUCTION: The magnitude of Coronavirus Disease 2019 (COVID-19) infection among the elderly population is expected to rise. Our study compares the clinical and computed tomographical (CT) features of pulmonary thromboembolic (PTE) disease associated with COVID-19 infection in geriatric and non-geriatric cases, and explores the 60-day mortality rate in these two groups. MATERIALS AND METHODS: We conducted this retrospective cross-sectional study in Hospital Tengku Ampuan Rahimah, Selangor, Malaysia. Patients admitted in April 2021 and May 2021 with concomitant COVID-19 infection and PTE disease were included. Demographic, clinical and laboratory data were retrieved, whilst CTPA images were analysed by a senior radiologist. RESULTS: A total of 150 patients were recruited, comprising 45 geriatric patients and 105 non-geriatric patients. The prevalence rate of hypertension, diabetes mellitus and dyslipidaemia were higher among the geriatric cohort. Evidently, the percentage of patients with fever and diarrhoea were significantly higher among the non-geriatric cohort. The geriatric cohort also recorded a significantly lower absolute lymphocyte count at presentation and albumin level during admission. Despite earlier presentation, the geriatric cohort suffered from more severe diseases. Analysis of the CT features demonstrated that the most proximal pulmonary thrombosis specifically limited to the segmental and subsegmental pulmonary arteries in both cohorts. The elderly suffered from a significantly higher inhospital mortality rate and their cumulative probability of survival was significantly lower. CONCLUSION: Typical COVID-19 symptoms may be absent among the elderly, prompting a lower threshold of suspicion during the COVID-19 pandemic. Additionally, the elderly demonstrated a higher probability of adverse outcomes despite earlier presentation and treatment.
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COVID-19 , Embolia Pulmonar , Humanos , Idoso , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Estudos Retrospectivos , Estudos Transversais , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologiaRESUMO
INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.