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PURPOSE: The purpose of the study was to explore how caring for older adults with both diabetes and functional limitations impacts caregiver depressive symptoms and whether this impact is moderated by caregivers' expressive social support and psychological resilience. METHOD: Cross-sectional data of 278 dyads, each comprising an older adult with functional limitations and his/her primary family caregiver were analyzed. Older adult diabetes status (yes/no) was based on ever-diagnosis of diabetes. Caregiver depressive symptoms, expressive social support, and psychological resilience were measured using standard scales. Multivariable linear regression was used to assess the association of interest and its moderation by caregiver expressive social support and psychological resilience. RESULTS: Caregivers of older adults with both diabetes and functional limitations had a higher depressive symptoms score compared to caregivers of older adults with only functional limitations. This association was inversely moderated by caregiver expressive social support. As caregiver expressive social support increased, the difference in depressive symptoms between caregivers of older adults with diabetes and functional limitations and caregivers of older adults with only functional limitations reduced. CONCLUSION: Family caregivers of older adults with functional limitations and diabetes have a higher depressive symptoms score. However, enhancing caregiver expressive social support could mitigate this risk. Service providers should prioritize support for caregivers in such vulnerable situations and strive to enhance their expressive social support.
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Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.
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Proteínas , Polonia , Proteínas/química , Biología Molecular , Ácidos Nucleicos/química , HumanosRESUMEN
BACKGROUND: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.
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Índice de Masa Corporal , Neoplasias de la Mama , Ensayos Clínicos como Asunto , Obesidad , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Femenino , Obesidad/complicaciones , Obesidad/epidemiología , Antineoplásicos/uso terapéutico , Resultado del TratamientoRESUMEN
Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients with breast cancer and are understudied at the metastatic level. Here, we characterized the histology of metastases from two patients with primary mixed IBC-NST/ILC from the postmortem tissue donation program UPTIDER (NCT04531696). The 14 and 43 metastatic lesions collected at autopsy had morphological features and E-cadherin staining patterns consistent with pure ILC. While our findings still require further validation, they may challenge current clinical practice and imaging modalities used in these patients.
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Neoplasias de la Mama , Carcinoma Lobular , Humanos , Femenino , Carcinoma Lobular/patología , Neoplasias de la Mama/patología , Persona de Mediana Edad , Cadherinas/metabolismo , Cadherinas/análisis , Anciano , AutopsiaRESUMEN
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 Sexuales , Adulto , Femenino , Masculino , Humanos , Análisis de Clases Latentes , Estudios Transversales , Pandemias , COVID-19/epidemiología , Análisis por Conglomerados , Estilo de VidaRESUMEN
Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting.
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Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.
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Drawing on the social practice theory, theory of planned behavior, social contagion theory, and social exchange theory, this study focused on tourist behaviors affecting tourism social sustainability and their drivers. Besides its unique contribution to distinguishing positive behaviors from negative ones, this study is the first exploring tourism social sustainability in remote communities in Vietnam, an emerging country and focusing on domestic tourists. The study reveals that tourists' knowledge about tourism social sustainability is not only the safeguard against conducting improper behaviors. Behaviors negatively impacting tourism social sustainability can be instigated by crowd, pampering of one's convenience, and superiority feeling. Furthermore, inappropriate behaviors can be nurtured by the community and service providers. This study also indicates a mixed finding regarding the role of tour operators and tour guides in enforcing the code of conduct and regulations; however, both leader and members of the community can play a critical role in promoting socially sustainable tourist behaviors.
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BACKGROUND: In 2022, many universities transitioned from virtual learning back to in-person teaching. Significant changes in working conditions, along with COVID-19-related anxiety during the pandemic, might impact the well-being of lecturers. OBJECTIVE: This study aims to assess the perceived stress, self-rated physical and occupational health of Vietnamese lecturers in 2022 compared to the pre-pandemic levels, and to identify their associating factors. METHOD: This is a cross-sectional study conducted in May-June 2022 through an online survey questionnaire. A sample of 425 university lecturers were included. Participants' stress levels were assessed using the Perceived Stress Scale. Participants were asked to compare their current physical and occupational health with before the pandemic. Explanatory variables included (1) COVID-19 exposure; and (2) perceptions of changes in working environment due to the pandemic. Multivariable ordinal least squared regression analyses were used to estimate the coefficient and 95% confidence intervals for the associations between COVID-19 exposure variables, work conditions, and each outcome. RESULTS: Our findings indicated that over 60% of participants experienced moderate stress, while nearly half reported worsened physical and occupational health during the pandemic. Gender, age, perceptions of workload, workplace safety, COVID-19 infection, and incentive programs were significant factors associated with higher stress levels and worse self-rated health. CONCLUSION: To ensure occupational safety and support lecturers as they return to in-person classes, it is crucial to provide appropriate psychological and health support services.
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COVID-19 , Humanos , COVID-19/psicología , COVID-19/epidemiología , Masculino , Estudios Transversales , Femenino , Adulto , Encuestas y Cuestionarios , Universidades , Persona de Mediana Edad , Vietnam/epidemiología , SARS-CoV-2 , Pandemias , Lugar de Trabajo/psicología , Lugar de Trabajo/normas , Salud Laboral , Estrés Psicológico/psicología , Estrés Psicológico/etiología , Estrés Laboral/psicología , Autoinforme , Estado de Salud , Autoevaluación DiagnósticaRESUMEN
Inflammatory breast cancer (IBC) is a rare (1%-5%), aggressive form of breast cancer, accounting for approximately 10% of breast cancer mortality. In the localized setting, standard of care is neoadjuvant chemotherapy (NACT) ± anti-HER2 therapy, followed by surgery. Here we investigated associations between clinicopathologic variables, stromal tumor-infiltrating lymphocytes (sTIL), and pathologic complete response (pCR), and the prognostic value of pCR. We included 494 localized patients with IBC treated with NACT from October 1996 to October 2021 in eight European hospitals. Standard clinicopathologic variables were collected and central pathologic review was performed, including sTIL. Associations were assessed using Firth logistic regression models. Cox regressions were used to evaluate the role of pCR and residual cancer burden (RCB) on disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). Distribution according to receptor status was as follows: 26.4% estrogen receptor negative (ER-)/HER2-; 22.0% ER-/HER2+; 37.4% ER+/HER2-, and 14.1% ER+/HER2+. Overall pCR rate was 26.3%, being highest in the HER2+ groups (45.9% for ER-/HER2+ and 42.9% for ER+/HER2+). sTILs were low (median: 5.3%), being highest in the ER-/HER2- group (median: 10%). High tumor grade, ER negativity, HER2 positivity, higher sTILs, and taxane-based NACT were significantly associated with pCR. pCR was associated with improved DFS, DRFS, and OS in multivariable analyses. RCB score in patients not achieving pCR was independently associated with survival. In conclusion, sTILs were low in IBC, but were predictive of pCR. Both pCR and RCB have an independent prognostic role in IBC treated with NACT. SIGNIFICANCE: IBC is a rare, but very aggressive type of breast cancer. The prognostic role of pCR after systemic therapy and the predictive value of sTILs for pCR are well established in the general breast cancer population; however, only limited information is available in IBC. We assembled the largest retrospective IBC series so far and demonstrated that sTIL is predictive of pCR. We emphasize that reaching pCR remains of utmost importance in IBC.
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Neoplasias Inflamatorias de la Mama , Humanos , Neoplasias Inflamatorias de la Mama/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/química , Terapia Neoadyuvante , Receptor ErbB-2/análisis , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.
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Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted an after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.
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COVID-19 , Pandemias , Estados Unidos , Humanos , Vietnam/epidemiología , Pandemias/prevención & control , COVID-19/epidemiología , Brotes de EnfermedadesRESUMEN
The adoption of Unmanned Aerial Vehicle (UAV) remote sensing for the regulatory monitoring of turbidity plumes induced by land reclamation operations remains a difficult task. Compared to UAV remote sensing on ambient turbidity in estuaries and rivers, such monitoring of construction-induced turbidity plumes requires significantly higher spatial resolutions and accuracy as well as wider turbidity ranges with nonlinear reflectance. In this study, a pilot-scale deployment of UAV-based hyperspectral sensing is carried out for this objective, with specific new elements developed to overcome the challenges and minimise the uncertainties involved. In particular, Machine learning (ML) models for the turbidity determination were trained by the large dataset collected to better capture the non-linearity of the relationship between the water leaving reflectance and turbidity level. The models achieve a good accuracy with a R2 score of 0.75 that is deemed acceptable in view of the uncertainties associated with construction and land reclamation work.
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Tecnología de Sensores Remotos , Dispositivos Aéreos No Tripulados , AmbienteRESUMEN
PURPOSE: Invasive lobular carcinoma (ILC) represents up to 15% of all breast carcinomas. While the proportion of women with overweight and obesity increases globally, the impact of body mass index (BMI) at primary diagnosis on clinicopathological features of ILC and the prognosis of the patients has not been investigated yet. PATIENTS AND METHODS: We performed a multicentric retrospective study including patients diagnosed with non-metastatic pure ILC. The association of BMI at diagnosis with clinicopathological variables was assessed using linear or multinomial logistic regression. Univariable and multivariable survival analyses were performed to evaluate the association of BMI with disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). RESULTS: The data of 2856 patients with ILC and available BMI at diagnosis were collected, of which 2570/2856 (90.0%) had oestrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2) not amplified/overexpressed (ER+/HER2-) ILC. Of these 2570 patients, 80 were underweight (3.1%), 1410 were lean (54.9%), 712 were overweight (27.7%), and 368 were obese (14.3%). Older age at diagnosis, a higher tumour grade, a larger tumour size, a nodal involvement, and multifocality were associated with a higher BMI. In univariable models, higher BMI was associated with worse outcomes for all end-points (DFS: hazard ratio (HR) 1.21, 95CI 1.12-1.31, p value<0.01; DRFS: HR 1.25, 95CI 1.12-1.40, p value<0.01; OS: HR 1.25, 95CI 1.13-1.37, p value<0.01). This association was not statistically significant in multivariable analyses (DFS: HR 1.09, 95CI 0.99-1.20, p value 0.08; DRFS: HR 1.03, 95CI 0.89-1.20, p value 0.67; OS: HR 1.11, 95CI 0.99-1.24, p value 0.08), whereas grade, tumour size, and nodal involvement were still prognostic for all end-points. CONCLUSION: Worse prognostic factors such as higher grade, larger tumour size, and nodal involvement are associated with higher BMI in ER+/HER2- ILC, while there was no statistical evidence for an independent prognostic role for BMI. Therefore, we hypothesise that the effect of BMI on survival could be mediated through its association with these clinicopathological variables.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Humanos , Femenino , Neoplasias de la Mama/patología , Índice de Masa Corporal , Carcinoma Lobular/patología , Sobrepeso , Estudios Retrospectivos , Pronóstico , Obesidad/complicaciones , Receptores de Estrógenos/metabolismo , Carcinoma Ductal de Mama/patologíaRESUMEN
Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Obesidad/complicaciones , Obesidad/genética , Biología Molecular , Sobrepeso , Genómica , Microambiente TumoralRESUMEN
The dyke system plays a vital role in cultivating rice intensively in the Vietnamese Mekong Delta, which protects rice paddy fields from annual floods. This study aimed to examine whether the full-dyke system (FD, which restricts water exchange for a long time) can cause degradation of surface water quality and reduction in benthic invertebrate biodiversity. The surface water quality and benthic invertebrate community were compared between the FD and semi-dyke systems (SD, which permits water exchange during flooding season) using a large number of samples collected seasonally in 2019. The results showed that the surface water quality within the FD system had significantly higher concentrations of TSS, COD, BOD5, N-NO3-, N-TKN, P-PO43-, and TP than compared to the SD system (p < 0.05), indicating greater pollution levels. The benthic invertebrate community was less diverse in the FD system than in the SD system. Only 17 species (belonging to 4 families) were detected in the FD system, and 30 species (belonging to 5 families) were detected in the SD system. The benthic invertebrate community structure changes and biodiversity loss were associated with degraded water quality. The P-PO43- and TP parameters were negatively correlated with the number of species, density, and biomass in the FD system and with the Shannon-Wiener (H') index in the SD system. In conclusion, the FD system has been degrading water quality and causing biodiversity loss.
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Invertebrados , Ríos , Humanos , Animales , Vietnam , Ríos/química , Invertebrados/química , Calidad del Agua , BiodiversidadRESUMEN
BackgroundVaccines play a crucial role in the response to COVID-19 and their efficacy is thus of great importance.AimTo assess the robustness of COVID-19 vaccine efficacy (VE) trial results using the fragility index (FI) and fragility quotient (FQ) methodology.MethodsWe conducted a Cochrane and PRISMA-compliant systematic review and meta-analysis of COVID-19 VE trials published worldwide until 22 January 2023. We calculated the FI and FQ for all included studies and assessed their associations with selected trial characteristics using Wilcoxon rank sum tests and Kruskal-Wallis H tests. Spearman correlation coefficients and scatter plots were used to quantify the strength of correlation of FIs and FQs with trial characteristics.ResultsOf 6,032 screened records, we included 40 trials with 54 primary outcomes, comprising 909,404 participants with a median sample size per outcome of 13,993 (interquartile range (IQR): 8,534-25,519). The median FI and FQ was 62 (IQR: 22-123) and 0.50% (IQR: 0.24-0.92), respectively. FIs were positively associated with sample size (p < 0.001), and FQs were positively associated with type of blinding (p = 0.023). The Spearman correlation coefficient for FI with sample size was moderately strong (0.607), and weakly positive for FI and FQ with VE (0.138 and 0.161, respectively).ConclusionsThis was the largest study on trial robustness to date. Robustness of COVID-19 VE trials increased with sample size and varied considerably across several other important trial characteristics. The FI and FQ are valuable complementary parameters for the interpretation of trial results and should be reported alongside established trial outcome measures.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Anti-HER2 antibody-drug conjugates (ADCs) have shown important efficacy in HER2-low metastatic breast cancer (mBC). Criteria for receiving ADCs are based on a single assay on the primary tumour or a small metastatic biopsy. We assessed the intra-patient inter-metastasis heterogeneity of HER2-low status in HER2-negative mBC. PATIENTS AND METHODS: We included samples of 10 patients (7 ER-positive and 3 ER-negative) donated in the context of our post-mortem tissue donation program UPTIDER. Excisional post-mortem biopsies of 257 metastases and 8 breast tumours underwent central HER2 immunohistochemistry (IHC), alongside 41 pre-mortem primary or metastatic samples. They were classified as HER2-zero, HER2-low (HER2-1+ or HER2-2+, in situ hybridisation [ISH] negative) or HER2-positive (HER2-3+ or HER2-2+, ISH-positive) following ASCO/CAP guidelines 2018. HER2-zero was further subdivided into HER2-undetected (no staining) and HER2-ultralow (faint staining in ≤10% of tumour cells). RESULTS: Median post-mortem interval was 2.5 h. In 8/10 patients, HER2-low and HER2-zero metastases co-existed, with the proportion of HER2-low lesions ranging from 5% to 89%. A total of 32% of metastases currently classified as HER2-zero were HER2-ultralow. Intra-organ inter-metastasis heterogeneity of HER2-scores was observed in the liver in 3/6 patients. Patients with primary ER-positive disease had a higher proportion of HER2-low metastases as compared to ER-negative disease (46% versus 8%, respectively). At the metastasis level, higher percentages of ER-expressing cells were observed in HER2-low or -ultralow as compared to HER2-undetected metastases. CONCLUSIONS: Important intra-patient inter-metastasis heterogeneity of HER2-low status exists. This questions the validity of HER2-low in its current form as a theranostic marker.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptor ErbB-2/genética , Biomarcadores de Tumor/análisis , Hibridación in Situ , BiopsiaRESUMEN
Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted a after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.
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COVID-19 , Pandemias , Estados Unidos , Humanos , Vietnam/epidemiología , COVID-19/epidemiología , Brotes de EnfermedadesRESUMEN
Identifying modifiable risk factors that contribute to cancer is essential in setting up preventive strategies. Therefore, this study aimed to estimate the number and proportion of cancer cases and deaths attributable to five behavior-related risk factors-tobacco smoking, second-hand smoking, alcohol consumption, high body mass index and insufficient physical activity in Vietnam in 2020. Population attributable fractions were calculated for relationships of risk factors and cancer types based on sufficient evidence according to IARC or strong evidence according to WCRF/AICR. Relative risks were retrieved from meta-analyses where possible. Prevalence of risk factors was obtained from the most current available nationally representative population surveys in Vietnam. Cancer cases and deaths were obtained from GLOBOCAN 2020. An estimated 40.5% of all cancer cases in men (39 924 cases) and 7.8% in women (6542 cases) were attributable to these risk factors. The proportions of cancer deaths attributable to these risk factors were 44.0% in men (32 807 cases) and 8.9% in women (4235 cases). Tobacco smoking was the leading cause of cancer cases and deaths in men, followed by alcohol consumption and high BMI. In women, high BMI accounted for the highest proportion of cancer cases and second-hand smoking accounted for the highest proportion of cancer deaths. Lung and upper aerodigestive tract cancer cases and deaths could have been reduced at least by half if these risk factors had been eliminated. To reduce cancer incidence and mortality, preventive actions focusing on tobacco control are likely to have the most significant impact, especially in men.