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Bound states in the continuum (BICs)1-3 are peculiar topological states that, when realized in a planar photonic crystal lattice, are symmetry-protected from radiating in the far field despite lying within the light cone4. These BICs possess an invariant topological charge given by the winding number of the polarization vectors5, similar to vortices in quantum fluids such as superfluid helium and atomic Bose-Einstein condensates. In spite of several reports of optical BICs in patterned dielectric slabs with evidence of lasing, their potential as topologically protected states with theoretically infinite lifetime has not yet been fully exploited. Here we show non-equilibrium Bose-Einstein condensation of polaritons-hybrid light-matter excitations-occurring in a BIC thanks to its peculiar non-radiative nature, which favours polariton accumulation. The combination of the ultralong BIC lifetime and the tight confinement of the waveguide geometry enables the achievement of an extremely low threshold density for condensation, which is reached not in the dispersion minimum but at a saddle point in reciprocal space. By bridging bosonic condensation and symmetry-protected radiation eigenmodes, we reveal ways of imparting topological properties onto macroscopic quantum states with unexplored dispersion features. Such an observation may open a route towards energy-efficient polariton condensation in cost-effective integrated devices, ultimately suited for the development of hybrid light-matter optical circuits.
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BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).
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Antirretrovirales , Antituberculosos , Dexametasona , Glucocorticoides , Infecciones por VIH , Tuberculosis Meníngea , Adulto , Humanos , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Método Doble Ciego , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/complicaciones , Seropositividad para VIH/tratamiento farmacológico , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/tratamiento farmacológico , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Quimioterapia Combinada/efectos adversos , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéuticoRESUMEN
Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.
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BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
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BACKGROUND: Atezolizumab plus bevacizumab is the standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, although was only evaluated in patients with Child-Pugh (CP) A liver function in the IMbrave150 trial. We sought to determine the outcomes of these patients based on CP score and ALBI grade in the US population. METHODS: This multicenter cohort study included patients with HCC who received atezolizumab with bevacizumab as first-line systemic therapy between March 2018 and November 2023. Overall survival (OS) was determined using the Kaplan-Meier method and multivariate analyses were performed using Cox proportional hazard regression method. RESULTS: Among 322 patients, 226, 86, and 10 patients had CP-A, CP-B, and CP-C liver function, respectively. Median age was 66.5 years, 78.6% were male, and 82.6% were White. Median OS (mOS) was 21.6 months for those with CP-A, 9.1 months for those with CP-B7, and 4.7 months for those with CP-B8-C12 (Pâ <â .0001). Among patients with CP-A, those with ALBI grade 1 had an mOS of 34.9 months versus 14.2 months in those with grade 2. In multivariate analyses, CP score, ALBI grade, hepatitis B, performance status, and macrovascular invasion were significantly associated with survival. CONCLUSIONS: CP score is an important prognostic tool for patients with HCC receiving atezolizumab plus bevacizumab, and this regimen remains a viable option for patients with CP-B7 with no additional safety concern, although the benefit is significantly less than those with CP-A. ALBI score has independent predictive value in patients with CP-A liver function.
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Entanglement in bipartite systems has been applied to generate secure random numbers, which are playing an important role in cryptography or scientific numerical simulations. Here, we propose to use multipartite entanglement distributed between trusted and untrusted parties for generating randomness of arbitrary dimensional systems. We show that the distributed structure of several parties leads to additional protection against possible attacks by an eavesdropper, resulting in more secure randomness generated than in the corresponding bipartite scenario. Especially, randomness can be certified in the group of untrusted parties, even when there is no randomness in either of them individually. We prove that the necessary and sufficient resource for quantum randomness in this scenario is multipartite quantum steering when each untrusted party has a choice between only two measurements. However, the sufficiency no longer holds with more measurement settings. Finally, we apply our analysis to some experimentally realized states and show that more randomness can be extracted compared with the existing analysis.
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An Endocrine Disrupting Chemical (EDC) is any compound that disrupts the function of the endocrine system in humans and is ubiquitous in the environment either as a result of natural events or through anthropogenic activities. Bisphenol A, phthalates, parabens, pesticides, triclosan, polychlorinated biphenyls, and heavy metals, which are frequently found in the pharmaceutical, cosmetic, and packaging sectors, are some of the major sources of EDC pollutants. EDCs have been identified to have a deteriorating effect on the female reproductive system, as evidenced by the increasing number of reproductive disorders such as endometriosis, uterine fibroids, polycystic ovary syndrome, premature ovarian failure, menstrual irregularity, menarche, and infertility. Studying EDCs in relation to women's health is essential for understanding the complex interactions between environmental factors and health outcomes. It enables the development of strategies to mitigate risks, protect reproductive and overall health, and inform public policy decisions to safeguard women's well-being. Healthcare professionals must know the possible dangers of EDC exposure and ask about environmental exposures while evaluating patients. This may result in more precise diagnosis and personalized treatment regimens. This review summarises the existing understanding of prevalent EDCs that impact women's health and involvement in female reproductive dysfunction and underscores the need for more research. Further insights on potential mechanisms of action of EDCs on female has been emphasized in the article. We also discuss the role of nutritional intervention in reducing the effect of EDCs on women's reproductive health. EDC pollution can be further reduced by adhering to strict regulations prohibiting the release of estrogenic substances into the environment.
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Disruptores Endocrinos , Contaminantes Ambientales , Humanos , Femenino , Disruptores Endocrinos/toxicidad , Salud Reproductiva , Reproducción , Contaminantes Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Salud de la MujerRESUMEN
Mulberry (Morus alba L.) is highly important crop in Vietnam, playing a key role in the country's economy through sericulture, food supply, pharmaceuticals, and beverage industries (Nguyen et al., 2018; Rohela et al., 2020). Recently, many mulberry-growing areas in Lam Dong, Vietnam have reported severe symptoms associated with nematode infection, including yellowing leaves, stunted growth, and severe root galling, leading to a significant decline in mulberry productivity. From April to December 2022, twenty soil and root samples from mulberry-growing areas in Lam Dong (Da Teh: 11°28'48.11"N; 107°28'23.74"E elevation: 133m; Lam Ha 11°48'25.13"N; 108°14'7.13"E elevation: 848m) were collected to uncover the presence of Meloidogyne enterolobii parasitizing mulberry in Vietnam. One nematode population was randomly selected for characterizing in this study among analyzed nematode populations. Females were extracted from heavily galled roots (Fig. S1) from a single mulberry tree in Lam Dong, Vietnam, using a needle and forceps (Subbotin et al., 2021). The perineal patterns of adult females (n = 10) have an oval shape, with clearly visible phasmids, along with a prominently high and squared dorsal arch. The striae are smooth and coarse, while the perivulval region remains devoid of striae. The lateral lines appear indistinct, and the tail tip is easily observable. Morphometric measurements were as follows: body length = 585 ± 78 (464-724) µm, body width = 367 ± 75 (271-529) µm, neck length = 221.5 ± 30.7 (167-269.6) µm, stylet length = 13.1 ± 1.2 (11.4-15.1) µm, vulva-slit length 16.3±2.3 (10.4-18) µm, vulva-anus distance = 16.8±3.0 (11.4-18) µm, anus-tail tip distance = 10.3±2.1 (6.9-14.2) µm, interphasmidial distance = 15.9 ± 3.7 (10.3-23.4) µm. The morphology of this nematode population is highly in agreement with the original description of M. enterolobii (Yang & Eisenback, 1983). This population was also identified using the D2-D3 of 28S rRNA and 18S rRNA (Powers et al., 2017; Subbotin et al., 2006) regions. The D2-D3 of 28S rRNA sequences from this study (accession numbers: OR889633) exhibited 99.5-99.8% similarity to the sequences of M. enterolobii from GenBank (accession numbers: OR214950 and ON496981). While the 18S rRNA sequences (accession numbers: OR896547) showed 99.2-99.3% similarity to the sequences of M. enterolobii from GenBank (accession numbers: MZ955995, MZ531901, and MW488150). To carry out Koch's postulates, 2000 J2s from collected M. enterolobii egg masses (initial population) were inoculated on two-month-old plantlets of mulberry (n = 6), planted on 2L pots within a screenhouse, non-inoculated plantlets (n=6) served as negative controls. After 90 days post-inoculation, nematode reproduction factors (RF = final density (nematodes were extracted from the whole root system and corresponding soil samples (Subbotin et al., 2021)) / initial population) and root damage symptoms were evaluated. The inoculated plantlets exhibited consistent yellowing leaves, stunting, and root galling symptoms (Fig. S1), mirroring observations from the field, with an average RF of 11.5. Control plants displayed no symptoms. Root-knot nematodes extracted from the roots were identified as M. enterolobii through molecular analyses of D2-D3 of 28S and 18S rRNA regions (GenBank accession numbers: OR889634 (D2-D3 of 28S) and OR896548 (18S)), thereby confirming that mulberry acts as a host for M. enterolobii. Currently, this nematode has been reported to be associated with two different host plants, including guava (Trinh et al., 2022) and pomelo (Le et al., 2023). Our discovery marks the first documented case of Meloidogyne enterolobii parasitizing mulberry in Vietnam. While the impact on mulberry productivity remains to be really important for sericulture food supply, pharmaceuticals, and beverage industries; the aggressive nature of M. enterolobii, as observed in the field and confirmed by the screenhouse tests, raises concerns about potential economic losses in mulberry production. Therefore, further investigations are needed to assess the extent of M. enterolobii infestation in mulberry orchards and to develop effective control measures to safeguard the sustainability of mulberry cultivation in Vietnam.
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Microplastics are found ubiquitous in the natural environment and are an increasing source of worry for global health. Rapid industrialization and inappropriate plastic waste management in our daily lives have resulted in an increase in the amount of microplastics in the ecosystem. Microplastics that are <150 µm in size could be easily ingested by living beings and cause considerable toxicity. Microplastics can aggregate in living organisms and cause acute, chronic, carcinogenic, developmental, and genotoxic damage. As a result, a sustainable approach to reducing, reusing, and recycling plastic waste is required to manage microplastic pollution in the environment. However, there is still a significant lack of effective methods for managing these pollutants. As a result, the purpose of this review is to convey information on microplastic toxicity and management practices that may aid in the reduction of microplastic pollution. This review further insights on how plastic trash could be converted as value-added products, reducing the load of accumulating plastic wastes in the environment, and leading to a beneficial endeavor for humanity.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Microplásticos , Plásticos , Ecosistema , Contaminación Ambiental/prevención & control , Contaminantes Químicos del Agua/análisis , Monitoreo del AmbienteRESUMEN
Pratylenchus coffeae, belonging to the root-lesion nematode group, is a highly prevalent and destructive plant-parasitic nematode that is able to infest a wide range of host plants. Although this species' devastating impacts on coffee plantations across the world are widely known on other host plants, its association with Ming aralia has never been reported. Our study characterized two popu lations of P. coffeae (associated with Ming aralia and coffee) and compared them with other popu lations from previous studies in Vietnam and other countries in the world. The identification of P. coffeae in our study was confirmed by the comprehensive analysis encompassing morphological examination, morphometric data, and molecular characterizations of the COI mtDNA and D2D3 of 28S rRNA regions. The cluster and MDS analyses revealed that the two populations of P. coffeae from Vietnam are closely related to those from Japan and Indonesia. The D2-D3 sequences of 28S rRNA and COI mtDNA regions exhibited high similarity among these populations, indicating a stable genetic profile. Our research contributes to a better understanding of the distribution and genetic characterizations of P. coffeae by offering new morphological and molecular insights into the presence of this nematode in Vietnam. Additionally, this nematode species was found to be associated with host plant's symptoms such as chlorotic leaves, stunted growth and root lesion in both hosts. Given the economic significance of both Ming aralia and coffee crops in Vietnam, as well as the damaging potential of P. coffeae, this study emphasizes the need of proactive nematode management measures to control this destructive pest.
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The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
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BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Terapia Neoadyuvante , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hepatectomía , Resultado del TratamientoRESUMEN
Background: Critically ill patients are at high risk of multiple organ failure syndrome (MODS) and gastrointestinal (GI) injury and dysfunction, which are associated with increased mortality rates. The acute gastrointestinal injury (AGI) scale has shown promise in assessing GI dysfunction. However, the combined utility of AGI with established disease severity scores remains unclear. This study aimed to investigate the performance of AGI in conjunction with modified nutritional risk in critically ill (mNUTRIC), sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) scores for predicting mortality in critically ill patients. Materials and methods: A retrospective cross-sectional study was conducted in the intensive care unit (ICU) from May 2021 to December 2021. Demographic and clinical data were collected, including AGI grade, mNUTRIC score, SOFA score, APACHE II score, and mortality. Results: Among 93 critically ill patients, AGI was observed in 47.3% of cases, and the in-hospital mortality rate was 30.1%. The area under the curve (AUC) for AGI in predicting in-hospital mortality was 0.67 [95% confidence interval (CI), 0.56, 0.79; p = 0.008], similar to the AUCs of SOFA, APACHE II, and mNUTRIC scores. The combination of AGI with mNUTRIC, APACHE II, or SOFA scores improved the predictive performance compared with AGI alone. Conclusion: The AGI grade, in conjunction with disease severity scores, such as mNUTRIC, SOFA, and APACHE II scores, shows promise in predicting mortality in critically ill patients. Integrating AGI into evaluating critically ill patients can enhance prognostic accuracy. How to cite this article: Hai PD, Tot NH, Thao LT, Khoa Q, Thien DH. Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients. Indian J Crit Care Med 2024;28(6):575-580.
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BACKGROUND: Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum malaria in pregnancy. METHODS: A retrospective cohort study was conducted of severe falciparum malaria in pregnancy, as defined by the World Health Organization severe malaria criteria. The patients were managed prospectively by the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border or were included in hospital-based clinical trials in six Southeast Asian countries. Fixed-effects multivariable penalised logistic regression was used for analysing maternal mortality. RESULTS: We included 213 (123 SMRU and 90 hospital-based) episodes of severe falciparum malaria in pregnancy managed between 1980 and 2020. The mean maternal age was 25.7 (SD 6.8) years, and the mean gestational age was 25.6 (SD 8.9) weeks. The overall maternal mortality was 12.2% (26/213). Coma (adjusted odds ratio [aOR], 7.18, 95% CI 2.01-25.57, p = 0.0002), hypotension (aOR 11.21, 95%CI 1.27-98.92, p = 0.03) and respiratory failure (aOR 4.98, 95%CI 1.13-22.01, p = 0.03) were associated with maternal mortality. Pregnant women with one or more of these three criteria had a mortality of 29.1% (25/86) (95%CI 19.5 to 38.7%) whereas there were no deaths in 88 pregnant women with hyperparasitaemia (> 10% parasitised erythrocytes) only or severe anaemia (haematocrit < 20%) only. In the SMRU prospective cohort, in which the pregnant women were followed up until delivery, the risks of foetal loss (23.3% by Kaplan-Meier estimator, 25/117) and small-for-gestational-age (38.3%, 23/60) after severe malaria were high. Maternal death, foetal loss and preterm birth occurred commonly within a week of diagnosis of severe malaria. CONCLUSIONS: Vital organ dysfunction in pregnant women with severe malaria was associated with a very high maternal and foetal mortality whereas severe anaemia or hyperparasitaemia alone were not associated with poor prognosis, which may explain the variation of reported mortality from severe malaria in pregnancy. Access to antenatal care must be promoted to reduce barriers to early diagnosis and treatment of both malaria and anaemia.
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Nacimiento Prematuro , Recién Nacido , Embarazo , Humanos , Femenino , Adulto , Lactante , Estudios Prospectivos , Estudios Retrospectivos , Mianmar , FetoRESUMEN
Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Inhibidores de la Angiogénesis , Anticuerpos Monoclonales , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. DESIGN: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). RESULTS: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. CONCLUSION: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.
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Osteoartritis de la Rodilla , Femenino , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Rayos X , Imagen por Resonancia Magnética/métodos , RadiografíaRESUMEN
Signal transduction networks are responsible for transferring biochemical signals from the extracellular to the intracellular environment. Understanding the dynamics of these networks helps understand their biological processes. Signals are often delivered in pulses and oscillations. Therefore, understanding the dynamics of these networks under pulsatile and periodic stimuli is useful. One tool to do this is the transfer function. This tutorial outlines the basic theory behind the transfer function approach and walks through some examples of simple signal transduction networks.
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Modelos Biológicos , Transducción de Señal , Transducción de Señal/fisiologíaRESUMEN
Micro-structuration by etching is commonly used in integrated optics, adding complex and costly processing steps that can also potentially damage the device performance, owing to degradation of the etched sidewalls. For diffraction grating fabrication, different strategies have been developed to avoid etching, such as layer deposition on a structured surface or grating deposition on top of active layers. However, etching remains one of the best processes for making high aspect ratio diffraction gratings. In this work, we have developed fully structured diffraction gratings (i.e., like fully etched gratings) using lift-off based processing performed in pulsed laser deposited layers, since the combination of both techniques is of great interest for making micro-structures without etching. We have first studied the influence of the lithography doses in the lift-off process, showing that (1) micrometric spatial resolution can be achieved and (2) the sidewall angle can be controlled from 50° to 150° in 0.5â µm thick layers. Using such optimizations, we have then fabricated Er-doped Y2O3 uniaxial diffraction gratings with different periods ranging from 3 to 8â µm. The fabricated devices exhibit emission and reflectivity properties as a function of the collection angle in good agreement with the modeling, with a maximum luminescence enhancement of ×15 compared with an unstructured layer at a wavelength of 1.54â µm. This work thus highlights lift-off based processing combined with pulsed laser deposition as a promising technique for etch-free practical applications, such as luminescence enhancement in Er-doped layers.
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BACKGROUND: Social determinants of health lead to better cancer care. This multi-site, single-institution study sought to capture data on social determinants of health data in Asian Americans with hepatocellular carcinoma; this group constitutes 60% of patients with this malignancy and are often undertreated or not treated at all. METHODS: This study took advantage of an institutional initiative designed to capture and integrate social determinants of health data into the electronic medical record for all patients. Medical records of Asian Americans with hepatocellular cancer were reviewed to acquire data on housing instability, lack of transportation, financial concerns, and social isolation; a score of 1 indicated poor social determinants of health. RESULTS: Of 112 adult Asian American patients with hepatocellular cancer, 22 (20%) were Southeast Asian, and 74 (67%) described English proficiency/preference. Total noncompletion per domain (no question answered within that domain) was observed in 90 patients (80%) for housing instability; 90 (80%) for lack of transportation; 92 (82%) for financial hardship; and 90 (80%) for social isolation. A score of 1 (highest risk) was observed in 1 patient (0.9%) for housing instability; 1 (0.9%) lack of transportation; no patient for financial hardship; and 1 (0.9%) for social isolation. Of note, institution-wide benchmark total noncompletion rates were 0.3%, 0.3%, 47%, and 39% for these respective domains. CONCLUSION: High total noncompletion rates make social determinants of health data challenging to interpret and underscore the need for evidence-based guidelines on how best to capture such data in underserved patients.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Asiático , Determinantes Sociales de la Salud , Registros Electrónicos de SaludRESUMEN
BACKGROUND: Bevacizumab-induced gastrointestinal perforation is a rare but potentially devastating adverse event that has generated limited data on overall survival. Yet, such survival data are critical in guiding management. METHODS: This multi-site, single-institution retrospective study focused on all cancer patients who had received bevacizumab and who had suffered a well-documented gastrointestinal perforation from January 1, 2004 through January 20, 2022.The main goal was to report survival outcomes; Kaplan Meier curves and Cox survival models were used for this purpose. RESULTS: Eighty-nine patients are included in this report with a median age of 62 years (range 26-85). Colorectal cancer was the most common malignancy (n = 42). Thirty-nine patients underwent surgery for the perforation. Seventy-eight were deceased at the time of reporting with an overall median survival of all patients of 2.7 months (range 0-45 months), and 32 (36%) died within 30 days of perforation. In univariable survival analyses, no statistically significant associations were observed for age, gender, corticosteroid use, and time since last bevacizumab dose. However, surgically treated patients manifested a better survival (hazard ratio (HR) 0.49 (95% CI 0.31-0.78); p = 0.003). In multivariable analyses, surgery continued to be associated with improved survival (HR 0.47 (95% CI 0.29-0.74); p = 0.002), and corticosteroid use was associated with worse survival (HR 1.75 (95% CI 1.02-2.99); p = 0.04). CONCLUSION: Although gastrointestinal perforation after bevacizumab should be managed on a case-by-case basis, these descriptive survival data can help inform patients, their families, and healthcare providers as challenging management decisions arise.