22,909 research outputs found

    Impact of pre-antiretroviral treatment HIV-RNA on time to successful virological suppression and subsequent virological failure - two nationwide, population-based cohort studies

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    BACKGROUND: The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated. METHODS: We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50‚Ääcopies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200‚Ääcopies/ml or one >1000‚Ääcopies/ml). The study included 3366 Swedish and 2050 Danish ART na\uefve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios. RESULTS: In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000‚Ääcopies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000‚Ääcopies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained. CONCLUSION: High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure

    Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles

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    IntroductionLocal and regional recurrence after surgical intervention is a significant problem in cancer management. The multistage theory of carcinogenesis precisely places the presence of histologically normal but mutated premalignant lesions surrounding the tumor - field cancerization, as a significant cause of cancer recurrence. The relationship between tissue dynamics, cancer initiation and cancer recurrence in multistage carcinogenesis is not well known.MethodsThis study constructs a computational model for cancer initiation and recurrence by combining the Moran and branching processes in which cells requires 3 or more mutations to become malignant. In addition, a spatial structure-setting is included in the model to account for positional relativity in cell turnover towards malignant transformation. The model consists of a population of normal cells with no mutation; several populations of premalignant cells with varying number of mutations and a population of malignant cells. The model computes a stage of cancer detection and surgery to eliminate malignant cells but spares premalignant cells and then estimates the time for malignant cells to re-emerge.ResultsWe report the cellular conditions that give rise to different patterns of cancer initiation and the conditions favoring a shorter cancer recurrence by analyzing premalignant cell types at the time of surgery. In addition, the model is fitted to disease-free clinical data of 8,957 patients in 27 different cancer types; From this fitting, we estimate the turnover rate per month, relative fitness of premalignant cells, growth rate and death rate of cancer cells in each cancer type.DiscussionOur study provides insights into how to identify patients who are likely to have a shorter recurrence and where to target the therapeutic intervention

    Optimal strategy for delirium detection in older patients admitted to intensive care unit after non-cardiac surgery

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    BackgroundDelirium detection is challenging due to the fluctuating nature and frequent hypoactive presentation. This study aimed to determine an optimal strategy that detects delirium with higher sensitivity but lower effort in older patients admitted to the intensive care unit (ICU) after surgery.MethodsThis was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ‚Č•65 years) who were admitted to the ICU after elective noncardiac surgery were enrolled. Delirium was assessed with the Confusion Assessment Method for the ICU (CAM-ICU) twice daily during the first 7 days postoperatively. The sensitivity of different strategies in detecting delirium were analyzed and compared.ResultsOf all enrolled patients, 111 (15.9%; 95% CI: 13.3% to 18.8%) developed at least one episode of delirium during the first 7 postoperative days. Among patients who developed delirium, 60.4% (67/111) had their first delirium onset on postoperative day 1, 84.7% (94/111) by the end of day 2, 91.9% (102/111) by the end of day 3, and 99.1% (110/111) by the end of day 4. Compared with delirium assessment twice daily for 7 days, twice-daily measurements for 5 days detected 100% of delirium patients with 71% efforts; twice-daily measurements for 4 days detected 99% (95% CI: 94% to 100%) of delirium patients with 57% efforts; twice-daily assessment for 3 days detected 92% (95% CI: 85% to 96%) of delirium patients with only 43% efforts.ConclusionsFor older patients admitted to the ICU after elective noncardiac surgery, it is reasonable to detect delirium with the CAM-ICU twice daily for no more than 5 days, and if the personnel and funds are insufficient, 4 days could be sufficient

    Computertomographie-basierte Bestimmung von Aortenklappenkalk und seine Assoziation mit Komplikationen nach interventioneller Aortenklappenimplantation (TAVI)

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    Background: Severe aortic valve calcification (AVC) has generally been recognized as a key factor in the occurrence of adverse events after transcatheter aortic valve implantation (TAVI). To date, however, a consensus on a standardized calcium detection threshold for aortic valve calcium quantification in contrast-enhanced computed tomography angiography (CTA) is still lacking. The present thesis aimed at comparing two different approaches for quantifying AVC in CTA scans based on their predictive power for adverse events and survival after a TAVI procedure. ¬† Methods: The extensive dataset of this study included 198¬†characteristics for each of the 965¬†prospectively included patients who had undergone TAVI between November¬†2012 and December¬†2019 at the German Heart Center Berlin (DHZB). AVC quantification in CTA scans was performed at a fixed Hounsfield Unit (HU) threshold of 850¬†HU (HU¬†850 approach) and at a patient-specific threshold, where the HU threshold was set by multiplying the mean luminal attenuation of the ascending aorta by 2 (+100¬†% HUAorta approach). The primary endpoint of this study consisted of a combination of post-TAVI outcomes (paravalvular leak ‚Č•¬†mild, implant-related conduction disturbances, 30-day mortality, post-procedural stroke, annulus rupture, and device migration). The Akaike information criterion was used to select variables for the multivariable regression model. Multivariable analysis was carried out to determine the predictive power of the investigated approaches. ¬† Results: Multivariable analyses showed that a fixed threshold of 850¬†HU (calcium volume cut-off 146¬†mm3) was unable to predict the composite clinical endpoint post-TAVI (OR=1.13, 95¬†% CI 0.87 to 1.48, p=0.35). In contrast, the +100¬†% HUAorta approach (calcium volume cut-off 1421¬†mm3) enabled independent prediction of the composite clinical endpoint post-TAVI (OR=2, 95¬†% CI 1.52 to 2.64, p=9.2x10-7). No significant difference in the Kaplan-Meier survival analysis was observed for either of the approaches. ¬† Conclusions: The patient-specific calcium detection threshold +100¬†% HUAorta is more predictive of post-TAVI adverse events included in the combined clinical endpoint than the fixed HU¬†850 approach. For the +100¬†% HUAorta approach, a calcium volume cut-off of 1421¬†mm3 of the aortic valve had the highest predictive value.Hintergrund: Ein wichtiger Ausl√∂ser von Komplikationen nach einer Transkatheter-Aortenklappen-Implantation (TAVI) sind ausgepr√§gte Kalkablagerung an der Aortenklappe. Dennoch erfolgte bisher keine Einigung auf ein standardisiertes Messverfahren zur Quantifizierung der Kalklast der Aortenklappe in einer kontrastverst√§rkten dynamischen computertomographischen Angiographie (CTA). Die vorliegende Dissertation untersucht, inwieweit die Wahl des Analyseverfahrens zur Quantifizierung von Kalkablagerungen in der Aortenklappe die Prognose von Komplikationen und der √úberlebensdauer nach einer TAVI beeinflusst. ¬† Methodik: Der Untersuchung liegt ein umfangreicher Datensatz von 965 Patienten mit 198 Merkmalen pro Patienten zugrunde, welche sich zwischen 2012 und 2019 am Deutschen Herzzentrum Berlin einer TAVI unterzogen haben. Die Quantifizierung der Kalkablagerung an der Aortenklappe mittels CTA wurde einerseits mit einem starren Grenzwert von 850 Hounsfield Einheiten (HU) (HU 850 Verfahren) und andererseits anhand eines individuellen Grenzwertes bemessen. Letzterer ergibt sich aus der HU-D√§mpfung in dem Lumen der Aorta ascendens multipliziert mit 2 (+100 % HUAorta Verfahren). Der prim√§re klinische Endpunkt dieser Dissertation besteht aus einem aus sechs Variablen zusammengesetzten klinischen Endpunkt, welcher ungew√ľnschte Ereignisse nach einer TAVI abbildet (paravalvul√§re Leckage ‚Č•mild, Herzrhythmusst√∂rungen nach einer TAVI, Tod innerhalb von 30 Tagen, post-TAVI Schlaganfall, Ruptur des Annulus und Prothesendislokation). M√∂gliche St√∂rfaktoren, die auf das Eintreten der Komplikationen nach TAVI Einfluss haben, wurden durch den Einsatz des Akaike Informationskriterium ermittelt. Um die Vorhersagekraft von Komplikationen nach einer TAVI durch beide Verfahren zu ermitteln, wurde eine multivariate Regressionsanalyse durchgef√ľhrt. ¬† Ergebnisse: Die multivariaten logistischen Regressionen zeigen, dass¬†die Messung der Kalkablagerungen anhand der HU 850 Messung (Kalklast Grenzwert von 146 mm3) die Komplikationen und die √úberlebensdauer nicht vorhersagen konnten (OR=1.13, 95 % CI 0.87 bis 1.48, p=0.35). Die nach dem +100 % HUAorta Verfahren (Kalklast Grenzwert von 1421 mm3) individualisierte Kalkmessung erwies sich hingegen als sehr aussagekr√§ftig, da hiermit Komplikationen nach einer TAVI signifikant vorhergesagt werden konnten (OR=2, 95 % CI 1.52 bis 2.64, p=9.2x10-7). In Hinblick auf die postoperative Kaplan-Meier √úberlebenszeitanalyse kann auch mit dem +100 % HUAorta Verfahren keine Vorhersage getroffen werden. ¬† Fazit: Aus der Dissertation ergibt sich die Empfehlung, die Messung von Kalkablagerungen nach dem +100 % HUAorta Verfahren vorzunehmen, da Komplikationen wesentlich besser und zuverl√§ssiger als nach der g√§ngigen HU 850 Messmethode vorhergesagt werden k√∂nnen. F√ľr das +100 % HUAorta Verfahren lag der optimale Kalklast Grenzwert bei 1421 mm3

    Scalable and Accurate Self-supervised Multimodal Representation Learning without Aligned Video and Text Data

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    Scaling up weakly-supervised datasets has shown to be highly effective in the image-text domain and has contributed to most of the recent state-of-the-art computer vision and multimodal neural networks. However, existing large-scale video-text datasets and mining techniques suffer from several limitations, such as the scarcity of aligned data, the lack of diversity in the data, and the difficulty of collecting aligned data. Currently popular video-text data mining approach via automatic speech recognition (ASR) used in HowTo100M provides low-quality captions that often do not refer to the video content. Other mining approaches do not provide proper language descriptions (video tags) and are biased toward short clips (alt text). In this work, we show how recent advances in image captioning allow us to pre-train high-quality video models without any parallel video-text data. We pre-train several video captioning models that are based on an OPT language model and a TimeSformer visual backbone. We fine-tune these networks on several video captioning datasets. First, we demonstrate that image captioning pseudolabels work better for pre-training than the existing HowTo100M ASR captions. Second, we show that pre-training on both images and videos produces a significantly better network (+4 CIDER on MSR-VTT) than pre-training on a single modality. Our methods are complementary to the existing pre-training or data mining approaches and can be used in a variety of settings. Given the efficacy of the pseudolabeling method, we are planning to publicly release the generated captions

    Anu√°rio cient√≠fico da Escola Superior de Tecnologia da Sa√ļde de Lisboa - 2021

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    √Č com grande prazer que apresentamos a mais recente edi√ß√£o (a 11.¬™) do Anu√°rio Cient√≠fico da Escola Superior de Tecnologia da Sa√ļde de Lisboa. Como institui√ß√£o de ensino superior, temos o compromisso de promover e incentivar a pesquisa cient√≠fica em todas as √°reas do conhecimento que contemplam a nossa miss√£o. Esta publica√ß√£o tem como objetivo divulgar toda a produ√ß√£o cient√≠fica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal n√£o Docente da ESTeSL durante 2021. Este Anu√°rio √©, assim, o reflexo do trabalho √°rduo e dedicado da nossa comunidade, que se empenhou na produ√ß√£o de conte√ļdo cient√≠fico de elevada qualidade e partilhada com a Sociedade na forma de livros, cap√≠tulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunica√ß√Ķes orais e p√≥steres, bem como resultado dos trabalhos de 1¬ļ e 2¬ļ ciclo. Com isto, o conte√ļdo desta publica√ß√£o abrange uma ampla variedade de t√≥picos, desde temas mais fundamentais at√© estudos de aplica√ß√£o pr√°tica em contextos espec√≠ficos de Sa√ļde, refletindo desta forma a pluralidade e diversidade de √°reas que definem, e tornam √ļnica, a ESTeSL. Acreditamos que a investiga√ß√£o e pesquisa cient√≠fica √© um eixo fundamental para o desenvolvimento da sociedade e √© por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e pr√°tica baseada na evid√™ncia desde o in√≠cio dos seus estudos na ESTeSL. Esta publica√ß√£o √© um exemplo do sucesso desses esfor√ßos, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade cient√≠fica e o p√ļblico em geral. Esperamos que este Anu√°rio inspire e motive outros estudantes, profissionais de sa√ļde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avan√ßo da ci√™ncia e da tecnologia no corpo de conhecimento pr√≥prio das √°reas que comp√Ķe a ESTeSL. Agradecemos a todos os envolvidos na produ√ß√£o deste anu√°rio e desejamos uma leitura inspiradora e agrad√°vel.info:eu-repo/semantics/publishedVersio

    25(OH)D-but not 1,25(OH)2D‚ÄďIs an independent risk factor predicting graft loss in stable kidney transplant recipients

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    BackgroundVitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far.MethodsWe conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs.ResultsCompared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912‚ąí0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977‚ąí1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01‚ąí1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98‚ąí1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99‚ąí1.02) and mortality (OR = 1.01, 95% CI: 0.99‚ąí1.02).ConclusionBaseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs

    Receptor‚Äďligand pair typing and prognostic risk model of response or resistance to immune checkpoint inhibitors in lung adenocarcinoma

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    IntroductionCurrently, programmed cell death-1 (PD-1)-targeted treatment is ineffective for a sizable minority of patients, and drug resistance still cannot be overcome.MethodsTo explore the mechanisms of immunotherapy and identify new therapeutic opportunities in lung adenocarcinoma (LUAD), data from patients who did and did not respond to the anti-PD-1 treatment were evaluated using single-cell RNA sequencing, and bulk RNA sequencing were collected.ResultsWe investigated the gene expression that respond or not respond to immunotherapy in diverse cell types and revealed transcriptional characteristics at the single-cell level. To ultimately explore the molecular response or resistance to anti-PD-1 therapy, cell-cell interactions were carried out to identify the different LRIs (ligand-receptor interactions) between untreated patients vs. no-responders, untreated patients vs. responders, and responders vs. non-responders. Next, two molecular subgroups were proposed based on 73 LRI genes, and subtype 1 had a poor survival status and was likely to be the immunosuppressive tumor subtype. Furthermore, based on the LASSO Cox regression analysis results, we found that TNFSF13, AXL, KLRK1, FAS, PROS1, and CDH1 can be distinct prognostic biomarkers, immune infiltration levels, and responses to immunotherapy in LUAD.DiscussionAltogether, the effects of immunotherapy were connected to LRIs scores, indicating that potential medications targeting these LRIs could contribute to the clinical benefit of immunotherapy. Our integrative omics analysis revealed the mechanisms underlying the anti-PD-1 therapy response and offered abundant clues for potential strategies to improve precise diagnosis and immunotherapy

    LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer

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    IntroductionBladder cancer (BLCA) is a highly heterogeneous disease influenced by the tumor microenvironment, which may affect patients' response to immune checkpoint blockade therapy. Therefore, identifying molecular markers and therapeutic targets to improve treatment is essential. In this study, we aimed to investigate the prognostic significance of LRP1 in BLCA.MethodsWe analyzed TCGA and IMvigor210 cohorts to investigate the relationship of LRP1 with BLCA prognosis. We utilized gene mutation analysis and enrichment to identify LRP1-associated mutated genes and biological processes. Deconvolution algorithms and single-cell analysis were used to understand the tumor-infiltrated cells and biological pathways associated with LRP1 expression. Immunohistochemistry was conducted to validate the bioinformatics analysis.ResultsOur study revealed that LRP1 was an independent risk factor for overall survival in BLCA patients and was associated with clinicopathological features and FGFR3 mutation frequency. Enrichment analysis demonstrated that LRP1 was involved in extracellular matrix remodeling and tumor metabolic processes. Furthermore, the ssGSEA algorithm revealed that LRP1 was positively correlated with the activities of tumor-associated pathways. Our study also found that high LRP1 expression impaired patients' responsiveness to ICB therapy in BLCA, which was predicted by TIDE prediction and validated by IMvigor210 cohort. Immunohistochemistry confirmed the expression of LRP1 in Cancer-Associated Fibroblasts (CAFs) and macrophages in the tumor microenvironment of BLCA.DiscussionOur study suggests that LRP1 may be a potential prognostic biomarker and therapeutic target in BLCA. Further research on LRP1 may improve BLCA precision medicine and enhance the efficacy of immune checkpoint blockade therapy

    The effect of hypoxia on Daphnia magna performance and its associated microbial and bacterioplankton community: A scope for phenotypic plasticity and microbiome community interactions upon environmental stress?

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    The depletion of oxygen as a result of increased stratification and decreased oxygen solubility is one of the most significant chemical changes occurring in aquatic ecosystems as a result of global environmental change. Hence, more aquatic organisms will be exposed to hypoxic conditions over time. Deciphering the effects of hypoxia on strong ecological interactors in this ecosystem’s food web is critical for predicting how aquatic communities can respond to such an environmental disturbance. Here (sub-)lethal effects of hypoxia and whether these are genotype specific in Daphnia, a keystone species of freshwater ecosystems, are studied. This is especially relevant upon studying genetic responses with respect to phenotypic switches upon environmental stress. Further, we investigated the effect of hypoxia on the Daphnia microbial community to test if the microbiome plays a role in the phenotypic switch and tolerance to hypoxia. For this, two Daphnia genotypes were exposed for two weeks to either hypoxia or normoxia and host performance was monitored together with changes in the host associated and free-living microbial community after this period. We detected phenotypic plasticity for some of the tested Daphnia performance traits. The microbial community of the bacterioplankton and Daphnia associated microbial community responded via changes in species richness and community composition and structure. The latter response was different for the two genotypes suggesting that the microbiome plays an important role in phenotypic plasticity with respect to hypoxia tolerance in Daphnia, but further testing (e.g., through microbiome transplants) is needed to confirm this
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