Real-time intraoperative ultrasound registration for accurate surgical navigation in patients with pelvic malignancies.

Purpose: Surgical navigation aids surgeons in localizing and adequately resecting pelvic malignancies. Accuracy of the navigation system highly depends on the preceding registration procedure, which is generally performed using intraoperative fluoroscopy or CT. However, these ionizing methods are time-consuming and peroperative updates of the registration are cumbersome.

Blood pressure targets for hypertension in people with chronic renal disease.

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4.

The unreasonable effectiveness of equilibrium gene regulation through the cell cycle.

Systems like the prototypical lac operon can reliably hold repression of transcription upon DNA replication across cell cycles with just 10 repressor molecules per cell and behave as if they were at equilibrium. The origin of this phenomenology is still an unresolved question. Here, we develop a general theory to analyze strong perturbations in quasi-equilibrium systems and use it to quantify the effects of DNA replication in gene regulation.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review (protocol).

Objective: To determine the efficacy and safety of CAR-T therapy in the treatment of patients with hematologic malignancies, in comparison with other current therapies.

Design: A living systematic review.

Methods: We will include randomized trials evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, best supportive care or any other intervention in patients with hematologic malignancies.

Nanocrystal Assemblies: Current Advances and Open Problems.

We explore the potential of nanocrystals (a term used equivalently to nanoparticles) as building blocks for nanomaterials, and the current advances and open challenges for fundamental science developments and applications. Nanocrystal assemblies are inherently multiscale, and the generation of revolutionary material properties requires a precise understanding of the relationship between structure and function, the former being determined by classical effects and the latter often by quantum effects. With an emphasis on theory and computation, we discuss challenges that hamper current assembly strategies and to what extent nanocrystal assemblies represent thermodynamic equilibrium or kinetically trapped metastable states.

Systematic review and meta-analysis on the effectiveness of multidisciplinary interventions to address polypharmacy in community-dwelling older adults.

Interventions to address polypharmacy in community-dwelling older adults often focus on medication-related outcomes. The aim was to explore the impact of multidisciplinary interventions to manage polypharmacy on clinical outcomes for community-dwelling older adults. This systematic review and meta-analysis included randomized controlled trials (RCTs) on interventions by at least a pharmacist and a physician, indexed in MEDLINE, EMBASE or CENTRAL up to January 2023.

Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles.

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139 days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight.

Effectiveness of homologous/heterologous booster COVID-19 vaccination schedules against severe illness in general population and clinical subgroups in three European countries.

Using 4 data-sources (Spain, Italy, United Kingdom) data and a 1:1 matched cohort study, we aimed to estimate vaccine effectiveness (VE) in preventing SARS-CoV-2 infections with hospitalisations (±30 days) and death (±56 days) in general population and clinical subgroups with homologous/heterologous booster schedules (Comirnaty-BNT and Spikevax-MOD original COVID-19 vaccines) by comparison with unboosted individuals, during Delta and beginning of Omicron variants. Hazard Ratio (HR, by Cox models) and VE ([1-HR]*100) were calculated by inverse probability weights. Between December 2020-February 2022, in adults without prior SARS-CoV-2 infection, we matched 5.

Dynamics-informed deconvolutional neural networks for super-resolution identification of regime changes in epidemiological time series.

The ability to infer the timing and amplitude of perturbations in epidemiological systems from their stochastically spread low-resolution outcomes is crucial for multiple applications. However, the general problem of connecting epidemiological curves with the underlying incidence lacks the highly effective methodology present in other inverse problems, such as super-resolution and dehazing from computer vision. Here, we develop an unsupervised physics-informed convolutional neural network approach in reverse to connect death records with incidence that allows the identification of regime changes at single-day resolution.

Multi-landmark alignment of genomic signals reveals conserved expression patterns across transcription start sites.

The prevalent one-dimensional alignment of genomic signals to a reference landmark is a cornerstone of current methods to study transcription and its DNA-dependent processes but it is prone to mask potential relations among multiple DNA elements. We developed a systematic approach to align genomic signals to multiple locations simultaneously by expanding the dimensionality of the genomic-coordinate space. We analyzed transcription in human and uncovered a complex dependence on the relative position of neighboring transcription start sites (TSSs) that is consistently conserved among cell types.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies.

Background: Chimeric antigen receptor T-cell (CAR-T) cell therapies have been claimed to be curative in responsive patients. Nonetheless, response rates can vary according to different characteristics, and these therapies are associated with important adverse events such as cytokine release syndrome, neurologic adverse events, and B-cell aplasia.

Objectives: This living systematic review aims to provide a timely, rigorous, and continuously updated synthesis of the evidence available on the role of CAR-T therapy for the treatment of patients with hematologic malignancies.

Efficacy and safety of N-acetylcysteine for preventing post-intravenous contrast acute kidney injury in patients with kidney impairment: a systematic review and meta-analysis.

Objectives: N-Acetylcysteine (NAC) may confer protection against post-contrast acute kidney injury (PC-AKI), although evidence is sparse and conflicting. The objective was to analyse the evidence on the efficacy and safety of NAC vs no administration of NAC in preventing PC-AKI in patients with pre-existing kidney impairment undergoing a non-interventional radiological examination requiring intravenous (IV) contrast media (CM) administration.

Methods: We carried out a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE, and Clinicaltrials.

Effect of the combination of diuretics, renin-angiotensin-aldosterone system inhibitors, and non-steroidal anti-inflammatory drugs or metamizole (triple whammy) on hospitalisation due to acute kidney injury: A nested case-control study.

Purpose: Concomitant use of diuretics, renin-angiotensin-aldosterone system (RAAS) inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as 'triple whammy' (TW), has been associated with an increased risk of acute kidney injury (AKI). Nevertheless, there is still uncertainty on its impact in hospitalisation and mortality. The aim of the study was to analyse the association between exposure to TW and the risk of hospitalisation for AKI, all-cause mortality and the need for renal replacement therapy (RRT).

P-element invasion fuels molecular adaptation in laboratory populations of Drosophila melanogaster.

Transposable elements (TEs) are mobile genetic parasites that frequently invade new host genomes through horizontal transfer. Invading TEs often exhibit a burst of transposition, followed by reduced transposition rates as repression evolves in the host. We recreated the horizontal transfer of P-element DNA transposons into a Drosophila melanogaster host and followed the expansion of TE copies and evolution of host repression in replicate laboratory populations reared at different temperatures.

Restoring Study PRGF: a randomized clinical trial on plasma rich in growth factors for knee osteoarthritis.

Background: A randomized clinical trial assessing plasma rich in growth factors (PRGF) versus hyaluronic acid for knee osteoarthritis was published in 2012 (sponsor trial ID BTI-01-EC/07/ART). Evidence of misreporting was discovered following access to unpublished materials. In accordance with the principles of the Restoring Invisible and Abandoned Trials (RIAT) initiative, we sought to re-analyse Study PRGF based on the unpublished trial materials.

Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data.

Objective: The FOURIER trial showed a benefit of the PCSK9 inhibitor evolocumab over placebo with respect to cardiovascular outcomes in patients with cardiovascular disease. However, we observed some inconsistencies between the information in the Clinical Study Report (CSR) and that in the 2017 primary trial results publication. We aimed to restore the mortality data in the FOURIER trial based on the information contained in the death narratives in the CSR.

Meta-analysis: Efficacy and safety of albumin in the prevention and treatment of complications in patients with cirrhosis.

Introduction: Albumin is used in multiple situations in patients with cirrhosis, but the evidence of its benefit is not always clear. The aim was to synthesise the evidence on the efficacy and safety of albumin compared to other treatments or no active intervention in cirrhotic patients.

Materials And Methods: We conducted a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE and CENTRAL up to May 2022.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

Background: This is the third update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial.

Magnetic Multi-Enzymatic System for Cladribine Manufacturing.

Enzyme-mediated processes have proven to be a valuable and sustainable alternative to traditional chemical methods. In this regard, the use of multi-enzymatic systems enables the realization of complex synthetic schemes, while also introducing a number of additional advantages, including the conversion of reversible reactions into irreversible processes, the partial or complete elimination of product inhibition problems, and the minimization of undesirable by-products. In addition, the immobilization of biocatalysts on magnetic supports allows for easy reusability and streamlines the downstream process.

Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain.

Although intermittent androgen deprivation therapy was introduced many years ago to improve patients' quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that intermittency could be underutilised. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.

Role of Pharmacogenomics in the Efficacy and Safety of Thiopurines in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background: Thiopurines' toxicity often leads to dose reduction or discontinuation. This systematic review aims to synthesize the evidence on the effect of genotype-based dosing of thiopurines on treatment efficacy and safety in inflammatory bowel disease (objective #1), and the association between genotype status and the efficacy and safety profile (objective #2).

Methods: The Cochrane Library, MEDLINE, and EMBASE were searched in August 2021.

Robustness of DNA looping across multiple cell divisions in individual bacteria.

DNA looping has emerged as a central paradigm of transcriptional regulation, as it is shared across many living systems. One core property of DNA looping-based regulation is its ability to greatly enhance repression or activation of genes with only a few copies of transcriptional regulators. However, this property based on a small number of proteins raises the question of the robustness of such a mechanism with respect to the large intracellular perturbations taking place during growth and division of the cell.