OligoDistiller: A Platform Agnostic Software Tool for MS and MS Data Analysis of Complex Oligonucleotides and Their Impurities.

Oligonucleotides are currently one of the most rapidly advancing classes of therapeutic modalities. Understanding critical quality attributes, such as the impurity profile, stability, potential metabolites, and sequence conformity, is the key to their ultimate success. To obtain the information presented above, liquid chromatography-mass spectrometry (LC-MS) is often employed.

Identifying the main drivers of transmission in the early phase of the COVID-19 pandemic in Portugal.

In this study, we employed a modeling approach to describe how changes in age-specific epidemiological characteristics, such as behaviour, i.e. contact patterns, susceptibility and infectivity, influence the basic reproduction number , while accounting for heterogeneity in transmission.

Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2.

Background: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.

Laboratory biosafety: A visual analysis in the web of science database from 2000 to 2022: A review.

To conduct a visual analysis of institutional publications, individual publications and publication keywords in the field of laboratory biosafety using the Web of Science database from 2000 to 2022.VOSviewer 1.6.

Linear Mixed Modeling of Federated Data When Only the Mean, Covariance, and Sample Size Are Available.

In medical research, individual-level patient data provide invaluable information, but the patients' right to confidentiality remains of utmost priority. This poses a huge challenge when estimating statistical models such as a linear mixed model, which is an extension of linear regression models that can account for potential heterogeneity whenever data come from different data providers. Federated learning tackles this hurdle by estimating parameters without retrieving individual-level data.

Resin-Based Yttrium-90 Radioembolization as a Bridging or Downstaging Treatment to Liver Transplantation for Hepatocellular Carcinoma.

Purpose: To evaluate the outcomes of resin-based yttrium-90 (Y) transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) as a bridging or downstaging therapy to liver transplantation (LT) in terms of safety, tumor response, recurrence, and survival.

Materials And Methods: A single-center retrospective analysis of patients with HCC treated with resin-based TARE as bridging or downstaging treatment to LT between January 2006 and April 2021 was performed. TARE-related liver toxicity was assessed.

Community antibiotic consumption in the European Union/European economic area: late-pandemic rebound and seasonality analysis.

Background: A rebound in antibiotic consumption has been observed in the European community at the end of the COVID-19 pandemic. Here we evaluate the extent of this increase, when it exactly occurred, and how the seasonality in antibiotic use changed during the late-pandemic period.

Methods: Data on community antibiotic consumption were available from the European Surveillance of Antimicrobial Consumption Network for 28 European countries between 2015 and 2022.

Identifying Process Differences with ToF-SIMS: An MVA Decomposition Strategy.

In time-of-flight secondary ion mass spectrometry (ToF-SIMS), multivariate analysis (MVA) methods such as principal component analysis (PCA) are routinely employed to differentiate spectra. However, additional insights can often be gained by comparing processes, where each process is characterized by its own start and end spectra, such as when identical samples undergo slightly different treatments or when slightly different samples receive the same treatment. This study proposes a strategy to compare such processes by decomposing the loading vectors associated with them, which highlights differences in the relative behavior of the peaks.

The intestinal mucin isoform landscape reveals region-specific biomarker panels for inflammatory bowel disease patient stratification.

Background And Aims: Mucosal healing is considered as a key therapeutic endpoint in inflammatory bowel diseases (IBD) and comprises endoscopic improvement of inflammation without taking barrier healing into account. Mucins are critical components of the mucosal barrier function that give rise to structurally diverse isoforms. Unraveling disease-associated mucin isoforms that could act as an indication for barrier function would greatly enhance IBD management.

Comparison of PSMA immunohistochemistry scoring systems to parametric [F]PSMA-1007 PET/MRI in primary prostate cancer.

Purpose: Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard.

Methods: Primary intermediate- and high-risk prostate cancer patients received an [F]PSMA-1007 PET/MRI followed by radical prostatectomy.

Evaluating the direct effect of vaccination and non-pharmaceutical interventions during the COVID-19 pandemic in Europe.

Background: Across Europe, countries have responded to the COVID-19 pandemic with a combination of non-pharmaceutical interventions and vaccination. Evaluating the effectiveness of such interventions is of particular relevance to policy-makers.

Methods: We leverage almost three years of available data across 38 European countries to evaluate the effectiveness of governmental responses in controlling the pandemic.

Rationale and Design of the DECONGEST (Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment) Study.

Aims: To evaluate whether early-combination diuretic therapy guided by serial post-diuretic urine sodium concentration (UNa) assessments in acute heart failure (AHF) facilitates safe and effective decongestion.

Methods: The Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST) study is a pragmatic, 2-center, randomized, parallel-arm, open-label study aiming to enroll 104 patients with AHF and clinically evident fluid overload requiring treatment with intravenous loop diuretics. Patients are randomized to receive standard of care or a bundled approach comprising: (1) systematic post-diuretic UNa assessments until successful decongestion, defined as no remaining clinical signs of fluid overload with a post-diuretic UNa ≤ 80 mmol/L; (2) thrice-daily intravenous loop diuretic bolus therapy, with dosing according to estimated glomerular filtration rate; (3) upfront use of intravenous acetazolamide (500 mg once daily [OD]); and (4) full nephron blockade with high-dose oral chlorthalidone (100 mg OD) and intravenous canreonate (200 mg OD) for diuretic resistance, defined as persisting signs of fluid overload with a post-diuretic UNa ≤ 80 mmol/L.

A competing risks model to estimate the risk of graft failure and patient death after kidney transplantation using continuous donor-recipient age combinations.

Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well described in real-world transplant data.

Incidence of contralateral metachronous inguinal hernia on long term follow-up after unilateral inguinal hernia repair: a systematic review and meta-analysis.

Background: The repair of inguinal hernias is a common surgical procedure. Some patients will need a second operation after developing a metachronous contralateral inguinal hernia (MCIH). The suggestion has been made to strengthen the contralateral side at the same time as primary unilateral surgery.

Modeling antigen-specific T cell dynamics following Hepatitis B Vaccination indicates differences between conventional and regulatory T cell dynamics.

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial.

Innovative approaches for vaccine trials as a key component of pandemic preparedness - a white paper.

Background: WHO postulates the application of adaptive design features in the global clinical trial ecosystem. However, the adaptive platform trial (APT) methodology has not been widely adopted in clinical research on vaccines.

Methods: The VACCELERATE Consortium organized a two-day workshop to discuss the applicability of APT methodology in vaccine trials under non-pandemic as well as pandemic conditions.

Polymyalgia rheumatica is a risk factor for more recalcitrant disease in giant cell arteritis: A retrospective cohort study.

Objectives: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms.

Methods: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively.

Results: We included 398 GCA patients, of which 181 (45%) with PMR symptoms.

Clinical Study Report and Individual Participant Data Transparency for US Food and Drug Administration-Approved Anticancer Drugs: A Call for Systematic Data Availability.

Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.

Effects of Cyclodextrin Curcumin Formulation on Ischemia-Reperfusion Injury in Porcine DCD Liver Transplantation.

Background: Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD).

Methods: In a preclinical pig model of DCD-liver transplantation, livers exposed to 15' of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 µmol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage.

Antibiotic or gastric acid inhibitor use during pregnancy and postpartum depression: Population-based cohort study.

Introduction: Postpartum depression is one of the most common non-obstetric postnatal complications. As the microbiome (and gut-brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth).

Material And Methods: This population-based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016.