Technical and biological sources of noise confound multiplexed enhancer AAV screening.

-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patterns , a process that currently requires gold-standard one-by-one testing.

Correction: Kirkegaard-Biosca et al. Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria. 2024, , 874.

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Evaluation of an Alternative Screening Method for Gestational Diabetes Diagnosis During the COVID-19 Pandemic (DIABECOVID STUDY): An Observational Cohort Study.

To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from six hospitals across Catalonia, Spain, from April 2020 to April 2022.

Systematic Ultrasound Screening for Lower Extremity Deep Vein Thrombosis in ICU Patients with Severe COVID-19: A Randomized Clinical Trial.

Background: Venous thromboembolism (VTE), whether pulmonary embolism (PE) or deep vein thrombosis (DVT), is common in patients with COVID-19. Recommendations on systematic screening in the intensive care unit (ICU) are lacking.

Research Question: Is there any clinical benefit of systematic screening for DVT in critically ill patients with severe COVID-19?

Study Design And Methods: Single-center randomized clinical trial (RCT) of COVID-19 cases admitted to the ICU.

Continuous cell type diversification throughout the embryonic and postnatal mouse visual cortex development.

The mammalian cortex is composed of a highly diverse set of cell types and develops through a series of temporally regulated events that build out the cell type and circuit foundation for cortical function. The mechanisms underlying the development of different cell types remain elusive. Single-cell transcriptomics provides the capacity to systematically study cell types across the entire temporal range of cortical development.

Therapeutic drug monitoring-guided high-dose isavuconazole therapy for invasive pulmonary aspergillosis in a patient on extracorporeal membrane oxygenation support.

We review the case of a 58-year-old female on extracorporeal membrane oxygenation (ECMO) support diagnosed with invasive pulmonary aspergillosis (IPA). Intravenous isavuconazole was started, requiring dose escalation to achieve isavuconazole trough concentration (ISA-Cmin) within the therapeutic range (2.5-5.

Understanding Cancer Treatment Decision Making Among Cancer Survivors: Weighing Cancer Recurrence Versus Cardiotoxicity.

Background: Nearly 20% of US cancer survivors develop cardiovascular disease (CVD) from cardiotoxic cancer treatments. Patients and providers may consider alternative treatments to lower cardiotoxicity risk, but these may be less effective at preventing relapse/recurrence, presenting a difficult tradeoff.

Aims: This study explored survivors' cancer treatment decision-making when weighing this tradeoff.

Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

Impact of hyper- and hypothermia on cellular and whole-body physiology.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes.

Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.

Background: Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.

Methods: A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell-derived astrocytes from adrenoleukodystrophy patients.

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long-chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC).

The renin-angiotensin-aldosterone-system in sepsis and its clinical modulation with exogenous angiotensin II.

Dysregulation of the renin-angiotensin-aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II.

The COSMOS Registry of CytoSorb Hemoadsorption Therapy in Critically Ill Patients: Protocol for an International, Prospective Registry.

Background: Extracorporeal blood purification with CytoSorb has been increasingly used as an adjunctive therapy in several hyperinflammatory critical care conditions, as well as to remove elevated levels of myoglobin or bilirubin in patients with rhabdomyolysis or liver failure. Despite the increasing worldwide use of hemoadsorption, data from large international multicenter studies are still lacking.

Objective: The COSMOS (CytoSorb Treatment Of Critically Ill Patients) registry is a company-sponsored registry by CytoSorbents Corporation and CytoSorbents Medical Inc.

Smooth trends in fermium charge radii and the impact of shell effects.

The quantum-mechanical nuclear-shell structure determines the stability and limits of the existence of the heaviest nuclides with large proton numbers Z ≳ 100 (refs. ). Shell effects also affect the sizes and shapes of atomic nuclei, as shown by laser spectroscopy studies in lighter nuclides.

Autophagy and autophagic cell death in sepsis: friend or foe?

In sepsis, inflammation, and nutrient deficiencies endanger cellular homeostasis and survival. Autophagy is primarily a mechanism of cellular survival under fasting conditions. However, autophagy-dependent cell death, known as autophagic cell death, is proinflammatory and can exacerbate sepsis.

Ten take-home messages on vasopressin use in critically ill patients.

The most used vasopressors in critically ill patients are exogenous catecholamines, mainly norepinephrine. Their use can be associated with serious adverse events and even increased mortality, especially if administered at high doses. In recent years, the addition of vasopressin has been proposed to counteract the deleterious effects of high doses of catecholamines (decatecholaminization) with the intention of improving the prognosis of these patients.

Mitochondrial Damage in Sepsis.

Mitochondria not only generate adenosine triphosphate (ATP) and act as the powerhouse of the cell but also contribute to host defense by producing reactive oxygen species. Therefore, mitochondrial damage in sepsis directly results in a shortage of energy currency and dysregulation of the immune system. Other than those, mitochondrial damage results in the release of highly dangerous mitochondrial DNA, facilitating acidosis by modulating the metabolism and inducing programmed cell death, thereby facilitating disease progression in sepsis.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

Prokinetic agents in adult intensive care unit patients (PATIENCE)-An international inception cohort study protocol.

Background: Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU).

Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 spp., 7 , and 5 sp.

Pre-Surgery Cortisol Levels as Biomarker of Evolution after Bariatric Surgery: Weight Loss and Weight Regain.

Bariatric surgery (BS) is effective for achieving significant weight loss. However, weight regain (WR) is an emerging problem. To assess the prognostic value of morning serum cortisol, a 1 mg dexamethasone suppression test (DST), 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) in a cohort of patients with severe obesity (pwSO) undergoing BS in terms of weight loss and WR.