DeepExtremeCubes: Earth system spatio-temporal data for assessing compound heatwave and drought impacts.

With climate extremes' rising frequency and intensity, robust analytical tools are crucial to predict their impacts on terrestrial ecosystems. Machine learning techniques show promise but require well-structured, high-quality, and curated analysis-ready datasets. Earth observation datasets comprehensively monitor ecosystem dynamics and responses to climatic extremes, yet the data complexity can challenge the effectiveness of machine learning models.

Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

Ferroptosis triggers mitochondrial fragmentation via Drp1 activation.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed.

The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.

Epigenetic variation in light of population genetic practice.

The evolutionary impact of epigenetic variation depends on its transgenerational stability and source - whether genetically determined, environmentally induced, or due to spontaneous, genotype-independent mutations. Here, we evaluate current approaches for investigating an independent role of epigenetics in evolution, pinpointing methodological challenges. We further identify opportunities arising from integrating epigenetic data with population genetic analyses in natural populations.

Impact of single versus dual arterial supply on perfusion and function in finger replantation after complex hand injuries.

Finger amputations following complex hand injuries (CHI) pose a significant challenge in hand surgery due to severe tissue trauma and neurovascular damage, necessitating precise arterial repair. While restoring arterial perfusion is critical, it remains unclear whether reconstructing both proper palmar digital arteries is required for optimal outcomes. This study evaluates whether restoring one or both arteries in finger replantation after complex injuries impacts perfusion and overall outcomes.

Cell-free DNA release following psychosocial and physical stress in women and men.

Cell-free DNA (cfDNA) is continuously shed by all cells in the body, but the regulation of this process and its physiological functions are still largely unknown. Previous research has demonstrated that both nuclear (cf-nDNA) and mitochondrial (cf-mtDNA) cfDNA levels increase in plasma in response to acute psychosocial and physical stress in males. This study further investigated these findings by testing 31 female participants (16 using oral hormonal contraception and 15 not using oral hormonal contraception), and the results were subsequently compared with those of 16 male participants.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p.

DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.

The neural basis of the insight memory advantage.

Creative problem solving and memory are inherently intertwined: memory accesses existing knowledge while creativity enhances it. Recent studies show that insights often accompanying creative solutions enhance long-term memory. This insight memory advantage (IMA) is explained by the 'insight as prediction error (PE)' hypothesis which states that insights arise from PEs updating predictive solution models and thereby enhancing memory.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Revealing microRNA regulation in single cells.

MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation.

Influence of frailty status on the incidence of intraoperative hypotensive events in elective surgery: Hypo-Frail, a single-centre retrospective cohort study.

Background: Frailty is a predictor of morbidity and mortality in older patients. This study aimed to investigate the influence of frailty status on likelihood, rate, duration, and severity of intraoperative hypotension (IOH), which can lead to severe organ dysfunction.

Methods: Surgical patients (≥70 yr old) with preoperative frailty assessment were analysed retrospectively.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al.

Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.

Background: Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.

Objectives: To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.

Trends in work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs): Data from the German National Database (2010-2022).

Objective: To analyse work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs), namely rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ANCA-associated vasculitis (AAV).

Methods: A cross-sectional sample of 16 421 patients from the National Database of the German Collaborative Arthritis Centers, aged <65 years were analysed. For each diagnosis, yearly rates of absenteeism, employment and disability pensions were analysed from 2010 to 2022.

Ex Vivo Fluorescence Confocal Microscopy for intraoperative evaluations of staple lines and surgical margins in specimens of the lung - a proof-of-concept study.

Intraoperative consultation is frequently used during the surgical treatment of lung tumors for the diagnosis of malignancy and the assessment of surgical margins. The latter is often problematic given the nature of the applied staple lines, which cannot be readily examined in frozen sections. Seventy-nine samples of surgical margins (71 staple lines and 8 open margins) from 52 lung specimens were examined using an ex vivo fluorescence confocal microscope (FCM).

Classification of Fibro-osseous Tumors in the Craniofacial Bones using DNA Methylation and Copy Number Alterations.

Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS.

Characterization of the putative yeast mitochondrial triacylglycerol lipase Tgl2.

Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are the main components of mitochondrial membranes. In the cell, neutral lipids like triacylglycerides (TAGs) are stored in lipid droplets, playing an important role in maintaining cellular health.