Boreal forests are heading for an open state.

The boreal forest biome is warming four times faster than the global average. Changes so far are moderate, but time lags in responses may transiently maintain forest states which are no longer supported by current environmental conditions. Here, we explore whether tree cover dynamics hint at the state to which the biome may be shifting.

Confined cell migration along extracellular matrix space in vivo.

Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order.

Integrin-activating protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets.

Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato , , 262-265 (2009); T. Sato , , 1762-1772 (2011)].

infection accelerates postnatal maturation of the intestinal epithelium.

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.

Comparing integrative ventilatory and renal acid-base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m.

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.

Palmitoylation-dependent association with Annexin II directs hepatitis E virus ORF3 sorting into vesicles and quasi-enveloped virions.

Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.

Internet-based cognitive rehabilitation for working cancer survivors: A process evaluation.

Objective: To evaluate the process of an online cognitive rehabilitation program aimed at supporting cancer survivors experiencing cognitive problems at work.

Methods: Cancer survivors (n = 279) were randomized to one of the intervention groups (i.e.

Long-Term Clinical Outcomes for Bone-Anchored Hearing Implants: 3-Year Comparison Between Minimally Invasive Ponto Surgery and the Linear Incision Technique With Tissue Preservation.

Objective: To compare the 3-year outcomes of the modified minimally invasive Ponto surgery (m-MIPS) to both the original MIPS (o-MIPS) and linear incision technique with soft tissue preservation (LIT-TP) for inserting bone-anchored hearing implants (BAHIs).

Study Design: Prospective study with three patient groups: m-MIPS, o-MIPS, and LIT-TP.

Setting: Tertiary referral center.

Development and validation of a high-throughput qPCR platform for the detection of soil-transmitted helminth infections.

Background: Historically, soil-transmitted helminth (STH) control and prevention strategies have relied on mass drug administration efforts targeting preschool and school-aged children. While these efforts have succeeded in reducing morbidity associated with STH infection, recent modeling efforts have suggested that expanding intervention to treatment of the entire community could achieve transmission interruption in some settings. Testing the feasibility of such an approach requires large-scale clinical trials, such as the DeWorm3 cluster randomized trial.

Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma.

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.

Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Gemcitabine + oxaliplatin (GemOx) with rituximab, a standard salvage therapy, yields complete response (CR) rates of approximately 30% and median overall survival (OS) of 10-13 months. Patients with refractory disease fare worse, with a CR rate of 7% for subsequent therapies and median OS of 6 months.

Artificial intelligence-driven analysis of embryo morphokinetics in singleton, twin, and triplet pregnancies.

In recent years, the transfer of more than one embryo has become less frequent to diminish multiple pregnancies. Even so, there is still a risk of one embryo splitting into two or even three. This report presents the case of a triamniotic monochorionic gestation in a 35-year-old woman, obtained after the transfer of a single day 5 embryo that had been previously hatched with a laser and subsequently transferred in a fresh IVF cycle.

Predicting the risk of intensive care unit admission in patients with COVID-19 presenting in the emergency room: Development and evaluation of the CROSS score.

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with the Coronavirus Disease 2019 (COVID-19). This study aimed to develop and evaluate an accurate and calculator-free clinical tool for predicting ICU admission at emergency room (ER) presentation.

Methods: Data from patients with COVID-19 in a nationwide German cohort (March 2020-January 2023) were analyzed.

Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency.

Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies.

Long, Synthetic Type 8 Capsular Oligosaccharides Reveal Structural Epitopes for Effective Immune Recognition.

is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the cell wall and have been proposed as promising candidate antigens.

Ten simple rules for good model-sharing practices.

Computational models are complex scientific constructs that have become essential for us to better understand the world. Many models are valuable for peers within and beyond disciplinary boundaries. However, there are no widely agreed-upon standards for sharing models.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis.

Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients.

Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics.

Instruments for Value Elucidation in Older Adults in Clinical Practice-A Scoping Review.

Background: To ensure appropriate care for the individual older adult, an ideal treatment should align with patients' values. However, healthcare professionals struggle with how to elucidate patient values effectively. To offer guidance to healthcare professionals, we performed a scoping review, thereby mapping and categorizing instruments specifically developed to elucidate values of older adults in clinical practice.

The NeuroML ecosystem for standardized multi-scale modeling in neuroscience.

Data-driven models of neurons and circuits are important for understanding how the properties of membrane conductances, synapses, dendrites, and the anatomical connectivity between neurons generate the complex dynamical behaviors of brain circuits in health and disease. However, the inherent complexity of these biological processes makes the construction and reuse of biologically detailed models challenging. A wide range of tools have been developed to aid their construction and simulation, but differences in design and internal representation act as technical barriers to those who wish to use data-driven models in their research workflows.

FragPT2: Multifragment Wave Function Embedding with Perturbative Interactions.

Embedding techniques allow the efficient description of correlations within localized fragments of large molecular systems while accounting for their environment at a lower level of theory. We introduce FragPT2: a novel embedding framework that addresses multiple interacting active fragments. Fragments are assigned separate active spaces, constructed by localizing canonical molecular orbitals.

Massive Localized Lymphedema, Wound Care Without Major Surgical Excision: A Case Report.

Massive localized lymphedema (MLL) is a benign overgrowth of lymphoproliferative tissue that is primarily observed in adults with class III obesity. Patients present with a painless mass that has usually been present for a considerable period. Consultation of a healthcare professional typically takes place when MLL-related complaints interfere with daily living.

The effectiveness of psychologically-informed physiotherapy for people with neck pain and the mediating role of illness perceptions: a replicated single-case experimental design study.

Purpose: (1) To evaluate the effectiveness of personalised psychologically-informed physiotherapy in people with neck pain; (2) To explore the mediating role of changes in illness perceptions.

Method: In this replicated single-case study, 14 patients with non-specific neck pain at risk for chronicity received a personalised intervention addressing unhelpful illness perceptions and dysfunctional movement behaviour, according to principles of cognitive functional therapy. Outcomes included the mediating role of illness perceptions on overall effect, function, pain intensity and self-efficacy.

Diversification of -harbouring plasmids among carbapenemase-producing , 11 years after a large outbreak in a general hospital in the Netherlands.

Genes encoding OXA-48-like carbapenem-hydrolyzing enzymes are often located on plasmids and are abundant among carbapenemase-producing (CPE) worldwide. After a large plasmid-mediated outbreak in 2011, routine screening of patients at risk of CPE carriage on admission and every 7 days during hospitalization was implemented in a large hospital in the Netherlands. The objective of this study was to investigate the dynamics of the hospitals' 2011 outbreak-associated plasmid among CPE collected from 2011 to 2021.