Detection of fungal sequences in human brain: rDNA locus amplification and deep sequencing.

The aetiology of Alzheimer's disease (AD) and Parkinson's disease (PD) are unknown and tend to manifest at a late stage in life; even though these neurodegenerative diseases are caused by different affected proteins, they are both characterized by neuroinflammation. Links between bacterial and viral infection and AD/PD has been suggested in several studies, however, few have attempted to establish a link between fungal infection and AD/PD. In this study we adopted a nanopore-based sequencing approach to characterise the presence or absence of fungal genera in both human brain tissue and cerebrospinal fluid (CSF).

A sterilization method for human decellularized vaginal matrices.

Vaginal reconstruction is necessary for various congenital and acquired conditions, including vaginal aplasia, trauma, tumors, and gender incongruency. Current surgical and non-surgical treatments often result in significant complications. Decellularized vaginal matrices (DVMs) from human tissue offer a promising alternative, but require effective sterilization to ensure safety and functionality.

Deep learning on CT scans to predict checkpoint inhibitor treatment outcomes in advanced melanoma.

Immune checkpoint inhibitor (ICI) treatment has proven successful for advanced melanoma, but is associated with potentially severe toxicity and high costs. Accurate biomarkers for response are lacking. The present work is the first to investigate the value of deep learning on CT imaging of metastatic lesions for predicting ICI treatment outcomes in advanced melanoma.

Evolutionary origins and functional diversification of Auxin Response Factors.

The Auxin Response Factors (ARFs) family of transcription factors are the central mediators of auxin-triggered transcriptional regulation. Functionally different classes of extant ARFs operate as antagonistic auxin-dependent and -independent regulators. While part of the evolutionary trajectory to the present auxin response functions has been reconstructed, it is unclear how ARFs emerged, and how early diversification led to functionally different proteins.

Effect of selective dorsal rhizotomy on bladder dysfunction in children with spastic cerebral palsy.

This study investigated the prevalence and severity of lower urinary tract symptoms (LUTS) in children with spastic cerebral palsy (SCP) and evaluated the effect of selective dorsal rhizotomy (SDR) in alleviating these symptoms. The study also explored the correlation between postoperative LUTS improvement and intraoperative electrophysiological findings. Prospective data were collected from a consecutive cohort of 247 children with SCP who underwent SDR and were retrospectively analyzed.

Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.

Continuous decoupled redox electrochemical CO capture.

Electrochemical CO capture driven by renewable electricity holds significant potential for efficient decarbonization. However, the widespread adoption of this approach is currently limited by issues such as instability, discontinuity, high energy demand, and challenges in scaling up. In this study, we propose a scalable strategy that addresses these limitations by transforming the conventional single-step electrochemical redox reaction into a stepwise electrochemical-chemical redox process.

Deep neural networks and humans both benefit from compositional language structure.

Deep neural networks drive the success of natural language processing. A fundamental property of language is its compositional structure, allowing humans to systematically produce forms for new meanings. For humans, languages with more compositional and transparent structures are typically easier to learn than those with opaque and irregular structures.

Strontium isoscape of sub-Saharan Africa allows tracing origins of victims of the transatlantic slave trade.

Strontium isotope (Sr/Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving Sr/Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the Sr/Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression.

Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.

The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention.

Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.

Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.

Multidisciplinary team meetings: dynamic routines that (re)make palliative care.

Multidisciplinary team meetings are part of the everyday working life of palliative care staff. Based on ethnographic material from community and hospital palliative care teams in England, this article examines these meetings as dynamic routines. Although intended to have a prescribed format to review deaths and collect standardised information to monitor service performance, in practice, the content and conduct of the meetings were fluid, reflecting how this structure did not always match the concerns held by the team.

In vitro susceptibility of 147 international clinical Mycobacterium abscessus isolates to epetraborole and comparators by broth microdilution.

Background: Mycobacterium abscessus is a highly drug-resistant non-tuberculous mycobacterium (NTM) for which treatment is limited by the lack of active oral antimycobacterials and frequent adverse reactions. Epetraborole is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis, and has been shown to have anti-M. abscessus activity in preclinical studies.

The known unknowns of the Hsp90 chaperone.

Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases.

Cesarean section: One procedure, varied techniques. Detailed observations of 1013 first cesarean sections in a tertiary hospital in Ghana.

Objective: Cesarean sections (CS) are among the most performed surgical procedures in the world. Small variations in surgical techniques could have a significant impact on a global scale, for example, in postoperative complications. In the present study we aimed to observe and audit every single step used during first time CS.

Plant Species Richness and the Root Economics Space Drive Soil Fungal Communities.

Trait-based approaches have been increasingly used to relate plants to soil microbial communities. Using the recently described root economics space as an approach to explain the structure of soil-borne fungal communities, our study in a grassland diversity experiment reveals distinct root trait strategies at the plant community level. In addition to significant effects of plant species richness, we show that the collaboration and conservation gradient are strong drivers of the composition of the different guilds of soil fungi.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Non-smoking and Non-drinking Oral Cancer Patients Are at Higher Risk of Second Primary Tumours.

Objectives: This study aimed to explore differences in demographics, tumour characteristics and outcomes in oral squamous cell carcinoma (OSCC) patients with a history of non-smoking, non-drinking (NSND) versus smoking and/or drinking (SD).

Materials And Methods: Newly diagnosed OSCC patients undergoing curative surgical treatment were prospectively included in OncoLifeS, a data biobank. Cox regression analysis was performed yielding hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Resilience to Alzheimer's disease associates with alterations in perineuronal nets.

Introduction: Some individuals show intact cognition despite the presence of neuropathological hallmarks of Alzheimer's disease (AD). The plasticity of parvalbumin (PV)-containing interneurons might contribute to resilience. Perineuronal nets (PNNs), that is, extracellular matrix structures around neurons, modulate PV neuron function.

The versatility of the Supinator to Posterior Interosseus Nerve (SPIN) transfer: Indications and outcomes, a Case Series.

Background: Transfer of the supinator motor branches to the posterior interosseous nerve (SPIN) was first described as a reliable method of restoration of digit extension in cases of paralysis when there is retained function in the 5th and 6th cervical nerve roots with loss of function in the 8th cervical nerve root.

Methods: We performed a retrospective review of all the SPIN transfers that were performed in our unit which included 16 limbs in 14 patients over a 6-year period. The median age was 49 years (range 22-74).

Cytosolic-enhanced dark Epac-based FRET sensors allow for intracellular cAMP detection in live cells via FLIM.

Fluorescence resonance energy transfer (FRET)-based biosensors are powerful tools for studying second messengers with high temporal and spatial resolution. FRET is commonly detected by ratio imaging, but fluorescence lifetime imaging microscopy (FLIM), which measures the donor fluorophore's lifetime, offers a robust and more quantitative alternative. We have introduced and optimized four generations of FRET sensors for cAMP, based on the effector molecule Epac1, including variants for either ratio imaging or FLIM detection.

Environmental Conditions Modulate Warming Effects on Plant Litter Decomposition Globally.

Empirical studies worldwide show that warming has variable effects on plant litter decomposition, leaving the overall impact of climate change on decomposition uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, using natural and standardised plant material, to assess the overarching effect of warming on litter decomposition and identify potential moderating factors. We determined that at least 5.

A Socioecological Approach to Support the Transition to Adult Care for Youth With Medical Complexity: Family Perspectives and Recommendations.

Introduction: The transition from paediatric to adult health care (i.e., 'health care transition') poses many challenges for youth with medical complexity (YMC) and their families.

Perfusion Pressures and Weight Loss During Normothermic Machine Perfusion of Human Donor Livers.

Background: Normothermic machine perfusion (NMP) is increasingly used to preserve and assess donor livers prior to transplantation. Due to its success, it is expected that more centers will start using this technology. However, NMP may also cause adverse effects.