Reports of proteins in fossilized bones have been a subject of controversy in the scientific literature because it is assumed that fossilization results in the destruction of all organic components. In this paper, a novel combination of analytical techniques is used to address this question for an exceptionally well-preserved sacrum excavated from the Upper Cretaceous strata of the South Dakota Hell Creek Formation. Cross-polarized light microscopy (XPol) shows birefringence consistent with collagen presence.
View Article and Find Full Text PDFIntroduction: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer in the world. Metastases occur in up to 40 % of cases and bones are the second most frequent site. Metastases in extremities are uncommon with very few publications covering distal lower-limb bone metastasis.
View Article and Find Full Text PDFIntroduction: Conventional methods for evaluating the management of spasticity, a complex neuromuscular disorder, typically fail to directly measure the muscle forces and loads applied through tendons, which is crucial for accurate diagnostics and treatment. To bridge this gap, we developed a novel modular buckle transducer (BT) designed to measure tendon forces . This device adjusts to accommodate tendon sizes ranging from 3 mm to 5 mm, maintaining accuracy within this range and avoiding the need for identical tendon calibration.
View Article and Find Full Text PDFThis study explores the vapochromic and vapoluminescent behaviors of [Pt(tpy)Cl]PF host molecules (tpy = 2,2':6',2''-terpyridine) under acetonitrile (CHCN) vapor guest, challenging the conventional view that these phenomena arise solely from direct host-guest interactions. Our findings reveal a cooperative mechanism where mechanochromic surface perturbations prime the Pt(II) host for guest incorporation, leading to initial color and luminescence changes prior to significant structural alterations. While the color transition between the yellow [Pt(tpy)Cl]PF form and the red/orange [Pt(tpy)Cl]PF·CHCN form is reversible, repeated vapor cycling induces a loss of crystallinity, as indicated by diffraction peak broadening and emission shifts.
View Article and Find Full Text PDFBackground: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.
View Article and Find Full Text PDFPrecision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.
View Article and Find Full Text PDFObjectives: Previous investigations comparing intraosseous (IO) and intravenous (IV) epinephrine delivery in out-of-hospital cardiac arrest (OHCA) suggest that epinephrine is oftentimes more expeditiously administered the IO route, but this temporal benefit doesn't always translate to clinical benefit. However, very few studies adequately controlled for indication and resuscitation time biases, making the influence of first epinephrine route on OHCA outcomes unclear. To determine the association between first epinephrine route and return of spontaneous circulation (ROSC) while controlling for resuscitation time bias and other potential confounders.
View Article and Find Full Text PDFIntroduction: Cardiac arrest patients presenting with non-shockable rhythms have a low probability of survival, and epinephrine is one of the few pharmaceutical options for this group. The recommended 1.0 mg adult dose is extrapolated from early animal studies and lacks adjustment for patient weight.
View Article and Find Full Text PDFThe 2023 wildfire season in Canada was unprecedented in its scale and intensity, spanning from mid-April to late October and across much of the forested regions of Canada. Here, we summarize the main causes and impacts of this exceptional season. The record-breaking total area burned (~15 Mha) can be attributed to several environmental factors that converged early in the season: early snowmelt, multiannual drought conditions in western Canada, and the rapid transition to drought in eastern Canada.
View Article and Find Full Text PDFSoil microbial fuel cells (SMFCs) function as bioelectrochemical energy harvesters that convert electrons stored in soil organic matter into useful electrical energy. Broadly, an SMFC comprises three essential components: an anode buried in the soil (the negative terminal), a colony of exoelectrogenic microorganisms residing on this anode, and a cathode (the positive terminal). As the exoelectrogens respire, they release electrons to the anode, which acts as an external receptor.
View Article and Find Full Text PDFPurpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.
Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.
Pulsar timing arrays perform Bayesian posterior inference with expensive Markov chain Monte Carlo (MCMC) methods. Given a dataset of ∼10-100 pulsars and O(10^{3}) timing residuals each, producing a posterior distribution for the stochastic gravitational wave background (SGWB) can take days to a week. The computational bottleneck arises because the likelihood evaluation required for MCMC is extremely costly when considering the dimensionality of the search space.
View Article and Find Full Text PDFA subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of , a replisome accelerator. However, the nature of the vulnerability responsible for intrinsic sensitivity remains undetermined.
View Article and Find Full Text PDFPyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis.
View Article and Find Full Text PDFThe International Classification of Diseases (ICD) hierarchical taxonomy is used for so-called clinical coding of medical reports, typically presented in unstructured text. In the Czech Republic, it is currently carried out manually by a so-called clinical coder. However, due to the human factor, this process is error-prone and expensive.
View Article and Find Full Text PDFProtein-protein and protein-water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations makes them difficult to analyze. Here, we introduce a state space representation and associated "rarity" measure to identify and quantify transition state passage (transit) events. Applying this representation to a long MD simulation trajectory that captured multiple folding and unfolding events of the GTT WW domain, a small protein often used as a model for the folding process, we identified three transition categories: Highway (faster), Meander (slower), and Ambiguous (intermediate).
View Article and Find Full Text PDFObjective: Previous investigations of the relationship between obesity and difficult airway management have provided mixed results. Almost universally, these studies were conducted in the hospital setting, and the influence of patient body weight on successful prehospital airway management remains unclear. Because patient weight could be one readily identifiable risk factor for problematic airway interventions, we sought to evaluate this relationship.
View Article and Find Full Text PDFCommunities interspersed throughout the Canadian wildland are threatened by fires that have become bigger and more frequent in some parts of the country in recent decades. Identifying the fireshed (source area) and pathways from which wildland fire may ignite and spread from the landscape to a community is crucial for risk-reduction strategy and planning. We used outputs from a fire simulation model, including fire polygons and rate of spread, to map firesheds, fire pathways and corridors and spread distances for 1980 communities in the forested areas of Canada.
View Article and Find Full Text PDFBinary systems of supermassive black holes are promising sources of low-frequency gravitational waves (GWs) and bright electromagnetic emission. Pulsar timing array GW searches for individual binaries have been limited to only a few candidate systems due to computational demands, which get worse as more pulsars are added. By modeling the GW signal using only components from when the GW passes Earth (rather than also each pulsar), we find constraints on the binary's total mass and GW frequency that are similar to a full signal analysis, yet ∼70 times more efficient.
View Article and Find Full Text PDFObjective: To identify and agree on what outcome domains should be measured in research and clinical practice when working with stroke survivors who have dysarthria.
Design: Delphi process, two rounds of an online survey followed by two online consensus meetings.
Setting: UK and Australia.