Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the molecular mechanism of cold‐adaption of an alkaline protease mutant by molecular dynamics simulations and residue interaction network

Psychrophilic proteases have attracted enormous attention in past decades, due to their high catalytic activity at low temperatures in a wide range of industrial processes, especially in the detergent and leather industries. Among them, H5 is an alkaline protease mutant, which featuring psychrophilic‐like behavior, but the reasons that H5 with higher activity at low temperatures are still poorly understood. Herein, the molecular dynamics (MD) simulations combined with residue interaction network (RIN) were utilized to investigate the mechanisms of the cold‐adaption of mutant H5. The results demonstrated that two loops involved in the substrate binding G100‐S104 and S125‐S129 in H5 had higher mobility, and the distance enlargement between the two loops modulated the substrate's accessibility compared with wild type counterpart. Besides, H5 enhanced conformational flexibility by weakening salt bridges and increasing interaction with the solvent. In particular, the absence of Lys251–Asp197–Arg247 salt bridge network may contribute to the structural mobility. Based on the free energy landscape and molecular mechanics Poisson−Boltzmann surface area of the wild type and H5, it was elucidated that H5 possessed a large population of interconvertible conformations, resulting in the weaker substrate binding free energy. The calculated RIN topology parameters such as the average degree, average cluster coefficient, and average path length further verified that the mutant H5 attenuated residue‐to‐residue interactions. The investigation of the mechanisms by which how the residue mutation affects the stability and activity of enzymes provides a theoretical basis for the development of cold‐adapted protease.
N-acetylcysteine modulates redox imbalance and inflammation in macrophages and mice exposed to formaldehyde

Abstract This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice (n = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days. In vitro, formaldehyde promoted a decrease in cell viability and increased ROS, while NAC reduced formaldehyde-induced ROS production. Animals exposed to formaldehyde presented higher leukocyte counts in the blood and in the bronchoalveolar lavage fluid, and promoted secretion of inflammatory markers IL-6, IL-15, and IL-10. The exposure to formaldehyde also promoted redox imbalance and oxidative damage characterized by increased activities of superoxide dismutase, catalase, decreased GSH/GSSG ratio, as well as it increased levels of protein carbonyls and lipid peroxidation. NAC administration after formaldehyde exposure attenuated oxidative stress markers, secretion of inflammatory mediators and lung inflammation. In conclusion, both in in vitro and in vivo models, NAC administration exerted protective effects, which modulated the inflammatory response and redox imbalance, thus preventing the development airway injury induced by formaldehyde exposure.
Magnetic susceptibility of soil: an evaluation of conflicting theories using a national data set

Magnetic susceptibility values for topsoils across England arc combined with data for soil type, geochemistry and concentrations of magnetotactic bacteria in order to evaluate different theories for explaining soil magnetism. Strongly magnetic soils in unpolluted areas are found over weakly magnetic substrates and are dominated by ultrafine superparamagnetic grains. Magnetotactic bacteria are present in insufficient concentrations to account for strongly magnetic soils, and crop burning is discounted as a major factor. A small number of samples show high values associated with either airborne magnetic particulates from pollution or residual primary ferrimagnetic minerals from igneous substrates. The results are used to construct a new mechanism for the formation of secondary ferrimagnetic minerals that links abiological weathering and biological fermentation processes. The fundamental driving force in the mechanism is Fe supply, which may be linked to climate. Observed causative associations between climate and the magnetic susceptibility of loess-palaeosol sequences are supported by the findings.
Hospital and emergency department discharge against medical advice in Western Australian Aboriginal children aged 0–4 years from 2002 to 2018: A cohort study

Abstract Background Discharge against medical advice (DAMA) is a priority issue for the health system. Little is known about the factors associated with DAMA for Aboriginal and/or Torres Strait Islander (Aboriginal) children in Australia. Objectives Investigate the associations between DAMA for hospital admissions and emergency department (ED) presentations and: (i) child, family and episode of service characteristics and (ii) 30‐day readmission/ re‐presentation. Methods We conducted a cohort study of Aboriginal children born in Western Australia (2002–2013) who had ≥1 hospital admissions (n = 16,931) or ED presentations (n = 26,546) within the first 5 years of life. The outcome of interest was hospital and ED DAMA and adjusted odds ratio were derived using multilevel mixed‐effects logistic regression. Results In the Hospital Cohort, there were 43,149 hospitalisations for 16,931 children, with 684 hospitalisations (1.6%) recorded as DAMA. In the ED Cohort, there were 232,082 ED presentations in 26,546 children, with 10,918 ED presentations (4.7%) recorded as DAMA. DAMA occurring in hospitals between 2014 and 2018, the adjusted odds decreased by 75% compared to the period between 2002 and 2005. The adjusted odds of ED DAMA increased by 46% over the same period. Hospital admissions in regional and remote hospitals were almost seven times the adjusted odds of DAMA compared with hospital admissions in Perth metropolitan hospitals. The adjusted odds of ED DAMA decreased by 12% for ED presentations in regional and remote hospitals compared to those in Perth metropolitan hospitals. There was no evidence of hospital DAMA being associated with hospital readmission within 30 days and limited evidence of ED DAMA being associated with re‐presenting to an ED within 30 days. Conclusions The study identified several important determinants of DAMA, including admission status, triage status, location and calendar year. These findings could inform targeted measures to decrease DAMA, particularly in regional and remote communities.
System of the 1:28 800 scale sheets of the Second Military Survey in Tyrol And Salzburg

The Second Military Survey of the Habsburg Empire (Franziszeische Landesaufnahme) was based on the first triangulation net of the Empire, ordered by Emperor Francis I in 1806. Eight horizontal control points were later used as projection centers for the different parts of the Empire. However, two provinces, mapped in the very early phase of the survey, have no real terrain objects as projection centers. In spite of the earlier literature items, mainly concerning the cadastral systems, the map sheet systems of the Second Military Survey of Tyrol and Salzburg do not follow the Soldner-Cassini projections centered at Innsbruck and Gusterberg, respectively. Indeed, the design of these sheets is similar to the one of the First Military Survey in cartographic point of view also with respect to their projection. The systems of the 1:28 800 sheets in these provinces are not centered at Vienna (St. Stephen) or Gusterberg as it was indicated in the literature. Projection analysis shows that for these provinces a unified sheet system was introduced. It can be connected to an Innsbruck-Pfarrturm-centered Cassini projection but the projection center is not at any distinct point (sheet center, corner or boundary halving point) of the sheet system. This Cassini projection, however, is not suitable for precise georeferencing of the sheets of Tyrol and Salzburg as it results errors up to one kilometer. The map sheets of these provinces can be rectified using quadratic formulae with remnant errors of maximum 220 meters (Tyrol) and 500 meters (Salzburg), which are much higher values than the fitting accuracy of the sheets in other parts of the Empire. According to the analysis, Liechtenstein is also without definite projection center but it is covered by only one extended sheet and its rectification can be done with an accuracy of 30 meters.
Evaluating the Efficacy of ChatGPT in Navigating the Spanish Medical Residency Entrance Examination (MIR): Promising Horizons for AI in Clinical Medicine

The rapid progress in artificial intelligence, machine learning, and natural language processing has led to increasingly sophisticated large language models (LLMs) for use in healthcare. This study assesses the performance of two LLMs, the GPT-3.5 and GPT-4 models, in passing the MIR medical examination for access to medical specialist training in Spain. Our objectives included gauging the model’s overall performance, analyzing discrepancies across different medical specialties, discerning between theoretical and practical questions, estimating error proportions, and assessing the hypothetical severity of errors committed by a physician. Material and methods: We studied the 2022 Spanish MIR examination results after excluding those questions requiring image evaluations or having acknowledged errors. The remaining 182 questions were presented to the LLM GPT-4 and GPT-3.5 in Spanish and English. Logistic regression models analyzed the relationships between question length, sequence, and performance. We also analyzed the 23 questions with images, using GPT-4’s new image analysis capability. Results: GPT-4 outperformed GPT-3.5, scoring 86.81% in Spanish (p < 0.001). English translations had a slightly enhanced performance. GPT-4 scored 26.1% of the questions with images in English. The results were worse when the questions were in Spanish, 13.0%, although the differences were not statistically significant (p = 0.250). Among medical specialties, GPT-4 achieved a 100% correct response rate in several areas, and the Pharmacology, Critical Care, and Infectious Diseases specialties showed lower performance. The error analysis revealed that while a 13.2% error rate existed, the gravest categories, such as “error requiring intervention to sustain life” and “error resulting in death”, had a 0% rate. Conclusions: GPT-4 performs robustly on the Spanish MIR examination, with varying capabilities to discriminate knowledge across specialties. While the model’s high success rate is commendable, understanding the error severity is critical, especially when considering AI’s potential role in real-world medical practice and its implications for patient safety.
MicroRNAs in Gingival Crevicular Fluid: An Observational Case-Control Study of Differential Expression in Periodontitis

Objectives: microRNAs (miRNAs) present in the gingival crevicular fluid (GCF) of patients with chronic periodontitis may serve as biomarkers of periodontal disease. The aim of this study was to perform a miRNA-sequencing study of all miRNAs present in GCF, comparing miRNA expression level profiles between advanced chronic periodontitis (CP) patients and healthy subjects (HS). Materials and methods: GCF samples were collected from the single-rooted teeth of patients with severe CP (n = 11) and of HS (n = 12). miRNAs were isolated from GCF using an miRNeasy Serum/Plasma kit(Qiagen GmbH, Hilden, Germany). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression levels of miRNA candidates involved in periodontal pathogenesis. Results: Of all the sequenced miRNAs, miR-199, miR-146a, miR-30a, and miR-338 were identified as best representing the CP patient samples. The validation study identified miR-199 as the most powerful biomarker used to define periodontitis. Conclusions: Upon sequencing all known miRNAs in GCF for the first time, we uncovered several potential biomarkers to define periodontitis. Identifying miRNAS in the GCF using high-throughput approaches will clarify the role of these molecules in periodontitis and provide biomarkers with potential applications.
Regional associations between inspiratory tongue dilatory movement and genioglossus activity during wakefulness in people with obstructive sleep apnoea

Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea–hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta = 0.089, 95% CI [0.000, 0.178], t(99) = 1.995, P = 0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta = −0.123, 95% CI [−0.224, −0.022], t(43) = −2.458, P = 0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P = 0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co‐activation of other airway dilator muscles.
Bowel Management Protocol

Purpose of Study: The project aimed to determine the impact of a standardized bowel regimen protocol for patients receiving opioids on the rate of stool softener prescription, occurrence of bowel movements of oncology patients, and improving the length of stay (LOS). Primary Practice of Setting: Oncology unit in a community hospital. Methodology and Sample: A posttest design was utilized, and a prospective medical record review of patients was completed after 8 weeks of the pilot study. The study sample (N = 164) included oncology patients admitted to a community hospital in the Southeast. The χ2 test was used to determine the impact of implementing a bowel panel order on the rate of stool softener prescriptions, the occurrence of bowel movements, and the LOS. Results: Only 43% (n = 40) of the patients from the comparison group were ordered laxatives, and more patients from the intervention group (68%; n = 49) received the bowel regimen protocol, whereas 26% (n = 19) of the patients used a laxative or stool softener using providers' preference and demonstrated statistical significance (p = .001). In the intervention group, 93% of the patients (n = 67) reported having bowel movements compared with the comparison group, whereas only 32% (n = 32) demonstrated statistical significance (p = .001). The average LOS in the intervention group is less than 9 days compared with the comparison group, which was at 9 days (p = .001). Implications to Case Management Practice: Case managers play a critical role in coordinating care, improving transitions of care, and reducing LOS. Case managers can have a significant impact by monitoring and reminding nurses to report the gastrointestinal movements of oncology patients and then escalate opioid-induced constipation with the providers immediately. Case managers can facilitate the implementation of bowel regimen protocols, which may reduce hospitalizations and enhance patient outcomes, by taking this action.
FKBP5 associated CD8 T cell infiltration is a novel prognostic biomarker in luminal B breast cancer

Objective To investigate the relationship between FKBP prolyl isomerase 5 (FKBP5) gene expression and CD8 T cells in tumour progression and immunology of the luminal B subtype of breast cancer (LBBC) using bioinformatics analyses. Methods The Gene Expression Profiling Interactive Analysis 2, Human Protein Atlas and breast cancer gene-expression miner v4.5 databases were used for data mining and analysing FKBP5, its co-expressed genes and CD8 T cell-related markers. The Tumor IMmune Estimation Resource 2.0 database was used for analysing the correlation and prognosis of FKBP5 and CD8 T cell infiltration level in LBBC. Results Upregulated FKBP5 expression was correlated with improved survival in LBBC. Upregulated FKBP5-related CD8 T cell markers were also demonstrated to be significantly correlated with better survival in LBBC and might play a role in the biological activity of FKBP5. Conclusion These findings suggest that FKBP5 and its associated CD8 T cell infiltration are potential benign prognostic indicators for LBBC.
Elastic Shape Analysis of Tree-Like 3D Objects Using Extended SRVF Representation

How can one analyze detailed 3D biological objects, such as neuronal and botanical trees, that exhibit complex geometrical and topological variation? In this paper, we develop a novel mathematical framework for representing, comparing, and computing geodesic deformations between the shapes of such tree-like 3D objects. A hierarchical organization of subtrees characterizes these objects – each subtree has a main branch with some side branches attached – and one needs to match these structures across objects for meaningful comparisons. We propose a novel representation that extends the Square-Root Velocity Function (SRVF), initially developed for Euclidean curves, to tree-shaped 3D objects. We then define a new metric that quantifies the bending, stretching, and branch sliding needed to deform one tree-shaped object into the other. Compared to the current metrics such as the Quotient Euclidean Distance (QED) and the Tree Edit Distance (TED), the proposed representation and metric capture the full elasticity of the branches (i.e., bending and stretching) as well as the topological variations (i.e., branch death/birth and sliding). It completely avoids the shrinkage that results from the edge collapse and node split operations of the QED and TED metrics. We demonstrate the utility of this framework in comparing, matching, and computing geodesics between biological objects such as neuronal and botanical trees. We also demonstrate its application to various shape analysis tasks such as (i) symmetry analysis and symmetrization of tree-shaped 3D objects, (ii) computing summary statistics (means and modes of variations) of populations of tree-shaped 3D objects, (iii) fitting parametric probability distributions to such populations, and (iv) finally synthesizing novel tree-shaped 3D objects through random sampling from estimated probability distributions.
Perimenopausal women’s voices: How does their period at the end of reproductive life affect wellbeing?

Objective To explore perimenopausal women’s feelings towards their periods, the impact on their wellbeing and how we can support them. Study design Participants were recruited for focus groups through social media advertisements. In 6 online focus groups, 31 perimenopausal women aged 40–55 living in the UK were asked 5 questions relating to periods and perimenopause, support and education. Main outcome measures Content analysis. Results When asked How do you feel about having a period? The participants often related back to the stress of menarche and said their period negatively impacted their wellbeing their whole lives. During perimenopause, their periods had become unpredictable, heavy, and a debilitating disruption to their lives. The women desired support at work through policy, and from family and friends. They believed that educating girls and boys during school was the best place to start, but that education through work and community groups was also needed. They felt healthcare professionals should have mandatory training regarding women’s health issues and menopause. Conclusion The study highlights the impact of menstrual experiences on the wellbeing of perimenopausal women, emphasising the need for improved menstrual education from an early age. Comprehensive menstrual education in schools involving both genders to enable informed decision-making and improved training for healthcare professionals are recommended. Support networks for perimenopausal women will promote better quality of life for women as they go through their perimenopause journey.
HIV‐1 replication requires optimal activation of the unfolded protein response

Several human diseases including viral infections activate the unfolded protein response (UPR) due to abnormal accumulation of unfolded/misfolded proteins. However, UPR modulation and its functional relevance in HIV‐1 infection lack comprehensive elucidation. This study reveals that HIV‐1 activates IRE1, PERK, and ATF6 signaling pathways of UPR. The knockdown of PERK and ATF6 reduces HIV‐1 long terminal repeat (LTR)‐driven gene expression, whereas the endoplasmic reticulum (ER) chaperone HSPA5 prevents proteasomal degradation of HIV‐1 p24 through its chaperone activity. Interestingly, overstimulation of UPR by a chemical inducer leads to anti‐HIV activity through an enhanced type‐1 interferon response. Also, treatment with a chemical ER stress inhibitor reduces HIV‐1 replication. These findings suggest that an optimal UPR activation is crucial for effective viral replication, as either overstimulating UPR or inhibiting ER stress leads to viral suppression.
Long-term exhumation of a Palaeoproterozoic orogen and the role of pre-existing heterogeneous thermal crustal properties: a fission-track study of SE Baffin Island

New apatite fission-track data from SE Baffin Island exhibit central ages that range from just under 200 Ma to 440 Ma, and mean track lengths that vary between c. 12 and 13.3 µm. First-order analysis of the data (a plot of central age v. mean track length) reveals an approximate ‘boomerang’ trend, typical of samples that have experienced contemporaneous cooling from an array of initial temperatures. One-dimensional inverse thermal modelling of single samples suggests that cooling through the partial annealing zone (c. 120–60 °C) occurred over discrete periods ranging from 100 to 300 Ma. Modelling the 3D exhumation of a heterogeneous crust with flat topography demonstrates that some of the variability in observed fission-track ages could be attributed to heterogeneity in crustal heat production and thermal conductivity. The remaining variability in the observed dataset is attributed here to differential erosion from a variable initial topography. However, age discontinuities over short distances require other explanations such as faulting and/or unidentified compositional effects. Collectively, these results suggest that the observed data are consistent with a simple exhumation scenario where the present-day high topography is a remnant of that created during Palaeoproterozoic orogenies. The new data do not require any recent (Cenozoic) periods of exhumation. Supplementary material: Data locations, and isotopic and petrographic results are available at www.geolsoc. org.uk/SUP18657.