Miracle-dz/UniFAR-FTUs huggingface dataset:
The Intersection of DNA Damage Response and Ferroptosis—A Rationale for Combination Therapeutics

Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis are gaining recognition, much remains unknown about its interaction with other biological processes and pathways. Recently, several studies have identified intricate and complicated interplay between ferroptosis, ionizing radiation (IR), ATM (ataxia–telangiectasia mutated)/ATR (ATM and Rad3-related), and tumor suppressor p53, which signifies the participation of the DNA damage response (DDR) in iron-related cell death. DDR is an evolutionarily conserved response triggered by various DNA insults to attenuate proliferation, enable DNA repairs, and dispose of cells with damaged DNA to maintain genome integrity. Deficiency in proper DDR in many genetic disorders or tumors also highlights the importance of this pathway. In this review, we will focus on the biological crosstalk between DDR and ferroptosis, which is mediated mostly via noncanonical mechanisms. For clinical applications, we also discuss the potential of combining ionizing radiation and ferroptosis-inducers for synergistic effects. At last, various ATM/ATR inhibitors under clinical development may protect ferroptosis and treat many ferroptosis-related diseases to prevent cell death, delay disease progression, and improve clinical outcomes.
Leaf Primordium Initiation and Expanded Leaf Production are Co-ordinated through Similar Response to Air Temperature in Pea (Pisum sativum L.)

Accurate prediction of the timing of leaf area development is essential to analyse and predict the responses of crops to the environment. In this paper, we analyse the two processes determining the chronology of leaf development—initiation of leaf primordia by the shoot meristem and production of expanded leaves out of the shoot tip—in several pea (Pisum sativumL.) cultivars in response to air temperature and plant growth rate. Contrasting levels of air temperature and plant growth rate during leaf development were induced by a wide range of sowing dates and plant densities in glasshouse or field experiments. Full leaf expansion was found to occur one phyllochron after full leaf unfolding, whatever the leaf nodal position. Primordium initiation and expanded leaf production rates presented similar quantitative responses to air temperature (linear response and commonx-intercept), whatever the plant growth rate, cultivar or period of cycle. As a consequence, they were co-ordinated and the numbers of initiated primordia or expanded leaves were easily deduced from simple visual observation of leaf unfolding. The change, over time, of the numbers of initiated leaf primordia and fully expanded leaves correlated with cumulated degree-days, with stable relationships in a wide range of environmental conditions. Two phases, with different production rates, had to be considered. These results allowed us to predict accurately the beginning and the end of individual leaf development from daily mean air temperatures. The relationships obtained here provide an effective way of analysing and predicting leaf development responses to the environment.
Randomized Trial on the Clinical Utility of a Novel Biomarker Panel to Identify Treatable Determinants of Chronic Pain

Millions suffer daily from chronic pain diagnosed anatomically and treated with opioids. Research shows that underlying nutritional, metabolic and oxidative stressors, which drive the development or worsening of chronic pain, are not diagnosed despite the fact that treatment of these primary pain pathways relieves pain and increases function. One of the main reasons for this gap in care is the lack of a simple diagnostic assay to help clinicians make these diagnoses. We examined the clinical utility of a urine-based pain biomarker panel. Primary care physicians were randomized into the test group and compared to controls. We measured their ability to make the diagnosis and treat a total of nine standardized patients, with common but challenging cases of chronic pain, over two rounds of data collection in a pre–post design using a fixed-effects model. Intervention doctors received educational materials on a novel pain biomarker panel after the baseline round and had access to biomarker test results. Provider responses were measured against evidence-based criteria. The two study arms at baseline provided similar, poor care for three different primary pain pathways: nutritional deficiencies (5.0% control versus 9.2% intervention treated, p = 0.208), metabolic abnormalities (1.0% control versus 0% for intervention treated, p = 0.314), and oxidative stress (1.2% control versus 0% intervention treated, p = 0.152). After the introduction of the Foundation Pain Index (FPI) biomarker test, physicians in the intervention group were 41.5% more likely to make the diagnosis of a micronutrient deficiency, 29.4% more likely to identify a treatable metabolic abnormality and 26.1% more likely to identify an oxidative stressor. These diagnostic and treatment improvements were seen across all three case types, ranging from a relative +54% (p = 0.004) for chronic neuropathic pain to +35% (p = 0.007) in chronic pain from other causes to +38% (p = 0.002) in chronic pain with associated mental health issues. Intervention doctors were also 75.1% more likely to provide a non-opioid treatment to patients on chronic opioids (O.R. 1.8, 95% C.I. 0.8–3.7), 62% less likely to order unnecessary imaging for their patients with low back pain (O.R. 0.38, 95% C.I. 0.15–0.97) and 66% less likely to order an unnecessary pain referral (O.R. 0.34, 95% C.I. 0.13–0.90). This experimental study showed significant clinical utility of a validated pain biomarker panel that determines nutritional deficiencies, metabolic abnormalities and oxidative stressors that drive underlying treatable causes of pain. When integrated into routine primary care practice, this testing approach could considerably improve diagnostic accuracy and provide more targeted, non-opioid treatments for patients suffering from chronic pain.
Risk Factors for Loosening of S2 Alar Iliac Screw: Surgical Outcomes of Adult Spinal Deformity

Study Design Retrospective study. Purpose To determine the risk factors for S2 alar iliac (S2AI) screw loosening and its association with lumbosacral fusion in patients with adult spinal deformity (ASD). Overview of Literature S2AI screws have been widely used for ASD surgery in recent years. However, no studies have analyzed the risk factors for loosening of S2AI screws and its association with lumbosacral fusion. Methods Cases of 50 patients with ASD who underwent long spinal fusion (>9 levels) with S2AI screws were retrospectively reviewed. Loosening of S2AI screws and S1 pedicle screws and bone fusion at the level of L5–S1 at 2 years after surgery were investigated using computed tomography. In addition, risk factors for loosening of S2AI screws were determined in patients with ASD. Results At 2 years after surgery, 33 cases (66%) of S2AI screw loosening and six cases (12%) of S1 pedicle screw loosening were observed. In 40 of 47 cases (85%), bone fusion at L5–S1 was found. Pseudarthrosis at L5–S1 was not significantly associated with S2AI screw loosening (19.3% vs. 6.3%, p=0.23), but significantly higher in patients with S1 screw loosening (83.3% vs. 4.9%, p<0.001). On multivariate logistic regression analyses, high upper instrumented vertebra (UIV) level (T5 or above) (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.0–18.6; p=0.045) and obesity (OR, 11.4; 95% CI, 1.2–107.2; p=0.033) were independent risk factors for S2AI screw loosening. Conclusions High UIV level (T5 or above) and obesity were independent risk factors for S2AI screw loosening in patients with lumbosacral fixation in surgery for ASD. The incidence of lumbosacral fusion is associated with S1 screw loosening, but not S2AI screw loosening.
Comparative Analysis of Clinical Characteristics, Imaging and Laboratory Findings of Different Age Groups with COVID-19

Objective: This study aims to provide scientific basis for rapid screening and early diagnosis of the coronavirus disease 2019 (COVID-19) through analysing the clinical characteristics and early imaging/laboratory findings of the inpatients. Methods: Three hundred and three patients with laboratory-confirmed COVID-19 from the East Hospital of People's Hospital of Wuhan University (Wuhan, China) were selected and divided into four groups: youth (20–40 years, n = 64), middle-aged (41–60 years, n = 89), older (61–80 years, n = 118) and elderly (81–100 years, n = 32). The clinical characteristics and imaging/laboratory findings including chest computed tomography (CT), initial blood count, C-reactive protein [CRP]), procalcitonin (PCT) and serum total IgE were captured and analysed. Results: (1) The first symptoms of all age groups were primarily fever (76%), followed by cough (12%) and dyspnoea (5%). Beside fever, the most common initial symptom of elderly patients was fatigue (13%). (2) Fever was the most common clinical manifestation (80%), with moderate fever being the most common (40%), followed by low fever in patients above 40 years old and high fever in those under 40 years (35%). Cough was the second most common clinical manifestation and was most common (80%) in the middle-aged. Diarrhoea was more common in the middle-aged (21%) and the older (19%). Muscle ache was more common in the middle-aged (15%). Chest pain was more common in the youth (13%), and 13% of the youth had no symptoms. (3) The proportion of patients with comorbidities increased with age. (4) Seventy-one per cent of the patients had positive reverse transcription–polymerase chain reaction results and 29% had positive chest CT scans before admission to the hospital. (5) Lesions in all lobes of the lung were observed as the main chest CT findings (76%). (6) Decrease in lymphocytes and increase in monocytes were common in the patients over 40 years old but rare in the youth. Eosinophils (50%), red blood cells (39%) and haemoglobin (40%) decreased in all age groups. (7) The proportion of patients with CRP and PCT elevation increased with age. (8) Thirty-nine per cent of the patients had elevated IgE, with the highest proportion in the old (49%). Conclusion: The clinical characteristics and imaging/laboratory findings of COVID-19 patients vary in different age groups. Personalised criteria should be formulated according to different age groups in the early screening and diagnosis stage.
Diagnostic value of endobronchial ultrasound image features: A specialized review

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) technology is important in the diagnosis of intrathoracic benign and malignant lymph nodes (LNs). With the development of EBUS imaging technology, its role in noninvasive diagnosis, as a supplement to pathology diagnosis, has been given increasing attention in recent years. Many studies have explored qualitative and quantitative methods for the three EBUS modes, as well as a variety of multimodal analysis methods, to find the optimal method for the noninvasive diagnosis using EBUS for LNs. Here, we review and comment on the research methods and predictive diagnostic value, discuss the existing problems, and look ahead to the future application of EBUS imaging.
Global visual salience of competing stimuli

Current computational models of visual salience accurately predict the distribution of fixations on isolated visual stimuli. It is not known, however, whether the global salience of a stimulus, that is, its effectiveness in the competition for attention with other stimuli, is a function of the local salience or an independent measure. Further, do task and familiarity with the competing images influence eye movements? Here, we investigated the direction of the first saccade to characterize and analyze the global visual salience of competing stimuli. Participants freely observed pairs of images while eye movements were recorded. The pairs balanced the combinations of new and already seen images, as well as task and task-free trials. Then, we trained a logistic regression model that accurately predicted the location—left or right image—of the first fixation for each stimulus pair, accounting too for the influence of task, familiarity, and lateral bias. The coefficients of the model provided a reliable measure of global salience, which we contrasted with two distinct local salience models, GBVS and Deep Gaze. The lack of correlation of the behavioral data with the former and the small correlation with the latter indicate that global salience cannot be explained by the feature-driven local salience of images. Further, the influence of task and familiarity was rather small, and we reproduced the previously reported left-sided bias. Summarized, we showed that natural stimuli have an intrinsic global salience related to the human initial gaze direction, independent of the local salience and little influenced by task and familiarity.
Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice

Background NCOR1 (nuclear receptor corepressor 1) is an essential coregulator of gene transcription. It has been shown that NCOR1 in macrophages plays important roles in metabolic regulation. However, the function of macrophage NCOR1 in response to myocardial infarction (MI) or vascular wire injury has not been elucidated. Methods and Results Here, using macrophage Ncor1 knockout mouse in combination with a mouse model of MI, we demonstrated that macrophage NCOR1 deficiency significantly reduced infarct size and improved cardiac function after MI. In addition, macrophage NCOR1 deficiency markedly inhibited neointimal hyperplasia and vascular remodeling in a mouse model of arterial wire injury. Inflammation and macrophage proliferation were substantially attenuated in hearts and arteries of macrophage Ncor1 knockout mice after MI and arterial wire injury, respectively. Cultured primary macrophages from macrophage Ncor1 knockout mice manifested lower expression of inflammatory genes upon stimulation by interleukin‐1β, interleukin‐6, or lipopolysaccharide, together with much less activation of inflammatory signaling cascades including signal transducer and activator of transcription 1 and nuclear factor‐κB. Furthermore, macrophage Ncor1 knockout macrophages were much less proliferative in culture, with inhibited cell cycle progression compared with control cells. Conclusions Collectively, our data have demonstrated that NCOR1 is a critical regulator of macrophage inflammation and proliferation and that deficiency of NCOR1 in macrophages attenuates MI and neointimal hyperplasia. Therefore, macrophage NCOR1 may serve as a potential therapeutic target for MI and restenosis.
Land snail richness and abundance along a sharp ecological gradient at two sampling scales: disentangling relationships

It is generally recognized that the number of land snail species increases with the number of individuals in samples. This correlation may be an artefact of sample size, but it may also reflect the similarity in microhabitat preference of many species. Biotic interactions (competition) might also influence this relationship: an upper limit to co-existence at a particular scale. Here, we model the relationships between number of species, abundance of live individuals and environmental factors in the snail faunas of treeless fens covering a broad range of calcium content. The models considered two scales of sampling: (i) a 12 litre sample collected at a 4×4 m plot (187 samples) capturing at least 80% of the site's known species pool, and (ii) a sampling of 25×25 cm plots (115 samples) usually capturing less than 40% of the site's species pool. At the larger scale, the number of species responded to the calcium gradient more tightly than did total densities; but this was reversed at the smaller scale. Variation in abundance explained about the half of the species richness variation at both scales, but the number of individuals collected was not limiting for the number of species recorded at the larger scale. Using simulated communities we discovered that an asymptotic relationship between number of species and individuals can arise from a nested pattern of species distributions towards calcareous sites and thus that it may not be simply a rarefaction effect. The shape of a species accumulation curve may be only a weak indication of sampling efficiency when there is environmental variation among sample areas. Further, the observed hump-shaped relationship between the numbers of live individuals and species at the small scale raises a classical question about interspecific competition in land snail assemblages.
A method for advanced stage evaluation of pasture species: a case study with bred lines of Macroptilium atropurpureum

A method is described for evaluating persistence and productivity of pasture species in the advanced stage of testing. Six bred lines of Macroptilium atropurpureum were compared with cv. Siratro at Samford, south-east Queensland, under stocking rates equivalent to 2.0 and 3.0 steers-ha-1. Each plot was grazed separately for 4 days every 6 weeks, without any mowing being imposed. Attributes measured over a 5-year period included presentation yield, legume density, weed invasion and soil seed reserves. One line of M. atropurpureum was superior to Siratro in yield and plant density, although it produced lower reserves of soil seed. These results were similar to those from a previous experiment under cutting. The advantages and limitations of the method are discussed.
Short Stature is Progressive in Patients with Heterozygous NPR2 Mutations.

BACKGROUND NPR2 encodes atrial natriuretic peptide receptor B (ANPRB), a regulator of skeletal growth. Biallelic loss-of-function mutations in NPR2 result in acromesomelic dysplasia Maroteaux type (AMDM; OMIM 602875), while heterozygous mutations may account for 2-6% of idiopathic short stature (ISS). OBJECTIVE Describe the physical proportions and growth characteristics of an extended family with novel NPR2 mutations including members with AMDM, ISS, or normal stature. DESIGN AND PARTICIPANTS We performed whole exome sequencing in two healthy parents and two children with AMDM. Detailed genotyping and phenotyping was performed on members of a multigenerational family in an academic medical center. We expressed mutant proteins in mammalian cells and characterized expression and function. RESULTS The sisters with AMDM were compound heterozygotes for missense mutations in the NPR2 gene, a novel p.P93S (maternal) and the previously reported p.R989L (paternal). Both mutant ANPRB proteins were normally expressed in HEK293T cells and exhibited dominant negative effects on wild type ANPRB catalytic activity. Heterozygous relatives had proportionate short stature (height z-scores -2.06 ± 0.97, median ± SD) compared to their wild type siblings (-1.37 ± 0.59). Height z-scores progressively and significantly decreased as NPR2-heterozygous children matured, while it remained constant in their wild type siblings. CONCLUSIONS Biallelic NPR2 mutations cause severe skeletal dysplasia (ADMD), whereas heterozygous mutations lead to a subtler phenotype characterized by progressive short stature characterized by increasing loss of height potential with age.
Improvement of Mechanical, Hydrophobicity and Thermal Properties of Chinese Fir Wood by Impregnation of Nano Silica Sol

In this paper, a wood-SiO2 composite material was prepared via in-situ polymerization using vacuum/pressure impregnation technology using commercial scale nano silica sol and Chinese Fir (Cunninghamia lanceolate (Lamb.) Hook. ). Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), and water contact angle were used to study the changes in the microstructure and physical and mechanical properties of this composite. The results showed that silica sol can penetrate and distribute into the wood cell cavities and surface of cell walls and hence combine with the substances of wood materials. FTIR results indicated that the –OH groups of wood can polycondense in-situ with silica sol to form Si–O–C covalent bonds, and amorphous SiO2 formed from Si–O–Si bonds between the –OH groups of silica sol did not change the crystalline structure of wood cell walls. This in-situ formulating composite significantly improved the compact microstructure, thermal and mechanical properties, and hydrophobicity of the composites.
Impact of an Electronic Health Service on Child Participation in Pediatric Oncology Care: Quasiexperimental Study

Background For children 6-12 years old, there is a shortage of electronic Health (eHealth) services that promote their participation in health care. Therefore, a digital communication tool, called Sisom, was developed to give children a voice in their health care. Children with long-term diseases want to be more involved in their health care and have the right to receive information, be listened to, express their opinions, and participate in decision making in health care. However, the outcomes of using Sisom in practice at pediatric oncology clinics have not been investigated. Objective The aim of this study was to investigate children’s participation during appointments with pediatricians at pediatric oncology clinics, with or without the use of the eHealth service Sisom. Methods A quasiexperimental design with mixed methods was used. We analyzed 27 filmed appointments with pediatricians for 14 children (8 girls and 6 boys) aged 6-12 years (mean 8.3 years) with a cancer diagnosis. The intervention group consisted of children who used Sisom prior to their appointments with pediatricians at a pediatric oncology clinic, and the control group consisted of children who had appointments with pediatricians at 4 pediatric oncology clinics. Data from observations from the videos were quantitatively and qualitatively analyzed. The quantitative analysis included manual calculations of how many times the pediatricians spoke directly to the children, the proportion of the appointment time that the children were talking, and levels of participation by the children. For the qualitative analysis, we used directed content analysis to analyze the children’s levels of participation guided by a framework based on Shier’s model of participation. Results Pediatricians directed a greater proportion of their discussion toward the child in the intervention group (731 occasions) than in the control group (624 occasions), but the proportion of the appointment time the children talked was almost the same for both the intervention and control groups (mean 17.0 minutes vs 17.6 minutes). The levels of participation corresponded to the first three levels of Shier’s participation model: children were listened to, children were supported to express their views, and children’s views were taken into account. The results showed an increased level of participation by the children in the intervention group. Several codes that were found did not fit into any of the existing categories, and a new category was thus formed: children received information. Conclusions This study shows that the eHealth service Sisom can increase children’s participation during appointments with health care professionals. Further studies employing a randomized control design focusing on the effects of eHealth services on children’s health outcomes, perceived participation, and cost-effectiveness could make a significant contribution to guiding the implementation of eHealth services in pediatric care.