Miracle-dz/UniFAR-FTUs huggingface dataset:
Fault plane orientations of intermediate‐depth and deep‐focus earthquakes in the Japan‐Kuril‐Kamchatka subduction zone

In the northwestern Pacific, the Pacific plate subducts to the west at the Japan, Kuril, and Kamchatka trenches. Throughout most of the subduction zone, the subducting slab is planar and dipping at an angle of 30°–60°, with the exception of a fold in the southern Kuril segment. To investigate how the slab deforms in response to the applied forces and which mechanism generates the earthquakes, we analyze the rupture properties of 111 large (MW≥5.7) intermediate‐depth and deep‐focus earthquakes (60–656 km depth) from 1990 to 2014 in the Japan‐Kuril‐Kamchatka subduction zone. For each earthquake, we use rupture directivity to estimate rupture direction and rupture speed and to distinguish the fault plane from the auxiliary plane of the focal mechanism. Seventy six percent of the earthquakes with sufficient station coverage are well modeled by unilateral rupture propagation. The estimated rupture speeds range from zero to supershear. The estimated rupture directions allow identification of the fault plane as the more horizontal nodal plane for 30 earthquakes, while an additional 11 earthquakes rupture toward the intersection of the nodal planes, so the fault plane cannot be identified. Combining our newly identified fault planes with previously identified fault planes in the region, we observe that in planar slab segments, most earthquakes slip along a dominant fault orientation. For a steeply dipping slab, this orientation is subhorizontal. In more sharply bent slab segments, such as the Kuril fold, deformation is accommodated along more variable fault orientations, including subvertical faults. The correlation of slab geometry with fault orientation suggests that the local stress field controls fault orientations.
Smoking and outcomes following personalized antiplatelet therapy in chronic coronary syndrome patients: A substudy from the randomized PATH‐PCI trial

Abstract Background This is a sub‐analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH‐PCI) trial in China to explore the relationship between smoking and outcomes following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). Methods As a single‐center, prospective, randomized controlled and open‐label trial, the PATH‐PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180‐day follow‐up evaluation. The primary endpoint was the net adverse clinical events (NACE). Results Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval [CI]: 0.595−3.559, p = .412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530−2.842, p = .632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290−0.908, p = .022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p > .05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277−0.849, p = .011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178−0.752, p = .006), respectively. When testing p‐values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (p int‐NACE = .184, p int‐bleeding = .660). Conclusion Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk.
GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice

In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as receptor for the growth differentiation factor 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in the mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction of food intake and body weight. GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.
Sociodemographic inequalities of suicide: A population-based cohort study of adults in England and Wales 2011-2021

Background: Risk of suicide is complex and often a result of multiple interacting factors. It is vital research identifies predictors of suicide to provide a strong evidence base for targeted interventions. Methods: Using linked Census and population level mortality data we estimated rates of suicide across different groups in England and Wales and examine which factors are independently associated with the risk of suicide. Findings: The highest rates of suicide were amongst those who reported an impairment affecting their day-to-day activities, those who were long term unemployed or never had worked, or those who were single or separated. Rates of suicide were highest in the White and Mixed/multiple ethnic groups compared to other ethnicities, and in people who reported a religious affiliation compared with those who had no religion. Comparison of minimally adjusted models (predictor, sex and age) with fully-adjusted models (sex, age, ethnicity, region, partnership status, religious affiliation, day-to-day impairments, armed forces membership and socioeconomic status) identified key predictors which remain important risk factors after accounting for other characteristics; day-to-day impairments were still found to increase the incidence of suicide relative to those whose activities were not impaired after adjusting for employment status. Overall, rates of suicide were higher in men compared to females across all ages, with the highest rates in 40-to-50-year-olds. Interpretation: The findings of this work provide novel population level insights into the risk of suicide by sociodemographic characteristics. Understanding the interaction between key risk factors for suicide has important implications for national suicide prevention strategies.
Pilot feasibility and efficacy of a strategy to sustain A1C improvement among diverse adults with type 2 diabetes completing a diabetes care management program

Introduction Evidence-based strategies are needed to sustain improvements in outcomes following diabetes care management (DCM) programs. We examined the impact of Boot Camp-Plus (BC-Plus), an innovative sustaining strategy, on A1C among adults with type 2 diabetes completing a 3-month Diabetes Boot Camp (DBC). This health system sponsored program consisted of diabetes self-management education and support, medical nutrition therapy and antihyperglycemic medications management. Research design and methods From March 2019 to July 2021, adult DBC completers with Medicare or a health system Medicaid or employee commercial plan were enrolled in BC-Plus for 9 months. DBC completers not meeting insurance eligibility or who declined to participate in BC-Plus acted as controls. During the first 3 months, BC-Plus participants received ongoing daily remote blood glucose (BG) monitoring; and during all 9 months, they received monthly check-in calls with BG review by a medical assistant who addressed needs for supplies/drugs, whether participants were checking BGs, and self-care encouragement. Escalation to a nurse practitioner occurred if the monthly BG trend was >200 mg/dL and/or several BG <80 mg/dL and/or new A1C >9.0% were identified. A1C was followed for an additional 9 months post-BC-Plus. A longitudinal mixed effects analysis was used to assess change in A1C from month 0 to month 21 of follow-up between BC-Plus participants versus controls. Results A total of 838 DCM completers were identified, among whom 281 joined the BC-Plus intervention and 557 acted as controls. Mean age was 55.9 years; 58.2% were women; 66.2% were black; and 30.6% insured by Medicare. BC-Plus participants experienced significantly lower A1C compared with controls and remained below 8.0% to month 18. Conclusions Among completers of a 3-month DCM program, a low intensity 9-month sustaining strategy maintained A1C under 8.0% (HEDIS (Healthcare Effectiveness Data and Information Set) threshold for diabetes control) compared with controls for 15 months after completion of the initial DCM intervention.
Effects of 460 MHz microwave radiation on Drosophila embryos under raised temperature

Combined effect of 460-MHz microwave irradiation and increased (up to 40 degrees C) temperature on Drosophila embryos of definite age was studied. It was demonstrated that the effect of 5-min exposures to non-modulated microwaves with 6 W/kg SAR accompanied with heating is only a little stronger than at normal temperature (24.5 degrees C). Irradiation with pulse-modulated microwaves with pulse repetition rates of 6, 10, 16, and 22 p.p.s. with average SAR of 0.12 W/kg (pulsed SAR 3 W/kg) combined with increased temperature caused some changes in PID dependent on the pulse rate. At 6 and 22 p.p.s, the increase in PID was close to that observed at normal temperature while at 10 and 16 p.p.s. the microwave irradiation did not produce any noticeable effect on development of the Drosophilas.
Exploring Ecological Wisdom of Traditional Human Settlements in a World Cultural Heritage Area: A Case Study of Dujiangyan Irrigation Area, Sichuan Province, China

Since the industrial revolution, the relationship between human and nature has not improved in line with technological and social innovations. In this paper, Dujiangyan irrigation area in the Chengdu Plain is selected as study subject. Historical comparative method is adopted to study the evolvement rule of ecological wisdom of human settlements. The results indicate that natural processes played a crucial role in determining human settlements in Dujiangyan irrigation area. Relationship between human and nature in these four phases reflects the transition from submission to nature through respect for nature, reconstruction of nature, and finally to the conquest of nature, respectively in the pre-construction period, original construction period, development period and modern period. The wisdom of the harmonious coexistence between social and natural systems has been revealed from the five aspects of the holistic view of Dao-Sheng-Wan-Wu (everything from the Tao), the practice view of Dao-Fa-Zi-Ran (following nature’s lead), the social view of sharing benefits across, the ethical view of Tao controls technology, and the good governance view of spontaneous order. Lastly, this paper points out several principles of landscape and urban planning in the presence of deep urban sustainability challenges: Coevolution of natural and social systems would help promote sustainability of human settlements; nature-guided human settlement practice can maintain various healthy life-support systems; maintain or reconstruct healthy natural process through planning practice; modular units should be constructed through integrating environmental management units with planned unit development; selfgovernance organizations could be fostered likely based on modular units; and finally but not lastly, some technology application should be subject to restriction of environmental ethics. 关键词: 世界文化遗产区;人类聚居;生态智慧;协同进化;都江堰灌区
Cognitive modeling of the Mnemonic Similarity Task as a digital biomarker for Alzheimer’s Disease

AD related pathologies, such as beta-amyloid (Aβ) and phosphorylated tau (pTau), are evident decades before any noticeable decline in memory occurs. Identifying individuals during this asymptomatic phase is crucial for timely intervention. The Mnemonic Similarity Task (MST), a modified recognition memory task, is especially relevant for early AD screening, as it assesses hippocampal integrity, a region affected (both directly and indirectly) early in the progression of the disease. Further, strong inferences on the underlying cognitive mechanisms that support performance on this task can be made using Bayesian cognitive modeling. We assessed whether analyzing MST performance using a cognitive model could detect subtle changes in cognitive function and AD biomarker status prior to overt cognitive decline. We analyzed MST data from >200 individuals (young, cognitively healthy older adults, and individuals with MCI), a subset of which also had existing CSF Aβ and pTau data. Traditional performance scores and cognitive modeling using multinomial processing trees was applied to each participants MST data using Bayesian approaches. We assessed how well each could predict age group, memory ability, MCI status, Aβ/pTau status using ROC analyses. Both approaches predicted age group membership equally, but cognitive modeling approaches exceeded traditional metrics in all other comparisons. This work establishes that cognitive modeling of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for both screening and monitoring older adults during the asymptomatic phase of AD.
A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers

Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of ‘OPM-MEG’ systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG – the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.
Understanding the complex interplay between tau, amyloid and the network in the spatiotemporal progression of Alzheimer’s Disease

It is well known that Aβ and tau proteins are deposited stereotypically in brain regions to cause Alzheimer’s disease. The interaction of amyloid and tau in neurodegenerative diseases is a central feature and key to understanding AD pathophysiology. However their mechanisms are controversial, and many aspects do not fit current theories that rely on cell-autonomous factors. While cell culture and animal studies point to various interaction mechanisms between amyloid and tau, their causal direction and mode (local, remote or network-mediated) remain unknown in human subjects. Further, cross-protein interaction is yet to be reconciled with canonical observations that the two species do not co-localize significantly either in space or in time, and do not target the same neuronal populations. To answer these questions quantitatively, in this study we employed a mathematical reaction-diffusion model encoding the biophysical mechanisms underlying self-assembly, trans-neuronal network propagation and enzymtic cross-species coupling of amyloid and tau. We first established that the spatiotemporal evolution of theoretical tau and Aβ correctly predicts empirical patterns of regional Aβ, tau and atrophy. Remarkably, the introduction of a 1-way Aβ→tau interaction was critical to the models’ success. In comparison, both the non-interacting and the 2-way interaction models were significantly worse. We also found that network-mediated spread is essential; alternative modes of spread involving proximity or fiber length fare much worse. This mathematical exposition of the “pas de deux” of co-evolving proteins provides crucial quantitative and whole-brain support to the concept of amyloid-facilitated-tauopathy rather than the classic amyloid-cascade or pure-tau hypotheses, and helps explain certain known but poorly understood aspects of AD.
Pharmacological inhibition of macrophage triglyceride biosynthesis pathways does not improve Mycobacterium tuberculosis control in infected mice

Triglyceride rich macrophages (foam cells) are a hallmark of necrotic granulomas in tuberculosis, and multiple antimicrobial functions are down-regulated in these cells. In this study, we assessed the ability of two different compounds to reduce triglyceride content and intracellular burden in Mycobacterium tuberculosis (Mtb)-infected macrophages: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1, an enzyme involved in triglyceride synthesis; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase, a serine/threonine kinase involved in mTORC-1dependent lipid biogenesis. Additionally, we evaluated the adjunctive activity of these inhibitors as host-directed therapies against chronic Mtb infection in C3HeB/FeJ mice. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected human monocyte-derived macrophages. In Mtb-infected mice, each inhibitor reduced the triglyceride content (P≤ 0.0001) in cells from bronchoalveolar lavage samples. Adjunctive treatment of DGATi with isoniazid and p70S6Ki monotherapy reduced the lipid droplet content (P≤ 0.05) within lung macrophages of Mtb-infected mice. However, neither inhibitor reduced the lung bacterial burden in Mtb-infected mice alone or in combination with isoniazid, and they did not alter lung inflammation. These findings provide further insights into the role of foam cells in tuberculosis pathogenesis and the utility of interventions targeting these cell populations as adjunctive host-directed therapies.
Developmental pyrethroid exposure disrupts molecular pathways for MAP kinase and circadian rhythms in mouse brain

Neurodevelopmental disorders (NDDs) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDDs, including attention deficit hyperactivity disorder (ADHD), is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used an integrated multiomics approach to determine the broadest possible set of biological changes in the mouse brain caused by developmental pyrethroid exposure (DPE). Using a litter-based, split-sample design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood, euthanized them, and pulverized and divided whole brain samples for split-sample transcriptomics, kinomics and multiomics integration. Transcriptome analysis revealed alterations to multiple canonical clock genes, and kinome analysis revealed changes in the activity of multiple kinases involved in synaptic plasticity, including the mitogen-activated protein (MAP) kinase ERK. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascades, regulation of apoptosis, and synaptic function. These results demonstrate that DPE causes a multi-modal biophenotype in the brain relevant to ADHD and identifies new potential mechanisms of action. NEW & NOTEWORTHY Here, we provide the first evidence that low-dose developmental exposure to the pyrethroid pesticide, deltamethrin, results in molecular disruptions in the adult mouse brain in pathways regulating circadian rhythms and neuronal growth (MAP kinase). This same exposure causes a neurodevelopmental disorder (NDD) relevant behavioral changes in adult mice, making these findings relevant to the prevention of NDDs.