Miracle-dz/UniFAR-FTUs huggingface dataset:
The Delayed Neuropathological Consequences of Traumatic Brain Injury in a Community-Based Sample

The late neuropathological effects of traumatic brain injury have yet to be fully elucidated, particularly with respect to community-based cohorts. To contribute to this critical gap in knowledge, we designed a multimodal neuropathological study, integrating traditional and quantitative approaches to detect pathologic changes in 532 consecutive brain autopsies from participants in the Adult Changes in Thought (ACT) study. Diagnostic evaluation including assessment for chronic traumatic encephalopathy (CTE) and quantitative immunoassay-based methods were deployed to examine levels of pathological (hyperphosphorylated) tau (pTau) and amyloid (A) β in brains from ACT participants with (n = 107) and without (n = 425) history of remote TBI with loss of consciousness (w/LOC). Further neuropathological assessments included immunohistochemistry for α-synuclein and phospho-TDP-43 pathology and astro- (GFAP) and micro- (Iba1) gliosis, mass spectrometry analysis of free radical injury, and gene expression evaluation (RNA sequencing) in a smaller sub-cohort of matched samples (49 cases with TBI and 49 non-exposed matched controls). Out of 532 cases, only 3 (0.6%–none with TBI w/LOC history) showed evidence of the neuropathologic signature of chronic traumatic encephalopathy (CTE). Across the entire cohort, the levels of pTau and Aβ showed expected differences for brain region (higher levels in temporal cortex), neuropathological diagnosis (higher in participants with Alzheimer's disease), and APOE genotype (higher in participants with one or more APOE ε4 allele). However, no differences in PHF-tau or Aβ1−42 were identified by Histelide with respect to the history of TBI w/LOC. In a subset of TBI cases with more carefully matched control samples and more extensive analysis, those with TBI w/LOC history had higher levels of hippocampal pTau but no significant differences in Aβ, α-synuclein, pTDP-43, GFAP, Iba1, or free radical injury. RNA-sequencing also did not reveal significant gene expression associated with any measure of TBI exposure. Combined, these findings suggest long term neuropathological changes associated with TBI w/LOC may be subtle, involve non-traditional pathways of neurotoxicity and neurodegeneration, and/or differ from those in autopsy cohorts specifically selected for neurotrauma exposure.
Treatment of Traumatised Sexuality

Based on therapeutic meetings with individuals who have experienced sexual violence and abuse, the challenge is how do we help these couples to establish sexual relationships on their own terms, without interference of defence or coping strategies they have used to protect themselves against the overwhelming experiences of violence or abuse in the past? This article will focus on therapeutic work with such couples and how to interact with them and support their efforts to establish satisfying sexual relationships, based on sexological experience as well as experience from work with traumatisation. The basis for our treatment is a modified version of William Masters and Virginia Johnson’s approach. The technique of sensate focus is central, modified by trauma theory, including the understanding of dissociation, and the need to integrate memories from different levels: somatic, emotional, and cognitive. The traumatised client needs special attention to the experiences of predictability and safety and respect due to their history of being transgressed against. The therapists must be aware of the issue of dissociation; different dissociated inner parts can play different roles in the interaction between client and therapist. While couples therapy is a necessary frame for this therapy, the therapist often needs to work with issues unique to each individual. Each partner must be able to identify their own responses and their own sexual needs and preferences. It may therefore be valuable to have a co-therapist. The central goal is for the clients to identify responses to stimulation as a here and now experience in a setting that feels safe and welcome.
The Role of Mitonuclear Incompatibility in Bipolar Disorder Susceptibility and Resilience Against Environmental Stressors

It has been postulated that mitochondrial dysfunction has a significant role in the underlying pathophysiology of bipolar disorder (BD). Mitochondrial functioning plays an important role in regulating synaptic transmission, brain function, and cognition. Neuronal activity is energy dependent and neurons are particularly sensitive to changes in bioenergetic fluctuations, suggesting that mitochondria regulate fundamental aspects of brain function. Vigorous evidence supports the role of mitochondrial dysfunction in the etiology of BD, including dysregulated oxidative phosphorylation, general decrease of energy, altered brain bioenergetics, co-morbidity with mitochondrial disorders, and association with genetic variants in mitochondrial DNA (mtDNA) or nuclear-encoded mitochondrial genes. Despite these advances, the underlying etiology of mitochondrial dysfunction in BD is unclear. A plausible evolutionary explanation is that mitochondrial-nuclear (mitonuclear) incompatibility leads to a desynchronization of machinery required for efficient electron transport and cellular energy production. Approximately 1,200 genes, encoded from both nuclear and mitochondrial genomes, are essential for mitochondrial function. Studies suggest that mitochondrial and nuclear genomes co-evolve, and the coordinated expression of these interacting gene products are essential for optimal organism function. Incompatibilities between mtDNA and nuclear-encoded mitochondrial genes results in inefficiency in electron flow down the respiratory chain, differential oxidative phosphorylation efficiency, increased release of free radicals, altered intracellular Ca2+ signaling, and reduction of catalytic sites and ATP production. This review explores the role of mitonuclear incompatibility in BD susceptibility and resilience against environmental stressors.
Biochanin A Attenuates Ovariectomy-Induced Cognition Deficit via Antioxidant Effects in Female Rats

Background: Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer’s disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated. Methods: All the rats except for the sham group underwent the resection of bilateral ovaries. Seven days after the OVX surgery, rats were randomly divided into six groups: sham, OVX, OVX + BCA (5 mg/kg), OVX + BCA (20 mg/kg), OVX + BCA (60 mg/kg), and OVX + estradiol (E2; 0.35 mg/kg), which were administrated daily by gavage for 12 weeks. Learning and memory were examined using the Morris water-maze test before the end of the experiment. Morphological changes of the rat hippocampus were observed by HE staining and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the hippocampus were measured. The effect of BCA on cell viability was measured in the presence of hydrogen peroxide (H2O2) using CCK8. Flow cytometry was used to measure neuronal apoptosis and reactive oxygen species (ROS) induced by H2O2. Expression of Bcl-2, Bax, and Caspase-3 was determined by Western blotting using hippocampal tissues and primary cultures of hippocampal neurons. Results: Chronic treatment with BCA mimicked the ability of E2 to reverse the deficit of learning and memory in the Morris water-maze test in OVX rats. BCA normalized OVX-induced morphological changes as revealed by HE staining and electron microscopy. In addition, BCA significantly decreased the levels of MDA, the biomarker of oxidative damage, and increased the activity of the intracellular antioxidant enzymes SOD and GSH-Px in OVX rats. Further, in primary cultures of hippocampal neurons, BCA reversed H2O2-induced decreases in cell viability and accumulation of ROS. Finally, BCA reversed OVX- or H2O2-induced increases in Bax and Caspase-3 and decreases in Bcl-2 in the hippocampus and primary cultures of hippocampal neurons. Conclusion: These results suggest that BCA improves memory through its neuroprotective properties in the brain under the circumstance of estrogen deficiency and can be used for treatment of memory loss in postmenopausal women.
The Aesthetics of Encounter: A Relational-Performative Design Approach to Human-Robot Interaction

This article lays out the framework for relational-performative esthetics in human-robot interaction, comprising a theoretical lens and design approach for critical practice-based inquiries into embodied meaning-making in human-robot interaction. I explore the centrality of esthetics as a practice of embodied meaning-making by drawing on my arts-led, performance-based approach to human-robot encounters, as well as other artistic practices. Understanding social agency and meaning as being enacted through the situated dynamics of the interaction, I bring into focus a process of bodying-thinging; entangling and transforming subjects and objects in the encounter and rendering elastic boundaries in-between. Rather than serving to make the strange look more familiar, aesthetics here is about rendering the differences between humans and robots more relational. My notion of a relational-performative design approach—designing with bodying-thinging—proposes that we engage with human-robot encounters from the earliest stages of the robot design. This is where we begin to manifest boundaries that shape meaning-making and the potential for emergence, transformation, and connections arising from intra-bodily resonances (bodying-thinging). I argue that this relational-performative approach opens up new possibilities for how we design robots and how they socially participate in the encounter.
The Role of Neutrophils and Neutrophil Elastase in Pneumococcal Pneumonia

Streptococcus pneumoniae, also known as pneumococcus, is a Gram-positive diplococcus and a major human pathogen. This bacterium is a leading cause of bacterial pneumonia, otitis media, meningitis, and septicemia, and is a major cause of morbidity and mortality worldwide. To date, studies on S. pneumoniae have mainly focused on the role of its virulence factors including toxins, cell surface proteins, and capsules. However, accumulating evidence indicates that in addition to these studies, knowledge of host factors and host-pathogen interactions is essential for understanding the pathogenesis of pneumococcal diseases. Recent studies have demonstrated that neutrophil accumulation, which is generally considered to play a critical role in host defense during bacterial infections, can significantly contribute to lung injury and immune subversion, leading to pneumococcal invasion of the bloodstream. Here, we review bacterial and host factors, focusing on the role of neutrophils and their elastase, which contribute to the progression of pneumococcal pneumonia.
In planta Genome Editing in Commercial Wheat Varieties

Limitations for the application of genome editing technologies on elite wheat (Triticum aestivum L.) varieties are mainly due to the dependency on in vitro culture and regeneration capabilities. Recently, we developed an in planta particle bombardment (iPB) method which has increased process efficiency since no culture steps are required to create stably genome-edited wheat plants. Here, we report the application of the iPB method to commercially relevant Japanese elite wheat varieties. The biolistic delivery of gold particles coated with plasmids expressing CRISPR/Cas9 components designed to target TaQsd1 were bombarded into the embryos of imbibed seeds with their shoot apical meristem (SAM) exposed. Mutations in the target gene were subsequently analyzed within flag leaf tissue by using cleaved amplified polymorphic sequence (CAPS) analysis. A total of 9/358 (2.51%) of the bombarded plants (cv. “Haruyokoi,” spring type) carried mutant alleles in the tissue. Due to the chimeric nature of the T0 plants, only six of them were inherited to the next (T1) generation. Genotypic analysis of the T2 plants revealed a single triple-recessive homozygous mutant of the TaQsd1 gene. Compared to wild type, the homozygous mutant exhibited a 7 days delay in the time required for 50% seed germination. The iPB method was also applied to two elite winter cultivars, “Yumechikara” and “Kitanokaori,” which resulted in successful genome editing at slightly lower efficiencies as compared to “Haruyokoi. ” Taken together, this report demonstrates that the in planta genome editing method through SAM bombardment can be applicable to elite wheat varieties that are otherwise reluctant to callus culture.
The Role of the Interplay Between Autophagy and NLRP3 Inflammasome in Metabolic Disorders

Autophagy is an important and conserved cellular pathway in which cells transmit cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell composition synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome can induce the maturation and secretion of Interleukin-1 beta (IL-1β) and IL-18 by activating caspase-1. It is involved in many diseases. In recent years, the interplay between autophagy and NLRP3 inflammasome has been reported to contribute to many diseases including metabolic disorders related diseases. In this review, we summarized the recent studies on the interplay between autophagy and NLRP3 inflammasome in metabolic disorders to provide ideas for the relevant basic research in the future.
DFT Study of Alkali Metal Atom Adsorption on Defect-Free MgO(001) Surface

The adsorption of isolated alkali metal atoms (Li, Na, K, Rb, and Cs) on defect-free surface of MgO(001) has been systemically investigated with density functional theory using a pseudopotential plane-wave approach. The adsorption energy calculated is about −0.72 eV for the lithium on top of the surface O site and about one third of this value for the other alkali metals. The relatively strong interaction of Li with the surface O can be explained by a more covalent bonding involved, evidenced by results of both the projected density of states and the charge density difference. The bonding mechanism is discussed in detail for all alkali metals.
Construction of Prognostic Risk Prediction Model of Oral Squamous Cell Carcinoma Based on Nine Survival-Associated Metabolic Genes

The aim was to investigate the independent prognostic factors and construct a prognostic risk prediction model to facilitate the formulation of oral squamous cell carcinoma (OSCC) clinical treatment plan. We constructed a prognostic model using univariate COX, Lasso, and multivariate COX regression analysis and conducted statistical analysis. In this study, 195 randomly obtained sample sets were defined as training set, while 390 samples constituted validation set for testing. A prognostic model was constructed using regression analysis based on nine survival-associated metabolic genes, among which PIP5K1B, NAGK, and HADHB significantly down-regulated, while MINPP1, PYGL, AGPAT4, ENTPD1, CA12, and CA9 significantly up-regulated. Statistical analysis used to evaluate the prognostic model showed a significant different between the high and low risk groups and a poor prognosis in the high risk group (P < 0.05) based on the training set. To further clarify, validation sets showed a significant difference between the high-risk group with a worse prognosis and the low-risk group (P < 0.05). Independent prognostic analysis based on the training set and validation set indicated that the risk score was superior as an independent prognostic factor compared to other clinical characteristics. We conducted Gene Set Enrichment Analysis (GSEA) among high-risk and low-risk patients to identify metabolism-related biological pathways. Finally, nomogram incorporating some clinical characteristics and risk score was constructed to predict 1-, 2-, and 3-year survival rates (C-index = 0.7). The proposed nine metabolic gene prognostic model may contribute to a more accurate and individualized prediction for the prognosis of newly diagnosed OSCC patients, and provide advice for clinical treatment and follow-up observations.
Spike Generators and Cell Signaling in the Human Auditory Nerve: An Ultrastructural, Super-Resolution, and Gene Hybridization Study

Background: The human auditory nerve contains 30,000 nerve fibers (NFs) that relay complex speech information to the brain with spectacular acuity. How speech is coded and influenced by various conditions is not known. It is also uncertain whether human nerve signaling involves exclusive proteins and gene manifestations compared with that of other species. Such information is difficult to determine due to the vulnerable, “esoteric,” and encapsulated human ear surrounded by the hardest bone in the body. We collected human inner ear material for nanoscale visualization combining transmission electron microscopy (TEM), super-resolution structured illumination microscopy (SR-SIM), and RNA-scope analysis for the first time. Our aim was to gain information about the molecular instruments in human auditory nerve processing and deviations, and ways to perform electric modeling of prosthetic devices. Material and Methods: Human tissue was collected during trans-cochlear procedures to remove petro-clival meningioma after ethical permission. Cochlear neurons were processed for electron microscopy, confocal microscopy (CM), SR-SIM, and high-sensitive in situ hybridization for labeling single mRNA transcripts to detect ion channel and transporter proteins associated with nerve signal initiation and conductance. Results: Transport proteins and RNA transcripts were localized at the subcellular level. Hemi-nodal proteins were identified beneath the inner hair cells (IHCs). Voltage-gated ion channels (VGICs) were expressed in the spiral ganglion (SG) and axonal initial segments (AISs). Nodes of Ranvier (NR) expressed Nav1.6 proteins, and encoding genes critical for inter-cellular coupling were disclosed. Discussion: Our results suggest that initial spike generators are located beneath the IHCs in humans. The first NRs appear at different places. Additional spike generators and transcellular communication may boost, sharpen, and synchronize afferent signals by cell clusters at different frequency bands. These instruments may be essential for the filtering of complex sounds and may be challenged by various pathological conditions.
Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts

Both canonical and non-canonical Wnt signaling pathway alterations have been documented in pulmonary disease pathogenesis and progression; therefore, they can be an attractive target for pharmaceutical management of severe asthma. Wnt/β-catenin signaling was shown to link early embryonic lung development impairment to later in life asthmatic airway remodeling. Here we explored the changes in Wnt signaling associated with asthma initiation and progression in epithelial and fibroblasts using a comprehensive approach based on in silico analysis and followed by in vitro validation. In summary, the in silico analysis showed that the bronchial epithelium of severe asthmatic patients showed a deranged balance between Wnt enhancer and Wnt inhibitors. A Th2-high phenotype is associated with upregulated Wnt-negative regulators, while inflammatory and neutrophilic severe asthmatics showed higher canonical Wnt signaling member enrichment. Most of these genes are regulators of healthy lung development early in life and, if disturbed, can make people susceptible to developing asthma early in life and prone to developing a severe phenotype. Most of the Wnt members are secreted, and their effect can be in an autocrine fashion on the bronchial epithelium, paracrine on nearby adjacent structural cells like fibroblasts and smooth muscles, or systemic in blood. Our results showed that canonical Wnt signaling is needed for the proper response of cells to proliferative stimuli, which puts cells under stress. Cells in response to this proliferative stress will activate the senescence mechanism, which is also dependent on Wnt signaling. Inhibition of Wnt signaling using FH535 inhibits both proliferation and senescence markers in bronchial fibroblasts compared to DMSO-treated cells. In fibroblasts from asthmatic patients, inhibition of Wnt signaling did not show that effect as the Wnt signaling is deranged besides other pathways that might be non-functional.
The Potential Risk Factors for Mortality in Patients After In-Hospital Cardiac Arrest: A Multicenter Study

Background and Purpose: In-hospital cardiac arrest (IHCA) has high mortality rate, which needs more research. This multi-center study aims to evaluate potential risk factors for mortality in patients after IHCA. Methods: Data for this study retrospectively enrolled IHCA patients from 14 regional hospitals, two district hospitals, and five medical centers between 2013 June and 2018 December. The study enrolled 5,306 patients and there were 2,871 patients in subgroup of intensive care unit (ICU) and emergency room (ER), and 1,894 patients in subgroup of general wards. Results: As for overall IHCA patients, odds ratio (OR) for mortality was higher in older patients (OR = 1.69; 95% CI:1.33–2.14), those treated with ventilator (OR = 1.79; 95% CI:1.36–2.38) and vasoactive agents (OR = 1.88; 95% CI:1.45–2.46). Whereas, better survival was reported in IHCA patients with initial rhythm as ventricular tachycardia (OR = 0.32; 95% CI: 0.21–0.50) and ventricular fibrillation (OR = 0.26; 95% CI: 0.16–0.42). With regard to ICU and ER subgroup, there was no mortality difference among different nursing shifts, whereas for patients in general wards, overnight shift (OR = 1.83; 95% CI: 1.07–3.11) leads to poor outcome. Conclusion: For IHCA patients, old age, receiving ventilator support and vasoactive agents reported poor survival. Overnight shift had poor survival for IHCA patients in general wards, despite no significance in overall and ICU/ER subgroups.
Tectonic Switch From Triassic Contraction to Jurassic-Cretaceous Extension in the Western Tarim Basin, Northwest China: New Insights Into the Evolution of the Paleo-Tethyan Orogenic Belt

We use stratigraphic, sedimentological, and borehole data and seismic profiles from the western Tarim Basin to document its Mesozoic tectonic evolution. A nearly 60-km-wide, Triassic fold-and-thrust belt along the southwestern margin of Tarim Basin is unconformably overlain by a Jurassic-Cretaceous sedimentary sequence along a regional angular unconformity. The Lower-Middle Jurassic strata consist mainly of an upward-fining sequence ranging from terrestrial conglomerates to turbidite deposits, which represent the products of an initial rift stage. Palaeocurrent analyses show that sediments for these rift deposits were derived from the paleo-Kunlun and paleo-Tienshan Mountains to the southwest and northern, respectively. The overlying Upper Jurassic-Cretaceous series consist of coarse-grained, alluvial fan to braided river deposits in the lower stratigraphic member, and lagoonal mudstones and marine carbonates in the upper member. These finer-grained rocks were deposited in a subsiding basin, indicating that a significant change and reorientation in the drainage system should have occurred within the basin during the Early Cretaceous. The western Tarim Basin evolved from a syn-rift stage to a post-rift stage during the Jurassic-Cretaceous. A post-orogenic stretch developed due to the evolution of the Paleo-Tethyan orogenic belt in Central Asia is a likely geodynamic mechanism for this major tectonic switch from a contractional episode in the Triassic to an extensional deformation phase in the Jurassic-Cretaceous.