Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent Auditory Nerve Encoding Deficits Between Two Common Etiologies of Sensorineural Hearing Loss

Speech intelligibility can vary dramatically between individuals with similar clinically defined severity of hearing loss based on the audiogram. These perceptual differences, despite equal audiometric-threshold elevation, are often assumed to reflect central-processing variations. Here, we compared peripheral-processing in auditory nerve (AN) fibers of male chinchillas between two prevalent hearing loss etiologies: metabolic hearing loss (MHL) and noise-induced hearing loss (NIHL). MHL results from age-related reduction of the endocochlear potential due to atrophy of the stria vascularis. MHL in the present study was induced using furosemide, which provides a validated model of age-related MHL in young animals by reversibly inhibiting the endocochlear potential. Effects of MHL on peripheral processing were assessed using Wiener–kernel (system identification) analyses of single AN fiber responses to broadband noise, for direct comparison to previously published AN responses from animals with NIHL. Wiener–kernel analyses show that even mild NIHL causes grossly abnormal coding of low-frequency stimulus components. In contrast, for MHL the same abnormal coding was only observed with moderate to severe loss. For equal sensitivity loss, coding impairment was substantially less severe with MHL than with NIHL, probably due to greater preservation of the tip-to-tail ratio of cochlear frequency tuning with MHL compared with NIHL rather than different intrinsic AN properties. Differences in peripheral neural coding between these two pathologies—the more severe of which, NIHL, is preventable—likely contribute to individual speech perception differences. Our results underscore the need to minimize noise overexposure and for strategies to personalize diagnosis and treatment for individuals with sensorineural hearing loss. SIGNIFICANCE STATEMENT Differences in speech perception ability between individuals with similar clinically defined severity of hearing loss are often assumed to reflect central neural-processing differences. Here, we demonstrate for the first time that peripheral neural processing of complex sounds differs dramatically between the two most common etiologies of hearing loss. Greater processing impairment with noise-induced compared with an age-related (metabolic) hearing loss etiology may explain heightened speech perception difficulties in people overexposed to loud environments. These results highlight the need for public policies to prevent noise-induced hearing loss, an entirely avoidable hearing loss etiology, and for personalized strategies to diagnose and treat sensorineural hearing loss.
A 122 fps, 1 MHz Bandwidth Multi-Frequency Wearable EIT Belt Featuring Novel Active Electrode Architecture for Neonatal Thorax Vital Sign Monitoring

A highly integrated, wearable electrical impedance tomography (EIT) belt for neonatal thorax vital multiple sign monitoring is presented. The belt has 16 active electrodes. Each electrode has an application-specific integrated circuit (ASIC) connected to it. The ASIC contains a fully differential current driver, a high-performance instrumentation amplifier, a digital controller, and multiplexors. The belt features a new active electrode architecture that allows programmable flexible electrode current drive and voltage sense patterns under simple digital control. It provides intimate connections to the electrodes for the current drive and to the IA for direct differential voltage measurement, providing superior common-mode rejection ratio. The ASIC was designed in a CMOS 0.35-μm high-voltage technology. The high-specification EIT belt has an image frame rate of 122 fps, a wide operating bandwidth of 1 MHz, and multi-frequency operation. It measures impedance with 98% accuracy and has less than 0.5 Ω and 1° variation across all possible channels. The image results confirmed the advantage of the new active electrode architecture and the benefit of wideband, multi-frequency EIT operation. The system successfully captured high-quality lung-respiration EIT images, breathing cycle, and heart rate. It can also provide boundary-shape information by using an array of MEMS sensors interfaced to the ASICs.
Segmental neurofibromatosis 1 with gonosomal mosaicism

A man in his forties presented with multiple cutaneous nodules on his left flank that had been present for more than 20 years. Family history was notable for neurofibromatosis 1 (NF1) in his 21-year-old daughter who has caf e au lait macules (CALM) and axillary freckling. There are no other affected family members, including his wife and two other children. Physical examination revealed approximately 20 soft, flesh-colored papulonodules on the left flank (Fig. 1). There were no axillary or inguinal freckles, CALM, or Lisch nodules. The patient did not have any neurological deficits or symptoms. Previous biopsy of the patient’s papulonodules showed a diffuse proliferation of spindle cells and scattered mast cells within a fibrillary matrix consistent with neurofibroma (Fig. 2). Given the constellation of findings, he was diagnosed with segmental NF1 (SNF1), which is characterized by cutaneous features of NF1 (CALM and/or neurofibromas), limited to one body segment. He had no evidence of plexiform disease or systemic complications, and was scheduled for follow-up with dermatology and ophthalmology for surveillance. The occurrence of one daughter with classical NF1 and two unaffected children in this patient with SNF1 is consistent with gonosomal mosaicism. Genetic counseling was offered and deferred as the patient and his spouse have no future plans to conceive. NF1 is an autosomal dominant disorder resulting from germline mutations in neurofibromin, NF1. SNF1 is a rare form of NF1 that is regionally limited and can present with CALM and/or neurofibromas, or plexiform neurofibromas alone. The distribution is usually unilateral but can be bilateral. SNF1 is generally thought to occur due to postzygotic mutations in NF1, resulting in somatic mosaicism, without affecting the germline. By contrast, mutations arising during very early stages of embryonic development can cause mosaicism in both somatic cells and germ cells (gonosomal mosaicism). Gonosomal mosaicism, while rare, has been previously reported with SNF1 and is important to recognize as NF1 is among the most common tumor-prone autosomal dominant diseases. Moreover, though NF1 can arise from de novo sporadic mutations, almost half of the cases arise from inherited germline mutations. Therefore, clinicians should be aware in order to facilitate genetic counseling in individuals with SNF1 about the risk of NF1 in their offspring. Lastly, genetic counseling should extend to instances of eggor sperm-donor pregnancies, where gonosomal mosaicism in donor cells has been reported to result in offspring affected by classical NF1.
The Effects of the Dietary and Nutrient Intake on Gynecologic Cancers

The contribution of diet to cancer risk has been considered to be higher in advanced countries than in developing countries. In this paper, I review the current issues (a review of the relevant literature), and the effects of the dietary and nutrient intake on three types of gynecologic cancer (cervical, endometrial and ovarian cancers). In cervical cancer, the most important roles of diet/nutrition in relation to cancer are prophylaxis and countermeasures against human papillomavirus (HPV) infection. The main preventive and reductive factors of cervical cancer are antioxidants, such as vitamin A, C, D and E, carotenoids, vegetables and fruits. These antioxidants may have different abilities to intervene in the natural history of diseases associated with HPV infection. For endometrial cancer, the increase in peripheral estrogens as a result of the aromatization of androgens to estrogens in adipose tissue in obese women and insulin resistance are risk factors. Thus, we must mainly take care to avoid the continuous intake of fat energy and sugar. In ovarian cancer, the etiology has not been fully understood. To the best of our knowledge, the long-term consumption of pro-inflammatory foods, including saturated fat, carbohydrates and animal proteins is a risk factor. The intake of acrylamide is also a risk factor for both endometrial and ovarian cancer. Most papers have been epidemiological studies. Thus, further research using in vitro and in vivo approaches is needed to clarify the effects of the dietary and nutrient intake in detail.
Structural and Functional Analyses of an Allosteric EYA2 Phosphatase Inhibitor That Has On-Target Effects in Human Lung Cancer Cells

EYA proteins (EYA1-4) are critical developmental transcriptional cofactors that contain an EYA domain (ED) harboring Tyr phosphatase activity. EYA proteins are largely downregulated after embryogenesis but are reexpressed in cancers, and their Tyr phosphatase activity plays an important role in the DNA damage response and tumor progression. We previously identified a class of small-molecule allosteric inhibitors that specifically inhibit the Tyr phosphatase activity of EYA2. Herein, we determined the crystal structure of the EYA2 ED in complex with NCGC00249987 (a representative compound in this class), revealing that it binds to an induced pocket distant from the active site. NCGC00249987 binding leads to a conformational change of the active site that is unfavorable for Mg2+ binding, thereby inhibiting EYA2′s Tyr phosphatase activity. We demonstrate, using genetic mutations, that migration, invadopodia formation, and invasion of lung adenocarcinoma cells are dependent on EYA2 Tyr phosphatase activity, whereas growth and survival are not. Further, we demonstrate that NCGC00249987 specifically targets migration, invadopodia formation, and invasion of lung cancer cells, but that it does not inhibit cell growth or survival. The compound has no effect on lung cancer cells carrying an EYA2 F290Y mutant that abolishes compound binding, indicating that NCGC00249987 is on target in lung cancer cells. These data suggest that the NCGC00249987 allosteric inhibitor can be used as a chemical probe to study the function of the EYA2 Tyr phosphatase activity in cells and may have the potential to be developed into an antimetastatic agent for cancers reliant on EYA2′s Tyr phosphatase activity.
Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.
Design of Suboptimal Local Piecewise Fuzzy Controller With Multiple Constraints for Quasi-Linear Spatiotemporal Dynamic Systems

This paper discusses the problem of suboptimal local piecewise <inline-formula> <tex-math notation="LaTeX">${H} _{\infty }$ </tex-math></inline-formula> fuzzy control of quasi-linear spatiotemporal dynamic systems with control magnitude constraints. A Takagi–Sugeno fuzzy partial differential equation (PDE) model with space-varying coefficient matrices is first assumed to be derived for exactly describing nonlinear system dynamics. In the light of the fuzzy model, a local piecewise fuzzy feedback controller is then constructed to guarantee the exponential stability with a prescribed <inline-formula> <tex-math notation="LaTeX">${H} _{\infty }$ </tex-math></inline-formula> disturbance attenuation level for the resulting closed-loop system, while the control constraints are also ensured. A sufficient condition on the existence of such fuzzy controller is developed by the Lyapunov direct method and an integral inequality and presented in terms of space algebraic linear matrix inequalities (LMIs) coupled with LMIs. By virtue of extreme value theorem, a suboptimal-constrained local piecewise <inline-formula> <tex-math notation="LaTeX">${H} _{\infty }$ </tex-math></inline-formula> fuzzy control design in the sense of minimizing the disturbance attenuation level is formulated as a minimization optimization problem with LMI constraints. Finally, the proposed method is applied to solve the feedback control of a quasi-linear FitzHugh–Nagumo equation with space-varying coefficients, and simulation results show its effectiveness and merit.
Cell Death Induced by Cationic Amphiphilic Drugs Depends on Lysosomal Ca2+ Release and Cyclic AMP

Repurposing cationic amphiphilic drugs (CAD) for cancer treatment is emerging as an attractive means to enhance the efficacy of chemotherapy. Many commonly used CADs, including several cation amphiphilic antihistamines and antidepressants, induce cancer-specific, lysosome-dependent cell death and sensitize cancer cells to chemotherapy. CAD-induced inhibition of lysosomal acid sphingomyelinase is necessary, but not sufficient, for the subsequent lysosomal membrane permeabilization and cell death, while other pathways regulating this cell death pathway are largely unknown. Prompted by significant changes in the expression of genes involved in Ca2+ and cyclic AMP (cAMP) signaling pathways in CAD-resistant MCF7 breast cancer cells, we identified here an early lysosomal Ca2+ release through P2X purinergic receptor 4 (P2RX4) and subsequent Ca2+- and adenylyl cyclase 1 (ADCY1)-dependent synthesis of cAMP as a signaling route mediating CAD-induced lysosomal membrane permeabilization and cell death. Importantly, pharmacologic and genetic means to increase cellular cAMP levels either by activating cAMP-inducing G-protein–coupled receptors (GPR3 or β2 adrenergic receptor) or ADCY1, or by inhibiting cAMP-reducing guanine nucleotide-binding protein G(i) subunit α2, C-X-C motif chemokine receptor type 4, or cAMP phosphodiesterases, sensitized cancer cells to CADs. These data reveal a previously unrecognized lysosomal P2RX4- and ADCY1-dependent signaling cascade as a pathway essential for CAD-induced lysosome-dependent cell death and encourage further investigations to find the most potent combinations of CADs and cAMP-inducing drugs for cancer therapy.
Principles and Issues for Physical Frailty Measurement and its Clinical Application.

INTRODUCTION "Frailty" has attracted attention for its promise of identifying vulnerable older adults, hence its potential use to better tailor geriatric health care. There remains substantial controversy, however, regarding its nature and ascertainment. Recent years have seen a proliferation of frailty assessment methods. We argue that the development of frailty assessments should be grounded in "validation"-the process of substantiating that a measurement accurately and precisely measures what it intends, identify unresolved measurement issues, and highlight measurement-related considerations for clinical practice. METHODS Principles for validating frailty measures are elucidated. We follow principles-articulated, for example, by Borsboom-in which a construct must be clearly defined and then analyses undertaken to substantiate that a measurement accurately and precisely measures what it intends. Key elements are content validity, criterion validity, and construct validity, with an emphasis on the latter. RESULTS We illustrate the principles for a physical frailty phenotype construct. CONCLUSIONS Unresolved conceptual issues include the roles of intersecting concepts such as cognition, disease severity, and disability in frailty measurement, conceptualization of frailty as a state versus a continuum, and the potential need for dynamic measures and systems concepts in furthering understanding of frailty. Clinical considerations include needs to distinguish interventions designed to address frailty "symptoms" versus underlying physiology, improve "pre-frailty" measures intended to screen individuals early in their frailty progression, address feasibility demands, and further visioning followed by rigorous efficacy research to address the landscape of potential uses of frailty assessment in clinical practice.
A meta-analysis of the possible behavioural and biological variables linking trait emotional intelligence to health

ABSTRACT Trait Emotional Intelligence (trait EI) is a constellation of correlated emotion-related traits that capture an individual’s typical way of processing emotion-related information and reacting in emotional situations. Numerous studies have shown that trait EI is a significant predictor of both subjective and objective health. This correlational meta-analysis (k = 106, N = 45,262) aims to explore the behavioural and biological variables that could account for these effects. It also aims to provide a roadmap for future research by identifying what should be studied (pinpointing dead-end roads and promising paths) and how (methodological improvements needed to draw stronger conclusions). The results revealed large associations of trait EI with social support, sleep quality, and hypothalamic–pituitary–adrenal axis activity in challenging situations as well as medium associations with dietary habits, physical activity, and substance use. Other candidate pathways have given rise to much less research. Based on both theoretical predictions and preliminary findings, the paper categorises these pathways as promising or not promising. Future research would benefit from using more diverse samples, measuring behavioural variables more objectively, controlling for personality, and systematically examining to what extent changes in EI (e.g., following training) lead to changes in behaviours and/or biological parameters.
The Effect of Substrate Biasing during DC Magnetron Sputtering on the Quality of VO2 Thin Films and Their Insulator–Metal Transition Behavior

In this work, VO2 thin films were deposited on Si wafers (onto (100) surface) by DC magnetron sputtering under different cathode bias voltages. The effects of substrate biasing on the structural and optical properties were investigated. The results show that the metal–insulator transition (MIT) temperature of VO2 thin films can be increased up to 14 K by applying a cathode bias voltage, compared to deposition conditions without any bias. The decrease in the transition efficiency and increase in the transition temperature are attributed to the enlarged grain size, increased defects, and the residual stress in the VO2 thin films induced by biasing. The optical transmittance measurements for different thickness films indicate an attenuation coefficient of 3.1 × 107 m−1 at 2000 nm or an extinction coefficient of 4.9 in the metal phase. The optical transmittance vs wavelength characteristics point to an indirect bandgap of 0.6 ± 0.5 eV and significant scattering in the bulk and/or at the interface.
Improved Value for the Gamow-Teller Strength of the ^{100}Sn Beta Decay.

A record number of ^{100}Sn nuclei was detected and new isotopic species toward the proton dripline were discovered at the RIKEN Nishina Center. Decay spectroscopy was performed with the high-efficiency detector arrays WAS3ABi and EURICA. Both the half-life and the β-decay end point energy of ^{100}Sn were measured more precisely than the literature values. The value and the uncertainty of the resulting strength for the pure 0^{+}→1^{+} Gamow-Teller decay was improved to B_{GT}=4. 4_{-0.7}^{+0.9}. A discrimination between different model calculations was possible for the first time, and the level scheme of ^{100}In is investigated further.
Neuropsychological impact of white matter hyperintensities in older adults without dementia

Abstract The purpose of this study was to determine (a) if simple clinical judgements of white matter hyperintensities (WMH) on imaging are associated with measurable cognitive impacts in otherwise cognitively normal older adults, (b) if neuropsychological measures can predict those with WMH, and (c) the frequency of low cognitive scores in those with WMH on a battery of measures. Forty-four individuals judged free of other cognitive disorders despite moderate to extensive WMH were compared with 50 individuals matched on age (mean of 83), education (college educated), and gender (predominantly female). Data was obtained from the National Alzheimer’s Coordinating Center database. The group with at least moderate WMH had lower scores on the Trail Making Test A, verbal fluency, and digit span. A component score derived from these measures was a significant predictor of the presence of WMH, though only correctly classified 68% of participants. Even in individuals free from other suspected conditions, clinically judged moderate to extensive WMH was associated with cognitive weaknesses for processing speed, working memory, and executive functioning. This shows that a relatively simple judgment of WMH burden is meaningfully associated with worse cognition. Implications and future directions for are discussed.
Comparing model‐based cerebrovascular physiomarkers with DTI biomarkers in MCI patients

To compare the novel model‐based hemodynamic physiomarker of Dynamic Vasomotor Reactivity (DVR) with biomarkers based on Diffusion Tensor Imaging (DTI) and some widely used neurocognitive scores in terms of their ability to delineate patients with amnestic Mild Cognitive Impairment (MCI) from age‐matched cognitively normal controls.