Miracle-dz/UniFAR-FTUs huggingface dataset:
Usefulness of stress-related hormones as predictors and prognostic factors for idiopathic sudden sensorineural hearing loss

Abstract Background The pathogenesis of Idiopathic sudden sensorineural hearing loss (ISSNHL) is ambiguous. Stress is commonly defined as a cause of the disease. Serum levels of stress-related hormone (cortisol, growth hormone, aldosterone, ADH, ACTH) may be elevated in patients with ISSNHL patients. Objectives We aimed to determine whether psychological factors and stress hormones in patients are associated with the severity of hearing loss and therapeutic outcomes. We hypothesized that the stress hormone level in the disease sequence is a strong prognostic factor of ISSNHL. Additionally, we investigated whether the subjective degree of psychological stress is likely to contribute to the therapeutic prognosis of ISSNHL, as determined using questionnaires. Methods We conducted a prospective study of patients aged between 19 and 65 years admitted for the treatment of ISSNHL at our hospital. All patients underwent pure tone audiometry (PTA) on day 0, day 5 and 2 weeks after discharge. As an objective indicator of stress, we measured the level of HPA axis-related hormones. So, we measured serum cortisol, adrenocorticotropic hormone (ACTH), aldosterone and dehydroepiandrosterone sulfate (DHEAS) levels in the venous blood sample of patients on day 1 and day 5 after admission. In addition, for subjective stress measurements, depression and anxiety levels were assessed using self-reported questionnaires, Beck Depression Inventory (BDI), and Perceived Stress Scale (PSS) in the revised to Korean versions. Results Eighteen patients diagnosed with ISSNHL at the Department of Otorhino-laryngology were enrolled. Serum DHEAS level measured on day 1 showed a statistically significant correlation with the hearing threshold in the hearing test performed at the time of diagnosis (p = .037, correlation coefficients(r) = 0.541). Serum ACTH level was measured on day 1, and patients were classified into normal and elevated groups based on a threshold of 1.5 pg/mL; the normal group had better hearing thresholds in the first and second hearing test than the elevated group (p = .040, 0.015, respectively). In the stress-related questionnaires, the BDI score showed a statistically significant correlation with the last hearing test (p = .015, correlation coefficients(r) = 0.613). Conclusion We demonstrated the possible role of stress-related hormones in the pathogenesis of ISSNHL and suggest that depressive stress response can be a strong predictor of treatment response in patients with ISSNHL. However, the impact of response to stress on the inner ear and endolymph homeostasis remains unknown. Since this is a cross-sectional study, we can only comment on the relationship between stress and ISSNHL, not a causal relationship. Further investigation is necessary to identify the mechanism of interaction between stress and hearing ability in the inner ear.
Pien-Tze-Huang attenuates neuroinflammation in cerebral ischaemia-reperfusion injury in rats through the TLR4/NF-κB/MAPK pathway

Abstract Context Pien-Tze-Huang (PTH) is traditionally applied to treat various inflammation-related diseases including stroke. However, literature regarding the anti-inflammatory effects and possible mechanisms of PTH in ischaemic stroke is unavailable. Objective This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke. Materials and methods Cerebral ischaemia-reperfusion injury was induced through 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in male Sprague-Dawley (SD) rats receiving oral pre-treatment with PTH (180 mg/kg) for 4 days. TLR4 antagonist TAK-242 (3 mg/kg) was injected intraperitoneally at 1.5 h after MCAO. MRI, HE staining, qRT-PCR, western blot, and immunofluorescence methods were employed. Results PTH treatment markedly reduced cerebral infarct volume (by 51%), improved neurological function (by 33%), and ameliorated brain histopathological damage in MCAO rats. It also reduced the levels of four inflammatory mediators including IL-1β (by 70%), IL-6 (by 78%), TNF-α (by 60%) and MCP-1 (by 58%); inhibited microglia and astrocyte activation; and decreased protein expression of iNOS and COX-2 in injured brains. Moreover, PTH down-regulated the protein expressions of TLR4, MyD88, and TRAF6; reduced the expression and nuclear translocation of NF-κB; and lowered the protein expressions of p-ERK1/2, p-JNK, and p-p38. Similar effects were observed in MCAO rats with TAK-242 treatment. However, combined administration of PTH and TAK-242 did not significantly reinforce the anti-inflammatory effects of PTH. Discussion and conclusion PTH improved cerebral ischaemia-reperfusion injury by inhibiting neuroinflammation partly via the TLR4/NF-κB/MAPK signalling pathway, which will help guide its clinical application.
Cerebral Venous Thrombosis.

Copyright © 2021 Massachusetts Medical Society. Cerebral venous thrombosis is an unusual cerebrovascular disorder that is of current interest, in part because of rare cases associated with certain of the coronavirus disease 2019 (Covid-19) vaccines. The characteristics of infarction caused by cerebral venous thrombosis differ from those of the usual forms of ischemic stroke caused by occlusion of arterial vessels. This brief review calls attention to the diagnosis of cerebral venous thrombosis, based on clinical and imaging features, and treatments that have become available since the subject was reviewed in the Journal in 2005.1
Does etiology really matter for epilepsy surgery outcome?

Multiple factors influence the outcomes of epilepsy surgery. Prognostic indicators varying from clinical characteristics, imaging findings, ictal, and interictal electrophysiological activity have been linked to surgical outcomes. In this review, we focus on the relatively under‐studied role of the underlying epilepsy histopathology in driving post‐surgical outcomes, specifically focusing on the broad categories of seizure outcomes and cognitive outcomes. For each of these two outcomes of interest, we answer two questions: 1)‐ does etiology matter? and 2)‐ how could it matter? The goal is to review the existing literature on the relationship between etiology and surgical outcomes to provide the best possible judgment as to whether a causal relationship exists between histopathology and the ultimate surgical outcome as an initial step. Then, we delve into the possible mechanisms via which such relationships can be explained. We conclude with a call to action to the epilepsy surgery and histopathology research community to push the mechanistic understanding of the pathology‐outcome interaction and identify actionable knowledge and biomarkers that could inform patient care in a timely fashion.
Elucidating clinical phenotypic variability associated with the polyT tract and TG repeats in CFTR

Biallelic pathogenic variants in CFTR manifest as cystic fibrosis (CF) or other CFTR‐related disorders (CFTR‐RDs). The 5T allele, causing alternative splicing and reduced protein activity, is modulated by the adjacent TG repeat element, though previous data have been limited to small, selective cohorts. Here, the risk and spectrum of phenotypes associated with the CFTR TG‐T5 haplotype variants (TG11T5, TG12T5, and TG13T5) in the absence of the p.Arg117His variant are evaluated. Individuals who received physician‐ordered next‐generation sequencing of CFTR were included. TG[11‐13]T5 variant frequencies (biallelic or with another CF‐causing variant [CFvar]) were calculated. Clinical information reported by the ordering provider or the individual was examined. Among 548,300 individuals, the T5 minor allele frequency (MAF) was 4.2% (TG repeat distribution: TG11 = 68.1%, TG12 = 29.5%, TG13 = 2.4%). When present with a CFvar, each TG[11‐13]T5 variant was significantly enriched in individuals with a high suspicion of CF or CFTR‐RD (personal/family history of CF/CFTR‐RD) compared to those with a low suspicion for CF or CFTR‐RD (hereditary cancer screening, CFTR not requisitioned). Compared to CFvar/CFvar individuals, those with TG[11‐13]T5/CFvar generally had single‐organ involvement, milder symptoms, variable expressivity, and reduced penetrance. These data improve our understanding of disease risks associated with TG[11‐13]T5 variants and have important implications for reproductive genetic counseling.
Evaluating patients' satisfaction and preferences with a secondary prevention cardiovascular polypill: the Aurora Study.

Aim: To evaluate the satisfaction, preferences and adherence of patients in secondary cardiovascular prevention treated with the CNIC cardiovascular polypill compared with patients treated with the separate monocomponents. Methods: Observational, cross-sectional and multicenter study. Satisfaction was evaluated by the Treatment Satisfaction Questionnaire for Medication 9 items, adherence by the Morisky-Green questionnaire and ad-hoc questions were asked regarding patient preferences. Results: Polypill patients reported higher satisfaction than patients treated with the monocomponents (77.3 vs 71.2%, p < 0.0001). 72.8% of patients treated with the monocomponents would prefer to change to the polypill. Patients treated with the polypill had significantly higher adherence than patients treated with the monocomponents (57.7 vs 41.1%) (p = 0.0027). Conclusion: Polypill patients show higher satisfaction and better adherence. Most patients receiving the monocomponents would prefer a polypill regime.
PML‐NB‐dependent type I interferon memory results in a restricted form of HSV latency

Herpes simplex virus (HSV) establishes latent infection in long‐lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency are unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also find that the subnuclear condensates, promyelocytic leukemia nuclear bodies (PML‐NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV‐1 genomes colocalize with PML‐NBs throughout a latent infection of neurons only when type I IFN is present during initial infection. Depletion of PML prior to or following infection does not impact the establishment latency; however, it does rescue the ability of HSV to reactivate from IFN‐treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response during de novo infection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.
CASPAM: a triple modality biosensor for multiplexed imaging of caspase network activity

Understanding signal propagation across biological networks requires to simultaneously monitor the dynamics of several nodes to uncover correlations masked by inherent intercellular variability. To monitor the enzymatic activity of more than two components over short time scales has proven challenging. Exploiting the narrow spectral width of homoFRET-based biosensors, up to three activities can be imaged through fluorescence polarization anisotropy microscopy. We introduce CASPAM (Caspase Activity Sensor by Polarization Anisotropy Multiplexing) a single-plasmid triple-modality-reporter of key nodes of the apoptotic network. Apoptosis provides an ideal molecular framework to study interactions between its three composing pathways (intrinsic, extrinsic and effector). We characterized the biosensor performance and demonstrated the advantages that equimolar expression has both in simplifying experimental procedure and reducing observable variation, thus enabling robust data-driven modelling. Tools like CASPAM become essential to analyze molecular pathways where multiple nodes need to be simultaneously monitored.
Summary concordance index for meta‐analysis of prognosis studies with a survival outcome

In prognosis studies to evaluate association between a continuous biomarker and a survival outcome, investigators often classify subjects into two subclasses of the high‐ and low‐expression groups and apply simple survival analysis techniques of the Kaplan‐Meier method and the logrank test. The high‐ and low‐expressions are defined according to whether or not the observation of the biomarker is higher than the cut‐off value, which is heterogeneous across studies. The heterogeneous definitions of the cut‐off value make it difficult to apply the standard meta‐analysis techniques. We propose a method to estimate the concordance index for a survival outcome synthesizing published prognosis studies, in which the Kaplan‐Meier estimates for the high‐ and low‐expression groups are reported. We illustrate our proposed method with a real dataset for meta‐analysis of prognosis studies evaluating Ki‐67 in early breast cancer and evaluate its performance with a simulation study.
Organizational Acceptability of Implementing SBIRT for Adolescents in Primary Care

Abstract Introduction Adolescent illicit drug, tobacco, and alcohol use can result in sudden and long-term negative health consequences. Primary care environments present the optimal opportunity for screening and brief interventions that target prevention and curtailing use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a service delivery method that could potentially be well-integrated into primary care settings and used to serve a high volume of adolescents. Methods: This qualitative analysis of clinic staff interviews (N = 20), collected during a large cluster-randomized trial to implement two models of adolescent SBIRT, examined barriers and facilitating factors to overall acceptability of SBIRT. This study was conducted in a large, urban Federally Qualified Health Center (FQHC) at 7 sites throughout Baltimore City, Maryland, USA. Participants from each clinic included a range of various roles and responsibilities including: medical assistants (n = 3), nurses (n = 3), primary care providers (n = 4), behavioral health counselors (n = 4), and administrators (n = 6). Results: Results indicate both barriers and facilitating factors for acceptability of SBIRT in terms of (1) universal screening, (2) provider time demands, (3) behavioral health collaboration, and (4) behavioral health caseloads. Discussion: Universal screening was acceptable to participants across organizational roles, but brief interventions and referrals to treatment were found substantially less acceptable.
Water‐soluble polymers in agriculture: xanthan gum as eco‐friendly alternative to synthetics

Water‐soluble polymers (WSPs) are a versatile group of chemicals used across industries for different purposes such as thickening, stabilizing, adhesion and gelation. Synthetic polymers have tailored characteristics and are chemically homogeneous, whereas plant‐derived biopolymers vary more widely in their specifications and are chemically heterogeneous. Between both sources, microbial polysaccharides are an advantageous compromise. They combine naturalness with defined material properties, precisely controlled by optimizing strain selection, fermentation operational parameters and downstream processes. The relevance of such bio‐based and biodegradable materials is rising due to increasing environmental awareness of consumers and a tightening regulatory framework, causing both solid and water‐soluble synthetic polymers, also termed ‘microplastics’, to have come under scrutiny. Xanthan gum is the most important microbial polysaccharide in terms of production volume and diversity of applications, and available as different grades with specific properties. In this review, we will focus on the applicability of xanthan gum in agriculture (drift control, encapsulation and soil improvement), considering its potential to replace traditionally used synthetic WSPs. As a spray adjuvant, xanthan gum prevents the formation of driftable fine droplets and shows particular resistance to mechanical shear. Xanthan gum as a component in encapsulated formulations modifies release properties or provides additional protection to encapsulated agents. In geotechnical engineering, soil amended with xanthan gum has proven to increase water retention, reduce water evaporation, percolation and soil erosion – topics of high relevance in the agriculture of the 21st century. Finally, hands‐on formulation tips are provided to facilitate exploiting the full potential of xanthan gum in diverse agricultural applications and thus providing sustainable solutions.
Fast nanoparticle rotational and translational diffusion in synovial fluid and hyaluronic acid solutions

Polymer-coated nanoparticles in synovial fluid and hyaluronic acid solutions diffuse faster than expected based on bulk viscosity. Nanoparticles are under investigation as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components. Here, we show that rotational and translational diffusion of polymer-coated nanoparticles in quiescent synovial fluid and in hyaluronic acid solutions is well described by the Stokes-Einstein relationship, albeit with an effective medium viscosity that is much smaller than the macroscopic low shear viscosity of the fluid. This effective medium viscosity is well described by an equation for the viscosity of dilute polymer chains, where the additional viscous dissipation arises because of the presence of the polymer segments. These results shed light on the diffusive behavior of polymer-coated inorganic nanoparticles in complex and crowded biological environments, such as in the joint.
Deletion or inhibition of prolyl oligopeptidase blocks lithium‐induced phosphorylation of GSK3b and Akt by activation of protein phosphatase 2A

Alterations in prolyl oligopeptidase (PREP) activity have been connected, for example, with bipolar and major depressive disorder, and several studies have reported that lack or inhibition of PREP blocks the effects of lithium on inositol 1,4,5‐triphosphate (IP3) levels. However, the impact of PREP modulation on other intracellular targets of lithium, such as glycogen synthase kinase 3 beta (GSK3b) or protein kinase B (Akt), has not been studied. We recently found that PREP regulates protein phosphatase 2A (PP2A), and because GSK3b and Akt are PP2A substrates, we studied if PREP‐related lithium insensitivity is dependent on PP2A. To assess this, HEK‐293 and SH‐SY5Y cells with PREP deletion or PREP inhibition (KYP‐2047) were exposed to lithium, and thereafter, the phosphorylation levels of GSK3b and Akt were measured by Western blot. As expected, PREP deletion and inhibition blocked the lithium‐induced phosphorylation on GSK3b and Akt in both cell lines. When lithium exposure was combined with okadaic acid, a PP2A inhibitor, KYP‐2047 did not have effect on lithium‐induced GSK3b and Akt phosphorylation. Therefore, we conclude that PREP deletion or inhibition blocks the intracellular effects of lithium on GSK3b and Akt via PP2A activation.
Particle Merging-and-Splitting

Robustly handling collisions between individual particles in a large particle-based simulation has been a challenging problem. We introduce particle merging-and-splitting, a simple scheme for robustly handling collisions between particles that prevents inter-penetrations of separate objects without introducing numerical instabilities. This scheme merges colliding particles at the beginning of the time-step and then splits them at the end of the time-step. Thus, collisions last for the duration of a time-step, allowing neighboring particles of the colliding particles to influence each other. We show that our merging-and-splitting method is effective in robustly handling collisions and avoiding penetrations in particle-based simulations. We also show how our merging-and-splitting approach can be used for coupling different simulation systems using different and otherwise incompatible integrators. We present simulation tests involving complex solid-fluid interactions, including solid fractures generated by fluid interactions.
Experimental evidence that effects of megaherbivores on mesoherbivore space use are influenced by species' traits.

The extinction of 80% of megaherbivore (>1,000 kg) species towards the end of the Pleistocene altered vegetation structure, fire dynamics, and nutrient cycling worldwide. Ecologists have proposed (re)introducing megaherbivores or their ecological analogues to restore lost ecosystem functions and reinforce extant but declining megaherbivore populations. However, the effects of megaherbivores on smaller herbivores are poorly understood. We used long-term exclusion experiments and multispecies hierarchical models fitted to dung counts to test 1) the effect of megaherbivore (elephant and giraffe) presence-absence on the occurrence (dung presence) and use intensity (dung-pile density) of mesoherbivores (2-1,000 kg), and 2) the extent to which the responses of each mesoherbivore species was predictable based on their traits (diet and shoulder height) and phylogenetic relatedness. Megaherbivores increased the predicted occurrence and use intensity of zebras but reduced the occurrence and use intensity of several other mesoherbivore species. The negative effect of megaherbivores on mesoherbivore occurrence was stronger for shorter species, regardless of diet or relatedness. Megaherbivores substantially reduced the expected total use intensity (i.e., cumulative dung density of all species) of mesoherbivores, but only minimally reduced the expected species richness (i.e., cumulative predicted occurrence probabilities of all species) of mesoherbivores (by <1 species). Simulated extirpation of megaherbivores altered use intensity by mesoherbivores, which should be considered during (re)introductions of megaherbivores or their ecological proxies. Species' traits (in this case shoulder height) may be more reliable predictors of mesoherbivores' responses to megaherbivores than phylogenetic relatedness, and may be useful for predicting responses of data-limited species.
Cuticular conductance of adaxial and abaxial leaf surfaces and its relation to minimum leaf surface conductance.

Cuticular conductance to water (gcw ) is difficult to quantify for stomatous surfaces due to the complexity of separating cuticular and stomatal transpiration, and additional complications arise for determining adaxial and abaxial gcw . This has led to the neglect of gcw as a separate parameter in most common gas exchange measurements. Here, we describe a simple technique to simultaneously estimate adaxial and abaxial values of gcw , tested in two amphistomatous plant species. What we term the "Red-Light method" is used to estimate gcw from gas exchange measurements and a known CO2 concentration inside the leaf during photosynthetic induction under red light. We provide an easy-to-use web application to assist with the calculation of gcw . While adaxial and abaxial gcw varies significantly between leaves of the same species we found that the ratio of adaxial/abaxial gcw (γn ) is stable within a plant species. This has implications for use of generic values of gcw when analysing gas exchange data. The Red-Light method can be used to estimate total cuticular conductance (gcw-T ) accurately with the most common setup of gas exchange instruments, i.e., a chamber mixing the adaxial and abaxial gases, allowing for a wide application of this technique.