Miracle-dz/UniFAR-FTUs huggingface dataset:
Cochlear Efferent Innervation Is Sparse in Humans and Decreases with Age

The mammalian cochlea is innervated by two cholinergic feedback systems called the medial olivocochlear (MOC) and lateral olivocochlear (LOC) pathways, which send control signals from the brainstem back to the outer hair cells and auditory-nerve fibers, respectively. Despite countless studies of the cochlear projections of these efferent fibers in animal models, comparable data for humans are almost completely lacking. The mammalian cochlea is innervated by two cholinergic feedback systems called the medial olivocochlear (MOC) and lateral olivocochlear (LOC) pathways, which send control signals from the brainstem back to the outer hair cells and auditory-nerve fibers, respectively. Despite countless studies of the cochlear projections of these efferent fibers in animal models, comparable data for humans are almost completely lacking. Here, we immunostained the cochlear sensory epithelium from 23 normal-aging humans (14 males and 9 females), 0–86 years of age, with cholinergic markers to quantify the normal density of MOC and LOC projections, and the degree of age-related degeneration. In younger ears, the MOC density peaks in mid-cochlear regions and falls off both apically and basally, whereas the LOC innervation peaks near the apex. In older ears, MOC density decreases dramatically, whereas the LOC density does not. The loss of MOC feedback may contribute to the age-related decrease in word recognition in noise; however, even at its peak, the MOC density is lower than in other mammals, suggesting the MOC pathway is less important for human hearing. SIGNIFICANCE STATEMENT The cochlear epithelium and its sensory innervation are modulated by the olivocochlear (OC) efferent pathway. Although the medial OC (MOC) reflex has been extensively studied in humans, via contralateral sound suppression, the cochlear projections of these cholinergic neurons have not been described in humans. Here, we use immunostaining to quantify the MOC projections to outer hair cells and lateral OC (LOC) projections to the inner hair cell area in humans 0–89 years of age. We show age-related loss of MOC, but not LOC, innervation, which likely contributes to hearing impairments, and a relative paucity of MOC terminals at all ages, which may account for the relative weakness of the human MOC reflex and the difficulty in demonstrating a robust functional role in human experiments.
Effects of Phenolic Pollution on Interspecific Competition between Microcystis aeruginosa and Chlorella pyrenoidosa and their Photosynthetic Responses

The demand for phenolic compounds has been increasing rapidly, which has intensified the production and usage of phenol at a commercial scale. In some polluted water bodies, phenol has become one of the typical aromatic contaminants. Such water bodies are inescapably influenced by nutrients from human activities, and also suffer from nuisance cyanobacterial blooms. While phenolic pollution threatens water safety and ecological balance, algal cells are ubiquitous and sensitive to pollutants. Therefore, effects of phenolic pollution on interspecific competition between a bloom-forming cyanobacterium and other common alga merit quantitative investigation. In this study, the effects of phenol on Microcystis aeruginosa (M. aeruginosa, a bloom-forming cyanobacterium) and Chlorella pyrenoidosa (C. pyrenoidosa, a ubiquitous green alga) were analyzed in mono- and co-cultures. The two species were exposed to a series of phenol treatments (0, 2, 20, and 200 μg mL−1). Population dynamics were measured by a flow cytometer and analyzed by the Lotka-Volterra model. The results showed that M. aeruginosa was more sensitive to phenol (EC50 = 80.8 ± 0.16 μg mL−1) compared to C. pyrenoidosa (EC50 = 631.4 ± 0.41 μg mL−1) in mono-cultures. M. aeruginosa won in the co-cultures when phenol was below or equal to 20 μg mL−1, while C. pyrenoidosa became the dominant species in the 200 μg mL−1 treatment. Photosynthetic activity was measured by a fluometer. Results showed phenol significantly impacted the photosynthetic activity of M. aeruginosa by inhibiting the acceptor side of its photosystem II (PSII), while such inhibition in C. pyrenoidosa was only observed in the highest phenol treatment (200 μg mL−1). This study provides a better understanding for predicting the succession of algal community structure in water bodies susceptible to phenolic contamination. Moreover, it reveals the mechanism on photosynthetic responses of these two species under phenolic stress.
Cognitive Function and Consumption of Fruit and Vegetable Polyphenols in a Young Population: Is There a Relationship?

Scientific evidence has shown the relationship between consumption of fruits and vegetables and their polyphenols with the prevention or treatment of diseases. The aim of this review was to find out whether the same relationship exists between fruits and vegetables and cognitive function, especially memory, in a young population. The mechanisms by which polyphenols of fruits and vegetables can exert cognitive benefits were also evaluated. These compounds act to improve neuronal plasticity through the protein CREB (Camp Response Element Binding) in the hippocampus, modulating pathways of signaling and transcription factors (ERK/Akt). In the same way, brain-derived neurotrophic factor (BDNF) is implicated in the maintenance, survival, growth, and differentiation of neurons. All these effects are produced by an increase of cerebral blood flow and an increase of the blood’s nitric oxide levels and oxygenation.
Given the Cold Shoulder: A Review of the Scientific Literature for Evidence of Reptile Sentience

Simple Summary Reptiles are popular pets around the world, although their welfare requirements in captivity are not always met, due in part to an apparent lack of awareness of their needs. Herein, we searched a selection of the scientific literature for evidence of, and explorations into, reptile sentience. We used these findings to highlight: (1) how reptiles are recognised as being capable of a range of feelings; (2) what implications this has for the pet trade; and (3) what future research is needed to help maximise their captive welfare. We found 37 studies that assumed reptiles to be capable of the following emotions and states; anxiety, stress, distress, excitement, fear, frustration, pain, and suffering. We also found four articles that explored and found evidence for the capacity of reptiles to feel pleasure, emotion, and anxiety. These findings have direct implications for how reptiles are treated in captivity, as a better understanding of their sentience is critical in providing them with the best quality of life possible. Abstract We searched a selection of the scientific literature to document evidence for, and explorations into reptile sentience. The intention of this review was to highlight; (1) to what extent reptile capability for emotions have been documented in the scientific literature; (2) to discuss the implications this evidence has for the trade in reptiles; and (3) to outline what future research is needed to maximise their captive welfare needs. We used 168 keywords associated with sentience, to search through four journal databases and one open-access journal. We recorded studies that explored sentience in reptiles and those that recognised reptile sentience in their experiments. We found that reptiles were assumed to be capable of the following emotions and states; anxiety, distress, excitement, fear, frustration, pain, stress, and suffering, in 37 articles. We also found four articles that explored and found evidence for the capacity of reptiles to feel pleasure, emotion, and anxiety. These findings show that reptiles are considered to be capable of experiencing a range of emotions and states. This has implications for how reptiles are treated in captivity, as a better understanding could help to inform a range of different operational initiatives aimed at reducing negative animal welfare impacts, including improved husbandry and consumer behaviour change programmes.
COL6A6 interacted with P4HA3 to suppress the growth and metastasis of pituitary adenoma via blocking PI3K-Akt pathway

The role and mechanism of collagen type VI alpha 6 (COL6A6) on tumor growth and metastasis in pituitary adenoma (PA) was determined. COL6A6 was downregulated in PA tissues and cell lines, which was negatively associated with the expression of prolyl-4-hydroxylase alpha polypeptide III (P4HA3) in the progression of PA. Overexpression of COL6A6 significantly suppressed tumor growth and metastasis capacity in PA. In addition, P4HA3 worked as the upstream of the PI3K-Akt pathway to alleviate the antitumor activity of COL6A6 on the growth and metastasis of both AtT-20 and HP75 cells. Furthermore, the inhibitory effect of COL6A6 on cell proliferation, migration and invasion, and epithelial-mesenchymal transition (EMT) was reversed by P4HA3 overexpression or activation of the PI3K-Akt pathway induced by IGF-1 addition, which provided a new biomarker for clinical PA treatment.
The Economic Burden of Malaria: Revisiting the Evidence

Abstract. A portion of the economics literature has long debated about the relative importance of historical, institutional, geographical, and health determinants of economic growth. In 2001, Gallup and Sachs quantified the association between malaria and the level and growth of per capita income over the period 1965–1995 in a cross-country regression framework. We took a contemporary look at Gallup and Sachs’ seminal work in the context of significant progress in malaria control achieved globally since 2000. Focusing on the period 2000–2017, we used the latest data available on malaria case incidence and other determinants of economic growth, as well as macro-econometric methods that are now the professional norm. In our preferred specification using a fixed-effects model, a 10% decrease in malaria incidence was associated with an increase in income per capita of nearly 0.3% on average and a 0.11 percentage point faster per capita growth per annum. Greater average income gains were expected among higher burden countries and those with lower income. Growth of industries with the same level of labor intensity was found to be significantly slower in countries with higher malaria incidence. To analyze the causal impact of malaria on economic outcomes, we used malaria treatment failure and pyrethroid-only insecticide resistance as exogeneous instruments in two-stage least squares estimations. Despite several methodological challenges, as expected in these types of analyses, our findings confirm the intrinsic link between malaria and economic growth and underscore the importance of malaria control in the agenda for sustainable development.
Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning

In-stent restenosis remains a major problem of arteriosclerosis treatment by stenting. Expansion-optimized stents could reduce this problem. With numerical simulations, stent designs/ expansion behaviours can be effectively analyzed. For reasons of efficiency, simplified models of balloon-expandable stents are often used, but their accuracy must be challenged due to insufficient experimental validation. In this work, a realistic stent life-cycle simulation has been performed including balloon folding, stent crimping and free expansion of the balloon-stent-system. The successful simulation and validation of two stent designs with homogenous and heterogeneous stent stiffness and an asymmetrically positioned stent on the balloon catheter confirm the universal applicability of the simulation approach. Dogboning ratio, as well as the final dimensions of the folded balloon, the crimped and expanded stent, correspond well to the experimental dimensions with only slight deviations. In contrast to the detailed stent life-cycle simulation, a displacement-controlled simulation can not predict the transient stent expansion, but is suitable to reproduce the final expanded stent shape and the associated stress states. The detailed stent life-cycle simulation is thus essential for stent expansion analysis/optimization, whereas for reasons of computational efficiency, the displacement-controlled approach can be considered in the context of pure stress analysis.
Sargassum Seaweed as a Source of Anti-Inflammatory Substances and the Potential Insight of the Tropical Species: A Review

Sargassum is recognized both empirically and scientifically as a potential anti-inflammatory agent. Inflammation is an important response in the body that helps to overcome various challenges to body homeostasis such as microbial infections, tissue stress, and certain injuries. Excessive and uncontrolled inflammatory conditions can affect the pathogenesis of various diseases. This review aims to explore the potential of Sargassum’s anti-inflammatory activity, not only in crude extracts but also in sulfated polysaccharides and purified compounds. The tropical region has a promising availability of Sargassum biomass because its climate allows for the optimal growth of seaweed throughout the year. This is important for its commercial utilization as functional ingredients for both food and non-food applications. To the best of our knowledge, studies related to Sargassum’s anti-inflammatory activity are still dominated by subtropical species. Studies on tropical Sargassum are mainly focused on the polysaccharides group, though there are some other potentially bioactive compounds such as polyphenols, terpenoids, fucoxanthin, fatty acids and their derivatives, typical polar lipids, and other groups. Information on the modulation mechanism of Sargassum’s bioactive compounds on the inflammatory response is also discussed here, but specific mechanisms related to the interaction between bioactive compounds and targets in cells still need to be further studied.
Tezacaftor and ivacaftor for the treatment of cystic fibrosis

ABSTRACT Introduction: Cystic fibrosis (CF) is a complex, multi-system, genetic disease affecting over 70,000 people worldwide. The underlying defect is a mutation in the CFTR gene. Dysfunctional CFTR protein results in abnormal anion movement across epithelial membranes in affected organs. There has been a paradigm shift in CF treatment over the last decade with the advent of CFTR modulation, treatments which target this underlying genetic defect and have the potential to change the course of CF clinical disease. Areas covered: Available CFTR modulators in current clinical practice are reviewed in this article, with a direct comparison and summary of relevant pivotal clinical trials. The approval of ivacaftor and subsequent development of lumacaftor and tezacaftor dual combinations represents an exciting development in CF management in recent years. Expert opinion: Tezacaftor/ivacaftor (tez/iva) appears to have a more favorable adverse event and drug–drug interaction profile than lumacaftor/ivacaftor. Tez/iva has been approved, alongside Phe508del, for a large number of ‘residual function’ CFTR mutations, with some based on response to in vitro culture. Dual therapy with tez/iva has paved the way for triple CFTR modulation currently in clinical trials with an ultimate view to provide modulation therapy to the majority of CF genotypes in the future.
The viral F-box protein P0 induces an ER-derived autophagy degradation pathway for the clearance of membrane-bound AGO1

Significance The viral suppressor of RNA silencing P0 is known to target plant antiviral ARGONAUTE (AGO) proteins for degradation via an autophagy-related process. Here we utilized P0 to gain insight into the cellular degradation dynamics of AGO1, the major plant effector of RNA silencing. We revealed that P0 targets endoplasmic reticulum (ER)-associated AGO1 by inducing the formation of ER-related bodies that are delivered to the vacuole with both P0 and AGO1 as cargos. This process involves ATG8-interacting proteins 1 and 2 (ATI1 and ATI2) that interact with AGO1 and negatively regulate its transgene-silencing activity. Together, our results reveal a layer of ER-bound AGO1 posttranslational regulation that is manipulated by P0 to subvert plant antiviral defense. RNA silencing is a major antiviral defense mechanism in plants and invertebrates. Plant ARGONAUTE1 (AGO1) is pivotal in RNA silencing, and hence is a major target for counteracting viral suppressors of RNA-silencing proteins (VSRs). P0 from Turnip yellows virus (TuYV) is a VSR that was previously shown to trigger AGO1 degradation via an autophagy-like process. However, the identity of host proteins involved and the cellular site at which AGO1 and P0 interact were unknown. Here we report that P0 and AGO1 associate on the endoplasmic reticulum (ER), resulting in their loading into ER-associated vesicles that are mobilized to the vacuole in an ATG5- and ATG7-dependent manner. We further identified ATG8-Interacting proteins 1 and 2 (ATI1 and ATI2) as proteins that associate with P0 and interact with AGO1 on the ER up to the vacuole. Notably, ATI1 and ATI2 belong to an endogenous degradation pathway of ER-associated AGO1 that is significantly induced following P0 expression. Accordingly, ATI1 and ATI2 deficiency causes a significant increase in posttranscriptional gene silencing (PTGS) activity. Collectively, we identify ATI1 and ATI2 as components of an ER-associated AGO1 turnover and proper PTGS maintenance and further show how the VSR P0 manipulates this pathway.
Data Science for Extubation Prediction and Value of Information in Surgical Intensive Care Unit

Besides the traditional indices such as biochemistry, arterial blood gas, rapid shallow breathing index (RSBI), acute physiology and chronic health evaluation (APACHE) II score, this study suggests a data science framework for extubation prediction in the surgical intensive care unit (SICU) and investigates the value of the information our prediction model provides. A data science framework including variable selection (e.g., multivariate adaptive regression splines, stepwise logistic regression and random forest), prediction models (e.g., support vector machine, boosting logistic regression and backpropagation neural network (BPN)) and decision analysis (e.g., Bayesian method) is proposed to identify the important variables and support the extubation decision. An empirical study of a leading hospital in Taiwan in 2015–2016 is conducted to validate the proposed framework. The results show that APACHE II and white blood cells (WBC) are the two most critical variables, and then the priority sequence is eye opening, heart rate, glucose, sodium and hematocrit. BPN with selected variables shows better prediction performance (sensitivity: 0.830; specificity: 0.890; accuracy 0.860) than that with APACHE II or RSBI. The value of information is further investigated and shows that the expected value of experimentation (EVE), 0.652 days (patient staying in the ICU), is saved when comparing with current clinical experience. Furthermore, the maximal value of information occurs in a failure rate around 7.1% and it reveals the “best applicable condition” of the proposed prediction model. The results validate the decision quality and useful information provided by our predicted model.
Multivariate Analysis of Electrophysiological Signals Reveals the Temporal Properties of Visuomotor Computations for Precision Grips

The frontoparietal networks underlying grasping movements have been extensively studied, especially using fMRI. Accordingly, whereas much is known about their cortical locus much less is known about the temporal dynamics of visuomotor transformations. Here, we show that multivariate EEG analysis allows for detailed insights into the time course of visual and visuomotor computations of precision grasps. The frontoparietal networks underlying grasping movements have been extensively studied, especially using fMRI. Accordingly, whereas much is known about their cortical locus much less is known about the temporal dynamics of visuomotor transformations. Here, we show that multivariate EEG analysis allows for detailed insights into the time course of visual and visuomotor computations of precision grasps. Male and female human participants first previewed one of several objects and, upon its reappearance, reached to grasp it with the thumb and index finger along one of its two symmetry axes. Object shape classifiers reached transient accuracies of 70% at ∼105 ms, especially based on scalp sites over visual cortex, dropping to lower levels thereafter. Grasp orientation classifiers relied on a system of occipital-to-frontal electrodes. Their accuracy rose concurrently with shape classification but ramped up more gradually, and the slope of the classification curve predicted individual reaction times. Further, cross-temporal generalization revealed that dynamic shape representation involved early and late neural generators that reactivated one another. In contrast, grasp computations involved a chain of generators attaining a sustained state about 100 ms before movement onset. Our results reveal the progression of visual and visuomotor representations over the course of planning and executing grasp movements. SIGNIFICANCE STATEMENT Grasping an object requires the brain to perform visual-to-motor transformations of the object's properties. Although much of the neuroanatomic basis of visuomotor transformations has been uncovered, little is known about its time course. Here, we orthogonally manipulated object visual characteristics and grasp orientation, and used multivariate EEG analysis to reveal that visual and visuomotor computations follow similar time courses but display different properties and dynamics.
Weight Loss After Stroke Through an Intensive Lifestyle Intervention (Group Lifestyle Balance-Cerebrovascular Accident): Protocol for a Randomized Controlled Trial

Background Weight gain can be a consequence of stroke, or cerebrovascular accident (CVA), because of impaired mobility, behavioral and emotional disorders, and sensory losses. Weight gain increases the patient’s risk of recurrent stroke and chronic diseases, such as diabetes, metabolic syndrome, and pulmonary and heart disease. Approaches to weight loss in this population are lacking, although necessary because of the unique physiological and cognitive needs of persons after a stroke. Evidence shows that intensive behavioral therapy interventions that address both physical activity and diet offer the greatest potential for weight loss. The Group Lifestyle Balance (GLB) intervention is a 12-month, evidence-based weight loss program that has been used extensively with the general population; this program was modified to meet the needs of people who have had a stroke (GLB-CVA). Objective This randomized controlled trial (RCT) aims to examine the efficacy of the GLB-CVA on weight and secondary outcomes, compared with that of a waitlist control group. Methods This RCT will enroll and randomize 64 patients over an 18-month period. Results Currently, 51 people are waitlisted, with 23 out of 51 screened and 16 out of 23 eligible. Conclusions It is anticipated that the findings from this RCT will contribute to the evidence base regarding weight loss strategies for people living with stroke. Clinical Trial ClinicalTrials.gov NCT03873467; https://clinicaltrials.gov/ct2/show/NCT03873467