Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Analysis of the Zinc Homeostasis Network in Pseudomonas aeruginosa and Its Gene Expression Dynamics

Zinc is one of the most important trace elements for life and its deficiency, like its excess, can be fatal. In the bacterial opportunistic pathogen Pseudomonas aeruginosa, Zn homeostasis is not only required for survival, but also for virulence and antibiotic resistance. Thus, the bacterium possesses multiple Zn import/export/storage systems. In this work, we determine the expression dynamics of the entire P. aeruginosa Zn homeostasis network at both transcript and protein levels. Precisely, we followed the switch from a Zn-deficient environment, mimicking the initial immune strategy to counteract bacterial infections, to a Zn-rich environment, representing the phagocyte metal boost used to eliminate an engulfed pathogen. Thanks to the use of the NanoString technology, we timed the global silencing of Zn import systems and the orchestrated induction of Zn export systems. We show that the induction of Zn export systems is hierarchically organized as a function of their impact on Zn homeostasis. Moreover, we identify PA2807 as a novel Zn resistance component in P. aeruginosa and highlight new regulatory links among Zn-homeostasis systems. Altogether, this work unveils a sophisticated and adaptive homeostasis network, which complexity is key in determining a pathogen spread in the environment and during host-colonization.
Do Shy Preschoolers Interact Differently When Learning Language With a Social Robot? An Analysis of Interactional Behavior and Word Learning

Temperamental traits can decisively influence how children enter into social interaction with their environment. Yet, in the field of child–robot interaction, little is known about how individual differences such as shyness impact on how children interact with social robots in educational settings. The present study systematically assessed the temperament of 28 preschool children aged 4–5 years in order to investigate the role of shyness within a dyadic child–robot interaction. Over the course of four consecutive sessions, we observed how shy compared to nonshy children interacted with a social robot during a word-learning educational setting and how shyness influenced children’s learning outcomes. Overall, results suggested that shy children not only interacted differently with a robot compared to nonshy children, but also changed their behavior over the course of the sessions. Critically, shy children interacted less expressively with the robot in general. With regard to children’s language learning outcomes, shy children scored lower on an initial posttest, but were able to close this gap on a later test, resulting in all children retrieving the learned words on a similar level. When intertest learning gain was considered, regression analyses even confirmed a positive predictive role of shyness on language learning gains. Findings are discussed with regard to the role of shyness in educational settings with social robots and the implications for future interaction design.
Effects of an Elevated Platform on Welfare Aspects in Male Conventional Broilers and Dual-Purpose Chickens

To avoid killing day-old male chicks, one possibility is to keep dual-purpose chicken strains. Here, the hens were kept for egg production, and the roosters were kept for meat production. Both sexes had moderate performances compared to the respective hybrid chicken strains. However, until now, little has been known about whether male dual-purpose chickens may profit from enrichment in the environment in which broiler chickens are raised under conventional conditions. This study aims to further investigate the suitability of elevated structures for dual-purpose chickens (Lohmann Dual) with moderate growth and for fast-growing male broiler chickens (Ross 308). In two consecutive trials, we kept 686 Ross and 672 Dual chickens in 24 compartments (2 trials × 2 strains × 6 compartments). Half of the compartments were equipped with elevated grid platforms at a height of 50 cm (enriched group). In the other half of the compartments, no platforms were installed (control group). We analyzed the usage of the elevated platforms by scan sampling and assessed animal-based (walking ability, plumage cleanliness, and foot health) and management-based (litter quality) indicators. Both strains showed increasing use of the elevated platforms from the first week of life onwards. However, the fast-growing chickens used the elevated platform less than the slow-growing chickens. At the end of the fattening period, the birds used the elevated grids more at night than during the daytime. Slow-growing chickens kept in enriched compartments showed a better walking ability. In general, slow-growing chickens had better plumage conditions and foot health compared to fast-growing chickens. Our results show that natural behaviors such as perching can be supported by offering elevated platforms and that animal-based indicators such as walking ability can be improved, at least in slow-growing chickens. Moreover, the use of an alternative chicken strain avoids killing day-old male chicks, and in addition, these chickens show fewer animal welfare problems than a conventional fattening strain. Thus, the use of male chickens of a dual-purpose strain can substantially contribute to improving animal welfare in broiler meat production.
A Comparison of Connected Speech Tasks for Detecting Early Alzheimer’s Disease and Mild Cognitive Impairment Using Natural Language Processing and Machine Learning

Alzheimer’s disease (AD) has a long pre-clinical period, and so there is a crucial need for early detection, including of Mild Cognitive Impairment (MCI). Computational analysis of connected speech using Natural Language Processing and machine learning has been found to indicate disease and could be utilized as a rapid, scalable test for early diagnosis. However, there has been a focus on the Cookie Theft picture description task, which has been criticized. Fifty participants were recruited – 25 healthy controls (HC), 25 mild AD or MCI (AD+MCI) – and these completed five connected speech tasks: picture description, a conversational map reading task, recall of an overlearned narrative, procedural recall and narration of a wordless picture book. A high-dimensional set of linguistic features were automatically extracted from each transcript and used to train Support Vector Machines to classify groups. Performance varied, with accuracy for HC vs. AD+MCI classification ranging from 62% using picture book narration to 78% using overlearned narrative features. This study shows that, importantly, the conditions of the speech task have an impact on the discourse produced, which influences accuracy in detection of AD beyond the length of the sample. Further, we report the features important for classification using different tasks, showing that a focus on the Cookie Theft picture description task may narrow the understanding of how early AD pathology impacts speech.
Energy-Efficient Integrated Circuit Solutions Toward Miniaturized Closed-Loop Neural Interface Systems

Miniaturized implantable devices play a crucial role in neural interfaces by monitoring and modulating neural activities on the peripheral and central nervous systems. Research efforts toward a compact wireless closed-loop system stimulating the nerve automatically according to the user's condition have been maintained. These systems have several advantages over open-loop stimulation systems such as reduction in both power consumption and side effects of continuous stimulation. Furthermore, a compact and wireless device consuming low energy alleviates foreign body reactions and risk of frequent surgical operations. Unfortunately, however, the miniaturized closed-loop neural interface system induces several hardware design challenges such as neural activity recording with severe stimulation artifact, real-time stimulation artifact removal, and energy-efficient wireless power delivery. Here, we will review recent approaches toward the miniaturized closed-loop neural interface system with integrated circuit (IC) techniques.
First-Episode Patients Report Cognitive Difficulties in Executive Functioning 1 Year After Initial Episode of Major Depressive Disorder

Objective: Major Depressive Disorder (MDD) is associated with cognitive impairment in general, and Executive Functioning (EF) in particular, even in remitted phase of the disorder, suggesting residual cognitive symptoms. The aim of the present study was to investigate self-reported EF 1 year after the first episode of MDD and to explore this in relation to depressive mood symptoms, remission and relapse. Method: The study included data from 24 patients and 23 healthy control subjects 1 year after the patients' initial first episode of MDD. All participants completed the Behavior Rating Inventory of Executive Functioning-Adult version (BRIEF-A), a standardized self-report measure of perceived EF in everyday life, measuring nine different EF. Total index scores for metacognitive functions, behavior/emotional regulation functions and a global EF score is also calculated. Results: The patient group in total, independent of symptom status, reported significantly lower EF in all indexes compared to the healthy controls 1 year after the initial episode. However, higher depressive mood symptom load correlated with self-reported difficulties in metacognitive functions and poor global EF scores. Regulatory control of behavior and emotional responses did not show such strong association with mood symptoms, but low self-report scores on this measure was associated with relapse during the first year after the initial episode. Conclusion: First-episode patients report significant lower executive functioning in everyday life compared to individually matched healthy controls, 1 year after onset, independent of symptom load. Residual cognitive symptoms seem to be evident and associated with risk of relapse and should be targeted in treatment and prevention of recurrence in MDD.
Whatever Next and Close to My Self—The Transparent Senses and the “Second Skin”: Implications for the Case of Depersonalization

In his paper “Whatever next? Predictive brains, situated agents, and the future of cognitive science,” Andy Clark seminally proposed that the brain's job is to predict whatever information is coming “next” on the basis of prior inputs and experiences. Perception fundamentally subserves survival and self-preservation in biological agents, such as humans. Survival however crucially depends on rapid and accurate information processing of what is happening in the here and now. Hence, the term “next” in Clark's seminal formulation must include not only the temporal dimension (i.e., what is perceived now) but also the spatial dimension (i.e., what is perceived here or next-to-my-body). In this paper, we propose to focus on perceptual experiences that happen “next,” i.e., close-to-my-body. This is because perceptual processing of proximal sensory inputs has a key impact on the organism's survival. Specifically, we focus on tactile experiences mediated by the skin and what we will call the “extended skin” or “second skin,” that is, immediate objects/materials that envelop closely to our skin, namely, clothes. We propose that the skin and tactile experiences are not a mere border separating the self and world. Rather, they simultaneously and inherently distinguish and connect the bodily self to its environment. Hence, these proximal and pervasive tactile experiences can be viewed as a “transparent bridge” intrinsically relating and facilitating exchanges between the self and the physical and social world. We conclude with potential implications of this observation for the case of Depersonalization Disorder, a condition that makes people feel estranged and detached from their self, body, and the world.
Muscles Affecting Minimum Toe Clearance

The aim of this study was to investigate how the anterior and posterior muscles in the shank (Tibialis Anterior, Gastrocnemius Lateralis and Medialis), influence the level of minimum toe clearance (MTC). With aging, MTC deteriorates thus, greatly increasing the probability of falling or tripping. This could result in injury or even death. For this study, muscle activity retention taping (MART) was used on young adults, which is an accepted method of simulating a poor MTC—found in elderly gait. The subject's muscle activation was measured using surface electromyography (SEMG), and the kinematic parameters (MTC, knee and ankle joint angles) were measured using an optical motion capture system. Our results indicate that MART produces significant reductions in MTC (P < α), knee flexion (P < α) and ankle dorsiflexion (P < α), as expected. However, the muscle activity increased significantly, contrary to the expected result (elderly individuals should have lower muscle activity). This was due to the subject's muscle conditions (healthy and strong), hence the muscles worked harder to counteract the external restriction. Yet, the significant change in muscle activity (due to MART) proves that the shank muscles do play an important role in determining the level of MTC. The Tibialis Anterior had the highest overall muscle activation, making it the primary muscle active during the swing phase. With aging, the shank muscles (specifically the Tibialis Anterior) would weaken and stiffen, coupled with a reduced joint range of motion. Thus, ankle-drop would increase—leading to a reduction in MTC.
Follow-Up SARS-CoV-2 PCR Testing Outcomes From a Large Reference Lab in the US

By analyzing COVID-19 sequential COVID-19 test results of patients across the United States, we herein attempt to quantify some of the observations we've made around long-term infection (and false-positive rates), as well as provide observations on the uncertainty of sampling variability and other dynamics of COVID-19 infection in the United States. Retrospective cohort study of a registry of RT-PCR testing results for all patients tested at any of the reference labs operated by Labcorp® including both positive, negative, and inconclusive results, from March 1, 2020 to January 28, 2021, including patients from all 50 states and outlying US territories. The study included 22 million patients with RT-PCR qualitative test results for SARS-CoV-2, of which 3.9 million had more than one test at Labcorp. We observed a minuscule <0.1% basal positive rate for follow up tests >115 days, which could account for false positives, long-haulers, and/or reinfection but is indistinguishable in the data. In observing repeat-testing, for patients who have a second test after a first RT-PCR, 30% across the cohort tested negative on the second test. For patients who test positive first and subsequently negative within 96 h (40% of positive test results), 18% of tests will subsequently test positive within another 96-h span. For those who first test negative and then positive within 96 h (2.3% of negative tests), 56% will test negative after a third and subsequent 96-h period. The sudden changes in RT-PCR test results for SARS-CoV-2 from this large cohort study suggest that negative test results during active infection or exposure can change rapidly within just days or hours. We also demonstrate that there does not appear to be a basal false positive rate among patients who test positive >115 days after their first RT-PCR positive test while failing to observe any evidence of widespread reinfection.
Protective Effects of Sacubitril/Valsartan on Cardiac Fibrosis and Function in Rats With Experimental Myocardial Infarction Involves Inhibition of Collagen Synthesis by Myocardial Fibroblasts Through Downregulating TGF-β1/Smads Pathway

Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts. Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107–10–5 M) or Sac/Val (107–105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry. Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively. Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.
Event-Related Desynchronization During Mirror Visual Feedback: A Comparison of Older Adults and People After Stroke

Event-related desynchronization (ERD), as a proxy for mirror neuron activity, has been used as a neurophysiological marker for motor execution after mirror visual feedback (MVF). Using EEG, this study investigated ERD upon the immediate effects of single-session MVF in unimanual arm movements compared with the ERD effects occurring without a mirror, in two groups: stroke patients with left hemiplegia and their healthy counterparts. During EEG recordings, each group performed one session of mirror therapy training in three task conditions: with a mirror, with no mirror, and with a covered mirror. An asymmetry index was calculated from the subtraction of the event-related spectrum perturbations between the C3 and C4 electrodes located over the sensorimotor cortices contralateral and ipsilateral to the moved arm. Results of the effect of task versus group in contralateral and ipsilateral motor areas showed that there was a significant effect of task condition at the contralateral motor area in the high beta band (17–35 Hz) at C3. High beta ERD showed that the suppression was greater over the contralateral hemisphere than it was over the ipsilateral hemisphere in both study groups. The magnitude of low beta (12–16 Hz) ERD in patients with stroke was more suppressed in contralesional C3 under the no mirror compared to that of the covered mirror and similarly more suppressed in ipsilesional C4 ERD under the no mirror compared to that of the mirror condition. The correlation analysis revealed that the magnitude of ERSP power correlated significantly with arm severity in the low and high beta bands in patients with stroke, and a higher asymmetry index in the low beta band was associated with higher arm functioning under the no-mirror condition. There was a shift in sensorimotor ERD toward the contralateral hemisphere as induced by MVF accompanying unimanual movement in both stroke patients and healthy controls. The use of ERD in the low beta band as a neurophysiological marker to indicate the relationships between the amount of MVF-induced ERD attenuation and motor severity, and the outcome indicator for improving stroke patients’ neuroplasticity in clinical trials using MVF are warranted to be explored in the future.
Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

Emerging evidence suggests that both central and peripheral immunological processes play an important role in the pathogenesis of Alzheimer’s disease (AD), but regulatory mechanisms remain unknown. The gut microbiota and its key metabolites are known to affect neuroinflammation by modulating the activity of peripheral and brain-resident immune cells, yet an overview on how the gut microbiota contribute to immunological alterations in AD is lacking. In this review, we discuss current literature on microbiota composition in AD patients and relevant animal models. Next, we highlight how microbiota and their metabolites may contribute to peripheral and central immunological changes in AD. Finally, we offer a future perspective on the translation of these findings into clinical practice by targeting gut microbiota to modulate inflammation in AD. Since we find that gut microbiota alterations in AD can induce peripheral and central immunological changes via the release of microbial metabolites, we propose that modulating their composition may alter ongoing inflammation and could therefore be a promising future strategy to fight progression of AD.
Association Analysis of Variants of DSCAM and BACE2 With Hirschsprung Disease Susceptibility in Han Chinese and Functional Evaluation in Zebrafish

Hirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. DSCAM and BACE2 are close together on the HSCR-associated critical region of chromosome 21. Common variants of DSCAM and rare variants of BACE2 were implicated to be associated with sporadic HSCR. However, the submucosal neuron defect of DS mouse model could not be rescued by normalization of Dscam. We aimed to explore the contribution of DSCAM and BACE2 to the development of the enteric nervous system (ENS) and HSCR susceptibility. We genotyped 133 tag single-nucleotide polymorphisms (SNPs) in DSCAM and BACE2 gene region in 420 HSCR patients and 1,665 controls of Han Chinese. Expression of DSCAM and BACE2 homologs was investigated in the developing gut of zebrafish. Overexpression and knockdown of the homologs were performed in zebrafish to investigate their roles in the development of ENS. Two DSCAM SNPs, rs430255 (PAddtive = 0.0052, OR = 1.36, 95% CI: 1.10–1.68) and rs2837756 (PAddtive = 0.0091, OR = 1.23, 95% CI: 1.05–1.43), showed suggestive association with HSCR risk. Common variants in BACE2 were not associated with HSCR risk. We observed dscama, dscamb, and bace2 expression in the developing gut of zebrafish. Knockdown of dscama, dscamb, and bace2 caused a reduction of enteric neurons in the hindgut of zebrafish. Overexpression of DSCAM and bace2 had no effects on neuron number in the hindgut of zebrafish. Our results suggested that common variation of DSCAM contributed to HSCR risk in Han Chinese. The dysfunction of both dscams and bace2 caused defects in enteric neuron, indicating that DSCAM and BACE2 might play functional roles in the occurrence of HSCR. These novel findings might shed new light on the pathogenesis of HSCR.