Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional role of RRS1 in breast cancer cell proliferation

RRS1 (human regulator of ribosome synthesis 1), an essential nuclear protein involved in ribosome biogenesis, is overexpressed in some human cancers, yet its role in breast cancer remains unclear. Here, we report a functional analysis of RRS1 in breast cancer and its likely mechanism. Immunohistochemistry (IHC) and RT‐qPCR analyses indicated that RRS1 was commonly overexpressed in breast cancer tissues. The copy numbers of RRS1 were higher in tumours compared with those for normal tissues. And there was a significant correlation between copy number and mRNA expression. In addition, RRS1 overexpression was significantly correlated with lymph node metastasis and poor survival. RRS1 mRNA and protein levels were also significantly increased in a panel of human breast cancer cell lines. RRS1 knockdown inhibited proliferation and induced apoptosis and cell cycle arrest in all three cell lines. Furthermore, RRS1 knockdown suppressed the tumour formation and growth of MDA‐MB‐231 cells in nude mice. Additionally, RRS1 knockdown activated p53 and p21 in MCF‐7 cells. A marked increase in the quantity of ribosome‐free RPL11 was detected by Western blot. Moreover, co‐immunoprecipitation (CoIP) experiments showed that RRS1 knockdown activated p53 by facilitating the direct contact of MDM2 and RPL11/RPL5. Taken together, our results suggest that RRS1 may contribute to breast cancer proliferation through RPL11/MDM2‐mediated p53 activation. Therefore, RRS1 may be a promising target for breast cancer therapy.
Repeated computerized cognitive testing: Performance shifts and test–retest reliability in healthy older adults

ABSTRACT Introduction: Repeated cognitive assessment is frequently required to monitor changes in cognitive functioning in older adults, but studies of repeated computerized testing in this population are scarce. To provide new insight into retest effects this study examined within- and between-day performance shifts and test–retest reliability among healthy older adults for test scores from a computerized cognitive battery. Method: Thirty older men (65–71 years) completed the battery six times. Testing occurred twice on each of three testing days, separated by 1 week. Results: Reaction times (RTs) on tasks intended to measure inhibition (Anti), response switching (Pro/Anti), selective attention (Simon and Flanker), and working memory (2-back) typically showed practice effects, which were most prominent between the first two time points. In most cases, these RTs showed moderate to good test–retest reliability (intraclass correlation coefficient, ICC, range = .34 to .93) with lower reliability between the first two time points. Two-back accuracy rates showed similar results. In contrast, RTs on a basic visuomotor task (Pro) and on compatible trials of the Simon task showed increases at later time points, presumably because of boredom, but demonstrated mostly moderate to good reliability (ICC range = .49 to .83). Scoring metrics from a computerized version of the Corsi Block-Tapping task (intended to measure short-term and working memory) and cost scores (performance differences between two related conditions/tasks) intended to isolate specific cognitive functions tended to show poor reliability (ICC range = –.23 to .62). Conclusions: Most of the RT tasks investigated showed suitability for use in repeated testing among older adults, although longer familiarization periods appear to be warranted in many cases to reduce practice effects and improve initial reliability. However, poor reliability indicated that scoring metrics from the computerized Corsi Block-Tapping task and cost scores are unsuitable for repeated testing.
Nutritive evaluation of spent green and black tea leaf silages by in vitro gas production characteristics, ruminal degradability and post-ruminal digestibility assessed with inhibitory activity of their tannins.

Spent tea leaf contains high levels of crude protein, suggesting that it may be used as an alternative source for ruminant feeding. We assessed the nutritive characteristics of spent green tea leaf silage (GTS) and black tea leaf silages (BTS) in comparison with soybean meal (SBM) and alfalfa hay cube (AHC) using in vitro assay. The effects of tannin on the nutritive characteristics were also evaluated by adding polyethylene glycol (PEG) as a tannin-binding agent. The amount of gas production was greater for SBM, followed by AHC, GTS, and BTS. A significant improvement in gas production upon addition of PEG was observed only for BTS. Ruminal protein degradability and post-ruminal digestibility was higher for SBM, followed by AHC, GTS, and BTS. The presence of PEG significantly increased ruminal degradability and post-ruminal protein digestibility for GTS and BTS, but not for AHC. The increment of protein digestibility by PEG was much greater for BTS than for GTS, indicating that GTS tannins suppress protein digestibility slightly, whereas BTS tannins do so strongly. According to these results, GTS but not BTS has a potential as an alternative to AHC as a ruminant feedstuff.
Mass Production of Lemna minor and Its Amino Acid and Fatty Acid Profiles

The surface floating duckweed Lemna minor (Lemnaceae) is a potential ingredient to replace the application of fish-meal in the aqua-feed. The culture technique of the duckweed was standardized in outdoor tanks and then applied in the pond. Three consecutive experiments were conducted in tanks (1.2 × 0.35 × 0.3 m). In experiment 1, four different manures were used. In manure 1 (organic manure, OM) and manure 3 (2x OM), cattle manure, poultry droppings, and mustard oil cake (1:1:1) were used; in manure 2 (inorganic fertilizer, IF), urea, potash, triple superphosphate were used; manure 4 (2x OM+IF) was a combination of manure 2 and manure 3. In experiment 2, manure 1 (OM) and manure 2 (IF) were used, and manure 3 (OM+IF) was a combination of both manures. In experiment 3, OM and IF were selected. In pond (20 × 10 × 0.5 m), OM was applied. Fresh duckweed was seeded after 5 days of manure application. In experiments 1 and 3, total production was significantly (P < 0.05) higher in OM compared to other treatments. In experiment 2, there was no significant (P > 0.05) difference in production between OM and IF. In pond, relative growth rate (RGR) of duckweed ranged from 0.422 to 0.073 g/g/day and total production was 702.5 Kg/ha/month (dry weight). Protein, lipid, and ash contents were higher in duckweed cultured in OM compared to IF. The duckweed was a rich source of essential (39.20%), non-essential (53.64%), and non-proteinogenic (7.13%) amino acids. Among essential amino acids, leucine, isoleucine, and valine constituted 48.67%. Glutamic acid was 25.87% of total non-essential amino acids. Citrulline, hydroxiproline, taurine, etc. were found in the duckweed. The fatty acid composition was dominated by PUFA, 60–63% of total fatty acids, largely α-linolenic acid (LNA, 18:3n-3) at around 41 to 47% and linoleic acid (LA, 18:2n-6) at 17–18%. The nutritional value of duckweeds and their production potential in the pond conditions were evaluated. Duckweed biomass may thus be used to replace commercial fish-meal that is currently used in aquaculture.
Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but little work to date has illuminated the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to experimentally assess the causal contribution of cortical regions to threat-related ideological shifts. In the example protocol provided here, participants are exposed to a threat prime-an explicit reminder of their own inevitable death and bodily decomposition-following a downregulation of the posterior medial frontal cortex (pMFC) or a sham stimulation. Next, disguised within a series of distracter tasks, participants' relative degree of ideological adherence is assessed-in the present example, with regard to coalitional prejudice and religious belief. Participants for whom the pMFC has been downregulated exhibit less coalitionally biased responses to an immigrant critical of the participants' national in-group, and less conviction in positive afterlife beliefs (i.e., God, angels, and heaven), despite having recently been reminded of death. These results complement prior findings that continuous theta burst stimulation of the pMFC influences social conformity and sharing and illustrate the feasibility of investigating the neural basis of high-level social cognitive shifts using transcranial magnetic stimulation.
MetaArms: Body Remapping Using Feet-Controlled Artificial Arms

We introduce MetaArms, wearable anthropomorphic robotic arms and hands with six degrees of freedom operated by the user's legs and feet. Our overall research goal is to re-imagine what our bodies can do with the aid of wearable robotics using a body-remapping approach. To this end, we present an initial exploratory case study. MetaArms' two robotic arms are controlled by the user's feet motion, and the robotic hands can grip objects according to the user's toes bending. Haptic feedback is also presented on the user's feet that correlate with the touched objects on the robotic hands, creating a closed-loop system. We present formal and informal evaluations of the system, the former using a 2D pointing task according to Fitts' Law. The overall throughput for 12 users of the system is reported as 1.01 bits/s (std 0.39). We also present informal feedback from over 230 users. We find that MetaArms demonstrate the feasibility of body-remapping approach in designing robotic limbs that may help us re-imagine what the human body could do.
A non‐isolated high step‐up DC‐DC converter with integrated 3 winding coupled inductor and reduced switch voltage stress

In this paper, a non‐isolated high step‐up dc‐dc converter based on coupled inductor is proposed. The proposed converter can be used in renewable energy applications. In suggested converter, the high voltage is achieved using 3‐winding coupled inductor, which leads to low voltage rate of the switch. A clamp circuit is used to recycle the leakage inductance energy. Also, the clamp circuit prevents the creation of voltage spikes on semiconductor devices and causes the voltage stress of elements are limited to less than the output voltage. The presented theoretical analyses show that the operation of suggested converter in continuous conduction mode needs to small magnetic inductor. Therefore, the size of coupled inductor's core is reduced, and so the size and cost of presented converter will be decreased. Analysis of the proposed converter is provided with laboratory results to verify its performance.
Treatment of Tricuspid Regurgitation With the FORMA Repair System

Background: Tricuspid regurgitation (TR) is common and undertreated as the risk of surgery is high in this patient population. Transcatheter devices offer treatment with a lower procedural risk. The FORMA Tricuspid Valve Therapy system (Edwards Lifesciences) will be reviewed here. Device Description: The system combines a spacer placed in the regurgitant orifice and a rail, over which the spacer is delivered, that is anchored to the endocardial surface of the RV. The spacer provides a surface for leaflet coaptation. Outcomes: Eighteen compassionate care patients and 29 patients included in the US EFS trial are reviewed. Patients were elderly (76 years) and high risk (Euroscore 2 was 9.0 and 8.1%, respectively). There were 2 procedural failures in both groups. Mortality at 30 days was 0% in the compassionate group and 7% in the EFS trial. TR was reduced in both groups; 2D/3D EROA 2.1 ± 1.8 to 1.1 ± 0.9 cm2 in the EFS trial and vena contracta width 12.1 ± 3.3 to 7.1 ± 2.2 mm. Symptomatic improvement was seen in both groups; the proportion of patients in NYHA class III/IV decreased from 84 to 28% at 30 days in the EFS group, and from 94 to 21% at 1 year, in the compassionate group. Conclusions: Reduction of TR with FORMA system is feasible and sustained. Despite residual TR post-procedure, the significant relative reduction in TR severity contributes to substantial clinical improvements in patients with a FORMA device in place.
Comparing phasic dopamine dynamics in the striatum, nucleus accumbens, amygdala, and medial prefrontal cortex

Midbrain dopaminergic neurons project to and modulate multiple highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. Dopamine regulates behaviors associated with action selection in the striatum, reward in the nucleus accumbens (NAc), emotional processing in the amygdala, and executive functioning in the medial prefrontal cortex (mPFC). The multifunctionality of dopamine likely occurs at the individual synapses, with varied levels of phasic dopamine release acting on different receptor populations. This study aimed to characterize specific aspects of stimulation‐evoked phasic dopamine transmission, beyond simple dopamine release, using in vivo fixed potential amperometry with carbon fiber recording microelectrodes positioned in either the dorsal striatum, NAc, amygdala, or mPFC of anesthetized mice. To summarize results, the present study found that the striatum and NAc had increased stimulation‐evoked phasic dopamine release, faster dopamine uptake (leading to restricted dopamine diffusion), weaker autoreceptor functioning, greater supply levels of available dopamine, and increased dopaminergic responses to DAT blockade compared to the amygdala and mPFC. Overall, these findings indicate that phasic dopamine may have different modes of communication between striatal and corticolimbic regions, with the first being profuse in concentration, rapid, and synaptically confined and the second being more limited in concentration but longer lasting and spatially dispersed. An improved understanding of regional differences in dopamine transmission can lead to more efficient treatments for disorders related to dopamine dysfunction.
Effects of phospholipase D during cultured osteoblast mineralization and bone formation

Mammalian phospholipase D (PLD) mostly hydrolyzes phosphatidylcholine producing phosphatidic acid. PLD activity was previously detected in different osteoblastic cell models, and was increased by several growth factors involved in bone homeostasis. To confirm possible actions of PLD isoforms during mineralization process, we analyzed their effects in osteoblastic cell models and during bone formation. PLD1 expression, along with PLD activity, increased during differentiation of primary osteoblasts and Saos‐2 cells, and peaked at the onset of mineralization. Subsequently, both PLD1 expression and PLD activity decreased, suggesting that PLD1 function is regulated during osteoblast maturation. In contrast, PLD2 expression was not significantly affected during differentiation of osteoblasts. Overexpression of PLD1 in Saos‐2 cells improved their mineralization potential. PLD inhibitor Halopemide or PLD1‐selective inhibitor, led to a decrease in mineralization in both cell types. On the contrary, the selective inhibitor of PLD2, did not affect the mineralization process. Moreover, primary osteoblasts isolated from PLD1 knockout (KO) mice were significantly less efficient in mineralization as compared with those isolated from wild type (WT) or PLD2 KO mice. In contrast, bone formation, as monitored by high‐resolution microcomputed tomography analysis, was not impaired in PLD1 KO nor in PLD2 KO mice, indicating that the lack of PLD1 or that of PLD2 did not affect the bone structure in adult mice. Taken together, our findings indicate that PLD activity, especially which of PLD1 isoform, may enhance the mineralization process in osteoblastic cells. Nonetheless, the lack of PLD1 or PLD2 do not seem to significantly affect bone formation in adult mice.
Wearable Kinesthetic I/O Device for Sharing Muscle Compliance

In this paper, we present a wearable kinesthetic I/O device, which is able to measure and intervene in multiple muscle activities simultaneously through the same electrodes. The developed system includes an I/O module, capable of measuring the electromyogram (EMG) of four muscle tissues, while applying electrical muscle stimulation (EMS) at the same time. The developed wearable system is configured in a scalable manner for achieving 1) high stimulus frequency (up to 70 Hz), 2) wearable dimensions in which the device can be placed along the limbs, and 3) flexibility of the number of I/O electrodes (up to 32 channels). In a pilot user study, which shared the wrist compliance between two persons, participants were able to recognize the level of their confederate's wrist joint compliance using a 4-point Likert scale. The developed system would benefit a physical therapist and a patient, during hand rehabilitation, using a peg board for sharing their wrist compliance and grip force, which are usually difficult to be observed in a visual contact.
Potential Factors Associated with Cognitive Improvement of Individuals Diagnosed with Mild Cognitive Impairment or Dementia in Longitudinal Studies

Despite the progressive nature of Alzheimer’s disease and other dementias, it is observed that many individuals that are diagnosed with mild cognitive impairment (MCI) in one clinical assessment, may return back to normal cognition (CN) in a subsequent assessment. Less frequently, such ‘back-transitions’ are also observed in people that had already been diagnosed with later stages of dementia. In this study, an analysis was performed on two longitudinal cohort datasets provided by 1) the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 2) the National Alzheimer’s Coordinating Centre (NACC). The focus is on the observed improvement of individuals’ clinical condition recorded in these datasets to explore potential associations with different factors. It is shown that, in both datasets, transitions from MCI to CN are significantly associated with younger age, better cognitive function, and the absence of ApoE ɛ4 alleles. Better cognitive function and in some cases the absence of ApoE ɛ4 alleles are also significantly associated with transitions from types of dementia to less severe clinical states. The effect of gender and education is not clear-cut in these datasets, although highly educated people who reach MCI tend to be more likely to show an improvement in their clinical state. The potential effect of other factors such as changes in symptoms of depression is also discussed. Although improved clinical outcomes can be associated with many factors, better diagnostic tools are required to provide insight into whether such improvements are a result of misdiagnosis, and if they are not, whether they are linked to improvements in the underlying neuropathological condition.
Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells

Abstract Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al2O3 nanoparticles, while AlCl3 showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 µg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.
Convergent analysis of genome‐wide genotyping and transcriptomic data suggests association of zinc finger genes with lithium response in bipolar disorder

Lithium is the mainstay treatment in bipolar disorder (BD) for its effectiveness in the acute phases of illness and in prevention of recurrences. Lithium's mechanism of action is complex, and while it modulates the function of hundreds of molecular targets, most of these effects could be unspecific and not relevant for its clinical efficacy. In this study, we applied an integrated analytical approach using genome‐wide expression and genotyping data from BD patients to identify lithium‐responsive genes that may serve as biomarkers of its efficacy. To this purpose, we tested the effect of treatment with lithium chloride 1 mM on the transcriptome of lymphoblasts from 10 lithium responders (LR) and 10 nonresponders (NR) patients and identified genes significantly influenced by the treatment exclusively in LR. These findings were integrated with gene‐based analysis on genome‐wide genotyping data from an extended sample of 205 BD patients characterized for lithium response. The expression of 29 genes was significantly changed by lithium exclusively in LR. Gene‐based analysis showed that two of these genes, zinc finger protein 429 (ZNF429) and zinc finger protein 493 (ZNF493), were also significantly associated with lithium response. Validation with quantitative real‐time polymerase chain reaction confirmed the lithium‐induced downregulation of ZNF493 in LR (p = .036). Using convergent analyses of genome‐wide expression and genotyping data, we identified ZNF493 as a potential lithium‐responsive target that may be involved in modulating lithium efficacy in BD. To our knowledge, this is the first evidence supporting the involvement of zinc finger proteins in lithium response.