Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of awareness of the perturbation during motor adaptation on hand localization

Explicit awareness of a task is often evoked during rehabilitation and sports training with the intention of accelerating learning and improving performance. However, the effects of awareness of perturbations on the resulting sensory and motor changes produced during motor learning are not well understood. Here, we use explicit instructions as well as large rotation sizes to generate awareness of the perturbation during a visuomotor rotation task and test the resulting changes in both perceived and predicted sensory consequences as well as implicit motor changes. We split participants into 4 groups which differ in both magnitude of the rotation (either 30° or 60°) during adaptation, and whether they receive a strategy to counter the rotation or not prior to adaptation. Performance benefits of explicit instruction are largest during early adaptation but continued to lead to improved performance through 90 trials of training. We show that with either instruction, or with large perturbations, participants become aware of countering the rotation. However, we find a base amount of implicit learning, with equal magnitudes, across all groups, even when asked to exclude any strategies while reaching with no visual feedback of the hand. Participants also estimate the location of the unseen hand when it is moved by the robot (passive localization) and when they generate their own movement (active localization) following adaptation. These learning-induced shifts in estimates of hand position reflect both proprioceptive recalibration and updates in the predicted consequences of movements. We find that these estimates of felt hand position, which reflect updates in both proprioception and efference based estimates of hand position, shift significantly for all groups and were not modulated by either instruction or perturbation size. Our results indicate that not all processes of motor learning benefit from an explicit awareness of the task. Particularly, proprioceptive recalibration and the updating of predicted sensory consequences are largely implicit processes.
Association of Acupuncture Treatment with Mortality of Type 2 Diabetes in China: Evidence of a Real-World Study

The prevalence and mortality rates of diabetes are increasing globally, posing severe challenges to health systems. Acupuncture is used worldwide as a non-drug treatment for diabetes. However, empirical evidence of the effect of combined acupuncture and drug treatments on diabetic-associated mortality is limited. This study aimed to examine this association of acupuncture treatment with mortality of type 2 diabetes based on real-world data. A four-year cohort study was conducted in Shanghai between 2015 and 2018, The database consisted of 37,718 patients (acupuncture group: 6865 type 2 diabetes mellitus (T2DM) patients, non-acupuncture (control) group: 30,853 T2DM patients) in 2016. The objective was to analyze the impact of receiving acupuncture prescriptions for diabetes in 2016 on all-cause mortality in 2018 based on real-world data. An Inverse Probability Weighted Regression Adjustment (IPWRA) and Propensity Score Matching (PSM) were used to minimize the bias due to potential confounding variables to increase the reliability of differences in comparisons between the two groups. Our inverse probability weighted regression results suggest that the coefficient of the key dependent variable of accepted acupuncture in 2016 was negative (coefficient: −0.0002; 95% CI: −0.0024–0.0019, p = 0.857), but it is not statistically significant. In robustness check, PSM with the nearest-neighbor method with replacement at a 1:4 ratio and 1:3 ratio and kernel matching showed that the average treatment effect was negative. Therefore, there was a negative correlation between acupuncture combined with other drugs and the mortality of diabetic patients, but it was not statistically significant.
Evaluation Study of Intraoperative Cytology Smear and Frozen Section of Glioma

Objective: Glioma is the commonest primary malignant brain tumour. Diagnosis is made based on cytology smear, frozen section and histopathological examination. Intraoperative pathological diagnosis using either cytology smear, frozen section or combination of both, plays a crucial role in patient’s future management and prognosis. This study aims to determine the accuracy of cytology smear and frozen section in glioma, and to compare the difference between both techniques. Methods: A cross-sectional study was conducted involving 22 cases of glioma diagnosed intraoperatively from January 2013 until August 2019 in Hospital Universiti Sains Malaysia. The selected tissues were processed for cytology smear and frozen section. The remaining tissues were proceeded for paraffin section. The diagnosis was categorized as either low-grade or high-grade glioma based on cellularity, nuclear pleomorphism, mitotic count, microvascular proliferation and necrosis. The sensitivity and specificity of frozen section and cytology smears were determined based on paraffin section being as the gold standard. The accuracy of both techniques was compared using statistical analysis. Results: The overall sensitivity and specificity of cytology smear were 100% and 76.9%, respectively. Meanwhile, the sensitivity and specificity of frozen section were 100% and 84.6%. There was no significant difference in diagnostic accuracy between cytology smear and frozen section in glioma (p>0.05). Conclusion: Cytology smears provides an alternative method for frozen section due to good cellularity and morphology on smear. Cytology smear is rapid, inexpensive, small amount of tissue requirement and less technical demand. This finding may benefit to the hospital or treatment centres where frozen section facility is unavailable.
Automatic Prediction of Cognitive and Functional Decline Can Significantly Decrease the Number of Subjects Required for Clinical Trials in Early Alzheimer’s Disease

Background: While both cognitive and magnetic resonance imaging (MRI) data has been used to predict progression in Alzheimer’s disease, heterogeneity between patients makes it challenging to predict the rate of cognitive and functional decline for individual subjects. Objective: To investigate prognostic power of MRI-based biomarkers of medial temporal lobe atrophy and macroscopic tissue change to predict cognitive decline in individual patients in clinical trials of early Alzheimer’s disease. Methods: Data used in this study included 312 patients with mild cognitive impairment from the ADNI dataset with baseline MRI, cerebrospinal fluid amyloid-β, cognitive test scores, and a minimum of two-year follow-up information available. We built a prognostic model using baseline cognitive scores and MRI-based features to determine which subjects remain stable and which functionally decline over 2 and 3-year follow-up periods. Results: Combining both sets of features yields 77%accuracy (81%sensitivity and 75%specificity) to predict cognitive decline at 2 years (74%accuracy at 3 years with 75%sensitivity and 73%specificity). When used to select trial participants, this tool yields a 3.8-fold decrease in the required sample size for a 2-year study (2.8-fold decrease for a 3-year study) for a hypothesized 25%treatment effect to reduce cognitive decline. Conclusion: When used in clinical trials for cohort enrichment, this tool could accelerate development of new treatments by significantly increasing statistical power to detect differences in cognitive decline between arms. In addition, detection of future decline can help clinicians improve patient management strategies that will slow or delay symptom progression.
RNA editing with CRISPR-Cas13

Precise transcriptome engineering Efficient and precise RNA editing to correct disease-relevant transcripts holds great promise for treating genetic disease. Cox et al. took advantage of the ability of Cas13b, an effector from a type VI CRISPR-Cas system, to target specific RNAs directly (see the Perspective by Yang and Chen). They fused Cas13b with the ADAR2 adenosine deaminase domain and used rational protein engineering to improve the resultant enzyme. These approaches yielded an RNA knockdown and editing platform that allowed efficient and specific RNA depletion and correction in mammalian cells. Science, this issue p. 1019; see also p. 996 An RNA-editing technology is developed to efficiently and specifically deplete and correct RNA directly in mammalian cells. Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), which has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineered this system to create a high-specificity variant and minimized the system to facilitate viral delivery. REPAIR presents a promising RNA-editing platform with broad applicability for research, therapeutics, and biotechnology.
Representing the Urban Heat Island Effect in Future Climates

<p>An increasing fraction of people living in urban areas and the expected increase in long lasting heat waves highlight the important role of urban climates in terms of future climate change impacts, especially with relation to the heat-health sector. Due to the urban heat island (UHI) effect and its (generally) increased intensity particularly during nighttime, people living in urban areas happen to be more affected by heat-related discomfort and health risks than those in non-urban regions. In this contribution, temperatures of both rural and urban sites (station couples) in Switzerland and Southern Germany are analyzed, using (i) observed as well as (ii) bias-corrected and downscaled climate model data for daily minimum (tmin) and daily maximum temperature (tmax) to account for the UHI in future climates. As meteorological data are often restricted to locations of long-term measurements at rural sites only, they need to be transferred to urban sites first. For this purpose, the well-established quantile mapping technique (QM) is tested in a two-step manner. The resulting products are urban time series at daily resolution for tmin and tmax. By analyzing the temperature differences of the observed climate at rural sites and their respective urban counterparts and by assuming a stationary relationship between both, we can represent the UHI in future climates, which is quantified in terms of heat indices based on tmin and tmax (tropical nights, summer days, hot days). </p><p>The QM performance is evaluated using long-term weather station data of a Zurich station couple in a comprehensive cross-validation framework. Results reveal a promising performance in the present-day climate, given very low biases in the validation. </p><p>Applying the proposed method to the employed station couples, projections indicate distinct urban-rural temperature differences (UHI) during nighttime (considering the frequency of tropical nights based on tmin) compared to weak differences during the day (considering the frequency of summer days and hot days based on tmax). Moreover, scenarios suggest the frequency of all indices to dramatically rise at the urban site by the end of the century under a strong emission scenario (RCP8.5): compared to the rural site, the number of tropical nights almost doubles while the number of summer days reveals about 15% more days at the urban site when focusing on the station couple in Zurich and the late scenario period. The lack of nighttime relief, indicated by tmin not falling below 20&#176;C (i.e. a tropical night), is especially problematic in terms of human health and makes the study of the urban climate in general and the UHI effect in particular indispensable. </p>
Spirulina platensis Provides a Small Advantage in Vertical Jump and Sprint Performance But Does Not Improve Elite Rugby Players’ Body Composition

Abstract The present study aimed to examine the effects of Spirulina supplementation on anthropometrical measurements and physical performance in elite rugby players. Twenty-two elite male Rugby Union players (21–36 years old) volunteered to participate in this study. They were randomly assigned to a Spirulina group (SPI: n = 11), or a placebo group (PLA: n = 11) in a double-blind design. Subjects were supplemented with Spirulina platensis (5.7 g/d) or placebo (isoproteic and caloric) for 7 weeks. At baseline (W0) and after 7 weeks of supplementation (W7), the same anthropometric measurements and physical performance test battery were performed. These tests included isokinetic leg strength and power, vertical jump, speed, and aerobic fitness assessment. For anthropometric data, the fat mass percentage was significantly reduced in both groups without significant difference between groups. While both groups exhibited significant improvements for Squat Jump (SJ), Countermovement Jump (CMJ), and 10- and 30-m sprints between W0 and W7, higher percentage improvements with the SPI group did not reach significance. Neither training alone (PLA) nor training associated with Spirulina supplementation affected leg maximal strength and power or aerobic fitness. Seven weeks of Spirulina supplementation in elite rugby players did not improve body composition or substantially increase physical performance. We only observed a non-significant small advantage in vertical jump and sprint performance in the SPI group. Based on the data from this study, Spirulina supplementation has modest effects in elite rugby players during the competitive phase. Further studies are required to verify Spirulina supplementation effects among athletes of different sports, ages, genders, and athletic levels with longer durations and higher dosages.
The development, recognition, and learning mechanisms of animal-like neural network

How animal neural system addresses the object identity-preserving recognition problem is largely unknown1. Artificial neural network such as convolution network2(CNN) has reached human level performance in recognition tasks, however, animal neural system does not support such kernel scanning operation across retinal neurons, and thus the neuronal responses do not match that of CNN units. Here, we used an alternative recognition-reconstruction network (RRN) architecture as an analogy to animal-like system, and the resulting neural characteristics agreed fairly well with electrophysiological measurements in monkey studies3,4. First, in network development study, the RRN also experienced critical developmental stages characterized by specificities in neuronal types, connectivity strength and firing pattern, from early stage of coarse salience map recognition to mature stage of fine structure recognition. In digit recognition study, we witnessed that the RRN could maintain object invariance representation under various viewing conditions by coordinated adjustment of responses of population neurons. And such concerted population responses contained untangled object identity and properties information that could be accurately extracted via a simple weighted summation decoder. In the learning and forgetting study, novel structure recognition was implemented by adjusting entire synapses in low magnitude while pattern specificities of original synaptic connectivity were preserved, which guaranteed a learning process without disrupting the existing functionalities. This work benefits the understanding of human neural mechanism and the development of humane-like machine intelligence.
Do erythrocytic miRNA have a function

Despite being translationally null, erythrocytes contain miRNA at concentrations equal to nucleated cells, meaning that of the miRNA found in peripheral blood ~ 99 % is located in red cells. Despite this huge abundance, the literature currently regards erythrocytic miRNA (e-miRNA) as redundant. Data from Hamilton lab challenges this notion as it shows that e-miRNA are stable, maintain a catalytic potential, and have sequence profiles similar across species, indicating conservation. This thesis investigates what the potential function of emiRNA could be, both within erythrocytes and in other cells. To develop hypotheses, RISC-protein interactions were evaluated unearthing the appearance of an apparently post-translationally modified AGO2; what this modification is, remains to be defined. As part of a homeostatic hypothesis, the idea that e-miRNA may act as a molecular signal and regulate the transcriptome of phagocytosing cells was evaluated. However, it was discovered that e-miRNA are lost as RBCs age, potentially through vesicularisation. The differences between RBC vesicles that occur in vivo and those that occur when blood is stored ready for transfusion were evaluated. This highlighted a potential artefact within the literature with regards to what is termed as “microvesicles” (MVs). The clinical concern regarding storage MVs was evaluated through the generation of a phago/endocytosis model, and consistent with recent publications, no mal-effect was observed. This portion of the study highlighted a secondary structure within macrophages that is not a phagolysosome, but does process internalised RBC-MVs.
Transient Breakage of the Nucleocytoplasmic Barrier Controls Spore Maturation via Mobilizing the Proteasome Subunit Rpn11 in the Fission Yeast Schizosaccharomyces pombe

Forespore membrane (FSM) closure is a process of specialized cytokinesis in yeast meiosis. FSM closure begins with the contraction of the FSM opening and finishes with the disassembly of the leading-edge proteins (LEPs) from the FSM opening. Here, we show that the FSM opening starts to contract when the event of virtual nuclear envelope breakdown (vNEBD) occurs in anaphase II of the fission yeast Schizosaccharomyces pombe. The occurrence of vNEBD controls the redistribution of the proteasomal subunit Rpn11 from the nucleus to the cytosol. To investigate the importance of Rpn11 re-localization during vNEBD, Rpn11 was sequestered at the inner nuclear membrane by fusion with the transmembrane region of Bqt4 (Rpn11-GFP-INM). Remarkably, in the absence of endogenous rpn11+, the cells carrying Rpn11-GFP-INM had abnormal or no spore formation. Live-cell imaging analysis further reveals that the FSM opening failed to contract when vNEBD occurred, and the LEP Meu14 was persistently present at the FSM in the rpn11-gfp-INM cells. The results suggest that the dynamic localization of Rpn11 during vNEBD is essential for spore development.
Short- vs. Long-Course Antibiotic Treatment for Acute Streptococcal Pharyngitis: Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis. METHODS: Randomized controlled trials comparing short-course antibiotic therapy (≤5 days) with long-course antibiotic therapy (≥7 days) for patients with streptococcal pharyngitis were included. Two primary outcomes: early clinical cure and early bacterial eradication. RESULTS: Fifty randomized clinical trials were included. Overall, short-course antibiotic treatment was as effective as long-course antibiotic treatment for early clinical cure (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.79 to 1.15). Subgroup analysis showed that short-course penicillin was less effective for early clinical cure (OR 0.43; 95% CI, 0.23 to 0.82) and bacteriological eradication (OR 0.34; 95% CI, 0.19 to 0.61) in comparison to long-course penicillin. Short-course macrolides were equally effective, compared to long-course penicillin. Finally, short-course cephalosporin was more effective for early clinical cure (OR 1.48; 95% CI, 1.11 to 1.96) and early microbiological cure (OR 1.60; 95% CI, 1.13 to 2.27) in comparison to long-course penicillin. In total, 1211 (17.7%) participants assigned to short-course antibiotic therapy, and 893 (12.3%) cases assigned to long-course, developed adverse events (OR 1.35; 95% CI, 1.08 to 1.68). CONCLUSIONS: Macrolides and cephalosporins belong to the list of “Highest Priority Critically Important Antimicrobials”; hence, long-course penicillin V should remain as the first line antibiotic for the management of patients with streptococcal pharyngitis as far as the benefits of using these two types of antibiotics do not outweigh the harms of their unnecessary use.
Quality assessment of yogurt enriched with different types of fibers

ABSTRACT This study evaluated the effect of the addition of four different types of dietary fibers on the rheological, physicochemical and sensory characteristics of yogurt. The four types of fibers (inulin, pea, oat and wheat) were added in the yogurt formulation in different proportions (1%–2.5%) using classical technology adapted to laboratory conditions. The obtained results showed that, the most viscous samples were obtained with wheat fibers addition (1% and 1.5%), while the best viscous characteristics were obtained for the samples with oat fibers addition (2% and 2.5%). The lowest syneresis value (38.86 ± 0.2) were observed for the samples with 1.5% pea fibers addition. Yogurt samples with the highest acceptance scores were samples with 2% wheat fibers and respectively with 2.5% pea fibers addition. All the tested fibers were compatible with the yogurt-manufacturing process. Therefore, the fibers addition in yogurt could be considered an alternative to incorporate dietary fibers in the human diet.
Master regulators of genetic interaction networks mediating statin drug response in Saccharomyces cerevisiae vary with genetic background

Determination of genetic interaction networks (GINs) surrounding drug targets identifies buffering genes and provides molecular insight into drug response in individuals. Here we used backcross methodology to create Saccharomyces cerevisiae deletion libraries in three genetic backgrounds resistant to statins, which are additional to the statin-sensitive S288C deletion library that has provided much of what is known about GINs in eukaryotes. Whole genome sequencing and linkage group analysis confirmed the genomic authenticity of the new deletion libraries. Statin response was probed by drug-gene interactions with atorvastatin and cerivastatin treatments, as well as gene-gene interactions with the statin target HMG1 and HMG2 genes or the sterol homeostatic ARV1 gene. The 20 GINs generated from these interactions were not conserved by function or topology across the four genetic backgrounds. Centrality measures and hierarchical agglomerative clustering identified master regulators that if removed collapsed the networks. Community structure distinguished a characteristic early secretory pathway pattern of gene usage in each genetic background. ER stress in statin-resistant backgrounds was buffered by protein folding genes, which was confirmed by reduced activation of the unfolded protein response in statin-resistant backgrounds relative to the statin-sensitive S288C background. These network analyses of new gene deletion libraries provide insight into the complexity of GINs underlying individual drug response.