Miracle-dz/UniFAR-FTUs huggingface dataset:
Online polarity-dependent effects of cerebellar transcranial direct current stimulation on motor speed and fine manual dexterity. A randomized controlled trial.

OBJECTIVES To investigate the role of cerebellar transcranial direct current stimulation (ctDCS) in modulating cerebellar functions in the motor domains of fine motor dexterity and motor speed. Methods: A single-blind, randomized sham-controlled study was conducted between January and July 2018 at the neuroscience laboratory of Imam Abdulrahman Bin Faisal University. A total of 63 healthy participants were assessed for eligibility. Sixty subjects met the criteria of the study and were randomly divided into 3 groups that received anodal, cathodal or sham ctDCS. Subjects performed 2 motor tasks, The Grooved Pegboard test (GPT) assessed fine manual dexterity and the Finger Tapping Task (FTT) assessed motor speed. Subjects undertook the 2 tasks in a single intervention session while 20 minutes of 2mA ctDCS was administered online. The short form of the Edinburgh Handedness Inventory was used to assess handedness and both tasks were performed first with the dominant and then the non-dominant hand. The primary outcome measures included the time of completion of GPT for fine manual dexterity and the mean number of finger-taps for motor speed of each hand. Results: ANOVA revealed a highly significant polarity dependent Group*Task interaction (p less than 0.01) for FTT scores. ANOVA also revealed a non-significant Group*Task interaction for GPT scores. Conclusion: Findings indicate that ctDCS has a modulatory effect on motor speed and could be a promising therapeutic intervention for treatment of neurological conditions with motor deficits.
Electrophysiological responses to sugars and amino acids in the nucleus of the solitary tract of type 1 taste receptor double knockout mice.

Strong evidence supports a major role for heterodimers of the Type 1 taste receptor (T1R) family in the taste transduction of sugars (T1R2+T1R3) and amino acids (T1R1+T1R3), but there are also neural and behavioral data supporting T1R-independent mechanisms. Most neural evidence for alternate mechanisms comes from whole-nerve recordings in mice with deletion of a single T1R family member, limiting conclusions about the functional significance and T1R independence of the remaining responses. To clarify these issues, we recorded single-unit taste responses from the nucleus of the solitary tract (NST) in T1R double-knockout (double-KO) mice lacking functional T1R1+T1R3 [KO1+3] or T1R2+T1R3 [KO2+3] receptors and their WT background strains (WT; (C57BL/6J [B6], 129X1/SvJ [S129]). In both double-KO strains, responses to sugars and a moderate concentration of an MSG+amiloride+IMP cocktail (0.1M, i.e, umami) were profoundly depressed, whereas a panel of 0.6M amino acids were mostly unaffected. Strikingly, in contrast to WT mice, no double-KO neurons responded selectively to sugars and umami, precluding segregation of this group of stimuli from those representing other taste qualities in a multidimensional scaling analysis. Nevertheless, residual sugar responses, mainly elicited by monosaccharides, persisted as small "sideband" responses in double-KO's. Thus, other receptors may convey limited information about sugars to the CNS but T1R's appear critical for coding the distinct perceptual features of sugar and umami stimuli. The persistence of amino acid responses supports previous proposals of alternate receptors, but because these stimuli affected multiple neuron types, further investigations are necessary.
Decoding fairness motivations from multivariate brain activity patterns

Abstract A preference for fairness may originate from prosocial or strategic motivations: we may wish to improve others’ well-being or avoid the repercussions of selfish behavior. Here, we used functional magnetic resonance imaging to identify neural patterns that dissociate these two motivations. Participants played both the ultimatum and dictator game (UG–DG) as proposers. Because responders can reject the offer in the UG, but not the DG, offers and neural patterns between the games should differ for strategic players but not prosocial players. Using multivariate pattern analysis, we found that the decoding accuracy of neural patterns associated with UG and DG decisions correlated significantly with differences in offers between games in regions associated with theory of mind (ToM), such as the temporoparietal junction, and cognitive control, such as the dorsolateral prefrontal cortex and inferior frontal cortex. We conclude that individual differences in prosocial behavior may be driven by variations in the degree to which self-control and ToM processes are engaged during decision-making such that the extent to which these processes are engaged is indicative of either selfish or prosocial motivations.
Population Pharmacokinetics of Vancomycin under Continuous Renal Replacement Therapy using a Polymethylmethacrylate Hemofilter.

BACKGROUND Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) has not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter). METHODS This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed and CLhemofilter was assessed. RESULTS Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5 ± 18.3 mL/min for blood flow rate and 26.3 ± 6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were: distribution volume of the central compartment (V1), 59.1 L; clearance of the central compartment (CL1), 1.35 L/h; distribution volume of the peripheral compartment (V2), 56.1 L; and clearance of the peripheral compartment (CL2), 3.65 L/h. BW and SOFA score were significantly associated with V1 (P < 0.05) and CL1 (P < 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration-time curve/minimum inhibitory concentration ≥ 400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 h for maintenance; these dosages were affected by BW and SOFA score. Mean CLhemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL1. CONCLUSIONS The authors clarified the pharmacokinetics and CLhemofilter of VCM in PMMA-CHDF patients. The pharmacokinetics of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW, but also with SOFA score.
Characteristics of Academic-Affiliated Health Systems

Supplemental Digital Content is available in the text. Purpose Changing market forces increasingly are leading academic medical centers (AMCs) to form or join health systems. But it is unclear how this shift is affecting the tripartite academic mission of education, research, and high-quality patient care. To explore this topic, the authors identified and characterized the types of health systems that owned or managed AMCs in the United States in 2016. Method The authors identified AMCs as any general acute care hospitals that had a resident-to-bed ratio of at least 0.25 and that were affiliated with at least one MD- or DO-granting medical school. Using the Agency for Healthcare Research and Quality 2016 Compendium of U.S. Health Systems, the authors also identified academic-affiliated health systems (AHSs) as those health systems that owned or managed at least one AMC. They compared AMCs and other general acute care hospitals, AHSs and non-AHSs, and AHSs by type of medical school relationship, using health system size, hospital characteristics, undergraduate and graduate medical education characteristics, services provided, and ownership. Results Health systems owned or managed nearly all AMCs (361, 95.8%). Of the 626 health systems, 230 (36.7%) met the definition of an AHS. Compared with other health systems, AHSs included more hospitals, provided more services, and had a lower ratio of primary care doctors to specialists. Most AHSs (136, 59.1%) had a single, shared medical school relationship, whereas 38 (16.5%) had an exclusive medical school relationship and 56 (24.3%) had multiple medical school relationships. Conclusions These findings suggest that several distinct types of relationships between AHSs and medical schools exist. The traditional vision of a medical school having an exclusive relationship with a single AHS is no longer prominent.
Superconductivity and magnetism in RbEu(Fe1−xCox)4As4

We studied the cobalt-doping effect on superconductivity and magnetism in a hole self-doped RbEuFe4As4 magnetic superconductor which shows superconductivity at 36.5 K and Eu2+ -spin ordering at 15 K. The Co solubility limit in RbEu(Fe1−xCox)4As4 achieves x = 0.21 for the solid-state reaction at 880 °C. With increasing x, decreases gradually, and superconductivity eventually disappears at . A spin-density-wave transition at 35–40 K is recovered for , which can be understood in terms of the hole-depletion and the disorder effects. On the other hand, remains unchanged despite the Co doping and, consequently, an intriguing superconducting ferromagnet without Meissner state is realized in the range of 0.125 0.155. Our results indicate that the Eu2+ spins essentially decouple with superconductivity over a wide doping range, making the coexistence of superconductivity and ferromagnetism possible in the 1144-type system.
Mapping neural dynamics underlying saccade preparation and execution and their relation to reaction time and direction errors

Our ability to control and inhibit automatic behaviors is crucial for negotiating complex environments, all of which require rapid communication between sensory, motor, and cognitive networks. Here, we measured neuromagnetic brain activity to investigate the neural timing of cortical areas needed for inhibitory control, while 14 healthy young adults performed an interleaved prosaccade (look at a peripheral visual stimulus) and antisaccade (look away from stimulus) task. Analysis of how neural activity relates to saccade reaction time (SRT) and occurrence of direction errors (look at stimulus on antisaccade trials) provides insight into inhibitory control. Neuromagnetic source activity was used to extract stimulus‐aligned and saccade‐aligned activity to examine temporal differences between prosaccade and antisaccade trials in brain regions associated with saccade control. For stimulus‐aligned antisaccade trials, a longer SRT was associated with delayed onset of neural activity within the ipsilateral parietal eye field (PEF) and bilateral frontal eye field (FEF). Saccade‐aligned activity demonstrated peak activation 10ms before saccade‐onset within the contralateral PEF for prosaccade trials and within the bilateral FEF for antisaccade trials. In addition, failure to inhibit prosaccades on anti‐saccade trials was associated with increased activity prior to saccade onset within the FEF contralateral to the peripheral stimulus. This work on dynamic activity adds to our knowledge that direction errors were due, at least in part, to a failure to inhibit automatic prosaccades. These findings provide novel evidence in humans regarding the temporal dynamics within oculomotor areas needed for saccade programming and the role frontal brain regions have on top‐down inhibitory control.
GDNF rescues the fate of neural progenitor grafts by attenuating Notch signals in the injured spinal cord in rodents

Glial-derived neurotrophic factor expression by grafted human neural progenitor cells enhances functional recovery after spinal cord injury. The fate-determining factor Neural progenitor cells (NPCs) emerged as a potential therapeutic approach for repairing and regenerating neurons after spinal cord injury. However, the hostile microenvironment of the injured spinal cord contributes to the limited degree of recovery observed after NPC transplant in rodents. Now, Khazaei et al. have shown that activation of Notch signaling in the spinal cord after injury reduces the therapeutic potential of the transplanted NPCs. Counteracting Notch activation by expressing GDNF in transplanted NPCs promoted differentiation toward a neuronal cell fate and improved motor function after injury in rodents. The results suggest that modulating the injured microenvironment might improve recovery after stem cell transplant. Neural progenitor cell (NPC) transplantation is a promising strategy for the treatment of spinal cord injury (SCI). In this study, we show that injury-induced Notch activation in the spinal cord microenvironment biases the fate of transplanted NPCs toward astrocytes in rodents. In a screen for potential clinically relevant factors to modulate Notch signaling, we identified glial cell–derived neurotrophic factor (GDNF). GDNF attenuates Notch signaling by mediating delta-like 1 homolog (DLK1) expression, which is independent of GDNF’s effect on cell survival. When transplanted into a rodent model of cervical SCI, GDNF-expressing human-induced pluripotent stem cell–derived NPCs (hiPSC-NPCs) demonstrated higher differentiation toward a neuronal fate compared to control cells. In addition, expression of GDNF promoted endogenous tissue sparing and enhanced electrical integration of transplanted cells, which collectively resulted in improved neurobehavioral recovery. CRISPR-induced knockouts of the DLK1 gene in GDNF-expressing hiPSC-NPCs attenuated the effect on functional recovery, demonstrating that this effect is partially mediated through DLK1 expression. These results represent a mechanistically driven optimization of hiPSC-NPC therapy to redirect transplanted cells toward a neuronal fate and enhance their integration.
Presidentialization of Electorate’s Behavior in the Election to Voivodeship Sejmiks in 2018

27 Abstract: The main category in this article is electoral presidentialization, understood as a tendency of voters’ behavior to mirror the decisions typical for presidential elections. Here, the category under consideration is analyzed in two dimensions: leader effect and social approval for the organization of television debates of the leaders of two most important parties. The author explains the process in question on the basis of quantitative and percentage distribution of answers to two questions to be found in three editions of the nation-wide electorate study “Political Preferences”. This article concerns voters’ preferences in a survey that was conducted just after the self-government election in 2018. In order to grasp the specificity of electoral behavior in this particular voting, the analysis was conducted in a comparative manner, and the subject of comparison was the 2015 election to the Sejm. The results of studies organized in 2012 and 2013, when no election was organized in Poland, were also referred to in a necessary scope.
Editorial 2020

We are pleased to report that Molecular Ecology continues to perform very well. Molecular Ecology ranks second among ecology or evolution journals in total impact as measured by Google Scholar's h5-index, which is the h-index for articles published in the last 5 years. With respect to the impact of individual articles, Molecular Ecology ranks third in h5-median for ecology or evolution journals. The h5-median is the median number of citations for the articles that make up a journal's h5-index. Both metrics are considered to offer a more accurate representation of journal quality and impact than ISI’s impact factors, which rely on citations over two year window only and are sensitive to the inclusion of a handful of very highly cited papers such as computer programs. In October 2019, we were pleased to welcome a new Managing Editor, Benjamin Sibbett. Ben has a PhD in plant molecular biology and has expertise in many of the bioinformatics and molecular methods employed by our authors. Before joining Wiley, he worked as a freelance peer review manager for another editorial company in the UK, where he gained expertise in managing the peer review process. In his brief time with Molecular Ecology and Molecular Ecology Resources, Ben has proven himself not only to be an efficient Managing Editor, but also one who is highly responsive to author questions and concerns. We also want to take this opportunity to thank our previous Managing Editor, Karen Chambers, for her many contributions to Molecular Ecology and Molecular Ecology Resources over the past four years. In her first year as Managing Editor, Karen oversaw the transition of the journals from an external editorial office at the University of British Columbia to an internal Wiley office. It was a trial by fire! The new Editorial Office was under-resourced initially, which put a huge amount of stress on Karen, but she did her very best to manage the large volume of manuscripts and did not complain. She also made several changes to the editorial process and manuscript management system in ScholarOne, which made the review process run more smoothly and efficiently. While Karen has now moved to another editorial position at Wiley, she graciously introduced Ben to editorial processes at Wiley, as well as to the peer review system for Molecular Ecology and Molecular Ecology Resources. 2 | ANNOUNCEMENTS
METTL3-mediated m6A is required for murine oocyte maturation and maternal-to-zygotic transition

ABSTRACT N6-methyladenosine (m6A) is the most prevalent epigenetic modification of messenger RNA (mRNA) in higher eukaryotes; this modification is mainly catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. Although m6A modification has been proven to play an essential role in diverse biological processes, our knowledge of Mettl3 is still limited because Mettl3 mutations are lethal to embryos in both mammals and plants. In this study, we knocked down Mettl3 by microinjection of its specific short interfering RNAs (siRNAs) or morpholino into fully grown germinal vesicle (GV) oocytes. As a result, we demonstrated that knocking down Mettl3 in female germ cells severely inhibited oocyte maturation by decreasing mRNA translation efficiency and led to defects in the maternal-to-zygotic transition, probably due to its interference in disrupting mRNA degradation. The discovery from this study suggests that the reversible m6A modification has vital functions in mammalian oocyte maturation and pre-implantation embryonic development processes.
Nivolumab treatment for relapsed/refractory Epstein-Barr virus-associated hemophagocytic lymphohistocytosis in adults.

Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults if without allogeneic hematopoietic stem cell transplantation. Here, we retrospectively analyzed the data of seven r/r EBV-HLH patients treated with nivolumab on compassionate use in West China Hospital. Six patients responded. Five of them achieved and remained in clinical complete remission for a median follow-up of 16 months (range 11.4-18.9 months). Importantly, both plasma and cellular EBV were completely eradicated in four patients. Single cell RNA sequencing analysis showed that hyperactive monocytes/macrophages and ineffective CD8 T cells with an unbalanced activation program were associated with the syndrome. Nivolumab treatment expanded PD-1+ T cells and restored the expressions of HLH-associated degranulation and co-stimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a cure promise for r/r EBV-HLH, presumably by restoring the unbalanced anti-EBV program of the immune system.
Glycolysis regulated transglutaminase 2 activation in cardiopulmonary fibrogenic remodeling

The pathophysiology of pulmonary hypertension (PH) and heart failure (HF) includes fibrogenic remodeling associated with the loss of pulmonary arterial (PA) and cardiac compliance. We and others have previously identified transglutaminase 2 (TG2) as a participant in adverse fibrogenic remodeling. However, little is known about the biologic mechanisms that regulate TG2 function. We examined physiological mouse models of experimental PH, HF, and type 1 diabetes that are associated with altered glucose metabolism/glycolysis and report here that TG2 expression and activity are elevated in pulmonary and cardiac tissues under all these conditions. We additionally used PA adventitial fibroblasts to test the hypothesis that TG2 is an intermediary between enhanced tissue glycolysis and fibrogenesis. Our in vitro results show that glycolytic enzymes and TG2 are upregulated in fibroblasts exposed to high glucose, which stimulates cellular glycolysis as measured by Seahorse analysis. We examined the relationship of TG2 to a terminal glycolytic enzyme, pyruvate kinase M2 (PKM2), and found that PKM2 regulates glucose‐induced TG2 expression and activity as well as fibrogenesis. Our studies further show that TG2 inhibition blocks glucose‐induced fibrogenesis and cell proliferation. Our findings support a novel role for glycolysis‐mediated TG2 induction and tissue fibrosis associated with experimental PH, HF, and hyperglycemia.
A Systematic Review of Interventions for Hope/Hopelessness in Older Adults

ABSTRACT Objectives: Hope/hopelessness is an important determinant of health and death, and is a modifiable risk factor for older adults. The present review aimed to evaluate the effectiveness of interventions on hope among older populations. Methods: PsychINFO and PubMed were systematically searched. Publications reporting on interventions delivered to older adults that included quantitative data on hope/hopelessness were systematically reviewed. Results: Thirty-six studies were included, most with hope/hopelessness as a secondary outcome. Interventions based on CBT alone or combined with antidepressants significantly decreased hopelessness in depressed older adults. Psychological interventions based on life review effectively improved hope/hopelessness in a range of samples, including depressed, bereaving, or medically ill older adults. Little to no support was found for exercise programs for healthy older adults, educational interventions for medically ill individuals, or Dignity Therapy for palliative care patients. Conclusions: Hope/hopelessness in older adults can be improved using psychological interventions based on CBT and life review. Controlled trials with hope/hopelessness as a primary objective are needed to more clearly demonstrate effectiveness. Clinical implications: Cognitive-behavioral interventions can improve hopelessness in depressed older adults. Life-review based interventions can positively impact hope in a range of older populations. Dignity Therapy, physical exercise, and educational programs may not effectively improve hope/hopelessness in older adults.