Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical Excitability Dynamics During Fear Processing

Background: Little is known about the modulation of cortical excitability in the prefrontal cortex during fear processing in humans. Here, we aimed to transiently modulate and test the cortical excitability during fear processing using transcranial magnetic stimulation (TMS) and brain oscillations in theta and alpha frequency bands with electroencephalography (EEG). Methods: We conducted two separate experiments (no-TMS and TMS). In the no-TMS experiment, EEG recordings were performed during the instructed fear paradigm in which a visual cue (CS+) was paired with an aversive unconditioned stimulus (electric shock), while the other visual cue was unpaired (CS-). In the TMS experiment, in addition the TMS was applied on the right dorsomedial prefrontal cortex (dmPFC). The participants also underwent structural MRI (magnetic resonance imaging) scanning and were assigned pseudo-randomly to both experiments, such that age and gender were matched. The cortical excitability was evaluated by time-frequency analysis and functional connectivity with weighted phase lag index (WPLI). We further linked the excitability patterns with markers of stress coping capability. Results: After visual cue onset, we found increased theta power in the frontal lobe and decreased alpha power in the occipital lobe during CS+ relative to CS- trials. TMS of dmPFC increased theta power in the frontal lobe and reduced alpha power in the occipital lobe during CS+. The TMS pulse increased the information flow from the sensorimotor region to the prefrontal and occipital regions in the theta and alpha bands, respectively during CS+ compared to CS-. Pre-stimulation frontal theta power (0.75–1 s) predicted the magnitude of frontal theta power changes after stimulation (1–1.25 s). Finally, the increased frontal theta power during CS+ compared to CS- was positively correlated with stress coping behavior. Conclusion: Our results show that TMS over dmPFC transiently modulated the regional cortical excitability and the fronto-occipital information flows during fear processing, while the pre-stimulation frontal theta power determined the strength of achieved effects. The frontal theta power may serve as a biomarker for fear processing and stress-coping responses in individuals and could be clinically tested in mental disorders.
Arthroplasty infection rates in fractured neck of femur: single vs dual antibiotic cement.

INTRODUCTION Mortality rates following hip arthroplasty range between 10% and 40% after 12 months. A higher rate is attributed to postoperative complications, of which surgical site infection is one of the most significant. In an effort to reduce surgical site infection following arthroplasty, antibiotics can be added to the cement used. The primary aim of this study was to determine whether dual antibiotic impregnated cement can reduce the rate of deep surgical site infection in patients following cemented arthroplasty for fractured neck of femur compared with single antibiotic impregnated cement. The secondary aim was to compare the rate of superficial surgical site infection in single compared with dual antibiotic cement. MATERIALS AND METHODS A total of 206 patients were included. Group 1 included 108 retrospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using single antibiotic impregnated cement. Group 2 included 98 prospective patients who underwent arthroplasty for neck of femur fracture over a 12-month period using dual antibiotic impregnated cement. The rates of deep and superficial surgical site infection were investigated. RESULTS Group 1 had a deep surgical site infection rate of 2.9% (n = 3), Group 2 had a deep surgical site infection rate of 0% (n = 0). Group 1 had a superficial surgical site infection rate of 3.7% (n = 4), Group 2 had a superficial surgical site infection rate of 5.1% (n = 5). CONCLUSION Dual antibiotic cement reduced the rate of deep surgical site infection compared with conventional single antibiotic cement in arthroplasty for fractured neck of femur. Only a marginal difference in superficial surgical site infection was observed.
Regulation of Membrane Turnover by Phosphatidic Acid: Cellular Functions and Disease Implications

Phosphatidic acid (PA) is a simple glycerophospholipid with a well-established role as an intermediate in phospholipid biosynthesis. In addition to its role in lipid biosynthesis, PA has been proposed to act as a signaling molecule that modulates several aspects of cell biology including membrane transport. PA can be generated in eukaryotic cells by several enzymes whose activity is regulated in the context of signal transduction and enzymes that can metabolize PA thus terminating its signaling activity have also been described. Further, several studies have identified PA binding proteins and changes in their activity are proposed to be mediators of the signaling activity of this lipid. Together these enzymes and proteins constitute a PA signaling toolkit that mediates the signaling functions of PA in cells. Recently, a number of novel genetic models for the analysis of PA function in vivo and analytical methods to quantify PA levels in cells have been developed and promise to enhance our understanding of PA functions. Studies of several elements of the PA signaling toolkit in a single cell type have been performed and are presented to provide a perspective on our understanding of the biochemical and functional organization of pools of PA in a eukaryotic cell. Finally, we also provide a perspective on the potential role of PA in human disease, synthesizing studies from model organisms, human disease genetics and analysis using recently developed PLD inhibitors.
PYRUVATE OXIDATION IN DESULPHOVIBRIO DESULPHURICANS

The metabolism of Desulphovibrio desulphuricans does not appear to have been studied extensively. Stephenson and Stickland (1931) and Sisler and ZoBell (1950) showed that the organism can use gaseous hydrogen as a reducing agent for sulfate reduction. By growing cultures for several generations in mineral salt solution containing less than one part per million of sulfate, Sisler and ZoBell (1951a) were able to show that autotrophic sulfate-reducers can utilize C02 as the sole hydrogen acceptor. Neither growth nor hydrogen uptake, however, was nearly as rapid in the sulfate-free media as in similar media enriched with sulfate. However, washed cells of sulfate-reducers were found to reduce fumarate considerably more rapidly than sulfate (Sisler and ZoBell, 1951a). Sisler and ZoBell (1951b) reported the fixation of nitrogen by hydrogenase producing sulfate-reducers. Postgate (1952) reported that many strains of this organism were able to grow in the absence of sulfate if pyruvate was present. Pyruvate oxidation in bacterial extracts has been studied by several authors. In the presence of inorganic phosphate, cell-free extracts of Lactobacillus delbruecklii oxidatively decarboxyl-
Functional-Genomics-Based Identification and Characterization of Open Reading Frames Encoding α-Glucoside-Processing Enzymes in the Hyperthermophilic Archaeon Pyrococcus furiosus

ABSTRACT Bioinformatics analysis and transcriptional response information for Pyrococcus furiosus grown on α-glucans led to the identification of a novel isomaltase (PF0132) representing a new glycoside hydrolase (GH) family, a novel GH57 β-amylase (PF0870), and an extracellular starch-binding protein (1,141 amino acids; PF1109-PF1110), in addition to several other putative α-glucan-processing enzymes.
Bax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death

BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.
Alzheimer’s disease: future drug development and the blood-brain barrier

In 2019, there is not a single biologic that is FDA approved for brain disorders wherein the drug crosses the blood-brain barrier (BBB). Bevacizumab is approved for brain cancer, but bevacizumab does not cross the BBB [1] and works by sequestration of vascular endothelial growth factor within the blood volume of the tumor. Natalizumab is approved for multiple sclerosis but works by blocking the trafficking of immune cells at the intra-vascular endothelial membrane [2], without entry into the brain. Multiple clinical trials of brain disorders have been performed with biologics, all ending in trial failure [3], with the most recent failure being aducanumab, the anti-Abeta amyloid antibody (AAA) for Alzheimer’s disease (AD) [4]. Multiple explanations are proffered as to the reason for the clinical trial failure of a biologic for the CNS, but rarely is the role of the BBB considered. The BBB is important if (a) the biologic agent, such as aducanumab, a large molecule drug, does not cross the BBB, and (b) the biologic entered the CNS clinical trial without BBB delivery technology. In many cases, the CNS biologic drug developer believes that the drug does cross the BBB, but these conclusions about BBB penetration can arise from methodologic considerations and misinterpretation of brain drug uptake information. The three primary misinterpretations leading to the conclusion that the biologic does penetrate the BBB are discussed below. If the biologic drug, in fact, does not cross the BBB and does not reach the target in the brain, there is little chance of a successful clinical trial. At some point, a consensus within the pharmaceutical industry may emerge that places a central focus in CNS drug development on the re-engineering of biologics for BBB penetration. Biologics, including therapeutic antibodies for AD, can be re-engineered to enable BBB passage [3]. This is possible with molecular Trojan horse technology and the genetic engineering of dual function IgG fusion proteins, where the IgG domain is a monoclonal antibody (MAb) against an endogenous BBB receptor-mediated transport (RMT) system, such as the insulin receptor (IR) or transferrin receptor (TfR). If the biologic is also a MAb, such as aducanumab, then the problem is engineering a BBB-penetrating bispecific antibody (BSA) [5]. 2. Methodology of brain uptake of therapeutic antibodies
Factors Affecting Combination Trial Success (FACTS): Investigator Survey Results on Early-Phase Combination Trials

Experimental therapeutic oncology agents are often combined to circumvent tumor resistance to individual agents. However, most combination trials fail to demonstrate sufficient safety and efficacy to advance to a later phase. This study collected survey data on phase 1 combination therapy trials identified from ClinicalTrials.gov between January 1, 2003 and November 30, 2017 to assess trial design and the progress of combinations toward regulatory approval. Online surveys (N = 289, 23 questions total) were emailed to Principal Investigators (PIs) of early-phase National Cancer Institute and/or industry trials; 263 emails (91%) were received and 113 surveys completed (43%). Among phase 1 combination trials, 24.9% (95%CI: 15.3%, 34.4%) progressed to phase 2 or further; 18.7% (95%CI: 5.90%, 31.4%) progressed to phase 3 or regulatory approval; and 12.4% (95%CI: 0.00%, 25.5%) achieved regulatory approval. Observations of “clinical promise” in phase 1 combination studies were associated with higher rates of advancement past each milestone toward regulatory approval (cumulative OR = 11.9; p = 0.0002). Phase 1 combination study designs were concordant with Clinical Trial Design Task Force (CTD-TF) Recommendations 79.6% of the time (95%CI: 72.2%, 87.1%). Most discordances occurred where no plausible pharmacokinetic or pharmacodynamic interactions were expected. Investigator-defined “clinical promise” of a combination is associated with progress toward regulatory approval. Although concordance between study designs of phase 1 combination trials and CTD-TF Recommendations was relatively high, it may be beneficial to raise awareness about the best study design to use when no plausible pharmacokinetic or pharmacodynamic interactions are expected.
Toward Developing a Patient-Reported Outcome Measure for Fatigue in Hemodialysis.

Fatigue is a component of health-related quality of life and is one of the most frequently cited burdens for patients undergoing maintenance hemodialysis.1,2 Although the prevalence and implications of fatigue among patients treated with hemodialysis are being increasingly recognized by the nephrology community, there is no universally agreed upon psychometrically robust patient-reported outcome measure (PROM) to assess fatigue in these patients.3–5 A recent assessment of the Multidimensional Fatigue Inventory 20, a 20item scale designed to evaluate 5 components of fatigue (general, physical, mental, reduced motivation, and reduced activity), showed poor validity and reliability in hemodialysis.6,7 Thus, assessing the presence and severity of fatigue-related symptoms in end-stage kidney disease (ESKD) remains challenging in the absence of valid, efficient, and meaningful instruments.8
Peer reviewed evaluation of registered end-points of randomised trials (the PRE-REPORT study): protocol for a stepped-wedge, cluster-randomised trial

Introduction Clinical trials are critical to the advancement of medical knowledge. However, the reliability of trial conclusions depends in part on consistency between pre-planned and reported study outcomes. Unfortunately, selective outcome reporting, in which outcomes reported in published manuscripts differ from pre-specified study outcomes, is common. Trial registries such as ClinicalTrials.gov have the potential to help identify and stop selective outcome reporting during peer review by allowing peer reviewers to compare outcomes between registry entries and submitted manuscripts. However, the persistently high rate of selective outcome reporting among published clinical trials indicates that the current peer review process at most journals does not effectively address the problem of selective outcome reporting. Methods and analysis PRE-REPORT is a stepped-wedge cluster-randomised trial that will test whether providing peer reviewers with a summary of registered, pre-specified primary trial outcomes decreases inconsistencies between prospectively registered and published primary outcomes. Peer reviewed manuscripts describing clinical trial results will be included. Eligible manuscripts submitted to each participating journal during the study period will comprise each cluster. After an initial control phase, journals will transition to the intervention phase in random order, after which peer reviewers will be emailed registry information consisting of the date of registration and any prospectively defined primary outcomes. Blinded outcome assessors will compare registered and published primary outcomes for all included trials. The primary PRE-REPORT outcome is the presence of a published primary outcome that is consistent with a prospectively defined primary outcome in the study’s trial registry. The primary outcome will be analysed using a mixed effect logistical regression model to compare results between the intervention and control phases. Ethics and dissemination The Cooper Health System Institutional Review Board determined that this study does not meet criteria for human subject research. Findings will be published in peer-reviewed journals. Trial registration number ISRCTN41225307; Pre-results.
Entropy Measures Can Add Novel Information to Reveal How Runners' Heart Rate and Speed Are Regulated by Different Environments

Ecological psychology suggests performer-environment relationship is the appropriate scale for examining the relationship between perception, action and cognition. Developing performance requires variation in practice in order to design the attractor-fluctuation landscape. The present study aimed to identify the effects of varying levels of familiarity and sensorimotor stimuli within the environment in runners' speed and heart rate (HR) regularity degree, and short-term memory Twelve amateur runners accomplished three 45-min running trials in their usual route, in an unusual route, and an athletics 400-m track, wearing a GPS and an HR monitor. Sample entropy (SampEn) and complexity index (CI), over speed and HR, were calculated. Pre and post-trial, participants performed the Backward Digit Span task for cognitive assessment. Higher entropies were found for the 400-m track, compared to the usual and unusual routes. Usual routes increased speed SampEn (63% of chances), but decreased HR CI when compared to unusual routes (60% of chances). Runners showed higher overall short-term memory performance after unusual routes, when compared to usual routes (85% of chances), indicating positive relation to attentional control. The contexts of practice may contribute to change predictability from single to multiple timescales. Thus, by considering that time structuring issues can help diagnosing habituation of training routes, this study brings novel information to the long-term process of training.
Serendipity or Preparedness ? Quantifying Creativity in Scientific Enterprise

Human creativity is the ultimate driving force behind all of scientific progress. The building blocks of innovations are often embodied in existing knowledge, yet it is creativity that blends seemingly disparate concepts, ideas and theories. Existing studies attempt to understand this phenomenon by investigating reference relationships of scientific publications. Unfortunately, an article’s references, at best, only partially or remotely reflect its authors’ actual information consumption, highlighting a fundamental reality-perception gap in current effort. In this paper, using two Web-scale longitudinal datasets (120.1 million papers across all scientific fields and 53.5 billion Web requests spanning over 4.5 years), we explore the predictability in scientific creativity. By directly correlating authors’ raw information consumption behaviors with their publications, we find remarkable reproducible patterns [#] in scientific creative processes across all scientific fields. Further, by leveraging these findings, we develop Serendip, a first-of-its-kind mechanistic framework, that not only effectively predict disparate references likely to be connected by creativity, but also accurately identifies critical references for such linkings to happen. We believe our framework is of fundamental importance to studies of scientific creativity. It promotes strategies to foster creative processes and provides insights towards a more effective design of information recommendation platforms.
Human-Inspired Online Path Planning and Biped Walking Realization in Unknown Environment

The focus of research in biped locomotion has moved toward real-life scenario applications, like walking on uneven terrain, passing through doors, climbing stairs and ladders. As a result, we are witnessing significant advances in the locomotion of biped robots, enabling them to move in hazardous environments while simultaneously accomplishing complex manipulation tasks. Yet, considering walking in an unknown environment, the efficiency of humanoid robots is still far from being comparable with the human. Currently, bipeds are very sensitive to external changes and they have severe constraints for adaptation of walk to conditions from such a complex environment. Promising approaches for efficient generation and realization of walking in a complex environment are based on biological solutions that have been developed for many years of evolution. This work presents one such human-inspired methodology for path planning and realization of biped walk appropriate for motion in a complex unfamiliar environment. Path planning results in calculating clothoid curves that represent well the human-like walking path. The robot walk is realized by the composition of parametric motion primitives. Such an approach enables on-line modification of planned path and walk parameters at any moment, instantly. To establish the relationship between high-level path planner and the low-level joint motion realization, we had to find a way to extract the parameters of the clothoid paths that can be linked with the parameters of the walk and consequently to motion primitive parameters. This enabled the robot to adopt its walking for avoiding the obstacles and for a smooth transition between different paths. In this paper we provide a complete framework that integrates the following components: (i) bio-inspired online path planning, (ii) path-dependent automatic calculation of high-level gait parameters (step length, walking speed, direction, and the height of the foot sole), and (iii) automatic calculation of low-level joint movements and corresponding control terms (driving motor voltage) through the adaptation of motion primitives which realize walking pattern and preserves the dynamic balance of the robot.
Recognition of Spontaneous Emotions by Speech within Automotive Environment

Within the car, recognition of emotion largely helps to design communication more natural. Speech interaction is here used more broadly today, and affective cues are contained within acoustic and linguistic parameters. However, we introduce novel concepts and results considering the estimation of a driver’s emotion by focusing on acoustic information herein. As a database we recorded 2k dialog turns directed to an automotive infotainment interface during extensive usability studies. Speech recognition and natural language interpretation have thereby been realized once as a Wizard-of-Oz simulation, and once by actual recognition technology. Recorded utterances have been labelled using a closed set of four emotions, namely anger, confusion, joy, and neutrality. As acoustic features we apply a high number of prosodic, speech quality, and articulatory functionals derived by descriptive statistic analysis out of base contours as intonation, intensity, and spectral information. Self-learning feature generation and selection is employed to optimize complexity for the successive classification by Support Vector Machines. Semantic information is included by vector-space representation of the spoken content within an early feature fusion. Overall, high recognition performances can be reported for this task by the suggested approach.