Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial Learning Drives Rapid Goal Representation in Hippocampal Ripples without Place Field Accumulation or Goal-Oriented Theta Sequences

The hippocampus is critical for rapid acquisition of many forms of memory, although the circuit-level mechanisms through which the hippocampus rapidly consolidates novel information are unknown. Here, the activity of large ensembles of hippocampal neurons in adult male Long-Evans rats was monitored across a period of rapid spatial learning to assess how the network changes during the initial phases of memory formation and retrieval. In contrast to several reports, the hippocampal network did not display enhanced representation of the goal location via accumulation of place fields or elevated firing rates at the goal. Rather, population activity rates increased globally as a function of experience. These alterations in activity were mirrored in the power of the theta oscillation and in the quality of theta sequences, without preferential encoding of paths to the learned goal location. In contrast, during brief “offline” pauses in movement, representation of a novel goal location emerged rapidly in ripples, preceding other changes in network activity. These data demonstrate that the hippocampal network can facilitate active navigation without enhanced goal representation during periods of active movement, and further indicate that goal representation in hippocampal ripples before movement onset supports subsequent navigation, possibly through activation of downstream cortical networks. SIGNIFICANCE STATEMENT Understanding the mechanisms through which the networks of the brain rapidly assimilate information and use previously learned knowledge are fundamental areas of focus in neuroscience. In particular, the hippocampal circuit is a critical region for rapid formation and use of spatial memory. In this study, several circuit-level features of hippocampal function were quantified while rats performed a spatial navigation task requiring rapid memory formation and use. During periods of active navigation, a general increase in overall network activity is observed during memory acquisition, which plateaus during memory retrieval periods, without specific enhanced representation of the goal location. During pauses in navigation, rapid representation of the distant goal well emerges before either behavioral improvement or changes in online activity.
Short‐term dual antiplatelet therapy in diabetic patients admitted for acute coronary syndrome treated with a new‐generation drug‐eluting stent

The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug‐eluting stent (DES) remains unclear. This is a prespecified sub‐study from the Randomised Evaluation of short‐term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short‐term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent.
Identification of a two-component regulatory system involved in antimicrobial peptide resistance in Streptococcus pneumoniae

Two-component regulatory systems (TCS) are among the most widespread mechanisms that bacteria use to sense and respond to environmental changes. In the human pathogen Streptococcus pneumoniae, a total of 13 TCS have been identified and many of them have been linked to pathogenicity. Notably, TCS01 strongly contributes to pneumococcal virulence in several infection models. However, it remains one of the least studied TCS in pneumococci and its functional role is still unclear. In this study, we demonstrate that TCS01 cooperates with a BceAB-type ABC transporter to sense and induce resistance to structurally-unrelated antimicrobial peptides of bacterial origin that all target undecaprenyl-pyrophosphate or lipid II, which are essential precursors of cell wall biosynthesis. Even though tcs01 and bceAB genes do not locate in the same gene cluster, disruption of either of them equally sensitized the bacterium to the same set of antimicrobial peptides. We show that the key function of TCS01 is to upregulate the expression of the transporter, while the latter appears the main actor in resistance. Electrophoretic mobility shift assays further demonstrated that the response regulator of TCS01 binds to the promoter region of the bceAB genes, implying a direct control of these genes. The BceAB transporter was overexpressed and purified from E. coli. After reconstitution in liposomes, it displayed substantial ATPase and GTPase activities that were stimulated by antimicrobial peptides to which it confers resistance to, revealing new functional features of a BceAB-type transporter. Altogether, this inducible defense mechanism likely contributes to the survival of the opportunistic microorganism in the human host, in which competition among commensal microorganisms is a key determinant for effective host colonization and invasive path.
Internal Mammary Node Irradiation in Patients With Node-Positive Early Breast Cancer: Fifteen-Year Results From the Danish Breast Cancer Group Internal Mammary Node Study

PURPOSE The Danish Breast Cancer Group Internal Mammary Node study demonstrated improved 8-year overall survival (OS) with internal mammary node irradiation (IMNI) in patients with node-positive early breast cancer. Here, we present long-term results from the Danish Breast Cancer Group Internal Mammary Node study cohort. PATIENTS AND METHODS This nationwide, prospective cohort study allocated patients with node-positive early breast cancer to adjuvant radiotherapy with or without IMNI depending on cancer laterality. Patients with right-sided cancer received IMNI. Patients with left-sided cancer were treated without IMNI because of risk of radiation-induced heart disease. Other treatment was independent of laterality. The primary study end point was OS. Secondary end points were distant recurrence and breast cancer mortality. Analyses were by intention to treat. RESULTS During 2003-2007, 3,089 women were allocated to IMNI (right-sided, n = 1,491) or no IMNI (left-sided, n = 1,598). With a median follow-up of 14.8 years, 589 patients with and 701 patients without IMNI had died. The corresponding 15-year OS rates were 60.1% and 55.4%. The adjusted hazard ratio (HR) for death was 0.86 (95% CI, 0.77 to 0.96; P = .007) in favor of IMNI. The 15-year risk of developing distant recurrence was 35.6% (523 recurrences) and 38.6% (602 recurrences) with vs. without IMNI (adjusted HR, 0.88 [95% CI, 0.79 to 0.99; P = .04]). The 15-year breast cancer mortality with IMNI was 31.7% (467 deaths) compared with 33.9% (537 deaths) without IMNI (adjusted HR, 0.88 [95% CI, 0.78 to 1.00; P = .05]). The distribution of other deaths was similar across groups. CONCLUSION In patients with node-positive early breast cancer treated with IMNI or without IMNI depending on breast cancer laterality, IMNI reduced the risk of distant recurrence and death from breast cancer, thereby improving long-term survival.
The effect of manganese and iron on mediating resuscitation of lactic acid‐injured Escherichia coli

Lactic acid can induce sublethal injury of E. coli through oxidative stress. In this study, we investigated changes in SOD activity, CAT activity, GSH production and ROS production during sublethal injury and resuscitation of E. coli. Then, the effect of manganese and iron during resuscitation were studied. Both cations (≥1 mmol l−1) significantly promoted the resuscitation of sublethally injured E. coli induced by lactic acid and shortened the repair time (P < 0·05). Conversely, addition of N,N,N′,N′‐tetrakis (2‐pyridylmethyl) which is a metal chelator extended the repair time. Compared with minA, manganese and iron significantly improved SOD activity at 40, 80 and 120 min and decreased ROS production at 40 and 80 min, thereby recovering injured E. coli quickly (P < 0·05). The deletion of sodA encoding Mn‐SOD, sodB encoding Fe‐SOD or gshA/gshB encoding GSH significantly strengthened sublethal injury and extended the repair time (P < 0·05). It meant these genes‐related oxidative stress played important roles in the acid resistance of E. coli and recovery of sublethal injury. Therefore, manganese and iron can promote the recovery of lactic‐injured E. coli by the way of increasing SOD activity, scavenging ROS, and relieving oxidative stress.
Video Game Play Does Not Improve Spatial Skills When Controlling for Speed-Accuracy Trade-Off: Evidence From Mental-Rotation and Mental-Folding Tasks

Researchers have been divided on the efficacy of computerized cognitive training (CCT) for enhancing spatial abilities, transfer of training, and improving malleability of skills. In this study, we assessed the effects of puzzle video game training on subsequent mental rotation (MR) and mental folding (MF) performance among adults with no cognitive impairment. We assessed participants at baseline with the Shepard-Metzler MR test followed by the differential aptitude test: space relations MF test (i.e., far transfer). We ranked participants’ skills on these pre-tests and used a matching technique to form two skill groups from which we then randomly assigned members of each skill group either to an experimental group or a wait-list control group. The experimental group played two puzzle video games closely related to two-dimensional and three-dimensional MR tasks during 4-week training sessions (total of 12 hour of video games). Post-training, participants completed the MR and MF tests again. Two months later, we re-assessed only the experimental group’s spatial skills to explore the sustainability of the trained performance. In addition to response times (RT) and error scores (ES), reported separately, we combined these variables into rate correct scores (RCS) to form an integrated measure of potential speed-accuracy trade-offs (SAT). As a result, we did not find significant improvements in MR performance from CCT engagement, nor did participants show a transfer of skills obtained by practicing MR-related puzzle games to a MF task. Based on the current findings, we urge caution when proposing a game-based intervention as a training tool to enhance spatial abilities. We argue that separately interpreting individual test measures can be misleading, as they only partially represent performance. In contrast, composite scores illuminate underlying cognitive strategies and best determine whether an observed improvement is attributable to enhanced capacities or individual heuristics and learned cognitive shortcuts.
Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases

A “Leap-of-Faith” approach is used to treat patients with previously unknown ultrarare pathogenic mutations, often based on evidence from patients having dissimilar but more prevalent mutations. This uncertainty reflects the need to develop personalized prescreening platforms for these patients to assess drug efficacy before considering clinical trial enrollment. In this study, we report an 18-year-old patient with ultrarare Leigh-like syndrome. This patient had previously participated in two clinical trials with unfavorable responses. We established an induced pluripotent stem cell (iPSC)–based platform for this patient, and assessed the efficacy of a panel of drugs. The iPSC platform validated the safety and efficacy of the screened drugs. The efficacy of three of the screened drugs was also investigated in the patient. After 3 years of treatment, the drugs were effective in shifting the metabolic profile of this patient toward healthy control. Therefore, this personalized iPSC-based platform can act as a prescreening tool to help in decision-making with respect to patient’s participation in future clinical trials.
The microdissected gene expression landscape of nasopharyngeal cancer reveals vulnerabilities in FGF and noncanonical NF-κB signaling

Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with an extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of the tumor epithelial compartment has remained a mystery. Here, we use Smart-3SEQ to prepare transcriptome-wide gene expression profiles from microdissected NPC tumors, dysplasia, and normal controls. We describe changes in biological pathways across the normal to tumor spectrum and show that fibroblast growth factor (FGF) ligands are overexpressed in NPC tumors, while negative regulators of FGF signaling, including SPRY1, SPRY2, and LGALS3, are down-regulated early in carcinogenesis. Within the NF-κB signaling pathway, the critical noncanonical transcription factors, RELB and NFKB2, are enriched in the majority of NPC tumors. We confirm the responsiveness of EBV-positive NPC cell lines to targeted inhibition of these pathways, reflecting the heterogeneity in NPC patient tumors. Our data comprehensively describe the gene expression landscape of NPC and unravel the mysteries of receptor tyrosine kinase and NF-κB pathways in NPC.
ASSOCIATED FACTORS AND SURGICAL OUTCOMES OF MICROCYSTOID MACULAR EDEMA AND CONE BOUQUET ABNORMALITIES IN EYES WITH EPIRETINAL MEMBRANE

Supplemental Digital Content is Available in the Text. Preoperative microcystoid macular edema in eyes with macular pucker is associated with worse vision after pucker peeling and increased risk of postsurgical macular edema worsening. Purpose: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. Methods: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. Results: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3–12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97–0.99] for each 1-μm EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling (P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01–5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06–6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. Conclusion: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Müller cells may have an alleged role, and further imaging and functional tests are warranted.
The T-Cell Response to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease is Augmented with Anti-TNF Therapy

T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 vaccination in inflammatory bowel disease patients are poorly correlated. T-cell responses are preserved by most biologic therapies, but augmented by anti-tumor necrosis factor (anti-TNF) treatment. While anti-TNF therapy blunts the antibody response, cellular immunity after vaccination is robust.
The feasibility of baroreflex sensitivity measurements in heart failure subjects: The role of slow‐patterned breathing

Increased muscle sympathetic nerve activity (MSNA) indicates an adverse outcome in heart failure. Decreased baroreflex modulation of MSNA is a well‐known feature of the disease. The determinability of cardiovagal baroreflex sensitivity (BRS) in heart failure is low, however, the determinability of sympathetic BRS is not known.
Steady and Unsteady Simulations for Annular Internal Condensing Flows in a Channel

This paper highlights: (i) numerical methods developed to solve annular/stratified internal condensing flow problems, and (ii) the assessed effects of transverse gravity and surface tension on shear driven (horizontal channels) and gravity driven (inclined channels) internal condensing flows. A comparative study of the flow physics is presented with the help of steady and unsteady computational results obtained from the numerical solutions of the full two-dimensional governing equations for annular internal condensing flows. These simulations directly apply to recently-demonstrated innovative condenser operations which make the flow regime annular over the entire length of the condenser. The simulation algorithm is based on an active integration of our own codes developed on MATLAB with the standard single-phase CFD simulation codes available on COMSOL. The approach allows for an accurate wave simulation technique for the highly sensitive shear driven annular condensing flows.This simulation approach employs a sharp-interface model and uses a moving grid technique to accurately locate the dynamic interface by the solution of the interface tracking equation (employing the method of characteristics) along with the rest of the governing equations. The 4th order time-step accuracy in the method of characteristics has enabled, for the first time, the ability to track time-varying interface locations associated with wave phenomena and accurate satisfaction of all the interface conditions — including the more difficult to satisfy interfacial mass-flux equalities.A combination of steady and unsteady simulation results are also used to identify the effects of transverse gravity, axial gravity, and surface tension on the growth of waves. The results presented bring out the differences within different types of shear driven flows and differences between shear driven and gravity driven flows.The unsteady wave simulation capability has been used here to do the stability analysis for annular shear-driven steady flows. In stability analysis, an assessment of the dynamic response of the steady solutions to arbitrary instantaneous initial disturbance are obtained. The results mark the location beyond which the annular regime transitions to a non-annular regime (experimentally known to be a plug-slug regimes). The computational prediction of heat-flux values agree with the experimentally measured values (at measurement locations) obtained from relevant runs of our in-house experiments. Also, a comparison between the computationally predicted and experimentally measured values regarding the length of the annular regime is possible, and will be presented elsewhere. © 2014 ASME
in determining the poor outcome observed in patients with trisomy 11.

the cases. Similar results have been previously described, contradicting the intuitive acceptance that the γδ T-ALL blasts should not express CD4 and CD8, as their normal counterparts. Van Dongen et al. 1 described a small subset of normal γδ T-cells in the peripheral blood which was either CD4 or CD8 positive, in addition to the vast majority of double negative cells. Therefore, perhaps this small subset of normal CD4 or CD8 γδ T-cells is particu-larly prone to malignant transformation. Alternatively, the expression of CD4 or CD8 antigens in γδ T-cells may represent a phenomenon related to the neoplastic transformation. Taken together, these data give support to the concept that γδ T-ALL represents a distinctive subtype of leukemia, with peculiar clinical, laboratory and immunophenotypic characteristics.
Maladaptive Schemas and Posttraumatic Stress Disorder Symptom Severity: Investigating the Mediating Role of Posttraumatic Negative Self-Appraisals among Patients in a Partial Hospitalization Program

ABSTRACT Maladaptive schemas have been linked with increased posttraumatic stress disorder (PTSD) symptoms. Posttraumatic negative self-appraisals (i.e., posttraumatic shame and self-blame) have also been empirically supported as contributors to PTSD symptom severity following traumatic events. These associations are well known; however, the pathways between maladaptive schemas and PTSD symptoms remain largely unclear. The present study aimed to examine the mediating effects of posttraumatic negative self-appraisals (shame and self-blame) on the association between maladaptive schemas and PTSD symptom severity in patients completing a partial hospitalization program. Patients (N = 98) completed measures of early maladaptive schemas, posttraumatic shame, posttraumatic self-blame, and PTSD symptom severity at intake. Posttraumatic negative self-appraisals mediated the association between maladaptive schemas and PTSD symptom severity. When we examined the specific mediating effects of shame and blame – rather than negative self-appraisals overall – shame was a significant mediator (b = .153, 95% CI [.031, .296]), but not blame (b = .038, 95% CI [−.083, .204]). Further, posttraumatic shame mediated the association between two of the four schema domains – disconnection & rejection (b = .092, 95% CI [.030, .201]) and impaired autonomy & performance (b = .047, 95% CI [.002, .124]) – and PTSD symptom severity. These findings highlight the importance of posttraumatic shame in the association between maladaptive schemas and PTSD symptom severity. Theoretical and practical implications are discussed.
A Conceptual Framework For Designing Team Training In Engineering Classrooms

Changes in customers’ perceptions about service and products and technological advances have compelled companies to change the way they do business. The use of teams in organizations has become an effective way for organizations to satisfy new customers’ needs. Research has shown that teams promote creativity and enhance performance in the form of speedy processes and quality products and services. However, the team approach is not successful in every situation. Organizations recognize that new employees need to bring team work skills to the workplace. Although employers may be willing to provide on the job training, they expect that their new employees, at least, possess the understanding of why this skill is important in the organization 1 .
Impacts of light direction and window properties on students’ perceptual evaluations in design studios

This study aimed to determine how light direction, window proximity and window dimensions could affect students' perceptual evaluations in design studios. The design studios of the Nuh Naci Yazgan University in Kayseri were selected as the research setting. The ‘semantic differential scale’ composed of 10 adjective pairs was used for determining subjects’ perceptual evaluations of design studios having two different window dimensions. According to the results obtained, when making drawings, right-handed students who received light from a window on the left side were determined to perceive the physical environmental factors of design studios more positively compared to students who received light from a window on the right side. In addition, students sitting near a window in design studios were observed to generally perceive the physical environmental factors more positively than those sitting in the middle close to the window, in the middle away from the window and inside. Furthermore, students who sat in an area with floor to ceiling window were determined to perceive the place more positively compared to those who sat in an area with parapet to ceiling window. These results generally confirmed that light direction, window proximity and window dimensions in design studios are effective on students’ perceptual evaluations.