Miracle-dz/UniFAR-FTUs huggingface dataset:
The Sync/deSync Model: How a Synchronized Hippocampus and a Desynchronized Neocortex Code Memories

Neural oscillations are important for memory formation in the brain. The desynchronization of alpha (10 Hz) oscillations in the neocortex has been shown to predict successful memory encoding and retrieval. However, when engaging in learning, it has been found that the hippocampus synchronizes in theta (4 Hz) oscillations, and that learning is dependent on the phase of theta. This inconsistency as to whether synchronization is “good” for memory formation leads to confusion over which oscillations we should expect to see and where during learning paradigm experiments. This paper seeks to respond to this inconsistency by presenting a neural network model of how a well functioning learning system could exhibit both of these phenomena, i.e., desynchronization of alpha and synchronization of theta during successful memory encoding. We present a spiking neural network (the Sync/deSync model) of the neocortical and hippocampal system. The simulated hippocampus learns through an adapted spike-time dependent plasticity rule, in which weight change is modulated by the phase of an extrinsically generated theta oscillation. Additionally, a global passive weight decay is incorporated, which is also modulated by theta phase. In this way, the Sync/deSync model exhibits theta phase-dependent long-term potentiation and long-term depression. We simulated a learning paradigm experiment and compared the oscillatory dynamics of our model with those observed in single-cell and scalp-EEG studies of the medial temporal lobe. Our Sync/deSync model suggests that both the desynchronization of neocortical alpha and the synchronization of hippocampal theta are necessary for successful memory encoding and retrieval. SIGNIFICANCE STATEMENT A fundamental question is the role of rhythmic activation of neurons, i.e., how and why their firing oscillates between high and low rates. A particularly important question is how oscillatory dynamics between the neocortex and hippocampus support memory formation. We present a spiking neural-network model of such memory formation, with the central ideas that (1) in neocortex, neurons need to break out of an alpha oscillation to represent a stimulus (i.e., alpha desynchronizes), whereas (2) in hippocampus, the firing of neurons at theta facilitates formation of memories (i.e., theta synchronizes). Accordingly, successful memory formation is marked by reduced neocortical alpha and increased hippocampal theta. This pattern has been observed experimentally and gives our model its name—the Sync/deSync model.
Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy

Background An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cell-derived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice. Methods We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016. These patients had been administered nivolumab at a dose of 2mg/kg every 3 weeks. Results As for pretreatment prognostic factors, ECOG performance status (PS) ≥1, maximum tumor diameters of ≥30mm, elevated LDH and elevated C-reactive protein were significantly associated with poor overall survival (OS) (hazard ratio [HR] 0.29 [P<0.001], HR 0.40 [p=0.003], HR 0.29 [P<0.001], HR 0.42 [P=0.004], respectively) on univariate analysis. Among these factors, PS and LDH were identified as independent variables by multivariate analysis. As for early markers examined during therapy, patients with absolute lymphocyte count (ALC) ≥ 1000/μl (Week3: HR 0.40 [P=0.004], Week6: HR 0.33 [P=0.001]) and absolute neutrophil count (ANC) <4000/μl (Week3: HR 0.46 [P=0.014], Week6: HR 0.51 [P=0.046]) had significantly better OS. Conclusion ALC≥1000/μl and ANC<4000/μl during treatment appear to be early markers associated with OS. Nivolumab might have minimal efficacy in patients with a massive tumor burden.
Changes in Social Capital and Cigarette Smoking Behavior Over Time: A Population-Based Panel Study of Temporal Relationships.

INTRODUCTION Identifying factors that influence individuals' smoking behavior remains a huge public health concern. This study aimed to investigate changes in individuals' cigarette smoking while considering well-known smoking determinants, including social capital, its presence being postulated to reduce smoking. METHODS From British Household Panel Survey data, two baseline smoking cohorts were created ("smoking" and "not smoking"). The same individuals from this nationally representative sample (NT = 8114, aged 16-91 years) were interviewed on four occasions between years 2000 and 2007 to investigate changes in cigarette smoking behavior. Logistic regression models with random effects compensated for within-individual behavior over time. Temporal pathways were investigated by lagging independent variables (t - 1) in relation to our cigarette-use outcome at time (t). RESULTS Active social participation at (t - 1) was positively associated with smoking cessation at (t) (odds ratio [OR] = 1.39; 95% confidence interval [CI] [1.07-1.82]). Separating from one's spouse at (t - 1) increased risk for smoking relapse/initiation at (t) (OR = 6.63; 95% CI [1.70-28.89]). Conversely, being married protected against smoking cigarettes (OR = 1.87; 95% CI [1.15-3.04]). These associations held in our robustness checks. CONCLUSIONS Initial marital breakdown predicted a high risk of smoking relapse/initiation. The timing of this life event provides a critical window where adverse smoking behavior might occur. Conversely, the positive effects of active social participation on cigarette cessation remained consistent, its absence further predicting smoking relapse/initiation. Robustness of results confirms the important role that active participation has on cigarette smoking behavior. Group smoking cessation interventions could harness participatory elements to better achieve their goals. IMPLICATIONS By investigating temporal relationships between well-known smoking determinants and cigarette smoking outcomes, we identified that being "separated" (not "divorced") at time (t) predicted a higher risk of smoking relapse/initiation at (t). Tailored health messages could be employed to highlight the increased risk of cigarette smoking relapse/initiation during this stressful life event. Conversely, active social participation (a common social capital proxy) consistently predicted smoking cessation over time. Future group smoking cessation interventions could be designed explicitly to harness participatory elements to better achieve their goals.
Review Article a Systematic Review and Meta-analysis of Qigong for the Fibromyalgia Syndrome

Objectives. The fibromyalgia syndrome (FMS) is a chronic condition with only few evidence-based complementary and alternative therapies available. This paper presents a systematic review and meta-analysis of the effectiveness of Qigong for fibromyalgia syndrome. Methods. The PubMed/MEDLINE, Cochrane Library, Embase, PsycINFO, and Cambase databases were screened in December 2012 to identify randomized controlled trials comparing Qigong to control interventions. Major outcome measures were pain and quality of life; and secondary outcomes included sleep quality, fatigue, depression, and safety. Standardized mean differences (SMD) and 95% confidence intervals were calculated. Results. Seven trials were located with a total of 395 FMS patients. Analyses revealed low quality evidence for short-term improvement of pain, quality of life, and sleep quality and very low quality evidence for improvement of fatigue after Qigong for FMS, when compared to usual care. No evidence was found for superiority of Qigong compared to active treatments. No serious adverse events were reported. Discussion. This systematic review found that Qigong may be a useful approach for FMS patients. According to the quality of evidence, only a weak recommendation for Qigong can be made at this point. Further high quality RCTs are required for the conclusive judgment of its long-term effects.
Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis

The aim of the present study was to reveal the potential hub genes and regulatory mechanisms associated with senescence in human annulus cells by analyzing microarray data using bioinformatics. The gene expression dataset GSE17077, of senescent and non-senescent annulus cells obtained from patients with disc degenerative diseases (DDD), was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified. Functional and pathway annotations were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms, respectively. Web-based Gene Set Analysis Toolkit and Chip Enrichment Analysis were used to identify key transcription factors (TFs). A protein-protein interaction (PPI) network was constructed to analyze the hub genes associated with senescence in DDD. A total of 667 DEGs were screened, including 368 up- and 299 down-regulated genes. These DEGs were enriched in phosphorylation, regulation of apoptosis and regulation of programmed cell death. In addition, DEGs were involved in axon guidance, natural killer cell-mediated cytotoxicity, purine metabolism and the mitogen-activated protein kinase (MAPK) signaling pathway. The TFs activator protein 1 (AP1), specificity protein 1 and aryl hydrocarbon receptor may serve regulatory roles in gene expression in senescent cells. Certain key target genes of TFs, including heat shock protein 90 (HSP90) and C-X-C motif chemokine 5 (CXCL5), within the DEGs were revealed to have a high connectivity degree by PPI analysis. The results of the present study indicated that the MAPK-regulated AP1 pathway may contribute to senescence-associated disc degeneration. The DEGs, including HSP90 and CXCL5, with a high degree of connectivity may be potential targets for future investigations into molecular biomarkers.
Perceived needs for attaining a ‘new normality’ after surviving myocardial infarction: A qualitative study of patients’ experience

Abstract Background: A comprehensive understanding of the various aspects of patients’ myocardial infarction (MI) experiences may help to guide these patients and their relatives through the many uncertainties they face and help them to stabilize their lives after the disruption they experienced. Objectives: To explore MI patients’ experiences of life with MI, the challenges they face during the process of accepting their condition, and the setting and resetting of their personal goals. Methods: Thirty semi-structured, individual interviews were conducted. The grounded theory method was used, and Atlas.ti qualitative data analysis software was used to facilitate the analysis. Results: Three main themes and explanatory models emerged from the data analysis: a good adaptation – the ‘new normality;’ maladjustment – a continuous search for a ‘new normality;’ and perceived needs in the search for a new normality. Patients perceived several areas of need that they felt must be met before they could reach the state of a new normality. These needs included overcoming the anxiety of a possible MI recurrence; acquiring knowledge about MI in general and about ‘my MI’ in particular; the need for a timeline; for patience and steadiness; for both objective and subjective health status improvement; for taking control over the disease; and living within a supportive context. Conclusion: When faced with a dramatic life event, most patients succeed in achieving a new normality in which they live changed but still satisfying lives. The needs experienced by patients when searching for a new normality may guide practitioners in leading patient-centred consultations. KEY MESSAGES Most MI patients achieve a new normality. My physical identity is new: my body is different but still functional. My personal identity is new: I am not the same as before, the disease is part of me, but I retain parts of my previous self.
Evaluating quality of life and cost implications of prophylactic radiotherapy in mesothelioma: Health economic analysis of the SMART trial

Background The SMART trial is a UK-based, multicentre RCT comparing prophylactic radiotherapy and symptom-based (deferred) radiotherapy in 203 patients with Malignant Pleural Mesothelioma who had undergone large bore pleural interventions. Using costs and quality of life data collected alongside the clinical trial, we will estimate the cost-effectiveness of prophylactic radiotherapy compared to deferred radiotherapy over a 1-year period. Methods Healthcare utilization and costs were captured during the trial. Utility weights produced by the EQ-5D questionnaire were used to determine quality-adjusted life-years (QALY) gained. The incremental cost-effectiveness ratio was calculated over the one-year trial period. Results Costs were similar in the immediate and deferred radiotherapy groups: £5480.40 (SD = £7040; n = 102) and £5461.40 (SD = £7770; n = 101) respectively. There was also no difference in QALY: 0.498 (95% CI: [0.45, 0.547]) in the prophylactic radiotherapy group versus 0.525 (95% CI: [0.471, 0.580]) in the deferred group. At a willingness to pay threshold of £30,000/QALY there was only a 24% chance that prophylactic radiotherapy was cost-effective compared to deferred radiotherapy. Conclusions There was no significant effect of prophylactic radiotherapy on quality of life in the intervention group, nor was there any discernable decrease in healthcare costs. There is little evidence to suggest that prophylactic radiotherapy is a cost-effective intervention in this population. Trial registration ISRCTN72767336 with ISRCTN
Telephone Follow-Up by Nurse After Total Knee Arthroplasty: Results of a Randomized Clinical Trial

BACKGROUND/PURPOSE: Because of shorter hospitalizations, patients now have to take responsibility for their recovery period at a very early stage. We evaluated the effects of structured, nurse-managed telephone follow-up (TFU) after discharge from the hospital following total knee arthroplasty (TKA). METHOD/DESIGN: The design was a single-center, unblinded, parallel-group randomized clinical trial. The primary outcome was self-reported physical function according to the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Secondary outcomes were stiffness and pain according to the WOMAC Index; health-related quality of life, measured with the Medical Outcomes Study Short Form (SF-36); general self-efficacy, measured with the General Self-Efficacy Scale; and number of acute visits to the orthopaedic outpatient clinic. In total, 117 patients were randomized to 2 groups: an intervention group receiving TFU 4 and 14 days after discharge in addition to conventional treatment, and a control group receiving conventional treatment. The TFUs were structured by key subjects for health status, as defined by the VIPS model (the Swedish acronym for the concepts of Well-being, Integrity, Prevention, and Safety). The effect was measured 1 and 3 months postsurgery. RESULTS: No significant effects on physical function in the disease-specific WOMAC Index were identified. However, significant differences in scores were identified in favor of the intervention group on general self-efficacy (p = .014) and physical function (p = .031), measured with the Medical Outcomes Study Short Form 1 month after TKA, but this effect was not seen at 3 months. A positive improvement in several dimensions of health status and health-related quality of life was identified in favor of the intervention group, but patients who had TFU had more unscheduled visits to the outpatient clinic. CONCLUSIONS: Telephone follow-up did not improve physical function compared with conventional treatment, as measured with the WOMAC Index. A short-term effect was identified, improving general self-efficacy and physical function as dimensions of health-related quality of life.
Optimization of multilayered ZnO whisker radar absorbing coatings using microgenetic algorithm

An optimization technique based on the microgenetic algorithm(MGA) is presented for the design of multilayered radar absorbing materials made of tetrapod-shaped ZnO whisker.The fast optimization procedure is designed for a given maximum thickness and the optimization conditions were different in order to meet the practical requirements in the different frequency bands (the range is 2～18GHz). The effects of the thickness,the number of layers,and the restrained conditions on the optimization results are discussed in detail.
Implications of KRAS mutations in acquired resistance to treatment in NSCLC

Rationale KRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies. The focus of this review will be to provide an overview of the network related to the intricate molecular KRAS pathways, stressing on preclinical and clinical studies that investigate the predictive value of KRAS mutations in NSCLC patients. Materials and Methods A bibliographic search of the Medline database was conducted for articles published in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer, KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance.
Stop thinking, start tagging: tag semantics emerge from collaborative verbosity

Recent research provides evidence for the presence of emergent semantics in collaborative tagging systems. While several methods have been proposed, little is known about the factors that influence the evolution of semantic structures in these systems. A natural hypothesis is that the quality of the emergent semantics depends on the pragmatics of tagging: Users with certain usage patterns might contribute more to the resulting semantics than others. In this work, we propose several measures which enable a pragmatic differentiation of taggers by their degree of contribution to emerging semantic structures. We distinguish between categorizers, who typically use a small set of tags as a replacement for hierarchical classification schemes, and describers, who are annotating resources with a wealth of freely associated, descriptive keywords. To study our hypothesis, we apply semantic similarity measures to 64 different partitions of a real-world and large-scale folksonomy containing different ratios of categorizers and describers. Our results not only show that "verbose" taggers are most useful for the emergence of tag semantics, but also that a subset containing only 40% of the most 'verbose' taggers can produce results that match and even outperform the semantic precision obtained from the whole dataset. Moreover, the results suggest that there exists a causal link between the pragmatics of tagging and resulting emergent semantics. This work is relevant for designers and analysts of tagging systems interested (i) in fostering the semantic development of their platforms, (ii) in identifying users introducing "semantic noise", and (iii) in learning ontologies.
PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications

Abstract Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients’ prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.
Expression of Costimulatory Molecules B7-H4 in PBC Patients

Objective：To study the relationship between the levels of B7-H4 and PBC. Methods：Real-time quantitative PCR were used to detect the levels of B7-H4 mRNA on PBMCs. ELISA were used to detect the serum levels of IL-2. FACs were used to detect the CD4+and CD8+ T-lymphocytes frequencies. Results：Levels of B7-H4 mRNA and B7-H4 frequencies were significantly lower than non-PBC hepatic cirrhosis group and healthy controls (P<0.01). After PHA treated for 72h the frequencies of CD4+, CD8+, and CD4+CD8+ T-lymphocytes were all decreased (P<0.05). The same with serum levels of IL-2 (P<0.05). And the frequencies of CD4+ and CD4+CD8+ T-lymphocytes and serum levels of IL-2 were significantly higher in the PBC group than that of non-PBC hepatic cirrhosis group and healthy controls (P<0. 01). Conclusion：Levels of B7-H4 decreased in PBC and could play an important role in immunoregulation of PBC.
Spike timing in auditory‐nerve fibers during spontaneous activity and phase locking

In vertebrates, all acoustic information transmitted from the inner ear to the central auditory system is relayed by primary auditory afferents (auditory‐nerve fibers; ANFs). These neurons are also the most peripheral elements to use action potentials (spikes) to encode the acoustic information. Here, we review what is known about the spiking of ANFs during spontaneous activity, when spike timing might be regarded as largely random, and during stimulation by low‐frequency sounds, when spikes are phase locked to the stimulus waveform, a phenomenon generally considered a hallmark of temporal precision and speed in the auditory system. We focus on mammals, in which each ANF is driven by a single ribbon synapse in a single receptor cell, but also cover relevant research on ANFs of vertebrates from other classes. For spontaneous activity, we highlight several spike‐history effects in interspike interval distributions, hazard‐rate functions, serial interval correlations, and spike‐count statistics. We also review models that have attempted to account for these properties. For phase locking, we focus on the responses to low‐frequency tones, rather than to low‐frequency components of broadband signals such as noise or clicks. We critically review the measures commonly used to quantify phase locking and urge caution when interpreting such measures with respect to spike‐timing precision. We also review the dependence of phase locking on stimulus amplitude and frequency. Finally, we identify some open questions.