Miracle-dz/UniFAR-FTUs huggingface dataset:
Diabetic retinopathy predicts cardiovascular disease independently of subclinical atherosclerosis in individuals with type 2 diabetes: A prospective cohort study

Background Diabetic retinopathy (DR) and preclinical atherosclerosis are associated with higher cardiovascular risk. However, no studies have investigated the predictive role of DR and preclinical atherosclerosis jointly on cardiovascular events in subjects with type 2 diabetes (T2D). We aimed to assess the contribution of DR and subclinical atherosclerosis on the risk of adverse cardiovascular events in subjects with T2D without previous cardiovascular disease (CVD). Methods We included two prospective cohorts of subjects with T2D from the same geographical area. Assessment of subclinical atherosclerosis was performed by carotid ultrasound. An ophthalmologist classified DR according to standard criteria. Cardiovascular outcomes considered for analysis were the following: ischemic heart disease, stroke, heart failure, peripheral artery disease, revascularization procedures, and cardiovascular mortality. Bivariable and multivariable predictive models were performed. Results From a total of 374 subjects with T2D 44 developed cardiovascular events during the 7.1 years of follow-up. Diabetes duration, total cholesterol, and glycated hemoglobin (HbA1c) at baseline were higher in subjects who developed cardiovascular outcomes (p < 0.001, p = 0.026, and p = 0.040, respectively). Compared with subjects without events, those developing cardiovascular events had higher prevalence of retinopathy (65.9% vs. 38.8%, p = 0.001; respectively) and more than mild retinopathy (43.2% vs. 31.8%, p = 0.002; respectively). Furthermore, all-cause mortality was higher in subjects with MACE than those without events (13.6% vs. 3.3%, p = 0.009; respectively). The multivariable analyses showed that HbA1c and the presence of DR at baseline were predictive of cardiovascular outcomes (p = 0.045 and p = 0.023, respectively). However, the burden of subclinical atherosclerosis was not (p = 0.783 and p = 0.071, respectively). Conclusion DR is a strong predictor of cardiovascular events in T2D individuals at primary CVD prevention, even after accounting for the presence of preclinical carotid atherosclerosis. These results may help to individualize CVD prevention strategies in T2D.
Characterization of immunomodulatory responses induced by manuka honey

Manuka honey (MH) is known for its wound-healing, anti-microbial, anti-oxidant and anti-tumor properties. However, there is conflicting evidence regarding the role of MH in inflammatory responses, with some studies highlighting its pro-inflammatory capacity and others showing that it has a predominantly anti-inflammatory activity. The current study is aimed at characterizing the immunomodulatory capacity of MH using both in vitro and in vivo approaches, focusing on the underlying mechanisms. Treatment of RAW 264.7 macrophages with 1% MH (w/v) resulted in a significant increase in the gene expression (~26-fold) and secretion (~27-fold) of tumor necrosis factor-alpha (TNF-α). Similarly, an increase was observed in the gene expression of other inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS), as well as the chemokines; (C-X-C motif) ligand 2 (CXCL2) and (C-C) motif ligand 2 (CCL2). Using an in vivo model, intraperitoneal (i.p.) administration of MH in C57BL/6 mice elicited a peritoneal response characterized by a significant expansion in the number of peritoneal exudate cells (PECs), which was mainly due to a 35-fold increase in the recruitment of neutrophils. Importantly, this response was evident in toll-like receptor 4 (TLR4)-defective C3H/HeJ mice, indicating that the observed stimulatory effect occurs independently of TLR4 and unlikely to be mediated by any lipopolysaccharide (LPS) contaminant. MH administration also led to changes in the phenotypic expression and functional maturation of peritoneal macrophages, as evidenced by a shift towards the CD11blo F4/80lo phenotype and an increase in the expression of major histocompatibility complex (MHC) class II proteins. In contrast, the MH-initiated peritoneal response was largely abrogated in mice deficient in myeloid differentiation primary response 88 (MyD88) protein, a critical adaptor of most TLR signaling pathways. Thus, the current findings help to characterize the immunostimulatory properties of MH and their dependence on TLR signaling, and highlight the potential utility of MH as an immunomodulatory agent in a variety of disorders.
Homogenous distributions on spaces of Hermitean matrices.

Although the literature contains numerous results which have some relation to our problem (see [2], [3], [4], [5], [7], [8]) the above question seems to have been treated explicitly only in one case [4]. In fact, most of the cited work deals with another question which can be stated s follows: let Gi denote the kernel of χ in G; the problem is to describe the distributions invariant under Gl9 and in particular those supported on the Singular set (i.e. where P(x) = 0). However, except for some special circumstances, it would seem difficult to apply these results to the problem we are concerned with.
Expertise-dependent perceptual performance in chess tasks with varying complexity

Perceptual performance, anticipating opponents' strategies, and judging chess positions especially in subliminal processing is related to expertise level and dependent on chunking processes. It becomes obvious that chess expertise is a multidimensional phenomenon related predominantly to experience. Under consideration of chess expertise categorization, we conducted two priming experiments expanding existing designs by gradually increasing the target and task complexity. The main aim was the evaluation of potential visuocognitive limitations. The results reveal experts' perceptual superiority manifested by their faster reaction times in settings with increased stimulus and task complexity. Further, experts' priming effects seem to be affected by the target content and/ or priming duration. For short prime duration, experts show priming effects only for less complex prime-target content. Interestingly, for longer prime duration and more complex prime-target content, all participants reveal priming effects. In summary, we argue that experts' visuocognitive processing (i.e., detecting or anticipating potential threats to the king) is rooted in a more efficient visuocognition due to stored chunks of checking and mating constellations. We suggest that visuocognitive limitations are related also to the prime-target complexity as well as to the task. Further investigations must be conducted in order to elucidate the factors with an increased impact on chess players' performance.
Yang-Mills ghost propagator in linear covariant gauges

From first principles, using a screened expansion, a simple one-loop analytical expression is provided for the ghost propagator of pure SU(3) Yang-Mills theory in a generic linear covariant gauge. At variance with the Landau gauge, the ghost dressing function is suppressed in the infrared and vanishes at $p=0$, as predicted by other approaches in the continuum. However, in the very limited range where lattice data are available no detectable deviation is found from the Landau gauge, thus reconciling some recent lattice data and previous continuum predictions.
Tamper-sensitive pre-formed ReRAM-based PUFs: Methods and experimental validation

In this paper, we present the characterization of pre-formed resistive random access memories to design physical unclonable functions and experimentally validate inherent properties such as tamper sensitivity and a self-destroy mode. The physical unclonable functions were tested for repetitive use, temperature effects, and aging. The variations during successive response generation cycles and drift rates are quantized to explore their reliability. We define tamper-sensitivity as the ability to detect tampering attacks. To establish tamper sensitivity, the cells were characterized for higher current sweeps, and the injected current at which they break down is extracted and analyzed to determine suitable operating ranges. Our experimental results show that at least 91% of the cells can generate keys protected by the scheme, while 22% of the sensing elements are triggered. Finally, the cells were characterized for high Voltage sweeps to be able to destroy the physical unclonable functions on-demand when tampering activity is detected. A fixed Voltage of 1.9 V is enough to destroy the entire array.
Interleukin-6 and indoleamine-2,3-dioxygenase as potential adjuvant targets for Papillomavirus-related tumors immunotherapy

High-risk Human papillomavirus (HPV) infections represent an important public health issue. Nearly all cervical malignancies are associated with HPV, and a range of other female and male cancers, such as anogenital and oropharyngeal. Aiming to treat HPV-related tumors, our group developed vaccines based on the genetic fusion of the HSV-1 glycoprotein D (gD) with the HPV-16 E7 oncoprotein (gDE7 vaccines). Despite the promising antitumor results reached by gDE7 vaccines in mice, combined therapies may increase the therapeutic effects by improving antitumor responses and halting immune suppressive mechanisms elicited by tumor cells. Considering cancer immunosuppressive mechanisms, indoleamine-2,3-dioxygenase (IDO) enzyme and interleukin-6 (IL-6) stand out in HPV-related tumors. Since IL-6 sustained the constitutive IDO expression, here we evaluated the therapeutic outcomes achieved by the combination of active immunotherapy based on a gDE7 protein-based vaccine with adjuvant treatments involving blocking IDO, either by use of IDO inhibitors or IL-6 knockout mice. C57BL/6 wild-type (WT) and transgenic IL-6-/- mice were engrafted with HPV16-E6/E7-expressing TC-1 cells and treated with 1-methyl-tryptophan isoforms (D-1MT and DL-1MT), capable to inhibit IDO. In vitro, the 1MT isoforms reduced IL-6 gene expression and IL-6 secretion in TC-1 cells. In vivo, the multi-targeted treatment improved the antitumor efficacy of the gDE7-based protein vaccine. Although the gDE7 immunization achieves partial tumor mass control in combination with D-1MT or DL-1MT in WT mice or when administered in IL-6-/- mice, the combination of gDE7 and 1MT in IL-6-/- mice further enhanced the antitumor effects, reaching total tumor rejection. The outcome of the combined therapy was associated with an increased frequency of activated dendritic cells and decreased frequencies of intratumoral polymorphonuclear myeloid-derived suppressor cells and T regulatory cells. In conclusion, the present study demonstrated that IL-6 and IDO negatively contribute to the activation of immune cells, particularly dendritic cells, reducing gDE7 vaccine-induced protective immune responses and, therefore, opening perspectives for the use of combined strategies based on inhibition of IL-6 and IDO as immunometabolic adjuvants for immunotherapies against HPV-related tumors.
Genetic diversity and phylogeography of the endemic species Chimonobambusa utilis growing in southwest China: Chloroplast DNA sequence and microsatellite marker analyses

Chimonobambusa utilis (Keng) Keng F is an endemic species distributed only in the Daluoshan Mountains, southwest China. Ch. utilis is popular due to its unique flavor and deliciousness and plays an important role in the industrial revolution in many counties in China. A total of 20 natural populations were sampled from the entire distribution range of Ch. utilis. In the present study, we used five EST-SSR molecular markers, three chloroplast DNA (trnH-psbA, atpF-atpH, and psbK-psbI), and one ITS molecular marker to elucidate the genetic diversity and phylogeography analyses of these Ch. utilis populations. The results exhibited that Ch. utilis populations showed lower genetic diversity than other angiosperms (HT = 0.752, HS = 0.364, and FST = 0.05021 for EST-SSR; HT = 0.956, Hs = 0.507, and FST = 0.70121 for cpDNA; HT = 0.868, Hs = 0.495, and FST = 0.70121 for nrDNA). A total of 40 alleles were detected for five polymorphic loci. We detected 20 polymorphic sites and 11 haplotypes within 1,398 bp of cpDNA and 59 polymorphic sites and 32 haplotypes within the 589 bp of the ITS sequence. Based on the haplotype distribution, we infer that there were at least two glacial refuges of Ch. utilis populations during the Quaternary Ice Age. The genetic and geographic distance were correlated (p < 0.05), indicating that narrow distribution might be the primary cause of the low genetic differentiation of Ch. utilis populations. Based on the genetic diversity of Ch. utilis populations, we recommend implementing effective genetic resource management and sustainable utilization.
Moving the needle: Employing deep reinforcement learning to push the boundaries of coarse-grained vaccine models

Highly mutable infectious disease pathogens (hm-IDPs) such as HIV and influenza evolve faster than the human immune system can contain them, allowing them to circumvent traditional vaccination approaches and causing over one million deaths annually. Agent-based models can be used to simulate the complex interactions that occur between immune cells and hm-IDP-like proteins (antigens) during affinity maturation—the process by which antibodies evolve. Compared to existing experimental approaches, agent-based models offer a safe, low-cost, and rapid route to study the immune response to vaccines spanning a wide range of design variables. However, the highly stochastic nature of affinity maturation and vast sequence space of hm-IDPs render brute force searches intractable for exploring all pertinent vaccine design variables and the subset of immunization protocols encompassed therein. To address this challenge, we employed deep reinforcement learning to drive a recently developed agent-based model of affinity maturation to focus sampling on immunization protocols with greater potential to improve the chosen metrics of protection, namely the broadly neutralizing antibody (bnAb) titers or fraction of bnAbs produced. Using this approach, we were able to coarse-grain a wide range of vaccine design variables and explore the relevant design space. Our work offers new testable insights into how vaccines should be formulated to maximize protective immune responses to hm-IDPs and how they can be minimally tailored to account for major sources of heterogeneity in human immune responses and various socioeconomic factors. Our results indicate that the first 3 to 5 immunizations, depending on the metric of protection, should be specially tailored to achieve a robust protective immune response, but that beyond this point further immunizations require only subtle changes in formulation to sustain a durable bnAb response.
Relationships between proactive personality and creativity: Mindsets and golden mean thinking as parallel mediators among Chinese third language students

Third language (L3) learners have great potential in developing creativity; however, the factors affecting L3 learners’ creativity have received little attention. This study investigated the relationships between proactive personality, three different thinking patterns (i.e., growth mindset, fixed mindset, and golden mean thinking), and creativity among L3 learners. The participants were 220 Chinese students who attended an obligatory L3 course in college. The results showed that proactive personality, growth mindset, golden mean thinking, and creativity had significant intercorrelations. Moreover, the role of growth mindset and golden mean thinking as mediators of the proactive personality and creativity relation was supported, and the mediating effect of growth mindset was larger than that of golden mean thinking. However, the fixed mindset did not show a significant indirect effect on the path from proactive personality to creativity. This is the first research to treat growth mindset, fixed mindset, and golden mean thinking as mediating variables on the path from proactive personality to creativity, particularly demonstrating that golden mean thinking, which is specific to Asian students and located midway between a growth mindset and a fixed mindset, can cultivate creativity. Some suggestions for fostering creativity in L3 students were also included in this study.
The implications of stakeholder consultation on employee engagement: An African cross-border acquisition

Objective The objective of the study was to explore the power of stakeholder consultation on employee engagement during a cross-border acquisition in a multi-cultural context. Further, to describe the psychosocial factors at play during the employee involvement process towards enhancing employee engagement. Methods This qualitative study presents the results from data collected in Tanzania through semi-structured interviews (46 participants) and analyzed in accordance with the hermeneutic circle and Tesch’s content analysis method. Results The results of this study contribute to the body of knowledge to better understand the psychosocial factors at play within a multi-cultural environment which inform stakeholder consultation and will enable or hinder employee engagement. A transitional space should be created, fostering mature stakeholder engagement, promoting employee inclusion, engagement, and knowledge sharing. Conclusion Bringing together two worlds requires building bridges to cross the cliff between contexts and overcoming diversity challenges, while incorporating diversity management in the consulting process. A multi-cultural team should be established, incorporating diversity management, applying the principles of respect, participation and transparent communication, with regular feedback on decisions made. External stakeholders in authoritative positions are not well received and should consider traditional superiority versus business hierarchy when establishing leader-follower relationships.
Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine

Metabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands of metabolites in samples makes metabolomics a promising technique in predictive or personalized medicine-oriented researches and applications. Liquid chromatography-mass spectrometry is the most widely employed analytical strategy for metabolomics. In this current mini-review, we provide a brief update on the recent developments and novel applications of LC-MS based metabolomics in the predictive and personalized medicine sector, such as early diagnosis, molecular phenotyping or prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We also discuss the prospects of metabolomics in precision medicine-oriented researches, as well as critical issues that need to be addressed when employing metabolomic strategy in clinical applications.
Could cardiac autonomic modulation be an objective method to identify hypobaric hypoxia symptoms at 25.000ft among Brazilian military airmen?

Hypobaric hypoxia during a flight can cause accidents, resulting in deaths. Heart rate variability may be more sensitive than self-reported hypoxia symptoms to the effects of HH. The level of physical fitness can contribute to efficient cardiac autonomic modulation. However, no studies have examined the association between fitness, heart rate variability, and the time of onset of hypobaric hypoxia symptoms. To analyze the influence of hypobaric hypoxia on cardiac autonomic function at the time of onset of the first symptoms and its association with physical fitness. Male airmen trained and belonging to the staff of the Brazilian Air Force (n = 23; 30 ± 6.7 years) participated in a flight simulation in a 25.000 ft hypobaric chamber. Heart rate variability was recorded with a Polar® cardiac monitor. Data were analyzed in the time-domain method using Kubios software. We evaluated pulse oximetry with the Mindray PM-60 oximeter. Physical fitness assessment test results were collected from the archive. At moments rest vs. hypoxia revealed a decrease in heart rate variability indices iRR and RMSSD (p < 0.001). The individual analysis of hypoxia-rest variation showed that 100% of the airmen had a negative delta for both iRR and RMSSD indices. The time of onset of hypoxia symptoms was not associated with body composition, physical fitness, oxygen saturation, and HRV indices. Also, we suggest that cardiac autonomic modulation seems to be more sensitive to the effects of hypobaric hypoxia at 25.000 ft than the self-reported subjective perception of symptoms. Further devices that alert to a hypoxic condition during a flight should consider heart rate variability allowing more time and security to reestablish control of the flight.
The infrared spectrum of Comet Hale-Bopp

The infrared spectroscopic observations of the comet C/1995 O1 (Hale-Bopp), in April and September-October 1996, are summarized. High resolution spectra were obtained with the long and short wavelength spectrometers of the Infrared Space Observatory (ISO). The results showed that the dust in this comet contains crystalline silicates. The dust of Hale-Bopp is rather similar to that observed in the circumstellar disks of Vega-type stars.
Cost-effectiveness analysis of sugemalimab vs. placebo, in combination with chemotherapy, for treatment of first-line metastatic NSCLC in China

Objective The purpose of this study was to estimate the cost-effectiveness of sugemalimab plus chemotherapy (SC) vs. placebo plus chemotherapy (PC), as the first-line treatment for patients with non-small cell lung cancer (NSCLC) in China. Material and methods A three-state Markov model with a cycle of 3 weeks was built to assess the incremental cost-effectiveness ratio (ICER) of SC vs. PC as first-line treatment for patients with NSCLC over a 10-year horizon from Chinese health care perspective. Time-dependency transition probability and safety data were derived from a multicenter, randomized, double-blind, phase 3 clinical trial performed in China (GEMSTONE-302). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) and the ICER under a willingness-to-pay (WTP) threshold of $37,663/QALYs. Deterministic, scenario and probabilistic sensitivity analysis were employed to investigate the robustness of model outcomes. Results In base-case analysis, compared with PC, first-line SC for intention-to-treat (ITT) population gained an additional 0.57 QALYs with an incremental cost of $62,404.15, resulting in an ICER of $109,480.97/QALYs gained. When a patient assistance program (PAP) was available, the ICER decreased to $52,327.02/QALYs. In subgroup analysis, the ICER values were above the WTP threshold with or without PAP. Sensitivity analysis results suggested that the model outcomes were reliable. Conclusion From the perspective of Chinese healthcare system, the SC was not cost-effective in comparison to PC as first-line treatment for NSCLC, regardless of PD-L1 tumor expression level and pathological subtype.