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PURPOSE The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)–like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. PATIENTS AND METHODS An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. RESULTS Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. CONCLUSION We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.

Arranging tasks at the level of device design is an important part of supporting children's mental development in technical education classes. Due to little interest in this area of education, there is little research on children's task-solving skills in device design (por. Furmanek, 2007, part 1). This paper presents the situation of solving, by 8-year-old pupils, a task involving the use of a turnstile mechanism to design a device that sends planes into the air. The investigation showed that pupils make strong use of familiar devices (e.g. lift, crane) in designing the device. Referring to the names of the devices, they easily communicate with each other, and when designing a common structure, they complete their ideas and evaluate their practicality. Group creation of a new device is creative and stimulates children's thinking.

Background Identifying predictors of treatment outcome can guide treatment selection and optimize use of resources. In patients affected by obsessive-compulsive disorder (OCD), perfectionism has emerged as one possible predictor, with some data suggesting that cognitive-behavioral therapy outcomes are poorer for more perfectionistic patients. Findings so far are inconsistent, however, and research has yet to be extended to newer treatment approaches. Methods We administered measures of concern over mistakes, clinical perfectionism, as well as OCD and depression symptom severity to a sample of OCD patients in out-patient group treatments (N = 61), namely, metacognitive training (MCT-OCD) or mindfulness-based cognitive therapy (MBCT) for OCD. Hierarchical data over time was submitted to multi-level analysis. Results Neither concern over mistakes nor clinical perfectionism at baseline predicted OCD symptoms across time points. However, concern over mistakes at baseline did significantly predict comorbid depressive symptoms. Furthermore, exploratory analysis revealed change in clinical perfectionism during treatment as a predictor of OCD symptoms at follow-up. Conclusion These results suggest that initial concern over mistakes may not prevent patients with OCD from benefitting from third-wave treatments. Change in clinical perfectionism may present a putative process of therapeutic change. Limitations and avenues for future research are discussed.

Reactive neurotoxic aldheyde DOPAL, enzymatically produced from dopamine in cells and tissues, is associated with adverse physiological effects. Lysine-C-dots inhibit DOPAL-induced α-synuclein oligomerization and cytotoxicity.

At the early stages of schooling, existing misconceptions may cause that children find difficulties in accepting scientific explanations. The article presents childrens beliefs related to the phenomena of volcanic eruption, mountain formation and the accumulation of snow on mountain peaks. The research was conducted in the form of individual interviews with 50 children aged from 6 to 8 years old. The research results present childrens beliefs, which have been arranged from those consisting of personal experiences, through those including information obtained from adults, to those being close to scientific explanations. The knowledge of these beliefs allows teachers to organize educational situations in a better way.

Children begin to fully understand evaporation at the age of 11 years, but they already have some idea of this phenomenon in preschool age. The paper presents the results of a research exploring the understanding of evaporation by 6- and 9-year-old children. The research used the method of a narrative based on incorrect information in order to verify whether and how well children would discover the errors in that narrative and how they could explain the process of evaporation. The incorrect narrative method is inspired by the science fiction film genre, which uses false assumptions to prove something that is not true. According to the research, half of the children knew that evaporation accompanies the process of cloud formation, but only half of the children who knew that (one-fourth of the respondents) could detect an error in the narrative. The reason for that is believed to be children’s lack of critical thinking and limited structured knowledge of evaporation in the water cycle in nature.

Patients with severe COVID-19 are at an increased risk of Acute Respiratory Distress Syndrome (ARDS) and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators.This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and non-critically ill COVID-19 patients.This cross-sectional study recruited 646 participants that tested positive for SARS-CoV-2 from 6 collection sites across the United Arab Emirates. Medical files were accessed to retrieve clinical data. Blood samples were collected from all participants. Patients were divided into two clinical groups; non-critical (n = 453) and critical (n = 193); according to WHO classification guidelines for COVID-19 patients. Cytokine analyses were conducted on serum of a subset of the cohort. specifically on 426 participants (non-critical = 264; critical = 162). Candidate gene analyses of 33 cytokine-related genes (2,836 variants) were extracted from a Genome-Wide Association Study (GWAS) to identify genetic variants with pleiotropic effects on a specific cytokine and the severity of COVID-19 disease.Age, Body Mass Index (BMI), and pre-existing medical conditions were found to be significant risk factors that contribute to COVID-19 disease severity. After correcting for age, gender and BMI, IP-10 (p0.001), IFN (p = 0.001), IL-6 (p0.001), and CXCL-16 (p0.001) serum levels were significantly higher among critical COVID-19 cases, when compared to non-critically ill patients. To investigate if the genetic variants involved in the serum cytokine levels are associated with COVID-19 severity, we studied several genes. Single Nucleotide Polymorphisms (SNPs) in IL6 (rs1554606; ORG = 0.67 (0.66, 0.68); p = 0.017), IFNG (rs2069718; ORG = 0.63 (0.62, 0.64); p = 0.001), MIP (rs799187; ORA = 1.69 (1.66, 1.72); p = 0.034), and CXCL16 (rs8071286; ORA = 1.42 (1.41, 1.44); p = 0.018) were found to be associated with critically ill patients. Polymorphisms in the CXCL10, CCL2, IL1, CCL7 and TNF genes were not associated with the COVID-19 critical phenotype. The genotypes of IL-6 (Gene: IL6 (7p15.3)) and CXCL-16 (Gene: CXCL16 (17p13.2)) were significantly associated with the serum levels of the respective cytokine in critical cases of COVID-19.Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients, and other infectious diseases.

Selective activation and controlled functionalization of C-H bonds in organic molecules is one of the most desirable processes in synthetic chemistry. Despite progress in heterogeneous catalysis using metal surfaces, this goal remains challenging due to the stability of C-H bonds and their ubiquity in precursor molecules, hampering regioselectivity. Here, we examine the interaction between 9,10-dicyanoanthracene (DCA) molecules and Au adatoms on a Ag(111) surface at room temperature (RT). Characterization via low-temperature scanning tunneling microscopy, spectroscopy, and noncontact atomic force microscopy, supported by theoretical calculations, revealed the formation of organometallic DCA-Au-DCA dimers, where C atoms at the ends of the anthracene moieties are bonded covalently to single Au atoms. The formation of this organometallic compound is initiated by a regioselective cleaving of C-H bonds at RT. Hybrid quantum mechanics/molecular mechanics calculations show that this regioselective C-H bond cleaving is enabled by an intermediate metal-organic complex which significantly reduces the dissociation barrier of a specific C-H bond. Harnessing the catalytic activity of single metal atoms, this regioselective on-surface C-H activation reaction at RT offers promising routes for future synthesis of functional organic and organometallic materials.

There is significant variation in post-treatment surveillance imaging for sinonasal malignancies. This study examined the utility of surveillance imaging in detecting recurrence in patients treated for sinonasal malignancies.We performed a retrospective review on an IRB-approved dataset of patients with sinonasal malignancies treated at a single institution between 2005 to 2021. Patients were categorized into groups based on the frequency of annual imaging and total number of imaging studies. We compared time-to-recurrence between the groups using log-rank test. A two-sided p-value of0.05 was considered as the threshold for significance.A total of 93 patients were eligible for this study with a median follow up of 42.3 months and 25.8% (n=24) of patients had documented recurrence. Sensitivity and specificity for recurrence based on computed tomography (CT) scans within one year of treatment completion were 50.0% and 19.5%; positron emission tomography/CT was 90.0% and 19.5%; and magnetic resonance imaging was 60.0% and 61.0%, respectively. Regardless of the type of imaging, symptomatic presentation after treatment had a specificity of 91.0% with a positive likelihood ratio of recurrence of 2.95 (95%CI=1.06-8.22). The frequency of scans was not associated with the risk of recurrence (HR=0.55; 95%CI=0.23-1.29, p=0.17). Similarly, no association was noted between the total number of scans and risk of recurrence (HR=0.64; 95%CI=0.27-1.51, p=0.31).The total number of frequency of scans within the first year after treatment had no association with time to recurrence of sinonasal malignancies. Symptomatic presentation was strongly associated with recurrence and should be investigated with appropriate imaging.

Despite evidence suggesting that excess weight is linked to gait alterations and foot disorders, its effect on peak plantar pressure (PPP) variability and complexity during walking remains poorly understood.This study aimed to examine the influence of overweight (BMI ≥ 25) on the dynamic PPP distribution during gait using traditional and nonlinear dynamic measures in young college students.Fifty-two overweight (BMI25, average 29.3 ± 4.02) and sixty-four control college students (BMI25, 21.7 ± 1.76) aged 18-25 years, walked across a Tekscan gait assessment system at their preferred speed. A t-test or a Mann Whitney U test was used for analysis, subject to data normality. Kinematic, kinetic, spatiotemporal, and GaitEn (sample entropy of 2D spatial PPP maps) for window lengths (m=2) at various filtering levels (r) were used to explore the impact of BMI on PPP alterations.The overweight group exhibited significantly higher mean PPP. The PPP under the forefoot region was also significantly higher for the overweight group as compared to the heel. The mean GaitEn values of overweight and control groups were found significantly different at r = (0.7-0.8) x STD, where GaitEn of the control group was relatively higher, which indicates better gait performance as compared to the overweight group in alignment with previous studies. A significant correlation of GaitEn with STD of PPP was revealed for the overweight group only, suggesting that overweight could significantly change the regularity or the complexity of the PPP series. Although no spatiotemporal parameters (stride length, step length, step width) were significantly affected by the increased BMI, GaitEn dynamic measure, along with spatiotemporal (decrease in gait velocity and cadence with increased BMI), and kinetic measures (increased maximum forces and plantar pressure with increased BMI), were significantly affected by overweight, indicating the feasibility of assessing the impact of increased BMI using pressure platforms in clinical settings.

How do religions and social order interact with each other? Scholars of religions have repeatedly explored this question from numerous perspectives. However, they have yet to utilise the approach of disability studies, which focuses on disability as a social ordering process, to address this question. As such, not only have the manifold empirical relationships between religions and disability often been disregarded, but a great theoretical potential also remains untapped. In this paper, I demonstrate what the study of religions can gain from analysing processes of disablement. In doing so, I introduce the concept of dis/abling religion, which integrates the study of religions and disability studies, making it possible to systematically grasp the entanglements between religions, disability, and social order.

High-resolution structures are crucial for understanding the functional properties of nanomaterials. We applied single-particle cryo-electron microscopy (cryo-EM), a method traditionally used for structure determination of biological macromolecules, to obtain high-resolution structures of synthetic non-biological filaments formed by photopolymerization of macrocyclic diacetylene (MDA) amphiphilic monomers. Tomographic analysis showed that the MDA monomers self-assemble into hollow nanotubes upon dispersion in water. Single-particle analysis revealed tubes consisting of six pairs of covalently bonded filaments held together by hydrophobic interactions, where each filament is composed of macrocyclic rings stacked in parallel "chair" conformations. The hollow MDA nanotube structures we found may account for the efficient scavenging of amphiphilic pollutants in water and subsequent photodegradation of the guest species.

Resveratrol, a natural polyphenol, exhibits beneficial health properties and has been touted as a potential anti-tumor agent. Here, we demonstrate potent anti-cancer effects of carbon dots (C-dots) synthesized from resveratrol. The mild synthesis conditions retained resveratrol functional moieties upon the carbon dots' (C-dots) surface, an important requisite for achieving specificity toward cancer cells and biological activities. Indeed, the disruptive effects of the resveratrol-C-dot were more pronounced in several cancer cell types compared to normal cells, underscoring targeting capabilities of the C-dots, a pertinent issue for the development of cancer therapeutics. In particular, we observed impairment of mitochondrial functionalities, including intracellular calcium release, inhibition of cytochrome-C oxidase enzyme activity, and mitochondrial membrane perturbation. Furthermore, the resveratrol C-dots were more potent than either resveratrol molecules alone, known anti-cancer polyphenolic agents such as curcumin and triphenylphosphonium, or C-dots prepared from different carbonaceous precursors. This study suggests that resveratrol-synthesized C-dots may have promising therapeutic potential as anti-cancer agents.

This phenomenological study brought a critical lens to the views and contexts of seven music therapists. Semi-structured interviews examined participants’ experiences of the sociocultural and privilege dynamics within music therapy education. Purposive sampling allowed the researcher to center the perspectives of participants who collectively described themselves with intersections of the following identities: black, white, Latinx, Chinese, South East Asian, male, female, non-binary, disabled, non-disabled, straight, pansexual, and one self-identified dyke. An iterative inductive analysis revealed several emergent themes related to inequity and the decentering of minoritized voices within music therapy: the theme A Very White Lens focused on a Eurocentric approach in education and practice that, by failing to acknowledge and center a variety of perspectives, reduces equitable access to both students and clients; Silenced Experiences of Minoritized Voices included participant experiences of anti-Blackness, white privilege, and white fragility within music therapy; When Does Culture Matter? captured responses to and the dangers of an approach that ignores cultural differences; and How We Talk About Culture included concerns and suggestions about the structure of the discourse around cultural intersections, privilege, and race in music therapy education and practice. These findings bring to light some of the structures of power and privilege at the core of music therapists’ education and training. Themes highlighted in this paper center the experiences of individuals who belong to minoritized populations and in so doing, emphasize the need to listen to a greater diversity of voices in the conversation about equity and inclusion in music therapy.

In contrast to the well-known stereotype of the boring, unsociable accountant, today’s public accounting professionals argue that they are boundary-spanners. Working at the intersection of the firm/client interface, these professionals contend that sociability is a requisite skill for routinely navigating the many interactions they have with multiple personnel at client organizations. This research aims to address this disconnect and confront whether the public perception is warranted. Using the Trait Emotional Intelligence Questionnaire (TEIQue), we assess the sociability of 176 public accounting professionals and discover that, contrary to the stereotype, male public accountants are more sociable than males in the general population. Our analysis also demonstrates that female public accountants are no more or less sociable than females in the general population. Additional analysis shows that while male public accountants are more sociable than female public accountants, this effect is attributable to differences at lower levels of the profession and that male-female differences disappear when comparing male managers and partners to female managers and partners. Given the importance of sociability in public accounting, this research offers recruiting strategies which will help to dispel the myth of the unsociable accountant and provides training tips for enhancing sociability within the ranks.

We report on ion emission from plasma produced on thick targets irradiated with nanosecond and femtosecond pulses delivered by mid-ultraviolet and soft x-ray lasers, respectively. To distinguish between different ion acceleration mechanisms, the maximum kinetic energy of ions produced under different interaction conditions is plotted versus laser fluence. The transformation of the time-of-flight detector signal into ion charge density distance-of-flight spectra makes it possible to determine the mean kinetic energy of the fastest ion groups based on the influence of the acoustic velocity of ion expansion. This allows obtaining additional characteristics of the ion production. The final energy of the group of fast ions determined using the ion sound velocity model is an order of magnitude larger in the fs-XFEL interaction than in the ns-UV one. On the contrary, the ablation yield of ions in our experiment is seven orders of magnitude greater when applying ns-UV laser pulses, not only due to higher energies of UV laser pulses, but also due to a significant difference in interaction and ion formation mechanisms.

Research suggests that patients with borderline personality disorder (BPD) share a range of cognitive biases with patients with psychosis. As the disorder often manifests in dysfunctional social interactions, we assumed associated reasoning styles would be exaggerated in a social setting. For the present study, we applied the Judge-Advisor System by asking participants to provide initial estimates of a person’s age and presumed hostility based on a portrait photo. Afterwards, we presented additional cues/advice in the form of responses by anonymous previous respondents. Participants could revise their estimate, seek additional advice, or make a decision. Contrary to our preregistered hypothesis, patients with BPD (n = 38) performed similarly to healthy controls (n = 30). Patients sought the same number of pieces of advice, were equally confident, and used advice in similar ways to revise their estimates. Thus, patients with BPD did trust advice. However, patients gave higher hostility ratings to the portrayed persons. In conclusion, patients with BPD showed no cognitive biases in seeking, evaluating, and integrating socially provided information. While the study implies emotional rather than cognitive biases in the disorder, cognitive biases may still prove to be useful treatment targets in order to encourage delaying and reflecting on extreme emotional responses in social interactions.

Purpose: The purpose of this study was to assess the effect of folic acid (FA) supplementation on colitis-associated colorectal cancer (CRC) using the azoxymethane/dextran sulfate sodium (AOM/DSS) model. Methods: Mice were fed a chow containing 2 mg/kg FA at baseline and randomized after the first DSS treatment to receive 0, 2, or 8 mg/kg FA chow for 16 weeks. Colon tissue was collected for histopathological evaluation, genome-wide methylation analyses (Digital Restriction Enzyme Assay of Methylation), and gene expression profiling (RNA-Seq). Results: A dose-dependent increase in the multiplicity of colonic dysplasias was observed, with the multiplicity of total and polypoid dysplasias higher (64% and 225%, respectively) in the 8 mg FA vs. the 0 mg FA group (p < 0.001). Polypoid dysplasias were hypomethylated, as compared to the non-neoplastic colonic mucosa (p < 0.05), irrespective of FA treatment. The colonic mucosa of the 8 mg FA group was markedly hypomethylated as compared to the 0 mg FA group. Differential methylation of genes involved in Wnt/β-catenin and MAPK signaling resulted in corresponding alterations in gene expression within the colonic mucosa. Conclusions: High-dose FA created an altered epigenetic field effect within the non-neoplastic colonic mucosa. The observed decrease in site-specific DNA methylation altered oncogenic pathways and promoted colitis-associated CRC.

BackgroundThe mammalian Leukocyte Receptor Complex (LRC) chromosomal region may contain gene families for the killer cell immunoglobulin-like receptor (KIR) and/or leukocyte immunoglobulin-like receptor (LILR) collections as well as various framing genes. This complex region is well described in humans, mice, and some domestic animals. Although single KIR genes are known in some Carnivora, their complements of LILR genes remain largely unknown due to obstacles in the assembly of regions of high homology in short-read based genomes.MethodsAs part of the analysis of felid immunogenomes, this study focuses on the search for LRC genes in reference genomes and the annotation of LILR genes in Felidae. Chromosome-level genomes based on single-molecule long-read sequencing were preferentially sought and compared to representatives of the Carnivora.ResultsSeven putatively functional LILR genes were found across the Felidae and in the Californian sea lion, four to five genes in Canidae, and four to nine genes in Mustelidae. They form two lineages, as seen in the Bovidae. The ratio of functional genes for activating LILRs to inhibitory LILRs is slightly in favor of inhibitory genes in the Felidae and the Canidae; the reverse is seen in the Californian sea lion. This ratio is even in all of the Mustelidae except the Eurasian otter, which has a predominance of activating LILRs. Various numbers of LILR pseudogenes were identified.ConclusionsThe structure of the LRC is rather conservative in felids and the other Carnivora studied. The LILR sub-region is conserved within the Felidae and has slight differences in the Canidae, but it has taken various evolutionary paths in the Mustelidae. Overall, the process of pseudogenization of LILR genes seems to be more frequent for activating receptors. Phylogenetic analysis found no direct orthologues across the Carnivora which corroborate the rapid evolution of LILRs seen in mammals.

This paper introduces a theory for assessing and optimizing the multiple-input-multiple-output performance of multi-port cluster antennas in terms of efficiency, channel correlation, and power distribution. A method based on a convex optimization of feeding coefficients is extended with additional constraints allowing the user to control a ratio between the power radiated by the clusters. The formulation of the problem makes it possible to simultaneously optimize total efficiency and channel correlation with a fixed ratio between power radiated by the clusters, thus examining a trade-off between these parameters. It is shown that channel correlation, total efficiency, and allocation of radiated power are mutually conflicting parameters. The trade-offs are shown and discussed. The theory is demonstrated on a four-element antenna array and on a mobile terminal antenna., 10 pages, 12 figures

Sudden cardiac death (SCD) is a leading cause of death among athletes, and those with a positive family history (FH) of SCD and/or cardiovascular disease (CVD) may be at increased risk. The primary objective of this study was to assess the prevalence and predictors of positive FH of SCD and CVD in athletes using four widely used preparticipation screening (PPS) systems. The secondary objective was to compare the functionality of the screening systems. In a cohort of 13,876 athletes, 1.28% had a positive FH in at least one PPS system. Multivariate logistic regression analysis identified the maximum heart rate as significantly associated with positive FH (OR = 1.042, 95% CI = 1.027–1.056, p < 0.001). The highest prevalence of positive FH was found using the PPE-4 system (1.20%), followed by FIFA, AHA, and IOC systems (1.11%, 0.89%, and 0.71%, respectively). In conclusion, the prevalence of positive FH for SCD and CVD in Czech athletes was found to be 1.28%. Furthermore, positive FH was associated with a higher maximum heart rate at the peak of the exercise test. The findings of this study revealed significant differences in detection rates between PPS protocols, so further research is needed to determine the optimal method of FH collection.

Submolecular charge distribution significantly affects the physical-chemical properties of molecules and their mutual interaction. One example is the presence of a π-electron-deficient cavity in halogen-substituted polyaromatic hydrocarbon compounds, the so-called π-holes, the existence of which was predicted theoretically, but the direct experimental observation is still missing. Here we present the resolution of the π-hole on a single molecule using the Kelvin probe force microscopy, which confirms the theoretical prediction of its existence. In addition, experimental measurements supported by theoretical calculations show the importance of π-holes in the process of adsorption of molecules on solid-state surfaces. This study expands our understanding of the π-hole systems and, at the same time, opens up possibilities for studying the influence of submolecular charge distribution on the chemical properties of molecules and their mutual interaction.

Many patients with obsessive-compulsive disorder (OCD) do not receive cognitive behavioral therapy with exposure and response prevention (first line treatment for OCD), for example, due to patients’ fear of the exposure and reservations of the therapists. Technology-supported exposure (e.g., exposure therapy with response prevention in mixed reality [MERP]) for patients with OCD may help to overcome this obstacle. Building upon findings of our pilot study objectives of this study are to evaluate the efficacy, expectations of treatment success, feasibility, and acceptance of MERP as well as to identify possible limitations. In total, 64 outpatients with contamination-related OCD will be recruited and randomized to one of two conditions: MERP (six sessions in six weeks) and self-guided exposure therapy (six exercises in six weeks). Participants will be assessed before (baseline), after the six-week intervention period (post), as well as three months after post assessment (follow-up) regarding symptomatology (Yale-Brown Obsessive Compulsive Scale; Y-BOCS), their subjective evaluation of MERP (acceptance) and sense of presence. The planned study is the first to investigate MERP in patients with OCD.

Heart failure is characterized by sympathetic activation and parasympathetic withdrawal leading to an abnormal autonomic modulation. Beta-blockers (BB) inhibit overstimulation of the sympathetic system and are indicated in heart failure patients with reduced ejection fraction. However, the effect of beta-blocker therapy on heart failure with preserved ejection fraction (HFpEF) is unclear. ECGs of 73 patients with HFpEF > 55% were recruited. There were 56 patients in the BB group and 17 patients in the without BB (NBB) group. The HRV analysis was performed for the 24-h period using a window size of 1,4 and 8-h. HRV measures between day and night for both the groups were also compared. Percentage change in the BB group relative to the NBB group was used as a measure of difference. RMSSD (13.27%), pNN50 (2.44%), HF power (44.25%) and LF power (13.53%) showed an increase in the BB group relative to the NBB group during the day and were statistically significant between the two groups for periods associated with high cardiac risk during the morning hours. LF:HF ratio showed a decrease of 3.59% during the day. The relative increase in vagal modulated RMSSD, pNN50 and HF power with a decrease in LF:HF ratio show an improvement in the parasympathetic tone and an overall decreased risk of a cardiac event especially during the morning hours that is characterized by a sympathetic surge.

Network effects, economies of scale, and lock-in-effects increasingly lead to a concentration of digital resources and capabilities, hindering the free and equitable development of digital entrepreneurship (SDG9), new skills, and jobs (SDG8), especially in small communities (SDG11) and their small and medium-sized enterprises (“SMEs”). To ensure the affordability and accessibility of technologies, promote digital entrepreneurship and community well-being (SDG3), and protect digital rights, we propose data cooperatives [1,2] as a vehicle for secure, trusted, and sovereign data exchange [3,4]. In post-pandemic times, community/SME-led cooperatives can play a vital role by ensuring that supply chains to support digital commons are uninterrupted, resilient, and decentralized [5]. Digital commons and data sovereignty provide communities with affordable and easy access to information and the ability to collectively negotiate data-related decisions. Moreover, cooperative commons (a) provide access to the infrastructure that underpins the modern economy, (b) preserve property rights, and (c) ensure that privatization and monopolization do not further erode self-determination, especially in a world increasingly mediated by AI. Thus, governance plays a significant role in accelerating communities’/SMEs’ digital transformation and addressing their challenges. Cooperatives thrive on digital governance and standards such as open trusted Application Programming Interfaces (APIs) that increase the efficiency, technological capabilities, and capacities of participants and, most importantly, integrate, enable, and accelerate the digital transformation of SMEs in the overall process. This policy paper presents and discusses several transformative use cases for cooperative data governance. The use cases demonstrate how platform/data-cooperatives, and their novel value creation can be leveraged to take digital commons and value chains to a new level of collaboration while addressing the most pressing community issues. The proposed framework for a digital federated and sovereign reference architecture will create a blueprint for sustainable development both in the Global South and North.

Open-shell benzenoid polycyclic aromatic hydrocarbons, known as magnetic nanographenes, exhibit unconventional p-magnetism arising from topological frustration or strong electronic-electron (e-e) interaction. Imprinting multiple strongly entangled spins into polyradical nanographenes creates a major paradigm shift in realizing non-trivial collective quantum behaviors and exotic quantum phases in organic quantum materials. However, conventional design approaches are limited by a single magnetic origin, which can restrict the number of correlated spins or the type of magnetic ordering in open-shell nanographenes. Here, we present a novel design strategy combing topological frustration and e-e interactions to fabricate the largest fully-fused open-shell nanographene reported to date, a 'butterfly'-shaped tetraradical on Au(111). We employed bond-resolved scanning tunneling microscopy and spin excitation spectroscopy to unambiguously resolve the molecular backbone and reveal the strongly correlated open-shell character, respectively. This nanographene contains four unpaired electrons with both ferromagnetic and anti-ferromagnetic interactions, harboring a many-body singlet ground state and strong multi-spin entanglement, which can be well described by many-body calculations. Furthermore, we demonstrate that the nickelocene magnetic probe can sense highly-correlated spin states in nanographene. The ability to imprint and characterize many-body strongly correlated spins in polyradical nanographenes not only presents exciting opportunities for realizing non-trivial quantum magnetism and phases in organic materials but also paves the way toward high-density ultrafast spintronic devices and quantum information technologies., 17 pages, 4 figures

Supplementary Figure 1 from Concordant DNA Methylation in Synchronous Colorectal Carcinomas

DNA promoter methylation of tumor suppressor genes and global DNA hypomethylation are common features of head and neck cancers. Our goal was to identify early DNA methylation changes in oral premalignant lesions (OPL) that may serve as predictive markers of developing oral squamous cell carcinoma (OSCC). Using high-throughput DNA methylation profiles of 24 OPLs, we found that the top 86 genes differentially methylated between patients who did or did not develop OSCC were simultaneously hypermethylated, suggesting that a CpG island methylation phenotype may occur early during OSCC development. The vast majority of the 86 genes were nonmethylated in normal tissues and hypermethylated in OSCC versus normal mucosa. We used pyrosequencing in a validation cohort of 44 patients to evaluate the degree of methylation of AGTR1, FOXI2, and PENK promoters CpG sites that were included in the top 86 genes and of LINE1 repetitive element methylation, a surrogate of global DNA methylation. A methylation index was developed by averaging the percent methylation of AGTR1, FOXI2, and PENK promoters; patients with a high methylation index had a worse oral cancer–free survival (P = 0.0030). On the other hand, patients with low levels of LINE1 methylation had a significantly worse oral cancer–free survival (P = 0.0153). In conclusion, AGTR1, FOXI2, and PENK promoter methylation and LINE1 hypomethylation may be associated with an increased risk of OSCC development in patients with OPLs. Cancer Prev Res; 8(11); 1027–35. ©2015 AACR.

Supplementary Figure 1: Flow-chart describing the selection of 86 candidate genes. Supplementary Figure 2: Promoter methylation of 62/86 candidate genes in head and neck cancer, normal mucosa and blood. Supplementary Figure 3: Promoter methylation of 13/86 candidate genes in normal tissues. Supplementary Fig. 4: Hierarchical clustering of paired normal, dysplastic lesions and carcinomas (in situ or invasive) collected from 10 patients (3), using methylation profiles of 60/86 of our candidate genes. Supplementary Figure 5: (A) Hierarchical cluster analysis of oral squamous cell carcinoma and oral normal mucosa using candidate genes expression profiles. Supplementary Figure 6: Correlation of the percentage methylation of AGTR1.

Supplementary Table 1: Description of the studies used for the in silico validation of the candidate genes in terms of number of samples analyzed, platform used and number of overlapping genes between our candidate gene list and the genes analyzed on the platform (HN: head and neck; SCC: squamous cell carcinoma). Supplementary Table 2: List of cell lines in which the level of promoter methylation of AGTR1, FOXI2, HOXA9, PENK and ZIC1 were evaluated (HNSCC: head and neck squamous cell carcinoma). Supplementary Table 3: Univariate Cox proportional hazards model for all other available variables. Supplementary table 4: Multi-covariable Cox Model analysis including histology (hyperplasia or dysplasia).

Whole blood DNA methylation analysis has been proposed to be a risk marker for cancer that can be used to target patients for preventive interventions. To test this, we examined whole blood DNA methylation of 16 CpG island promoters and LINE1 repetitive element in patients with gastric cancer and control subjects. Bisulfite pyrosequencing was used to quantify the methylation of 14 CpG island promoters (MINT25, RORA, GDNF, CDH1, RARAB2, ER, CDH13, MYOD1, SFRP1, P2RX7, SLC16A12, IGF2, DPYS, and N33) and LINE1 from 72 patients with gastric cancer, 67 control, and 52 healthy young individuals. Quantitative methylation-specific real-time PCR was also conducted for 3 CpG island promoters (MINT25, MYO3A, and SOX11). Among all sites tested, only a marginal increase in the methylation of the SFRP1 promoter was observed in the blood of patients with gastric cancer when compared with the control group (11.3 % vs 10.5%; age-adjusted P value: P = 0.009), and this association was also seen in a validation set of 91 patients with gastric cancer (11.5% vs 10.5%; age-adjusted P value: P = 0.001). The methylation of 9 sites (GDNF, CDH1, RARAB2, CDH13, MYOD1, SFRP1, SLC16A12, DPYS, N33, and LINE1) and their mean Z score was correlated with higher age (R = 0.41, P < 0.0001) and marginally with telomere shortening (R = −0.18, P = 0.01) but not with gastric cancer risk (other than SFRP1 methylation). Variability in whole blood DNA methylation of cancer markers is primarily associated with aging, reflecting turnover of white blood cells, and has no direct link to gastric cancer predisposition. SFRP1 methylation in whole blood may be associated with gastric cancer risk. Cancer Prev Res; 6(10); 1093–100. ©2013 AACR.

Epigenetic changes have been proposed as mediators of the field defect in colorectal carcinogenesis, which has implications for risk assessment and cancer prevention. As a test of this hypothesis, we evaluated the methylation status of eight genes (MINT1, 2, 31, MLH1, p16, p14, MGMT, and ESR1), as well as BRAF and KRAS mutations, in 57 multiple colorectal neoplasias (M-CRN) and compared these to 69 solitary colorectal cancers (S-CRC). There were no significant differences in methylation between M-CRNs and S-CRCs except for p14 and MGMT that was significantly higher in M-CRNs than S-CRCs (16.1% versus 9.3%; 26.5% versus 17.3%, respectively; P < 0.05). We found significant (P < 0.05) correlations for MINT1 (r = 0.8), p16 (r = 0.8), MLH1 (r = 0.9), and MGMT (r = 0.6) methylation between tumors pairs of the same site (proximal/proximal and distal/distal). KRAS showed no concordance in mutations. BRAF mutation showed concordance in proximal site pairs but was discordant in different site pairs. Histologically, eight of 10 paired cancers with similar locations were concordant for a cribriform glandular configuration. We conclude that synchronous colorectal tumors of the same site are highly concordant for methylation of multiple genes, BRAF mutations, and a cribriform glandular configuration, all consistent with a patient-specific predisposition to particular subtypes of colorectal cancers. Screening for and secondary prevention of colon cancer should take this fact into account.