Search

Social finance, an arena of international finance comprising social banking, impact investing, and microfinance, offers a powerful conceptual lens through which to interrogate the interface of finance and labor in financial capitalism. This article investigates social finance’s development at the crossroad of two processes. Social finance emerged in the context of a process of laboring finance, an often-coercive inclusion of workers and households into financial circuits of accumulation and expansion made possible by labor market changes that began in the 1970s. The global financial crisis occasioned the growth of social finance, which, by means of financing labor, placed the reproductive needs of labor—the needs of society’s most disadvantaged agents, the poor, the homeless, the marginal, and unemployed workers—at the center of financial accumulation. By informing an oscillatory movement between laboring finance and financing labor, and, affectively, between trust and distrust, social finance primes and cultivates financial market participants’ belief in purported solutions to the social problems financial capitalism has contributed to create. As a critical investigation of the complex interface between finance and labor that animates social finance’s operations, this article aims to provide conceptual resources that can contribute to releasing labor’s social cooperation from finance’s hegemony.

This study aimed to determine whether a single local driving cycle (LDC) can effectively represent different cities in the same country, in both urban and highway routes, and for cars and motorcycles. To achieve this, experienced drivers drove different monitored vehicles (five cars and three motorcycles) on seven selected routes in two Brazilian states (Pernambuco and São Paulo State), collecting 170 h of speed data in urban and highway routes during peak and off-peak hours. Using the micro-trip and Markov chain methods, LDCs were then developed based on the collected real-world data. The kinematic and energy parameters of different route groupings were compared, revealing that two LDCs, one for cars and one for motorcycles, could be used to represent all urban routes. However, each highway route required a unique LDC. When compared with standard driving cycles adopted in Brazil, the created LDCs presented a coefficient of variation of 13%–46% in kinematic characteristic parameters, highlighting the need for developing LDCs to better represent Brazilian traffic.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Residential electricity markets in European countries are still characterized by low consumer engagement, especially where regulated and liberalized markets coexist. Using an original dataset on 2015–2018 prices for the Italian electricity market, augmented with the number of residential consumers, we study the presence and magnitude of switching costs—i.e., time-based and cognitive-based costs on consumers changing providers—in the liberalized market. We find that switching from the incumbent involves high costs—almost as high as the yearly energy expenditure—while switching from competitors is less expensive. We also carry out two counterfactual analyses. In the first, we show that consumers would have incurred lower average switching costs over the years had the market been less concentrated. In the second, we simulate how switching costs could evolve once regulated prices are phased out, and the market is fully liberalized.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data.Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group).Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, “late” scleroderma patternat nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis.Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients’ subsets.

Industry 5.0, built on the foundation of Industry 4.0, aims to integrate human capabilities and principles for a sustainable and human-centric industrial paradigm. This article proposes a systematic literature review to explore the empirical effects of Industry 4.0/5.0 (I4.0/5.0) technologies on human factors, emphasizing the often overlooked physical, psychological, and cognitive dimensions. The methodology, adhering to PRISMA guidelines, involved a Scopus search spanning from 2005-2023, ultimately resulting in a selection of 15 articles. The preliminary results depict the studied I4.0/5.0 technologies and their impact on workers’ physical, psychological, and cognitive aspects. Some (I4.0/5.0) technologies received significant attention, such as human-robot communication and human-robot interaction, while others remain understudied. The limited number of papers makes it difficult to compare and generalize the empirical results reported. In this regard, we propose avenues for refining this systematic literature review in future research endeavors.

Metabolomics has emerged as a promising discipline in pharmaceuticals and preventive healthcare. However, analysing large metabolomics datasets remains challenging due to limited and incompletely annotated biological pathways. To address this limitation, we recently proposed training machine learning classifiers on molecular fingerprints of metabolites to predict their responses under specific conditions and analysing feature importance to identify key chemical configurations, providing insights into the affected biological processes. This study extends our previous research by evaluating various metabolite structural representations, including Morgan fingerprint and its variants, graph-based structural encodings and proposing novel representations to improve resolution and interpretability of the state-of-the-art approaches. These structural encodings were evaluated on mass spectrometry metabolomic data for a cellular model of the genetic disease Ataxia Telangiectasia. The study found that machine learning classifiers trained on the new representations improved in classification accuracy and interpretability. Notably, models trained on graph-based encoding do not exhibit performance gains, not even with pre-training on a larger metabolite dataset, underlining the efficacy of our proposed representations. Finally, feature importance analysis across different encoding methods consistently identifies similar structures as relevant for classification, underscoring the robustness of our approach across diverse structural representations.

CAR T-cell products targeting lineage-specific cell-of-origin antigens, thereby eliminating both tumor and healthy counterpart cells, are currently clinically approved therapeutics in B- and plasma-cell malignancies. While they represent a major clinical improvement, they are still limited in terms of efficacy by e.g. single, sometimes low-expressed antigen targeting, and in terms of safety by e.g., lack of on-off activity. Successful cell-of-origin non-discriminative targeting of heterogeneous hematopoietic stem and progenitor cell malignancies, such as acute myeloid leukemia (AML), will require antigen-versatile targeting and off-switching of effectors in order to then allow rescue by hematopoietic stem cell transplantation (HSCT), preventing permanent myeloablation. To address this, we developed adaptor-CAR (AdFITC-CAR) T-cells targeting fluoresceinated AML antigen-binding diabody adaptors. This platform enables the use of adaptors matching the AML-antigen-expression profile and conditional activity modulation. Combining adaptors significantly improved lysis of AML cells in vitro. In therapeutic xenogeneic mouse models, AdFITC-CAR T-cells co-administered with single diabody adaptors were as efficient as direct CAR T-cells, and combinatorial use of adaptors further enhanced therapeutic efficacy against both, cell lines and primary AML. Collectively, this study provides proof-of-concept that AdFITC-CAR T-cells and combinations of adaptors can efficiently enhance immune-targeting of AML.

Background: This commentary explores the potential of Vorasidenib, also known as AG-881. This emerging small-molecule inhibitor has garnered substantial attention within the realm of oncology due to its unique mechanism of action and potential therapeutic applications.Introduction: Gliomas are common malignant brain tumors characterized by diffuse brain infiltration. World Health Organization grade II and grade III diffuse gliomas are considered lower-grade gliomas (LGGs) and have isocitrate dehydrogenase (IDH) mutations. LGGs are challenging due to their infiltrative nature, making them capable of progressing into higher-grade malignancies. Vorasidenib is a novel therapeutic agent targeting mutant IDH1/2, sparking interest in the field.Mechanism of Action: Vorasidenib inhibits mutant IDH1/2 through a unique mechanism, reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG). This alteration affects key enzymes and DNA methylation, impacting tumor growth and invasion.Preclinical Evidence: Preclinical studies show vorasidenib's efficacy in inhibiting mutant IDH1/2 and 2-HG production in glioma models. It suppresses tumor growth, making it a potential treatment option.Clinical Evidence: Early clinical trials demonstrate vorasidenib's clinical activity in non-enhancing gliomas. It reduces 2-hydroxyglutarate levels and tumor cell proliferation, with an objective response rate and prolonged progression-free survival. The drug's safety profile is favorable.Challenges and Future Directions: Challenges include identifying predictive biomarkers and optimizing sequencing or combinations with existing therapies. Further research is needed to establish long-term effectiveness, evaluate side effects, and explore combinations with immunotherapy.Conclusion: Vorasidenib significantly advances LGG treatment, targeting a prevalent mutation and slowing tumor growth. Promising preclinical and clinical evidence and manageable side effects suggest its potential impact on LGG management. However, more research, including large trials, is needed to confirm its efficacy and role in treatment.

Energy communities are integral to achieving the European goal of carbon neutrality by 2050. While these communities are currently being emphasized as strictly place-based, with some states interpreting RED II’s proximity criterion stringently, our research offers a contrasting perspective: We argue that a sole focus on geographical proximity fails to capture the full contributions of energy community projects, especially those that function as communities of interest rather than merely as communities of place. In order to support this perspective, our study analyses data from 5402 responses and 31 semi-structured interviews from two main energy cooperatives: Ecopower in Flanders, Belgium, and ènostra in Italy, in both of which, members are not confined by geographical boundaries and are instead united by shared energy-related interests.

IMPORTANCE: Education is a social determinant of health. Quantifying its association with lifetime cardiovascular disease (CVD) risk has public health importance. OBJECTIVE: To calculate lifetime risk estimates of incident CVD and CVD subtypes and estimate years lived with and without CVD by education. DESIGN, SETTING, AND PARTICIPANTS: Included community-based cohort studies with adjudicated cardiovascular events used pooled individual-level data from 1985 to 2015 of 6 prospective cohort studies. The study team assessed the association between education and lifetime CVD risk with modified Kaplan-Meier and Cox models accounting for competing risk of noncardiovascular death. The study team estimated years lived with and without CVD by education with the Irwin restricted mean and the utility of adding educational attainment to CVD risk assessment. Participants (baseline 40 to 59 years old and 60 to 79 years old) were without CVD at baseline and had complete education, cardiovascular risk factors, and prospective CVD outcomes data. Data were analyzed from January 2022 to September 2022. EXPOSURES: Educational attainment (less than high school, high school completion, some college, or college graduate). MAIN OUTCOME AND MEASURES: Cardiovascular events (fatal and nonfatal coronary heart disease, heart failure, and stroke; CVD-related deaths; and total CVD encompassing any of these events). RESULTS: There were 40 998 participants (23 305 female [56.2%]) with a mean (SD) age of 58.1 (9.7) years for males and 58.3 (9.9) years for females. Compared with college graduates, those with less than high school or high school completion had higher lifetime CVD risks. Among middle-aged men, the competing hazard ratios (HRs) for a CVD event were 1.58 (95% CI, 1.38-1.80), 1.30 (95% CI, 1.10-1.46), and 1.16 (95% CI, 1.00-1.34) in those with less than high school, high school, and some college, respectively, compared with those with college completion. Among women, these competing HRs were 1.70 (95% CI, 1.49-1.95), 1.19 (95% CI, 1.05-1.35), and 0.98 (95% CI, 0.83-1.15). Individuals with higher education had longer duration of life prior to incident CVD. Education provided limited contribution toward enhancing CVD risk prediction. CONCLUSIONS AND RELEVANCE: Lower education was associated with lifetime CVD risk across adulthood; higher education translated to healthy longevity. Educational policy initiatives may associate with long-term health benefits.

This work presents the development of an OpenFOAM solver aimed at correctly predicting dynamics of concentrated suspensions when subjected to non-uniform shear flows. The newly implemented solver is able to predict the behavior of a heterogeneous mixture whose characteristics depend on the solid particle local concentration. To simulate such behavior, the conservation equation expressing the time variation of the particle volume fraction has been implemented in OpenFOAM; this was achieved by modifying a pre-existing solver, pimpleFoam, which discretizes the Navier–Stokes system of equation through the PIMPLE algorithm. As a first step, the formulation of the momentum equation has been adapted to correctly solve cases with non-Newtonian fluids. Successively, the Krieger’s correlation has been used to model the viscosity variation in the domain to take in account heterogeneous particle distributions. Finally, the iterative cycle for the solution of the migration equation has been included within the time loop. The above-mentioned code has been successfully validated by comparing the numerical results with the measured data provided by experiments reported in literature.

Monoterpene alkaloids encompass distinct chemical diversity and wide-ranging bioactivity. Their compact complexity has made them popular as synthetic targets and has inspired many distinct strategies and tactics in the field of heterocyclic chemistry. This article documents the evolution of a synthetic program aimed at accessing the unusual sulfonamide-containing natural product altemicidin, which was generally believed to be a monoterpene alkaloid throughout our entire synthetic investigations but has recently been found to originate through an unexpected and quite disparate biosynthetic pathway. By leveraging a pyridine dearomatization/cycloaddition strategy, we developed a concise pathway to the 5,6-fused bicyclic azaindane core and, after significant experimentation, an ultimate synthesis of altemicidin itself. Tactics to productively manipulate the multiple functional groups present on this highly polar scaffold proved challenging but were eventually realized via several carefully orchestrated and chemoselective transformations–investments that paid dividends in the form of significantly shorter chemical synthesis. Surprisingly, the bond-forming logic between our presumed abiotic synthetic strategy to this alkaloid class and its subsequently identified biosynthetic pathway is eerily similar.

Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. We report the design of a series of HTTpre-mRNA splicing modulators that lower huntingtin (HTT) protein, including the toxic mutant huntingtin (mHTT), by promoting insertion of a pseudoexon containing a premature termination codon at the exon 49–50 junction. The resulting transcript undergoes nonsense-mediated decay, leading to a reduction of HTTmRNA transcripts and protein levels. The starting benzamide core was modified to pyrazine amide and further optimized to give a potent, CNS-penetrant, and orally bioavailable HTT-splicing modulator 27. This compound reduced canonical splicing of the HTTRNA exon 49–50 and demonstrated significant HTT-lowering in both human HD stem cells and mouse BACHD models. Compound 27is a structurally diverse HTT-splicing modulator that may help understand the mechanism of adverse effects such as peripheral neuropathy associated with branaplam.

Copyright of Biblioteche Oggi is the property of Editrice Bibliografica SpA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABSTRACTIntroductionWe have previously described the preclinical developments in enzyme-loaded red blood cells to be used in the treatment of several rare diseases, as well as in chronic conditions.Area coveredSince our previous publication we have seen further progress in the previously discussed approaches and, interestingly enough, in additional new studies that further strengthen the idea that red blood cell-based therapeutics may have unique advantages over conventional enzyme replacement therapies in terms of efficacy and safety. Here we highlight these investigations and compare, when possible, the reported results versus the current therapeutic approaches.Expert opinionThe continuous increase in the number of new potential applications and the progress from the encapsulation of a single enzyme to the engineering of an entire metabolic pathway open the field to unexpected developments and confirm the role of red blood cells as cellular bioreactors that can be conveniently manipulated to acquire useful therapeutic metabolic abilities. Positioning of these new approaches versus newly approved drugs is essential for the successful transition of this technology from the preclinical to the clinical stage and hopefully to final approval.

The combination of an initial clinical approach aimed at evaluating the early risk of mortality with subsequent diagnostic and therapeutic approaches articulated on the overall patient’s profile is recommended in acute pulmonary embolism (PE). The presence of pulmonary hypertension associated with the persistence of chronic vascular obstructions in the pulmonary arteries after one or more acute thrombo-embolic events identifies a condition defined as chronic thrombo-embolic pulmonary hypertension (CTEPH). The evolution of technology and knowledge in the field of imaging has allowed us to qualify the computed tomography angiography of the pulmonary arteries as the gold standard for the diagnostic confirmation of both acute PE and CTEPH. In both these conditions, the first therapeutic step is the immediate initiation of anticoagulant therapy. In acute high-risk PE, in addition to anticoagulant therapy, thrombolytic therapy is recommended; in the event of contraindications to thrombolysis, surgical embolectomy or percutaneous catheter-directed treatment represents viable treatment options. In CTEPH, the combination of data collected from cardiac catheterization, computed tomography angiography, and conventional angiography of pulmonary arteries allows a team of experts to identify candidates for pulmonary endarterectomy surgery. Inoperable patients should be considered for percutaneous balloon angioplasty of the pulmonary arteries which can improve patients’ symptoms, quality of life, and prognosis.

'Crimson Cabernet' grape (Vitis vinifera) seeds showed physiological dormancy and germinated at ~60% after 60 days of chilling stratification. Fresh seeds harvested after physiological maturity and sown without drying failed to germinate after 30 days when sown on agar. In agar-sown fresh seeds cut at the distal seed end or intact seeds treated with gibberellic acid (GA), the seeds germinated at ~20% after 30 days. The highest germination percentages after 30 days were 63% to 83% in fresh, agar-sown seeds that were cut and treated with GA at 5000 mg L-1 regardless of stratification time. Similar results were seen in seeds allowed to dry before sowing. Seeds cut and treated with GA at 5000 mgL-1 germinated at 79% after 30 days. However, dry seeds sown on germination paper showed lower germination after cutting and GA treatment compared with agar-sown seeds. The highest germination percentages after 30 days in dry, cut seeds on germination paper treated with GA at 2000 and 5000 mgL-1 were 33% and 55%, respectively, compared with agar-sown seeds, which germinated at 76% and 79%, with the same treatments. Results from this study provide a system that reduces the need for chilling stratification for grape seed germination by using partial seedcoat removal and GA treatment. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Clinical trials guide evidence-based obstetrics and gynecology (OB-GYN) but often enroll nonrepresentative participants. OBJECTIVE: To characterize race and ethnicity reporting and representation in US OB-GYN clinical trials and their subsequent publications and to analyze the association of subspecialty and funding with diverse representation. DESIGN AND SETTING: Cross-sectional analysis of all OB-GYN studies registered on ClinicalTrials.gov (2007-2020) and publications from PubMed and Google Scholar (2007-2021). Analyses included logistic regression controlling for year, subspecialty, phase, funding, and site number. Data from 332 417 studies were downloaded. Studies with a noninterventional design, with a registration date before October 1, 2007, without relevance to OB-GYN, with no reported results, and with no US-based study site were excluded. EXPOSURES: OB-GYN subspecialty and funder. MAIN OUTCOMES AND MEASURES: Reporting of race and ethnicity data and racial and ethnic representation (the proportion of enrollees of American Indian or Alaskan Native, Asian, Black, Latinx, or White identity and odds of representation above US Census estimates by race and ethnicity). RESULTS: Among trials with ClinicalTrials.gov results (1287 trials with 591 196 participants) and publications (1147 trials with 821 111 participants), 662 (50.9%) and 856 (74.6%) reported race and ethnicity data, respectively. Among publications, gynecology studies were significantly less likely to report race and ethnicity than obstetrics (adjusted odds ratio [aOR], 0.54; 95% CI, 0.38-0.75). Reproductive endocrinology and infertility trials had the lowest odds of reporting race and ethnicity (aOR, 0.14; 95% CI, 0.07-0.27; reference category, obstetrics). Obstetrics and family planning demonstrated the most diverse clinical trial cohorts. Compared with obstetric trials, gynecologic oncology had the lowest odds of Black representation (ClinicalTrials.gov: aOR, 0.04; 95% CI, 0.02-0.09; publications: aOR, 0.06; 95% CI, 0.03-0.11) and Latinx representation (ClinicalTrials.gov: aOR, 0.05; 95% CI, 0.02-0.14; publications: aOR, 0.23; 95% CI, 0.10-0.48), followed by urogynecology and reproductive endocrinology and infertility. Urogynecology (ClinicalTrials.gov: aOR, 0.15; 95% CI, 0.05-0.39; publications: aOR, 0.24; 95% CI, 0.09-0.58) had the lowest odds of Asian representation. CONCLUSIONS AND RELEVANCE: Race and ethnicity reporting and representation in OB-GYN trials are suboptimal. Obstetrics and family planning trials demonstrate improved representation is achievable. Nonetheless, all subspecialties should strive for more equitably representative research.

IMPORTANCE: Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia’s often paroxysmal nature and individuals’ disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF. OBSERVATIONS: The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF. CONCLUSIONS AND RELEVANCE: Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.

The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (−5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE).

•Rivipansel was safe and well-tolerated in sickle cell patients hospitalized for VOC, but did not meet primary or secondary end points.•Rivipansel use early in the course of VOC appeared to shorten length of hospital stay and duration of IV opioid use in post-hoc analyses.

Electron doping of graphene has been extensively studied on graphene-supported surfaces, where the metallicity is influenced by the substrate. Herewith we propose potassium adsorption on free-standing nanoporous graphene, thus eluding any effect due to the substrate. We monitor the electron migration in the π* downward-shifted conduction band. In this rigid band shift, we correlate the spectral density of the π* state in the upper Dirac cone with the associated plasmon, blue-shifted with increasing K dose, as deduced by electron energy loss spectroscopy. These results are confirmed by the Dirac plasmon activated by the C 1s emitted electrons, thanks to spatially resolved photoemission. This crosscheck constitutes a reference on the correlation between the electronic π* states in the conduction band and the Dirac plasmon evolution upon in situ electron doping of fully free-standing graphene.

The use of electronic medical records (EMRs) has increased dramatically over the last 15 years. However, psychiatry has lagged. EMRs are not being used by many mental health professionals. There are many reasons, including financial burden, lack of technological support, stigma, disaggregation of upfront costs, indirect benefits, and concerns about privacy and Health Insurance Portability and Accountability Act compliance. Obtaining paper records is a lengthy process, making continuity of care and emergency care challenging. Even when records are made available, it is common for information to be incomplete. The objective of this article is to highlight how the continued use of paper charts may decrease the quality and timeliness of psychiatric care provided and to discuss the psychiatry-specific issues created by EMRs. A case illustrating the disruption of care by continued use of paper charts in psychiatric facilities is presented. The growing use of EMR creates new challenges that affect psychiatry in ways other fields are not affected. These challenges include confidentiality issues, the frequent change/spectrum of diagnoses, determining how much information should be recorded in a note, and what the implications are of the information recorded. This article will discuss the use of EMRs in psychiatry, as well as encourage medical students and residents to take a deeper dive into psychiatry-specific issues regarding the use of EMR. EMR use may have a profound impact on our patient outcomes, health care delivery system, shorter inpatient stay, as well as reduce health care costs.

The notion of quasi-particles is essential for understanding the behaviour of complex many-body systems. A prototypical example of a quasi-particle is a polaron, formed by an impurity strongly interacting with a surrounding medium. Fermi polarons, created in a Fermi sea, provide a paradigmatic realization of this concept. Importantly, such quasi-particles interact with each other via the modulation of the medium. However, although quantum simulation experiments with ultracold atoms have substantially improved our understanding of individual polarons, the detection of their interactions has so far remained elusive. Here we report the observation of mediated interactions between Fermi polarons consisting of K impurities embedded in a Fermi sea of Li atoms. Our results confirm two predictions of Landau’s Fermi-liquid theory: the shift in polaron energy due to mediated interactions, which is linear in the concentration of impurities; and its sign inversion with impurity quantum statistics. For weak-to-moderate interactions between the impurities and the medium, our results agree with the static predictions of Fermi-liquid theory. For stronger impurity–medium interactions, we show that the observed behaviour at negative energies can be explained by a more refined many-body treatment including retardation and dressed molecule formation.

The application of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, magnetic resonance imaging, cell tracking, and hyperthermia has been long exploited regarding their inducible magnetic properties. Nevertheless, SPIONs remain rapidly cleared from the circulation by the reticuloendothelial system (RES) or mononuclear phagocyte system, with uptake dependent on several factors such as the hydrodynamic diameter, electrical charge and surface coating. This rapid clearance of SPION-based theranostic agents from circulation is one of the main challenges hampering the medical applications that differ from RES targeting. This work proposes a strategy to render biocompatible SPIONs through their encapsulation in the red blood cells (RBCs). In this work, the research has been focused on the multi-step optimization of chemical synthesis of magnetic nanoparticles (MNPs), precisely iron oxide nanoparticles (IONPs) and zinc manganese-ferrite nanoparticles (Zn/Mn FNPs), for encapsulation in human and murine RBCs. The encapsulation through the transient opening of RBC membrane pores requires extensive efforts to deliver high-quality nanoparticles in terms of chemical properties, morphology, stability and biocompatibility. After reaching this goal, in vitroexperiments were performed with selected nanomaterials to investigate the potential of engineered MNP-RBC constructs in theranostic approaches.

Cognitive-behavioral therapy (CBT) is a form of psychological treatment that is based on the underlying assumption that mental disorders and psychological distress are maintained by cognitive factors, that is, that general beliefs about the world, the self, and the future contribute to the maintenance of emotional distress and behavioral problems. The overall goal of CBT is to replace dysfunctional constructs with more flexible and adaptive cognitions. The most relevant cognitive-behavioral techniques in clinical practice are: i. Cognitive Restructuring(also known as the ABCDE method) is indicated to support patients dealing with negative beliefs or thoughts. The different steps in the cognitive restructuring process are summarized by the letters in the ABCDE acronym that describe the different stages of this coaching model: Activating event or situation associated with the negative thoughts, Beliefs and belief structures held by the individual that explain how they perceive the world which can facilitate negative thoughts, Consequences or feelings related to the activating event, Disputation of beliefs to allow individuals to challenge their belief system, and Effective new approach or effort to deal with the problem by facilitating individuals to replace unhelpful beliefs with more helpful ones. ii. Problem-Solving(also known as SOLVE) to raise awareness for specific triggers, and evaluate and choose more effective options. Each letter of the SOLVE acronym identifies different steps of the problem-solving process: Select a problem, generate Options, rate the Likely outcome of each option, choose the Very best option, and Evaluate how well each option worked. For example, a suicide attempt is reconceptualized as a failure in problem-solving. This treatment approach attempts to provide patients with a better sense of control over future emerging problems. iii. Re-attributionis a technique that enables patients to replace negative self-statements (eg, “it is all my fault”) with different statements where responsibility is attributed more appropriately. Furthermore, decatastrophizing may help subjects, especially adolescents decide whether they may be overestimating the catastrophic nature of the precipitating event, and by allowing them to scale the event severity they learn to evaluate situations along a continuum rather than seeing them in black and white. iv. Affect Regulationtechniques are often used with suicidal adolescents to teach them how to recognize stimuli that provoke negative emotions and how to mitigate the resulting emotional arousal through self-talk and relaxation.

Despite prompt epicardial recanalization in patients presenting with ST-segment elevation myocardial infarction (STEMI), coronary microvascular obstruction and dysfunction (CMVO) is still fairly common and is associated with poor prognosis. Various pharmacological and mechanical strategies to treat CMVO have been proposed, but the positive results reported in preclinical and small proof-of-concept studies have not translated into benefits in large clinical trials conducted in the modern treatment setting of patients with STEMI. Therefore, the optimal management of these patients remains a topic of debate. In this Review, we appraise the pathophysiological mechanisms of CMVO, explore the evidence and provide future perspectives on strategies to be implemented to reduce the incidence of CMVO and improve prognosis in patients with STEMI.

Background and aims: The role of overweight and obesity in the development of atrial fibrillation (AF) is well established; however, the differential effect on the occurrence and recurrence of AF remains uncertain. The aim of this review is to compare the effect of underweight and varying degrees of obesity on onset of AF and in recurrent post-ablation AF, and, when possible, in relation to sex. Methods: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library from inception to January 31, 2023. Studies reporting frequency of newly-diagnosed AF and of recurrent post-ablation AF in different BMI categories, were included. 3400 records were screened and 50 met the inclusion criteria. Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were extracted from the manuscripts and were analyzed using a random effect model. The outcome was the occurrence of AF in population studies and in patients undergoing ablation. Results: Data from 50 studies were collected, of which 27 for newly-diagnosed AF and 23 for recurrent post-ablation AF, for a total of 15,134,939 patients, of which 15,115,181 in studies on newly-diagnosed AF and 19,758 in studies on recurrent post-ablation AF. Compared to normal weight, the increase in AF was significant (p&lt; 0.01) for overweight, obese, and morbidly obese patients for newly-diagnosed AF, and for obese and morbidly obese patients for recurrent post-ablation AF. Newly-diagnosed AF was more frequent in obese female than obese male patients. Conclusion: The effect of increased BMI was greater on the onset of AF, and obese women were more affected than men.

IntroductionExposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy.MethodThe cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE).ResultAcceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE.ConclusionThe current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

The “origins” of (geometric) space is examined from the perspective of the so-called “conceptual space” or “semantic space”. Semantic space is characterized by its fundamental “locality” that generates an “implicit” mode of geometrizing. This view is examined from within three perspectives. First, the role that various diagrammatic entities play in the everyday life and pragmatic activities of selected ethnic groups is illustrated. Secondly, it is shown how conceptual spaces are fundamentally linked to the meaning effects of particular natural languages and these are very different from the global and universal aspects of Euclidean spaces. Thirdly, it is contended that these modes of creating body and culture-based spatial frameworks and related cosmogonies and cosmologies can be described as forms of “latent geometry” that initially appear unexplainable in any rational way. Nonetheless, and thanks to the deep mathematical reflections provided by René Thom, it is illustrated how the various ways of generating space can be further analyzed as distortions of mainstream spatialization furnished by Euclidean geometry that established the dominant universality of the ideas of space (and time).

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P< 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P= 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P< 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

The positive impact of arbuscular mycorrhizal symbionts on plant growth and health has been reported for many species, and supports their use as biofertilizers and bioenhancers. Here, the potential role of the arbuscular mycorrhizal symbiont Funneliformis mosseaein the improvement of chicory (Cichorium intybusL.) nutritional value, in terms of nutrient uptake and accumulation of health-promoting compounds, was studied using an in vivo whole-plant system, allowing both plant and fungal tissue collection. Biomass and nutrient distribution were determined in plant and extraradical mycelium, and photosynthetic pigments and fructooligosaccharide concentrations were evaluated in chicory shoots and roots. Zinc shoot concentration of mycorrhizal chicory was significantly increased, as well as the whole-plant Fe uptake, while root Cu concentration was decreased, compared with uninoculated controls. F. mosseaeextraradical mycelium accumulated Cu, Zn, Mn, and Fe at high concentrations, compared with those of the host plant tissues, suggesting that it plays a double functional “scavenging-filtering” role, by its ability to balance the uptake of microelements or to limit their translocation depending on plant-soil concentrations. The higher Zn and Fe uptake by mycorrhizal plants was significantly correlated with higher carotenoid, inulin, and fructose levels, suggesting a relationship among the modulation of micronutrient uptake by mycorrhizal symbionts and the biosynthesis of health-promoting molecules by the host. Overall, data from this work may boost the implementation of arbuscular mycorrhizal fungal inoculation aimed at inducing plant biofortification and enhancement of nutritional value of plant-derived food.

IMPORTANCE: Oral anticoagulation (OAC) is underprescribed in underrepresented racial and ethnic group individuals with atrial fibrillation (AF). Little is known of how differential OAC prescribing relates to inequities in AF outcomes. OBJECTIVE: To compare OAC use at discharge and AF-related outcomes by race and ethnicity in the Get With The Guidelines–Atrial Fibrillation (GWTG-AFIB) registry. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis used data from the GWTG-AFIB registry, a national quality improvement initiative for hospitalized patients with AF. All registry patients hospitalized with AF from 2014 to 2020 were included in the study. Data were analyzed from November 2021 to July 2022. EXPOSURES: Self-reported race and ethnicity assessed in GWTG-AFIB registry. MAIN OUTCOMES AND MEASURES: The primary outcome was prescription of direct-acting OAC (DOAC) or warfarin at discharge. Secondary outcomes included cumulative 1-year incidence of ischemic stroke, major bleeding, and mortality postdischarge. Outcomes adjusted for patient demographic, clinical, and socioeconomic characteristics as well as hospital factors. RESULTS: Among 69 553 patients hospitalized with AF from 159 sites between 2014 and 2020, 863 (1.2%) were Asian, 5062 (7.3%) were Black, 4058 (5.8%) were Hispanic, and 59 570 (85.6%) were White. Overall, 34 113 (49.1%) were women; the median (IQR) age was 72 (63-80) years, and the median (IQR) CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) was 4 (2-5). At discharge, 56 385 patients (81.1%) were prescribed OAC therapy, including 41 760 (74.1%) receiving DOAC. OAC prescription at discharge was lowest in Hispanic patients (3010 [74.2%]), followed by Black patients (3935 [77.7%]) Asian patients (691 [80.1%]), and White patients (48 749 [81.8%]). Black patients were less likely than White patients to be discharged while taking any anticoagulant (adjusted odds ratio, 0.75; 95% CI, 0.68-0.84) and DOACs (adjusted odds ratio, 0.73; 95% CI, 0.65-0.82). In 16 307 individuals with 1-year follow up data, bleeding risks (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.53-2.83), stroke risks (aHR, 2.07; 95% CI, 1.34-3.20), and mortality risks (aHR, 1.22; 95% CI, 1.02-1.47) were higher in Black patients than White patients. Hispanic patients had higher stroke risk (aHR, 2.02; 95% CI, 1.38-2.95) than White patients. CONCLUSIONS AND RELEVANCE: In a national registry of hospitalized patients with AF, compared with White patients, Black patients were less likely to be discharged while taking anticoagulant therapy and DOACs in particular. Black and Hispanic patients had higher risk of stroke compared with White patients; Black patients had a higher risk of bleeding and mortality. There is an urgent need for interventions to achieve pharmacoequity in guideline-directed AF management to improve overall outcomes.

Colorectal malignancies are a leading cause of cancer-related death1and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4–7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity1. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC). Using spatially resolved paired whole-genome and transcriptome sequencing, we find that the majority of intratumour variation in gene expression is not strongly heritable but rather ‘plastic’. Somatic expression quantitative trait loci analysis identified a number of putative genetic controls of expression by cis-acting coding and non-coding mutations, the majority of which were clonal within a tumour, alongside frequent structural alterations. Consistently, computational inference on the spatial patterning of tumour phylogenies finds that a considerable proportion of CRCs did not show evidence of subclonal selection, with only a subset of putative genetic drivers associated with subclone expansions. Spatial intermixing of clones is common, with some tumours growing exponentially and others only at the periphery. Together, our data suggest that most genetic intratumour variation in CRC has no major phenotypic consequence and that transcriptional plasticity is, instead, widespread within a tumour.

This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy.

We evaluate the effects of population aging on the macroeconomic evolution of the Lebanese economy and the financial sustainability of its major pension schemes. We use an OLG model with labor market frictions as in de la Croix et al. (2013). Individuals are differentiated by their origin, age, gender, and education and choose the sector of activity, which implies that the size of the informal sector is endogenous. We assess the long-run implications of population aging and show that the public sector pension scheme is unsustainable. In contrast, the private sector scheme is insufficient to ensure decent living standards for the elderly. Finally, we evaluate the effects of two pension reforms. We first propose a mix of measures that guarantee the sustainability of the public sector scheme. Then, we evaluate the impact of the pension reform introduced in December 2023 and of an alternative reform aiming at increasing the size of the private sector scheme to improve the living standards for the elderly.

Supercapacitors with carbon electrodes derived from biomass and utilizing gel polymer electrolytes are currently a focal point in the development of highly efficient, environmentally friendly, and cost-effective energy storage devices. In this study, we present porous activated carbon derived from asparagus waste, prepared through chemical activation with ZnCl2followed by physical activation with CO2, as a high-performance electrode material for supercapacitors. The performance of electrodes has been discussed in comparison with supercapacitors employing both gel polymer electrolytes and conventional liquid electrolytes i.e. 7 M KOH. The flexible film of the gel polymer electrolyte exhibits noteworthy characteristics, including a high ionic conductivity of ∼6.3 mS cm−1, and a high electrochemical stability window of ∼4.5 V. Supercapacitors prepared with this gel polymer electrolyte outperform supercapacitors with liquid electrolytes thanks to a broader electrochemical stability window, showing optimal charge-discharge performance, a specific capacitance of 160 F g−1, a specific energy of 31 Wh kg−1, and an effective power of 0.56 kW kg−1. The superior rate performance is demonstrated by powering a LED for a substantial duration, highlighting the exceptional capabilities of the system. Additionally, the supercapacitor employing the gel polymer electrolyte displays an extended stability, sustaining approximately 10,000 charge-discharge cycles with only a modest initial fading of ∼16 % in specific capacitance and maintaining a high coulombic efficiency of ∼100 %.