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The quantum crystal of electrons, predicted more than 80 years ago by Eugene Wigner, remains one of the most elusive states of matter. In this study, we observed the one-dimensional Wigner crystal directly by imaging its charge density in real space. To image, with minimal invasiveness, the many-body electronic density of a carbon nanotube, we used another nanotube as a scanning-charge perturbation. The images we obtained of a few electrons confined in one dimension match the theoretical predictions for strongly interacting crystals. The quantum nature of the crystal emerges in the observed collective tunneling through a potential barrier. These experiments provide the direct evidence for the formation of small Wigner crystals and open the way for studying other fragile interacting states by imaging their many-body density in real space.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato‐protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato‐protective effect better than each drug alone. Thus, the current study examines the pancreato‐protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild‐type (WT) and Hpa over‐expressing (Hpa‐Tg) mice. Cerulein‐induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa‐Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti‐Hpa drug combinations constitute a novel therapy for this common orphan disease.

The central role of natriuretic peptides (NPs) in the complex cardio‐renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans‐membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss‐of‐function variant of the gene encoding corin (Cor−/−). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac‐derived ANP in these patients, as implied by Feldman et al. Yet, in this mini‐review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na+ and water exertion. Collectively, it seems that beside the classic well‐established cardio‐renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.

The coupling between electrons and phonons is at the heart of many fundamental phenomena in nature. Despite tremendous advances in controlling electrons or phonons in engineered nanosystems, control over their coupling is still widely lacking. Here we demonstrate the ability to fully tailor electron–phonon interactions using a new class of suspended carbon nanotube devices, in which we can form highly tunable single and double quantum dots at arbitrary locations along a nanotube mechanical resonator. We find that electron–phonon coupling can be turned on and off by controlling the position of a quantum dot along the resonator. Using double quantum dots we structure the interactions in real space to couple specific electronic and phononic modes. This tailored coupling allows measurement of the phonons’ spatial parity and imaging of their mode shapes. Finally, we demonstrate coupling between phonons and internal electrons in an isolated system, decoupled from the random environment of the electronic leads, a crucial step towards fully engineered quantum-coherent electron–phonon systems. A mechanism for coupling the electrons and vibrational motion of a suspended carbon nanotube is now demonstrated. Tailoring the coupling between specific electronic and phononic modes by controlling the position of quantum dots along the resonating tube enables spatial imaging of the mode shape.

Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation. Haemodynamic contributions to HFpEF include changes in left ventricular structure, diastolic and systolic dysfunction, left atrial myopathy, pulmonary hypertension, right ventricular dysfunction, chronotropic incompetence, and vascular dysfunction. Inflammation, fibrosis, impaired nitric oxide signalling, sarcomere dysfunction, and mitochondrial and metabolic defects contribute to the cellular and molecular changes observed in HFpEF. HFpEF impacts multiple organ systems beyond the heart, including the skeletal muscle, peripheral vasculature, lungs, kidneys and brain. The diagnosis of HFpEF can be made in individuals with signs and symptoms of heart failure with abnormality in natriuretic peptide levels or evidence of cardiopulmonary congestion, facilitated by the use of HFpEF risk scores and additional imaging and testing with the exclusion of HFpEF mimics. Management includes initiation of guideline-directed medical therapy and management of comorbidities. Given the significant impact of HFpEF on quality of life, future research efforts should include a particular focus on how patients can live better with this disease. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases, with a prevalence that is expected to rise with the growing ageing population. In this Primer, Hamo and colleagues summarize the epidemiology and pathophysiology of HFpEF and discuss HFpEF diagnosis, treatment and open research questions.

In the presence of interactions, electrons in condensed-matter systems can behave hydrodynamically, exhibiting phenomena associated with classical fluids, such as vortices and Poiseuille flow1–3. In most conductors, electron–electron interactions are minimized by screening effects, hindering the search for hydrodynamic materials; however, recently, a class of semimetals has been reported to exhibit prominent interactions4,5. Here we study the current flow in the layered semimetal tungsten ditelluride by imaging the local magnetic field using a nitrogen-vacancy defect in a diamond. We image the spatial current profile within three-dimensional tungsten ditelluride and find that it exhibits non-uniform current density, indicating hydrodynamic flow. Our temperature-resolved current profile measurements reveal a non-monotonic temperature dependence, with the strongest hydrodynamic effects at approximately 20 K. We also report ab initio calculations showing that electron–electron interactions are not explained by the Coulomb interaction alone, but are predominantly mediated by phonons. This provides a promising avenue in the search for hydrodynamic flow and prominent electron interactions in high-carrier-density materials.When interactions between electrons in a material are strong, they can start to behave hydrodynamically. Spatially resolved imaging of current flow in a three-dimensional material suggests that electron–electron interactions are mediated by phonons.

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and re-sensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers. Predicting an individual's response to therapy is an important goal for precision medicine. Here, the authors use an algorithm that takes into account the interaction type and directionality of signalling pathways in protein–protein interactions and find that their pathway analysis can predict essential genes, which may be a target for therapy.

One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. This study uses data on infections within households in order to estimate the susceptibility and infectivity of children compared to those of adults. The data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR (637 households, average household size of 5.3). In addition, serological tests were performed on a subset of the individuals in the study. Inspection of the PCR data shows that children are less likely to be tested positive compared to adults (25% of children positive over all households, 44% of adults positive over all households, excluding index cases), and the chance of being positive increases with age. Analysis of joint PCR/serological data shows that there is under-detection of infections in the PCR testing, which is more substantial in children. However, the differences in detection rates are not sufficient to account for the differences in PCR positive rates in the two age groups. To estimate relative transmission parameters, we employ a discrete stochastic model of the spread of infection within a household, allowing for susceptibility and infectivity parameters to differ among children and adults. The model is fitted to the household data using a simulated maximum likelihood approach. To adjust parameter estimates for under-detection of infections in the PCR results, we employ a multiple imputation procedure using estimates of under-detection in children and adults, based on the available serological data. We estimate that the susceptibility of children (under 20 years old) is 43% (95% CI: [31%, 55%]) of the susceptibility of adults. The infectivity of children was estimated to be 63% (95% CI: [37%, 88%]) relative to that of adults.

As energy demands increase and environmental issues loom, fuel cells (FCs) have attracted significant attention as an alternative to conventional energy sources. Their use encompasses portable applications, transportation, and a stationary grid-power mainly due to their low-temperature operation and quick start-up. However, the primary challenge is improving fuel cell durability to meet 2025 U.S. Department of Energy targets (e.g., 8,000+ h for automotive drive cycle). Proton exchange membrane fuel cell (PEMFC) catalysts currently suffer from low durability, undermining their wide-scale deployment into the consumer and industrial markets. Platinum group metals (PGMs) are still the most common catalysts used in PEMFCs as they provide among the highest activity for electrode reactions and lifetime stability. An effective way to decrease Pt loading is the adoption of supports to enhance both Pt dispersion and its durability. Corrosion of the carbon-based support was identified to be the major contributor to performance degradation as they suffer from parasitic oxidation to CO 2 (at the cathode). Therefore, there is a significant interest in exploring stable alternatives to replace carbon supports in PEMFCs. Transition metal carbides (TMCs) have attracted significant attention over the last several years as a possible candidate to replace carbon-based catalyst supports in fuel cells. Despite these advantages over carbon supports, the large-scale deployment of TMC-based supports in fuel cells is still hindered by concerns of durability at the high potential on the cathode during start-up and shutdown operation. Here, we address the most relevant studies concerning TMCs as supports for acidic oxygen reduction reaction (ORR) catalysis, including viewpoints about the surface and bulk design of the support, as well as the design of the catalyst itself to enhance the interaction and dispersion with the support.