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Background: Coffee consumption is inversely associated with type 2 diabetes. Cafestol, a bioactive compound in coffee, has demonstrated glucose-lowering and insulin-secretory properties in cell and animal studies. The acute effects of cafestol on glucose metabolism in humans have only been briefly investigated, and longer-term effects have not been explored. This study aimed to assess the effects of purified cafestol on insulin sensitivity and other metabolic parameters in healthy individuals with increased waist circumference at risk of developing type 2 diabetes. Methods: A 12-week randomized, placebo-controlled, parallel trial was conducted with 40 participants. Insulin suppression tests, mixed meal tests, and MRI scans were performed before and after the intervention. Results: Administering 6 mg of cafestol twice daily did not alter insulin sensitivity or glucose tolerance but led to significant reductions in body weight (2%), visceral fat volume (5%), and gamma-glutamyl transferase levels (15%) compared to the placebo. Conclusions: Cafestol may hold promise for weight and visceral fat reduction. Cafestol did not improve insulin sensitivity or glucose tolerance in this study but might still contribute to the observed inverse association between coffee consumption and type 2 diabetes. Future research should explore higher dosages and longer treatment durations, particularly in individuals with impaired glucose metabolism and type 2 diabetes.

In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles 1 , with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous disposal of batteries 2 . Only a small fraction of lithium-ion batteries are recycled, further exacerbating global material supply of strategic elements 3 – 5 . A potential alternative is to use organic-based redox-active materials 6 – 8 to develop rechargeable batteries that originate from ethically sourced, sustainable materials and enable on-demand deconstruction and reconstruction. Making such batteries is challenging because the active materials must be stable during operation but degradable at end of life. Further, the degradation products should be either environmentally benign or recyclable for reconstruction into a new battery. Here we demonstrate a metal-free, polypeptide-based battery, in which viologens and nitroxide radicals are incorporated as redox-active groups along polypeptide backbones to function as anode and cathode materials, respectively. These redox-active polypeptides perform as active materials that are stable during battery operation and subsequently degrade on demand in acidic conditions to generate amino acids, other building blocks and degradation products. Such a polypeptide-based battery is a first step to addressing the need for alternative chemistries for green and sustainable batteries in a future circular economy. An environmentally friendly, all-organic radical battery is demonstrated, in which redox-active polypeptides perform as both cathode and anode materials, with a metal-free organic electrolyte.

ObjectiveTo undertake a synthesis of evidence-based research for seven innovative models of care to inform the development of new hospitals.DesignUmbrella review.SettingInterventions delivered inside and outside of acute care settings.ParticipantsChildren and adults with one or more identified acute or chronic health conditions.Data sourcesPsycINFO, Ovid MEDLINE and CINAHL.Primary and secondary outcome measuresClinical indicators and mortality, healthcare utilisation, quality of life, self-management and self-care and patient knowledge.ResultsA total of 66 reviews were included, synthesising evidence from 1272 primary studies across the 7 models of care. Virtual care was the most common model studied, addressed by 47 (73%) of the reviews. Common outcomes evaluated across reviews were clinical indicators and mortality, healthcare utilisation, self-care and self-management, patient knowledge, quality of life and cost-effectiveness. The findings indicate that the innovative models of healthcare we identified in this review may be effective in managing patients with a range of acute and chronic conditions. Most of the included reviews reported evidence of comparable or improved care.ConclusionsA consideration of local infrastructure and individual patient characteristics, such as health literacy, may be critical in determining the suitability of models of care for patients and their implementation in local health systems.Trial registration number10.17605/OSF.IO/PS6ZU.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19 − CD138 + ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC. Autoantibody production is a hallmark of systemic lupus erythematosus (SLE). Here, the authors demonstrate that antibody-secreting cells from patients with SLE display features of premature maturation and increased survival, which are mediated by intrinsic and extrinsic programmes including autocrine APRIL.

A culturally tailored virtual program could meet the survivorship needs of Asian American women breast cancer survivors (AABC). This study aims to determine the efficacy of a culturally tailored virtual information and coaching/support program (TICAA) in improving AABC’s survivorship experience. A randomized clinical trial (NCT02803593) was conducted from January 2017 to June 2020 among 199 AABC. The intervention group utilized TICAA and the American Cancer Society [ACS] website while the control group used only ACS website for 12 weeks. The outcomes were measured using the SCNS-34SF (needs; primary), the MSAS-SF (symptoms; secondary), and the FACT-B (quality of life; secondary). The data were analyzed using an intent-to-treat approach. The intervention group showed significant reductions in their needs from the baseline (T0) to post 4 weeks (T1) and to post 12 weeks (T2). Although the changes were not statistically significant, the intervention group had decreased symptoms from T0 to T2 while the control group had an increase in their symptoms. The intervention group had a significant increase in their quality of life from T0 to T2. A culturally tailored virtual program could therefore improve quality of life in AABC patients. Trial Registration : To Enhance Breast Cancer Survivorship of Asian Americans (TICAA), NCT02803593, https://clinicaltrials.gov/ct2/show/NCT02803593?titles=TICAA&draw=2&rank=1 Virtual support methods have been shown to be an effective aid in cancer survivorship. Here, the authors created a culturally tailored information and support system for Asian American breast cancer patients and showed these resources improved quality of life.

Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity. Elevated body mass index is heritable and associated with many health conditions that impact morbidity and mortality. Here, the authors identify greater than 900 genetic loci for body mass index (BMI) and find over 300 diagnoses associated with increasing BMI.

The leakage of quantum information out of the two computational states of a qubit into other energy states represents a major challenge for quantum error correction. During the operation of an error-corrected algorithm, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of the logical error with scale, thus challenging the feasibility of quantum error correction as a path towards fault-tolerant quantum computation. Here, we demonstrate a distance-3 surface code and distance-21 bit-flip code on a quantum processor for which leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a tenfold reduction in the steady-state leakage population of the data qubits encoding the logical state and an average leakage population of less than 1 × 10−3 throughout the entire device. Our leakage removal process efficiently returns the system back to the computational basis. Adding it to a code circuit would prevent leakage from inducing correlated error across cycles. With this demonstration that leakage can be contained, we have resolved a key challenge for practical quantum error correction at scale.Physical realizations of qubits are often vulnerable to leakage errors, where the system ends up outside the basis used to store quantum information. A leakage removal protocol can suppress the impact of leakage on quantum error-correcting codes.

•Commercial vaccines confer suboptimal protection in ducks against H5N1 HPAI viruses.•H5N1 HPAI viruses are continuously changing genetically and antigenically.•It is important to monitor vaccine efficacy for the control of H5N1 HPAI in poultry. Domestic ducks are the second most abundant poultry species in many Asian countries including Vietnam, and play a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI) [FAO]. In this study, we examined the protective efficacy in ducks of two commercial H5N1 vaccines widely used in Vietnam; Re-1 containing A/goose/Guangdong/1/1996 hemagglutinin (HA) clade 0 antigens, and Re-5 containing A/duck/Anhui/1/2006 HA clade 2.3.4 antigens. Ducks received two doses of either vaccine at 7 and at 14 or 21 days of age followed by challenge at 30 days of age with viruses belonging to the HA clades 1.1, 2.3.4.3, 2.3.2.1.A and 2.3.2.1.B isolated between 2008 and 2011 in Vietnam. Ducks vaccinated with the Re-1 vaccine were protected after infection with the two H5N1 HPAI viruses isolated in 2008 (HA clades 1.1 and 2.3.4.3) showing no mortality and limited virus shedding. The Re-1 and Re-5 vaccines conferred 90–100% protection against mortality after challenge with the 2010 H5N1 HPAI viruses (HA clade 2.3.2.1.A); but vaccinated ducks shed virus for more than 7 days after challenge. Similarly, the Re-1 and Re-5 vaccines only showed partial protection against the 2011 H5N1 HPAI viruses (HA clade 2.3.2.1.A and 2.3.2.1.B), with a high proportion of vaccinated ducks shedding virus for more than 10 days. Furthermore, 50% mortality was observed in ducks vaccinated with Re-1 and challenged with the 2.3.2.1.B virus. The HA proteins of the 2011 challenge viruses had the greatest number of amino acid differences from the two vaccines as compared to the viruses from 2008 and 2009, which correlates with the lesser protection observed with these viruses. These studies demonstrate the suboptimal protection conferred by the Re-1 and Re-5 commercial vaccines in ducks against H5N1 HPAI clade 2.3.2.1 viruses, and underscore the importance of monitoring vaccine efficacy in the control of H5N1 HPAI in ducks.

Krabbe disease (KD) is a fatal lysosomal storage disorder caused by a deficiency in the enzyme galactosylceramidase (GALC), leading to toxic accumulation of psychosine. This results in widespread demyelination, inflammation, and neuronal damage. Early intervention is critical to mitigate disease progression and limit neurological injury. To assess the therapeutic potential of early enzyme replacement therapy (ERT), HeLa cells were genetically engineered to overexpress GALC, and extracellular vesicles (EVs) containing GALC were isolated. A single intrathecal injection of these GALC-loaded EVs was administered to neonatal GALC-deficient twitcher mice, a well-established model of KD. Although the treatment did not prolong overall survival, it significantly reduced neuroinflammation. Treated mice exhibited decreased astrogliosis and microgliosis, along with a notable reduction in cortical psychosine levels. Molecular analysis of neuroinflammatory markers showed increased expression of IL-10 and TREM2 in microglial cells following treatment. This study demonstrates that early intervention with GALC-loaded EVs can temporarily alleviate central neuropathology in KD by reducing inflammation and psychosine burden. While not curative, this approach shows potential as an adjunctive strategy to delay disease progression and improve the neuroinflammatory environment prior to hematopoietic stem cell transplantation.

Genetic studies may help identify causal pathways; therefore, we sought to identify genetic determinants of ideal CVH and their association with CVD outcomes in the multi-population Veteran Administration Million Veteran Program. An ideal health score (IHS) was calculated from 3 clinical factors (blood pressure, total cholesterol, and blood glucose levels) and 3 behavioral factors (smoking status, physical activity, and BMI), ascertained at baseline. Multi-population genome-wide association study (GWAS) was performed on IHS and binary ideal health using linear and logistic regression, respectively. Using the genome-wide significant SNPs from the IHS GWAS, we created a weighted IHS polygenic risk score (PRSIHS) which was used (i) to conduct a phenome-wide association study (PheWAS) of associations between PRSIHS and ICD-9 phenotypes and (ii) to further test for associations with mortality and selected CVD outcomes using logistic and Cox regression and, as an instrumental variable, in Mendelian Randomization. The discovery and replication cohorts consisted of 142,404 (119,129 European American (EUR); 16,495 African American (AFR)), and 45,766 (37,646 EUR; 5,366 AFR) participants, respectively. The mean age was 65.8 years (SD = 11.2) and 92.7% were male. Overall, 4.2% exhibited ideal CVH based on the clinical and behavioral factors. In the multi-population meta-analysis, variants at 17 loci were associated with IHS and each had known GWAS associations with multiple components of the IHS. PheWAS analysis in 456,026 participants showed that increased PRSIHS was associated with a lower odds ratio for many CVD outcomes and risk factors. Both IHS and PRSIHS measures of ideal CVH were associated with significantly less CVD outcomes and CVD mortality. A set of high interest genetic variants contribute to the presence of ideal CVH in a multi-ethnic cohort of US Veterans. Genetically influenced ideal CVH is associated with lower odds of CVD outcomes and mortality.