Browse Articles

Land tenure regimes influenced long-term restoration gains and reversals across Brazil’s Atlantic forest

Abstract Forest restoration is increasingly promoted to mitigate climate change, conserve biodiversity, and secure food and water sovereignty. Yet many restored forests do not persist in the long term, and the role of land tenure regimes in shaping these outcomes remains poorly understood. We examine restoration reversals (restored forests later deforested) and long-term restoration gains (restored forests that remained intact) across 1.9 million territories in Brazil’s Atlantic Forest from 1985 to 2022. We compare Indigenous lands, Afro-descendant ( Quilombola ) territories, agrarian-reform settlements, protected areas, and private properties, introducing a statistical matching technique– agglomerative matching –to account for systematic differences between land tenure regimes. We find that Indigenous lands and agrarian-reform settlements exhibit significantly more long-term restoration gains than private properties. Concurrently, and by a smaller margin and on a smaller land area, Indigenous lands and agrarian-reform settlements exhibit higher reversals. These results highlight the relatively low restoration longevity of private properties and emphasize the importance of socio-political conditions in enabling long-term restoration gains.

One SQ HEDGES DNA vector only dose produces durable hGLA or anti-SARS-CoV-2 mAb therapeutic serum protein levels

It is estimated that ~2 billion people worldwide cannot afford even basic medicines. B ioreactor-produced r ecombinant p rotein t herapies (BRPTs), among the world’s most-expensive medicines, have revolutionized treatment of a wide-spectrum of human-diseases, particularly the ~ 7,000 incurable, rare human single-protein, monogenic-deficiency diseases. Currently, BRPT are limited by toxicity, immunogenicity, short protein T 1 / 2 s and high-cost, creating a worldwide access-gap between those who can afford BRPTs versus those who cannot. Fabry disease (FD) is a monogenic deficiency disease caused by pathogenic-variants of the galactosidase-a (GLA) gene. FD damages heart, kidneys, CNS, gastrointestinal tract, and eyes. State-of-the-art anti-FD therapy, hGLA enzyme-replacement-therapy (ERT), requires bi-weekly IV infusions lifelong, costing ~ $200,000 per-patient per-year. High-lifetime costs can cause significant numbers of FD patients to permanently discontinue hGLA-ERT, thereby accelerating FD progression, which can lead to premature-death. Subcutaneously administered plasmid DNA alone has not been previously reported to transfect subcutaneous fat. Here we show one S ubcutaneous A dministration of H EDGES D NA vectors A lone ( SAHDA ) encoding the wildtype hGLA protein safely produces durable hGLA serum protein levels in the 1–10 ng/mL normal human hGLA range in immunocompetent mice. Unexpectedly, one administration of a highly-optimized SAHDA version encoding hGLA produced durable, ~ 100-fold higher hGLA serum protein levels than the 10 ng/mL high-normal human level. Importantly, components of the SADHA platform can be simply-modified to control the level and duration of hGLA serum protein-levels produced over a broad temporal-range in mice. Furthermore, one SAHDA-based administration of a HEDGES DNA-vector encoding a highly-neutralizing anti-SARS-CoV-2 monoclonal antibody (mAb) safely produces long-term protective serum mAb levels in immunocompetent-mice. SAHDA offers multiple advantages over BRPT, including not requiring an intact cold-chain and being readily freeze-dried. This combination enables SAHDA’s rapid deployment, then prolonged storage at ambient temperatures, even in equatorial-areas worldwide. SAHDA can readily be self-administered worldwide. It also obviates severe intravenous-infusion reactions. Taken-together, SAHDA may more effectively-, safely-, durably-, and cost-effectively-treat a spectrum of now poorly-treatable diseases worldwide.

Delayed integration of somatostatin interneurons into visual circuits

Correction: Image recognition technology for bituminous concrete reservoir panel cracks based on deep learning

CRISPR targeting of H3K4me3 activates gene expression and unlocks centromere-proximal crossover recombination in Arabidopsis

Abstract H3K4me3 is a fundamental and highly conserved chromatin mark across eukaryotes, playing a central role in many genome-related processes, including transcription, maintenance of cell identity, DNA damage repair, and meiotic recombination. However, identifying the causal function of H3K4me3 in these diverse pathways remains a challenge, and we lack the tools to manipulate it for agricultural benefit. Here we use the CRISPR-based SunTag system to direct H3K4me3 methyltransferases in the model plant, Arabidopsis thaliana . Targeting of SunTag-SDG2 activates the expression of the endogenous reporter gene, FWA . We show that SunTag-SDG2 can be employed to increase pathogen resistance by targeting the H3K4me3-dependent disease resistance gene, SNC1 . Meiotic crossover recombination rates impose a limit on the speed with which new traits can be transferred to elite crop varieties. We demonstrate that targeting of SunTag-SDG2 to low recombining centromeric regions can significantly stimulate proximal crossover formation. Finally, we reveal that the effect is not specific to SDG2 and is likely dependent on the H3K4me3 mark itself, as the orthogonal mammalian-derived H3K4me3 methyltransferase, PRDM9, produces a similar effect on gene expression with reduced off-target potential. Overall, our study supports an instructive role for H3K4me3 in transcription and meiotic recombination and opens the door to precise modulation of important agricultural traits.

Effect of imeglimin on metabolic dysfunction-associated steatotic liver disease in individuals with type 2 diabetes

Objective Preclinical studies, including animal and in vitro experiments, have suggested that imeglimin, a novel antidiabetic drug, may have beneficial effects on metabolic dysfunction-associated steatotic liver disease (MASLD). However, its effect on MASLD in individuals with type 2 diabetes remains unclear. This study aimed to evaluate whether imeglimin has beneficial effects in individuals with type 2 diabetes and hepatic enzyme abnormalities. Methods This multicenter, retrospective, single-arm study included 49 individuals with type 2 diabetes who newly initiated imeglimin treatment and continued it for six months. Individuals with chronic liver diseases other than MASLD were excluded. Treatment efficacy for liver function was defined as an ALT reduction of ≥11 IU/L, corresponding to the upper interquartile range of ALT reduction. Logistic regression analysis was performed to identify predictors of this treatment efficacy. Results Body mass index (BMI) and hemoglobin A1c (HbA1c) levels significantly decreased after six months of imeglimin treatment. Additionally, both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels significantly decreased (ALT: 21.0 IU/L [13.0–39.0] vs. 17.0 [12.5–28.0], p   = 0.002; AST: 21.0 IU/L [17.0–30.0] vs. 18.0 [16.0–26.0], p  =  0.010, respectively). Logistic regression analysis showed that baseline ALT and AST levels were significant predictors of treatment efficacy for liver function, after adjusting for HbA1c and BMI levels (OR 1.06, 95% CI 1.02–1.12, p = 0.006; OR 1.12, 95% CI 1.06–1.23, p = 0.002, respectively). Furthermore, the receiver operating characteristic (ROC) curve for baseline ALT as a predictor demonstrated excellent discriminatory performance (Area under the curve: 0.905, p   = 0.004). A cutoff value of 25 IU/L yielded 100% sensitivity and 77.8% specificity. Conclusion This exploratory study suggests that imeglimin may have beneficial effects in individuals with type 2 diabetes and elevated ALT (≥25 IU/L), potentially associated with MASLD. Randomized controlled trials are needed to confirm these findings.

Large-scale causal discovery using interventional data sheds light on gene network structure in k562 cells

Matching of XEN®45 and PRESERFLO™ MicroShunt cases: Outcomes of a 3-year follow-up

Objective To compare long-term outcomes of XEN®45 (XEN) and PRESERFLO™ MicroShunt (PRESERFLO) implants in the surgical management of glaucoma over a 3-year follow-up period, focusing on intraocular pressure (IOP) reduction, need of medication, surgical success, and postoperative complications. Methods A retrospective, matched case control study was conducted, including 42 eyes with preceded implantation of a XEN or PRESERFLO. Patients were statistically matched using SPSS algorithms for glaucoma diagnosis, previous surgery, and demographics. Standardized success criteria defined surgical outcomes: complete success (IOP ≤ 15 mmHg or ≤ 18 mmHg without medications) and qualified success (IOP ≤ 15 mmHg with < 3 medications). Postoperative care and needling or revision interventions were recorded. Statistical analyzes included Wilcoxon, Mann-Whitney U, and t-tests. Results Both devices significantly reduced IOP and glaucoma medication over 3 years. XEN reduced IOP from 22.1 ± 8.6 mmHg to 13.5 ± 3.8 mmHg, while PRESERFLO reduced IOP from 22.1 ± 6.6 mmHg to 12.6 ± 4.0 mmHg (p > 0.05 for between-groups, 3 years postoperative). Medication use decreased from 2.4 ± 1.0 to 0.9 ± 1.4 for XEN and 3.1 ± 1.1 to 1.1 ± 0.9 for PRESERFLO (p > 0.05 for between-groups). Surgical success rates were similar after 3 years. PRESERFLO showed fewer postoperative revisions (28.6% vs. 42.9% for XEN; p > 0.05). Early hypotony occurred more frequently with XEN (17 vs. 7 cases; p = 0.029). Conclusion Both XEN and PRESERFLO effectively reduce IOP and the need for glaucoma medication, with comparable surgical success rates after 3 years. PRESERFLO demonstrated a lower revision rate and reduced frequency of early postoperative hypotony. These findings support both implants as viable options for minimally invasive glaucoma surgery, with low risk profiles.

Lithium diffusion-controlled Li-Al alloy negative electrode for all-solid-state battery

Abstract Metal alloy negative electrodes are promising candidates for lithium all-solid-state batteries due to their high specific capacity and low cost. However, chemo-mechanical degradation and atomic transport limitations in the solid state remain unresolved challenges. Herein, we demonstrate a lithium-aluminum alloy negative electrode design (Li x Al 1 , x = molar ratio of lithium to aluminum) based on a comprehensive understanding of the underlying diffusion mechanisms within the lithium-poor α (0 ≤ x  ≤ 0.05) and lithium-rich β phases (0.95 ≤ x  ≤ 1). The lithium-aluminum alloy negative electrodes with a higher lithium to aluminum ratio facilitate lithium migration through the β-LiAl phases, which serve as highly lithium-conductive channels with a lithium diffusion coefficient that is ten orders of magnitude higher than that of the α phase. In addition, a bulk dense negative electrode and an intimate negative electrode-electrolyte interface is demonstrated in the cross-sections of the lithium-aluminum alloy negative electrodes. Consequently, a high-rate capability of 7 mA cm −2 is attained in LiNi 0.8 Co 0.1 Mn 0.1 O 2 -based full-cell operation. The optimal cell configuration of Li 0.5 Al 1  | |LiNi 0.8 Co 0.1 Mn 0.1 O 2 shows stable lithium reversibility during 2000 cycles with a capacity retention of 83% at 4 mA cm −2 with a LiNi 0.8 Co 0.1 Mn 0.1 O 2 loading of 5 mAh cm −2 .

Development and validation of an asthma self-knowledge questionnaire

Background Validated questionnaires for adequately assessing knowledge about asthma are scarce. Thus, the primary objective of the present study was to develop and validate an asthma self-knowledge questionnaire, based on international recommendations on the disease. The secondary objectives were to compare knowledge about asthma between asthmatic patients and non-asthmatic individuals; assessing whether asthma affects the level of self-knowledge of the disease and what factors may be associated with poorer self-knowledge of the disease. Methods The Bronchial Asthma Self-Knowledge Questionnaire was developed, and validation studies were performed: logical or apparent validity, content validity, construct validity; internal consistency (Cronbach’s alpha test), test-retest or reproducibility, in a face-to-face survey with 104 asthmatic patients and 131 non-asthmatic individuals (n = 235). Other questionnaires were also applied: Mini Mental State Examination (in individuals over 65 years of age), Depression Scales (CES-D for individuals under 65 and GDS for individuals over 65 years of age), Demographic Questionnaire, Health Literacy, and the Characterization Questionnaire for bronchial asthma. Results Regarding development of the questionnaire, content validity, determined using I-CVI allowed reducing the questionnaire to 21 items. The test proved to have an acceptable value of in-ternal consistency and the data were considered as normally distributed; the questionnaire presented good temporal stability, by test-retest, although Spearman rho values were significantly stronger in the asthmatic group. Finally, confirmatory factorial analysis yielded acceptable values for PCFI and PGFI, as well as a satisfactory value for RMSEA. In terms of the application of the questionnaire, both groups under study (asthmatics and non-asthmatics) showed statistically significant differences in replies of self-knowledge questionnaire items. Finally, factors such as health literacy disturbances seem to marginally influence self-knowledge of bronchial asthma. Conclusions The developed and validated questionnaire showed adequate psychometric robustness. In terms of construct validity, by known group (bronchial asthma) validity, the test was able to discriminate between patients with asthma and participants without asthma, regarding self-knowledge of the disease.

Real-world data and clinical experience from over 100,000 multi-cancer early detection tests

Scenario evolution modeling and probabilistic assessment of seawater intrusion accident in ports: An integrated framework combining disaster theory and multi-method simulation

As a typical marine disaster, seawater intrusion accidents have posed a serious threat to port production safety due to the double rise in the occurrence frequency and damage intensity. In favor of effectively controlling the scope of disaster impact and formulating more targeted emergency plans, it is particularly significant to carry out accident scenario evolution analysis. Based on the disaster system theory, this study constructed a model for the evolution of seawater intrusion accident scenarios in ports and clarified the probability of occurrence concerning each accident scenario by utilizing qualitative and quantitative methods. The main conclusions of this study were as follows: According to the theoretical framework of “disaster-causing body, disaster-affected body, and disaster-resistant body”, typical scenarios, such as concrete structure erosion and power supply interruption, were identified by scenario element method. By coupling the Petri net, cloud model, and Monte Carlo model, the quantitative derivation of evolutionary paths was realized, which not only retained the organic link between qualitative cognition and quantitative expression but also guaranteed the reliability of the results through ten thousand iterations. The probability grading system of accident scenarios was formed by combining the quantitative results. Among them, S11(Large equipment such as gantry and shore bridges stopped working due to power supply interruption) had the highest probability, with the corresponding value of 57.2%, and was in the “Moderately Likely” level according to the preset interval level. The research can provide a scientific basis for port enterprises to optimize the preparation with regard to emergency plans and improve the post-disaster recovery strategy, helping advance the comprehensive disaster prevention and mitigation capacity of ports.

Integrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer’s dementia

Correction: Associations of self-reported hearing problems with long-term trajectories of mental and functional health in middle-aged and older adults: The role of self-perceptions of aging

Multicolor cathodoluminescence imaging of single lanthanide nanoparticles

Utilization of interdisciplinary in-hospital early rehabilitation in COVID-19 patients - a multicenter cohort study in the National Pandemic Cohort Network (NAPKON) in Germany

Background Early rehabilitation in acute hospitals aims to prevent immobilization-related complications and improve the functional capacity of patients with severe or critical illness. Early rehabilitation can be a useful concept to improve functioning in COVID-19 patients. However, literature concerning early in-hospital rehabilitation in COVID-19 patients is scarce. Aim To analyze the utilization of in-hospital interdisciplinary early rehabilitation (IER) in COVID-19 patients and characterize the sample of IER patients. Design Prospective cohort study. Setting Hospitalized COVID-19 patient cases. Population This study used data from the National Pandemic Cohort Network (NAPKON) in Germany. Methods IER utilization rates were retrieved. Demographic and clinical data from hospitalized COVID-19 patients who had received IER during the course of their treatment were evaluated. Results Out of the 2,644 patients in the Cross-Sectoral Platform (German abbreviation: SUEP) cohort, 0.79% [95% CI: 0.51% to 1.22%] received IER during their stay in an acute care hospital. Among the subgroup of patients who had previously been treated in intensive care, 2.13% [95% CI: 1.16% to 3.63%] received IER. The most common comorbidities were cardiovascular diseases (66.7%) and neurological/psychiatric diseases (36.1%). The small sample size limited further analyses. Conclusion The low rate of early rehabilitation in acute hospitals for COVID-19 patients indicates an unmet need, particularly in severe cases. Structural changes in the health system are needed to close this gap. The WHO and the German Medical Council have recently acknowledged the necessity of early in-hospital rehabilitation and have issued a call for its implementation in acute hospitals.

How augmin establishes the angle of the microtubule branch site

Evaluation of the new blood-pool CT contrast agent VivoVist in mouse models

Small animal CT imaging provides high resolution imaging of bone structure, lungs, and gross anatomy. However, it is limited in its ability to provide high soft tissue contrast. Several blood pool CT contrast agents have been developed to enhance vascular and tissue contrast for preclinical imaging with varying enhancement capabilities. VivoVist TM is the most recent commercially available blood pool CT contrast agent for preclinical applications. This study independently evaluated its radiopacity and tissue enhancement compared to two existing preclinical CT contrast agents, Mvivo-Au, and Fenestra-HDVC. Healthy nude mice were administered one of the three contrast agents. CT imaging was performed before and at 5 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 96 hours, and 7 days post-injection. Tissue intensity and the enhancement ratio relative to pre-injection levels were quantified for each contrast agent at each time point. VivoVist demonstrated significantly higher blood enhancement compared to Mvivo-Au and Fenestra-HDVC at 5 minutes and 1 hour post-injection. However, the enhancement at 4 hours and later time points was inferior to that of Mvivo-Au. VivoVist exhibited the fastest blood clearance among the three contrast agents, with a blood half-life of 3.1 hours and was largely cleared from the blood by 24 hours post-injection. In CT imaging after 24 hours post-injection, VivoVist showed the highest liver enhancement, which remained high over the 7-day imaging period. Biodistribution assessment showed that the splenic uptake of VivoVist was extremely high. Histological examination of the tissues identified abundant contrast agent accumulation in the liver and spleen. No overt pathological changes were observed in either organ one month after the injection of VivoVist. Overall, the evaluation confirmed that VivoVist is an effective CT contrast agent for vascular and liver imaging with low toxicity. However, its relatively short blood half-life limits its use as a vascular contrast agent for a prolonged period.

Live attenuated influenza vaccine with low proportions of defective interfering particles elicits robust immunogenicity and cross-protection

Association between serum vitamin D deficiency and visceral fat indices in adolescents: The Ewha Birth and growth cohort study

Purpose Vitamin D plays a crucial role in cardiometabolic health, but its association with visceral fat in adolescents remains unclear. This study aimed to evaluate the relationship between vitamin D levels visceral fat indices—Hypertriglyceridemic Waist Phenotype (HWP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP)—which serve as practical markers for visceral fat. Methods This study analyzed 238 adolescents (aged 13–15) data from the Ewha Birth and Growth Study, a longitudinal Korean cohort. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured and categorized as deficiency (<20 ng/mL) or non-deficiency (≥20 ng/mL). Visceral fat was assessed using HWP, VAI, and LAP as surrogate markers for visceral adiposity. Logistic and linear regression analyses were performed to evaluate associations, adjusting for key covariates. Sensitivity analyses used alternative HWP definitions and vitamin D categorizations. Results Among 238 adolescents, 76.0% had vitamin D deficiency, and 7.1% had HWP. Logistic regression indicated a lower HWP risk in the non-deficiency group with a borderline level of significance ( p  = 0.060). Sensitivity analyses confirmed a significantly lower HWP risk in the non-deficiency group under the lowered TG criterion and also showed that, in the three-category classification of vitamin D status, the non-deficiency group had a significantly lower HWP risk than the severe deficiency group, with a decreasing trend as vitamin D levels increased. Multiple linear regression showed inverse associations between vitamin D levels and log VAI ( β  = –0.020, p  = 0.008) and log LAP ( β  = –0.018, p  = 0.060). Conclusions The inverse relationship observed between vitamin D levels and visceral fat indices suggests a potential role in adiposity regulation and cardiometabolic health. Enhancing vitamin D status may help prevent obesity and reduce cardiometabolic risks in adolescents.