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关键词： Phase 1 trials   healthy volunteers   clinical trial diversity   oncology  

摘要： The dominant narrative on equity, diversity, and inclusion in U.S. medical research emphasises the underrepresentation of Black and Hispanic participants in clinical trials, largely based on therapeutic phase 2 and 3 trials. Far less attention has been paid to phase 1 trials-particularly those involving healthy volunteers who assume health risks without therapeutic benefit, often for money. Focusing on inequalities in the distribution of research participation, risks, and potential benefits, this study analyses secondary data from 429 U.S. industry-involved phase 1 trials with 18,217 participants registered on *** between January 2018 and October 2024. We examined trial-level demographics-race, ethnicity, sex-by phase 1 trial type and U.S. geographic region, comparing enrolment with U.S. Census estimates. Quasi-binomial regression models were used to identify trial-level factors associated with enrolment patterns. Black and Hispanic individuals were overrepresented in healthy-volunteer trials by 14 and 16 percentage points, but underrepresented in oncology trials by 7 and 8 percentage points. Overrepresentation in healthy-volunteer trials was especially pronounced for Hispanic participants in the U.S. West and South and for Black participants in the Northeast and Midwest. Female participants were underrepresented, except in non-oncology disease trials. We found a strong association between higher male and Black participation but not Hispanic participation. These findings highlight intersecting race, ethnicity, and gender inequalities in the distribution of research risks and rewards. Promoting equity in medical research requires moving beyond one-dimensional underrepresentation narratives to address the structural inequalities shaping racialised and gendered patterns of inclusion and exclusion across clinical trial phases, types, and locations.

关键词： Land surface phenology   MODIS-like NDVI   spatiotemporal data fusion   global vegetation dynamics   remote sensing  

摘要： As climate change continues to reshape global ecosystems, accurately monitoring and understanding shifts in land surface phenology (LSP) has become increasingly critical for detecting vegetation responses, assessing ecosystem resilience, and improving predictions of climate-biosphere interactions. While several moderate-to-fine spatial resolution global LSP datasets exist, most are constrained to post-2000 records due to the availability of MODIS era observations, leaving a significant gap in long-term phenological information and limiting our ability to investigate multi decadal trends. To address this, we developed the first global 1 km resolution LSP dataset spanning 1982-2018. By integrating MODIS and AVHRR NDVI data through the enhanced Flexible Spatiotemporal Data Fusion (cuFSDAF) model, we reconstructed pre-2000 MODIS-like NDVI time series with improved temporal consistency and reduced cross sensor bias. Using logistic functions and third-order derivatives, we extracted four key phenological metrics, including the start of the growing season (SOS maturity, senescence, and the end of the growing season (EOS enabling detailed characterization of vegetation development stages across diverse biomes. In the Northern Hemisphere (NH SOS, maturity, and EOS advanced significantly from 1982 to 2018, while senescence was delayed, indicating a widespread lengthening of the growing season. In contrast, the Southern Hemisphere (SH) experienced delayed SOS, maturity, and senescence, with EOS occurring earlier, suggesting a shortening of the growing season and revealing contrasting hemispheric sensitivities to climate forcing. These metrics were validated against ground-based observations from multiple networks, demonstrating strong consistency, high accuracy, and reliable reconstruction of long term phenological signals. As the first dataset of its kind at 1 km resolution over such an extended period, it provides an invaluable resource for studying global vegetation dynamic

关键词： DKD   HIPK2   TGF-beta 1   EMT   HK-2  

摘要： Diabetic kidney disease (DKD) is a common and challenging microvascular complication of diabetes. TGF-beta 1-mediated epithelial-to-mesenchymal transition (EMT) in renal tubular epithelial cells, characterized by loss of epithelial polarity and intercellular adhesion alongside acquisition of a mesenchymal phenotype, is widely recognized as a key driver of DKD. Here, we reveal that renal interstitial fibrosis (RIF) and EMT constitute important pathological foundations for DKD progression, validated in both clinical DKD patients and DKD mouse models. Concurrently, we confirm the elevated expression of homoeotic domain-interacting protein kinase 2 (HIPK2) in DKD, though its regulatory role in EMT remains unclear. We further established a DKD-EMT cellular model by inducing human renal tubular epithelial cells (HK-2) with TGF-beta 1 combined with high glucose stimulation. Here, we found that inhibiting HIPK2 expression significantly delayed EMT progression and improved RIF in DKD. Thus, our study provides a novel therapeutic strategy for DKD progression and demonstrates that HIPK2 serves as a potential therapeutic target for DKD-EMT.

关键词： Rosacea   erythema   telangiectasia   ktp   laser   ivermectin  

摘要： Objective: Facial erythema and telangiectasia in rosacea are commonly treated with vascular lasers. Combination with ivermectin 1% cream, may enhance outcomes when combined with laser therapy. This study assesses whether topical ivermectin improves the efficacy of Potassium Titanyl Phosphate (KTP) 532 nm laser for facial erythema in rosacea. Methods: This is a randomized, evaluator-blinded, split-face study. 24 patients with rosacea received four KTP laser sessions;one facial side was additionally treated daily with ivermectin 1% cream. The primary outcome was the change in Normalized Erythema Index (NEI). Secondary measures included Skin Redness Index (SRI Clinical Erythema Assessment, Physician Global Assessment, telangiectasia score, inflammatory lesion counts, patient satisfaction, and safety. Results: At week 16, the combination side showed a significantly greater NEI reduction than laser alone (Delta NEI%: 16.6 vs 5.3;p = 0.04). No significant differences were observed in SRI, and all other scores. However, papule reduction across visits was significantly greater with ivermectin (p = 0.02). Both treatments were well tolerated, with no serious adverse events. Conclusion: KTP laser effectively reduces erythema and inflammatory lesions;adjunctive ivermectin may further enhance papulopustular lesions. The combination is well tolerated, suggesting a potential adjunctive role for topical ivermectin in laser-based rosacea therapy.

关键词： Antimicrobial peptide   hepcidin   anguillid herpesvirus 1   antiviral activity   envelope protein ORF51  

摘要： Frequent outbreaks of eel "mucus sloughing and hemorrhagic septicemia disease" caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to heavy losses on eel farms and the lack of protective vaccines or effective drugs, highlighting the urgent need for potent antiviral agents. In this study, we revealed a hepcidin homolog LJ-hep2 from Japanese seabass (Lateolabrax japonicus) can bind to AngHV and impede viral entry into cells. LJ-hep2 could directly destroy the viral envelope and showed a higher anti-AngHV activity than AA-hep (a hepcidin homolog cloned from Anguilla anguilla). It was found that the destruction of viral structure by LJ-hep2 was related to the binding of the peptide to AngHV envelope protein ORF51, and the two amino acid residues at the N-terminus of the peptide (lysine and phenylalanine) might play a key role. Comparative antiviral experiments with mutated LJ-hep2 (LJ-hep2A4A5) and multi-species hepcidin further confirmed this finding and demonstrated that these two amino acids were indispensable in the inhibition of AngHV infection by LJ-hep2. In an established eel immersion infection model, LJ-hep2 treatment reduced viral accumulation in tissues, inhibited horizontal transmission, alleviated skin lesions, and improved eel survival. Taken together, this study suggests that LJ-hep2 could inhibit AngHV infection in vitro and in vivo, and identify ORF51 as a potential target for the development of anti-AngHV drugs.

关键词： GM soybean   non-targeted metabolomics   substantial equivalence   omega-3 fatty acid  

摘要： The overexpression of the Physaria fendleri omega-3 fatty acid desaturase (PfFAD3-1) in soybean (Glycine max (L.) Merr.) substantially increases seed alpha-linolenic acid (18:3) content. To evaluate the compositional safety of PfFAD3-1 transgenic soybeans, we conducted a three-year, two-location field trial (Jeonju and Gunwi, Republic of Korea) and applied non-targeted metabolite profiling of polar and lipophilic metabolites. Multivariate analyses (PCA, PLS-DA) revealed that environmental factors (site and year) had a strong effect on seed metabolite composition. Volcano plot and variable importance in projection (VIP) analyses indicated that most metabolite differences between PfFAD3-1 lines and Kwangan (KA) varied across years and locations, reflecting gene - environment interactions. Importantly, the majority of metabolites in PfFAD3-1 lines remained within the natural variation range of non-GM reference cultivars, supporting substantial equivalence. The consistent deviation was an increase in beta-amyrin, a triterpenoid precursor of soyasaponins. LC - MS analysis further confirmed line- and environment-dependent increases in specific saponins, particularly soyasaponin I. Given the established safety of triterpenoids in soybean and the biological coherence of fatty acid - triterpenoid pathway cross-talk, these findings suggest that beta-amyrin accumulation represents an intended metabolic adjustment rather than an unintended effect. Collectively, our results demonstrate that non-targeted metabolomics complements conventional OECD-recommended compositional analyses, providing a robust framework for the safety assessment of nutritionally enhanced GM soybeans.

关键词： Adherence   efficacy   hepatitis B   people who use drugs   randomized controlled trial   vaccination schedule  

摘要： BackgroundTo compare the adherence and efficacy between the 0 - 7 - 21-day and the 0 - 1 - 6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China. Research design and methodsA randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20 mu g per-dose vaccine was used. HBV surface antibody (anti-HBs surface antigen, and core antibody were tested at months 7, 15, and 22 after the first dose.ResultsThird-dose coverage was significantly higher in the 0 - 7 - 21-day group (74.40%) than in the 0 - 1 - 6-month group (51.58%, p < 0.001 mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0 - 1 - 6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0 - 7 - 21-day schedule (74.23%, 49.40%, and 40.95%;all p < 0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p = 0.018). ConclusionsThe 0 - 7 - 21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics. Clinical trial registrationChinese Clinical Trial Registry (ChiCTR1900022403).

关键词： Myotonic dystrophy type 1 (DM1)   organ system involvement   clinical burden   economic burden   HCRU   healthcare cost   healthcare resource utilization  

摘要： Objectives: Myotonic dystrophy type 1 (DM1) is a multi-systemic disease affecting skeletal and smooth muscle, the eye, brain, and heart. No disease-modifying therapies are available. Prior studies on clinical care and economic burden combined DM1 and DM type 2. This study describes the US DM1 population aged >= 12 years, assessed organ system involvement over time, estimated healthcare resource utilization (HCRU associated costs, and identified predictors of high-cost status. Methods: Linked open claims and EHR data (Clarivate) from 1 January 2015 to 25 August 2023 were analyzed. Eligible individuals had a DM1 diagnosis (index >= 6 months pre-index data, and were aged >= 12 years;congenital DM was excluded. Organ system involvement rates up to 7 years post-index were estimated using the Kaplan-Meier method. Annual HCRU rates and costs to payers (2023 USD) were summarized by setting, type of care and specialty and compared by organ involvement. Predictors of high-cost status were evaluated using multivariable logistic regression. Results: The cohort included 1,343 people with DM1. Over 7 years, most experienced neurological, gastrointestinal, cardiac, pulmonary, and/or musculoskeletal system involvement. Annually post-index, approximately 24% of patients had emergency room visits, and 15% had inpatient visits. Common specialty visits included rehabilitation (13% cardiology (13% and neurology (11%). Frequent device use included noninvasive positive-pressure ventilation (12% assistive devices (7% and oxygen therapy (4%). Mean annual total cost of care was $20,687 (SD = $122,082 primarily driven by inpatient and outpatient hospital visits. Cardiac and pulmonary complications were significant predictors of high-cost status. Conclusion: DM1 imposes significant clinical and economic burden, marked by extensive organ involvement and variable healthcare costs. As any patient may progress to costly cardiac or pulmonary complications, early proactive management is critical. Th