bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid
Authors: Craft Jeffrey M , Watterson D Martin , Hirsch Emmet , Van Eldik Linda J 
Published: June 2005

Abstract

Background
Interleukin 1 (IL-1) is a key mediator of immune responses in health and disease. Although classically the function of IL-1 has been studied in the systemic immune system, research in the past decade has revealed analogous roles in the CNS where the cytokine can contribute to the neuroinflammation and neuropathology seen in a number of neurodegenerative diseases. In Alzheimer's disease (AD), for example, pre-clinical and clinical studies have implicated IL-1 in the progression of a pathologic, glia-mediated pro-inflammatory state in the CNS. The glia-driven neuroinflammation can lead to neuronal damage, which, in turn, stimulates further glia activation, potentially propagating a detrimental cycle that contributes to progression of pathology. A prediction of this neuroinflammation hypothesis is that increased IL-1 signaling in vivo would correlate with increased severity of AD-relevant neuroinflammation and neuronal damage.

Methods
To test the hypothesis that increased IL-1 signaling predisposes animals to beta-amyloid (Aβ)-induced damage, we used IL-1 receptor antagonist Knock-Out (IL1raKO) and wild-type (WT) littermate mice in a model that involves intracerebroventricular infusion of human oligomeric Aβ1–42. This model mimics many features of AD, including robust neuroinflammation, Aβ plaques, synaptic damage and neuronal loss in the hippocampus. IL1raKO and WT mice were infused with Aβ for 28 days, sacrificed at 42 days, and hippocampal endpoints analyzed.

Results
IL1raKO mice showed increased vulnerability to Aβ-induced neuropathology relative to their WT counterparts. Specifically, IL1raKO mice exhibited increased mortality, enhanced microglial activation and neuroinflammation, and more pronounced loss of synaptic markers. Interestingly, Aβ-induced astrocyte responses were not significantly different between WT and IL1raKO mice, suggesting that enhanced IL-1 signaling predominately affects microglia.

Conclusion
Our data are consistent with the neuroinflammation hypothesis whereby increased IL-1 signaling in AD enhances glia activation and leads to an augmented neuroinflammatory process that increases the severity of neuropathologic sequelae.
Genetic lesions within the 3a gene of SARS-CoV
Authors: Tan Timothy HP , Barkham Timothy , Fielding Burtram C , Chou Chih-Fong , Shen Shuo , Lim Seng Gee , Hong Wanjin , Tan Yee-Joo 
Published: June 2005

Abstract
A series of frameshift mutations within the 3a gene has been observed in culture-derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here that viral RNA from clinical samples obtained from SARS-CoV infected patients also contains a heterogeneous population of wild-type and mutant 3a transcripts.
Unimolecular Photochemistry of 4‐Thiouracils
Authors: Khvorostov Artem , Lapinski Leszek , Rostkowska Hanna , Nowak Maciej J. 
Published: June 2005

ABSTRACTUnimolecular phototautomeric reactions in 4‐thiouracil, 1‐methyl‐4‐thiouracil and 6‐aza‐4‐thiouracil were studied using the matrix‐isolation technique combined with infrared absorption spectroscopy. For monomers of these compounds, isolated in solid argon at 10 K, an intramolecular proton‐transfer photoreaction was observed. Upon UV (λ > 345 nm) irradiation, the initial oxo‐thione forms of 4‐thiouracils were converted into the corresponding oxo–thiol tautomers. The photogenerated oxo–thiol isomers were identified by comparing their experimental IR spectra with the spectra theoretically calculated at the DFT(B3LYP)/6‐311++ G(2d,p) level. Good agreement between the observed and predicted pattern of spectral bands allowed a reliable identification. This is the first report on experimental observation of isomeric forms of 4‐thiouracils other than the canonical oxo–thione tautomers.
Cardiovascular Hospitalizations Among Older Adults in the US and Denmark
Authors: Berg Frederikke Held , Lassen Mats C. Højbjerg , Vaduganathan Muthiah , Fonarow Gregg C. , Yeh Robert W. , Zheng ZhaoNian , Gislason Gunnar H. , Biering-Sørensen Tor , Wadhera Rishi K. 
Published: February 2025

ImportanceCardiovascular disease is the leading cause of death in the US. However, it remains unclear how the burden of cardiovascular events in the US compares with that of other high-income countries with distinct health care systems like Denmark, both overall and by income.ObjectiveTo compare cardiovascular hospitalization rates (acute myocardial infarction [MI], heart failure [HF], ischemic stroke) and associated outcomes among adults 65 years or older, overall and by income, between the US and Denmark.Design, Setting, and ParticipantsThis population-based cross-sectional study used national data from the US and Denmark from January 1, 2021, to January 1, 2022. The study population included all Medicare beneficiaries 65 years or older in the US and all adults 65 years or older in Denmark.Main Outcomes and MeasuresThe primary outcome was age- and sex-standardized hospitalization rates for MI, HF, and ischemic stroke, as well as 30-day all-cause mortality rates.ResultsThe US study population included 58 614 110 adults 65 years or older (mean [SE] age, 74.6 [7.7] years; 32 179 146 female [54.9%]) of whom 1 171 058 (2.0%) were hospitalized for a cardiovascular event. The Danish study population included 1 176 542 adults 65 years or older (mean [SE] age, 75.3 [7.1] years; 634 217 female [53.9%]) of whom 16 305 (1.4%) were hospitalized with a cardiovascular event. The overall age- and sex-standardized cardiovascular hospitalization rate was significantly higher in the US compared with Denmark (risk ratio [RR], 1.50; 95% CI, 1.47-1.52), as were associated 30-day all-cause mortality rates (RR, 1.12; 95% CI, 1.06-1.17). Across conditions, the risk of hospitalization for MI (RR, 1.56; 95% CI, 1.51-1.61) and HF (RR, 2.37; 95% CI, 2.31-2.43) was significantly higher in the US compared with Denmark, whereas hospitalizations for ischemic stroke were lower (RR, 0.90; 95% CI, 0.88-0.93). Overall cardiovascular hospitalization rates in the US were more than 2-fold higher among low-income adults compared with higher-income adults (RR, 2.38; 95% CI, 2.25-2.47), whereas the magnitude of income-based disparities was smaller in Denmark (RR, 1.45; 95% CI, 1.39-1.50).Conclusions and RelevanceIn this international cross-sectional study, cardiovascular hospitalization rates were significantly higher in the US compared with Denmark. There were income-based differences in the burden of cardiovascular hospitalizations in both countries, although the magnitude of these disparities was much greater in the US.
Salt Substitution and Recurrent Stroke and Death
Authors: Ding Xiong , Zhang Xinyi , Huang Liping , Xiong Shangzhi , Li Zhifang , Zhao Yi , Zhou Bo , Yin Xuejun , Xu Bingqing , Wu Yanfeng , Neal Bruce , Tian Maoyi , Yan Lijing L. 
Published: February 2025

ImportanceThe direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear.ObjectiveTo evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke.Design, Setting, and ParticipantsThe Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomized clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analyzed from November 2023 to August 2024.InterventionsParticipants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt.Main Outcomes and MeasuresThe primary outcome was recurrent stroke.ResultsAfter excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was −2.05 mm Hg (95% CI, −3.03 to −1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on hemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96).Conclusions and RelevanceResults of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke.Trial RegistrationClinicalTrials.gov Identifier: NCT02092090
Return on Investment of Enhanced Behavioral Health Services
Authors: Hawrilenko Matt , Smolka Casey , Ward Emily , Ambwani Geetu , Brown Millard , Mohandas Anita , Paulus Martin , Krystal John , Chekroud Adam 
Published: February 2025

ImportanceEmployer-sponsored benefit programs aim to increase access to behavioral health care, which may help contain health care costs. However, research has either focused solely on clinical outcomes or demonstrated reductions in medical claims without accounting for the costs of behavioral health services, leaving the financial return on investment unknown.ObjectiveTo determine whether a clinically effective employer-sponsored behavioral health benefit is associated with net medical cost savings.Design, Setting, and ParticipantsThis retrospective cohort study included participants eligible for an employer-sponsored behavioral health benefit between November 1, 2019, and May 31, 2023. Eligibility criteria included having a behavioral health diagnosis and, in the program group, attending at least 1 behavioral health appointment. Program users were matched to nonusers on medical risk scores, behavioral health diagnoses, date of diagnosis, age, sex, and employer. Participants were followed up for 1 year before and after the benefit launch.ExposureA digital platform screened individuals for common behavioral health conditions and provided access to video and in-person psychotherapy, medication management, care navigation, and self-guided digital content.Main Outcomes and MeasuresPrimary outcomes were per member per month (PMPM) medical spending, inclusive of all medical claims and program costs. A difference-in-differences analysis was used to compare changes in net medical spending between groups from the year before and up to 1 year after an index mental health diagnosis.ResultsThis study included 13 990 participants: 4907 of 4949 (99.1%) eligible program group members were matched to 9083 control participants. Their mean (SD) age was 37 (13.2) years, and most participants (65.5%) were female. Costs decreased in the program group relative to the control group, with a net difference-in-differences of −$164 PMPM (95% CI, −$228 to −$100 PMPM), corresponding to savings of $1070 per participant in the first program year and a return on investment of 1.9 times the costs (ie, every $100 invested reduced medical claims costs by $190). Behavioral health costs in the program group increased relative to the control group but were more than offset by decreases in physical health care costs. Savings were larger for participants with higher medical risk.Conclusions and RelevanceIn this cohort study, every $100 invested in an employer-sponsored behavioral health program with fast access to psychotherapy and medication management was associated with a reduction in medical claims costs by $190. These findings suggest that expanding access to behavioral health care may be a financially viable cost-reduction strategy for health care buyers.
Observational and Genetic Analyses of Traumatic Experiences and Endometriosis
Authors: Koller Dora , Løkhammer Solveig , Goroshchuk Oksana , Denner Veronika , Stiltner Brendan , Mitjans Marina , He Jun , Taylor Hugh S. , Lawn Rebecca B. , Koenen Karestan C. , Polimanti Renato 
Published: February 2025

ImportanceAlthough psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition.ObjectiveTo examine the relationship between traumatic experiences and endometriosis using observational and genetically informed analyses.Design, Setting, and ParticipantsFor this case-control study, the analyses were performed between May 13, 2023, and September 30, 2024. Genotypic and phenotypic information was combined from UK Biobank individual-level data (up to 8276 patients with endometriosis and 240 117 female controls) with genome-wide information available from a large meta-analysis (European ancestry: 21 779 patients and 449 087 female controls; East Asian ancestry: 1713 patients and 1581 female controls) and the FinnGen cohort (16 588 patients and 111 583 female controls of European descent).Main Outcomes and MeasuresPhenotypic associations via multiple regression; latent-class analysis (LCA) to investigate the co-occurrence patterns of different traumatic experiences in endometriosis cases and controls; genetic correlation and polygenic risk scoring (PRS) analyses to assess pleiotropy linking traumatic events to endometriosis.ResultsUp to 8276 women with endometriosis (mean [SD] age, 53.2 [13.0] years) and 240 117 female controls (mean [SD] age, 56.5 [9.6] years) were investigated in the study. Women with endometriosis were more likely to report childhood and adulthood traumatic experiences and stressful events (eg, contact trauma odds ratio [OR], 1.28; 95% CI, 1.02-1.26). Our LCA highlighted the association of endometriosis with emotional and physical trauma (225 [8%] vs 3948 [5%]; P &amp;lt; 2.2 × 10−16) and sexual trauma (414 [5%] vs 3158 [4%]; P = 2.9 × 10−3). Unaffected women (controls) were more likely assigned to the “no trauma” latent class (563 [20%] vs 18 949 [24%]; P = 7.4 × 10−14). Our genetic correlation (rg) analyses linked endometriosis to multiple trauma-related outcomes, including posttraumatic stress disorder (meta-analysis rg = 0.31, P = 7.1 × 10−16; FinnGen rg = 0.26, P = 4.7 × 10−15) and childhood maltreatment (meta-analysis rg = 0.23, P = 1.3 × 10−6; FinnGen rg = 0.16, P = 1 × 10−4). Endometriosis PRS was associated with increased odds of the disease (β = 0.31, P &amp;lt; 2.2 × 10−16), but no interaction was observed with different types of trauma events.Conclusions and RelevanceThe present study comprehensively investigated the impact of childhood and adulthood traumatic experiences and stressful events on endometriosis. In particular, our findings highlight the potential association between contact traumas and endometriosis, which appears to be independent of the disease genetic predisposition.
Use of 18F‐fluorodeoxyglucose Positron Emission Tomography to Monitor Disease Activity in Patients With Giant Cell Arteritis on Tocilizumab
Authors: Quinn Kaitlin A. , Ahlman Mark A. , Grayson Peter C. 
Published: February 2025

ObjectiveThe objective of this study was to assess the value of 18F‐fluorodeoxyglucose (FDG)– positron emission tomography (PET) scans to monitor disease activity in patients with giant cell arteritis (GCA) on tocilizumab.MethodsPatients with GCA were recruited into a prospective cohort in which they underwent clinical, laboratory, and imaging assessments, including FDG‐PET. FDG‐PET scans were interpreted as active or inactive based on global impression by two independent readers. The PET Vascular Activity Score (PETVAS) was calculated to quantify arterial FDG uptake (scale 0–27). Vascular FDG‐PET findings were described in patients with GCA on tocilizumab for at least six months. For patients in established clinical remission, FDG‐PET findings were compared between those treated with tocilizumab versus glucocorticoid monotherapy.ResultsA total of 36 patients with GCA underwent FDG‐PET imaging on tocilizumab. Five patients had active clinical symptoms, and FDG‐PET scans were active in all cases (PETVAS range: 20–27). For the 31 patients in clinical remission on tocilizumab, FDG‐PET was active in 16 of these patients (52%) across a wide range of PETVAS (range 11–27). There were no associations between FDG‐PET activity during remission and historical clinical features or longitudinal outcomes, including relapse risk or angiographic progression of disease. PETVAS was significantly lower during clinical remission in patients treated with tocilizumab compared to an additional 12 patients treated with glucocorticoid monotherapy (PETVAS 18 vs 24; P = 0.02).ConclusionFDG‐PET has limited value to guide management decisions or inform prognosis when obtained during remission in patients with GCA on tocilizumab. Compared to glucocorticoid monotherapy, tocilizumab significantly reduces, but often does not eliminate, vascular inflammation in GCA.
High‐Performance Infrared Self‐Powered Photodetector Based on 2D Van der Waals Heterostructures
Authors: Liu Weijing , Wu Yifan , Bao Xiaozhendong , Sun Lin , Xie Yuee , Chen Yuanping 
Published: February 2025

AbstractSelf‐powered photodetection is an effective way to resolve the issue of high dark current in infrared photodetectors under a bias voltage. To date, high‐performance infrared self‐powered photodetectors (ISPDs) are mostly based on heterostructures consisting of 2D and 3D materials, while those based on 2D/2D heterostructures are rare. This will hinder the development of infrared devices toward miniaturization and energy‐saving. By exploring some 2D/2D van der Waals (vdWs) heterostructures, constructed by typical 2D transition metal dichalcogenides (TMDs), it is found that the heterostructure PdSe2/MoTe2 is a high‐performance ISPD. It exhibits a good capability of self‐powered broadband detection from 300 to 1550 nm, even extending to 4050 nm. Especially, under near‐infrared illumination of 980 nm, its responsivity and detectivity can approach 395 mA W−1 and 1.92 × 1011 Jones, respectively, which can be comparable with the high‐performance 2D/3D ISPDs. The heterostructure also possesses good environmental stability and infrared imaging capability. In addition, Three necessary conditions are proposed to construct 2D/2D high‐performance ISPD, i.e., a large difference of work function, high infrared absorption, and a type‐II band alignment. This work will guide a way to search for excellent ISPDs.
Elucidating Synergistic Mechanism of Zinc Single‐Atom Sites and Lewis Acid–Base Pairs to Boost Zinc–Iodine Batteries Performance
Authors: Zhao Yuliang , Wang Yiyang , Xue Wenjuan , Huang Hongliang , Li Jianwei , Hu Chuangang , Liu Dong 
Published: February 2025

AbstractZinc–iodine batteries (ZIBs) are promising energy storage devices due to their nonflammable aqueous electrolyte and intrinsically safe zinc (Zn) anode but encounters thorny challenges, including soluble polyiodides shuttling and sluggish iodine redox kinetics. Here, an ionic porous organic polymers (iPOPs) with Lewis acid–base pairs (e.g., pyridine cation and free Br−) and Zn single‐atom sites (iPOP‐TPyPZn) is developed as an advanced I2 host to notably enhance the performance of ZIBs. The iPOP‐TPyPZn can not only significantly prevent polyiodides shuttling via the synergy of Lewis acid–base pairs but also expedite redox kinetics of I2 species through the combined action of Lewis acid sites and Zn single‐atom catalytic sites. Benefiting from the double synergistic mechanism, the assembled ZIBs with I2 loaded iPOP‐TPyPZn cathode exhibit outstanding electrochemical performance with ultra‐high cycling stability over 40 000 cycles at 8 A g−1. Combined in/ex situ spectral characterizations and theoretical calculations clearly reveal the reversible reaction mechanism of I2 species and the vital role of double synergistic mechanism in enhancing ZIBs performance. This work not only provides a promising path for precise preparation of advanced I2 hosts but also offers new insights into the reaction mechanism toward metal–I2 batteries.
Electrical Impedance Tomography Monitoring of Salt Transportation in Cellulose Hydrogel for Solar‐Driven Evaporative Desalination via Laser Defined Wettability
Authors: Xu Yang , Zhong Haosong , Lu Xupeng , Tang Miao , Chen Siyu , Yang Cuiyun , Chen Yi , Kim Minseong , Liu Yang , Li Mitch Guijun 
Published: February 2025

AbstractThe scarcity of clean water has become a growing problem worldwide. Solar‐driven desalination based on evaporation has become a promising green technology for obtaining drinking water from saline water for the welfare of human society. However, the accumulation of salt precipitated from the saline at the evaporator surface remains a severe problem in improving evaporation efficiency. To overcome this problem, it is crucial to investigate the transportation mechanism of salt in the saline during the evaporation process. Herein, an in situ monitoring strategy with the electrical impedance tomography (EIT) method is proposed to characterize the salt transportation and accumulation process inside the nano‐crystal cellulose (NCC)‐MnO2 nanoparticle solar evaporator. The coating of laser‐induced graphene (LIG) with tunable water wettability shows that the hydrophobic structures can suppress salt accumulation during evaporation. The collected condensation water generated from the bacteria‐polluted saline proves to be clean. It is hoped that this work can further inspire research on the salt‐resistive evaporator design.
A Potential 3‐in‐1 Combined AntiSARS‐CoV‐2 Therapy Using Pulmonary MIL‐100(Fe) Formulation
Authors: Fodor Beatrice , Álvarez‐Miguel Inés , Biglione Catalina , López Guillermo G. , González‐Fernández África , Salles Fabrice , Hidalgo Tania , Horcajada Patricia 
Published: February 2025

AbstractThe emergence and rapid propagation of infectious diseases, including the COVID‐19 pandemic, has evidenced the vulnerabilities in global health surveillance, the ease of transmission, and the imperative need for effective treatments. In this context, nanomedicines based on metal–organic frameworks (MOFs) have garnered great relevance as promising drug delivery platforms in a large range of complex diseases (e.g., cancer, and infections). However, most research has focused on sensing with scarce examples in antiviral therapies. Hence, here a pioneer combined 3‐in‐1 effect anti‐COVID pulmonary multitherapy based on the mesoporous iron(III) carboxylate MIL‐100(Fe) nanoparticles is proposed, with the proven intrinsic MOF effect, associated with favipiravir drug into their porosity and heparin on their external surface. A significant antiviral effect against a real scenario of COVID‐19 infection is demonstrated (≈70% inhibition), ensuring a suitable cellular viability. Further, a convenient pulmonary formulation is prepared based on mannitol‐based microspheres, testing its safety and biodistribution in healthy mice. No significant side effects are observed, reaching successfully the deep lungs, emphasizing a reduced immunological response compared to their controls. Therefore, these promising results open new horizons for future (pre)clinical trials targeting challenging infectious/pulmonary pathologies, enhancing the feasibility of designing customized therapeutic MOF platforms.