bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSV-1-Induced SOCS-1 Expression in Keratinocytes: Use of a SOCS-1 Antagonist to Block a Novel Mechanism of Viral Immune Evasion
Authors: Frey Kenneth G. , Ahmed Chulbul M. I. , Dabelic Rea , Jager Lindsey D. , Noon-Song Ezra N. , Haider S. Mohammad , Johnson Howard M. , Bigley Nancy J. 
Published: June 2009

Abstract
Keratinocytes are important for the acute phase of HSV-1 infection and subsequent persistence in sensory nervous tissue. In this study, we showed that keratinocytes (HEL-30) were refractory to IFN-γ induction of an antiviral state to HSV-1 infection, while IFN-γ did induce an antiviral state in fibroblasts (L929). This led us to examine the possible role of suppressor of cytokine signaling-1 (SOCS-1) in this refractiveness. RT-PCR analysis of SOCS-1 mRNA expression in HSV-1-infected cells showed a 4-fold increase for keratinocytes while having a negligible effect on fibroblasts. A similar pattern was observed at the level of SOCS-1 protein induction. Activation of STAT1α in keratinocytes was inhibited by HSV-1 infection. A direct effect of HSV-1 on the SOCS-1 promoter was shown in a luciferase reporter gene assay. We have developed a small peptide antagonist of SOCS-1, pJAK2(1001–1013), that had both an antiviral effect in keratinocytes against HSV-1 as well as a synergistic effect on IFN-γ induction of an antiviral state. HSV-1 ICP0 mutant was inhibited by IFN-γ in HEL-30 cells and was less effective than wild-type virus in induction of SOCS-1 promoter. We conclude that SOCS-1 plays an important role in the inhibition of the antiviral effect of IFN-γ in keratinocytes infected with HSV-1. The use of SOCS-1 antagonist to abrogate this refractiveness could have a transformational effect on therapy against viral infections.
Staffing and Antipsychotic Medication Use in Nursing Homes and Neighborhood Deprivation
Authors: Travers Jasmine L. , Hade Erinn M. , Friedman Steven , Raval Aasha , Hadson Kimberly , Falvey Jason R. 
Published: April 2024

ImportanceInappropriate use of antipsychotic medications in nursing homes is a growing public health concern. Residents exposed to higher levels of socioeconomic deprivation in the area around a nursing home may be currently exposed, or have a long history of exposure, to more noise pollution, higher crime rates, and have less opportunities to safely go outside the facility, which may contribute to psychological stress and increased risk of receiving antipsychotic medications inappropriately. However, it is unclear whether neighborhood deprivation is associated with use of inappropriate antipsychotic medications and whether this outcome is different by facility staffing levels.ObjectiveTo evaluate whether reported inappropriate antipsychotic medication use differs in severely and less severely deprived neighborhoods, and whether these differences are modified by higher levels of total nurse staffing.Design, Setting, and ParticipantsThis was a cross-sectional analysis of a national sample of nursing homes that linked across 3 national large-scale data sets for the year 2019. Analyses were conducted between April and June 2023.ExposureNeighborhood deprivation status (severe vs less severe) and total staffing hours (registered nurse, licensed practical nurse, certified nursing assistant).Main Outcome and MeasuresThis study estimated the association between neighborhood deprivation and the percentage of long-stay residents who received an antipsychotic medication inappropriately in the nursing home at least once in the past week and how this varied by nursing home staffing through generalized estimating equations. Analyses were conducted on the facility level and adjusted for state fixed effects.ResultsThis study included 10 966 nursing homes (1867 [17.0%] in severely deprived neighborhoods and 9099 [83.0%] in less deprived neighborhoods). Unadjusted inappropriate antipsychotic medication use was greater in nursing homes located in severely deprived neighborhoods (mean [SD], 15.9% [10.7%] of residents) than in those in less deprived neighborhoods (mean [SD], 14.2% [8.8%] of residents). In adjusted models, inappropriate antipsychotic medication use was higher in severely deprived neighborhoods vs less deprived neighborhoods (19.2% vs 17.1%; adjusted mean difference, 2.0 [95% CI, 0.35 to 3.71] percentage points) in nursing homes that fell below critical levels of staffing (less than 3 hours of nurse staffing per resident-day).Conclusions and RelevanceThese findings suggest that levels of staffing modify disparities seen in inappropriate antipsychotic medication use among nursing homes located in severely deprived neighborhoods compared with nursing homes in less deprived neighborhoods. These findings may have important implications for improving staffing in more severely deprived neighborhoods.
Health Perceptions, Multimorbidity, and New Fractures and Mortality Among Patients With a Fracture
Authors: Alarkawi Dunia , Tran Thach S. , Chen Weiwen , March Lyn M. , Blyth Fiona M. , Blank Robert D. , Bliuc Dana , Center Jacqueline R. 
Published: April 2024

ImportanceA high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored.ObjectiveTo examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture.Design, Setting, and ParticipantsThis prospective cohort study included participants from New South Wales, Australia, in the Sax Institute’s 45 and Up Study (n = 267 357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023.ExposuresCharlson Comorbidity Index (CCI) score and self-rated health (SRH).Main Outcomes and MeasuresThe main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males.ResultsOf 25 280 adults who sustained incident fractures, 16 191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher.Conclusions and RelevanceIn this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.
Incisional Wound Irrigation for the Prevention of Surgical Site Infection
Authors: Groenen Hannah , Bontekoning Nathan , Jalalzadeh Hasti , Buis Dennis R. , Dreissen Yasmine E. M. , Goosen Jon H. M. , Graveland Haitske , Griekspoor Mitchel , IJpma Frank F. A. , van der Laan Maarten J. , Schaad Roald R. , Segers Patrique , van der Zwet Wil C. , Orsini Ricardo G. , Eskes Anne M. , Wolfhagen Niels , de Jonge Stijn W. , Boermeester Marja A. 
Published: April 2024

ImportanceSurgical site infections (SSIs) are common postoperative complications and associated with significant morbidity, mortality, and costs. Prophylactic intraoperative incisional wound irrigation is used to reduce the risk of SSIs, and there is great variation in the type of irrigation solutions and their use.ObjectiveTo compare the outcomes of different types of incisional prophylactic intraoperative incisional wound irrigation for the prevention of SSIs in all types of surgery.Data SourcesPubMed, Embase, CENTRAL, and CINAHL databases were searched up to June 12, 2023.Study SelectionIncluded in this study were randomized clinical trials (RCTs) comparing incisional prophylactic intraoperative incisional wound irrigation with no irrigation or comparing irrigation using different types of solutions, with SSI as a reported outcome. Studies investigating intracavity lavage were excluded.Data Extraction and SynthesisThis systematic review and network meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two reviewers independently extracted the data and assessed the risk of bias within individual RCTs using the Cochrane Risk of Bias 2 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A frequentist network meta-analysis was conducted, and relative risks (RRs) with corresponding 95% CIs were reported.Main Outcome and MeasureThe primary study outcome was SSI.ResultsA total of 1587 articles were identified, of which 41 RCTs were included in the systematic review, with 17 188 patients reporting 1328 SSIs, resulting in an overall incidence of 7.7%. Compared with no irrigation, antiseptic solutions (RR, 0.60; 95% CI, 0.44-0.81; high level of certainty) and antibiotic solutions (RR, 0.46; 95% CI, 0.29-0.73; low level of certainty) were associated with a beneficial reduction in SSIs. Saline irrigation showed no statistically significant difference compared with no irrigation (RR, 0.83; 95% CI, 0.63-1.09; moderate level of certainty).Conclusions and RelevanceThis systematic review and network meta-analysis found high-certainty evidence that prophylactic intraoperative incisional wound irrigation with antiseptic solutions was associated with a reduction in SSIs. It is suggested that the use of antibiotic wound irrigation be avoided due to the inferior certainty of evidence for its outcome and global antimicrobial resistance concerns.
Compromise Design of Resonant Levels in GeTe‐Based Alloys with Enhanced Thermoelectric Performance
Authors: Liang Ruinian , Yan Gan , Geng Yang , Hu Lipeng , Liu Fusheng , Ao Weiqin , Zhang Chaohua 
Published: April 2024

AbstractResonant levels (RLs) are expected to increase the density of states (DOS) abruptly, thereby increasing the Seebeck coefficient for a high thermoelectric figure of merit (ZT). However, the negative effects of RLs on reducing the carrier mobility and band gap have rarely been explored. In this work, the pros and cons of resonant‐state doping of group IIIA elements (In, Ga) in GeTe‐based alloys are studied by experimental transport properties and density‐functional‐theory calculations. RLs effects of Fermi level pinning and increased effective mass are strong in Ge0.9‐xInxSb0.1Te but weak in Ge0.9‐y(In0.5Ga0.5)ySb0.1Te, which shows dependence on the hump DOS relative to the background, location of RLs, and energy width of RLs. Using the In‐Ga co‐doping strategy to make a compromise between the DOS, carrier mobility, and bipolar transport, combined with beneficial alloying effects of Pb and Sb, a peak ZT≈ 2.1 at 773 K and a high average ZT≈ 1.43 within 300–773 K can be obtained in Ge0.78In0.005Ga0.005Pb0.1Sb0.07Te. The corresponding single‐leg device shows a remarkable energy conversion efficiency of 13.7% at a temperature difference of 451 K. This work suggests that RLs are not always beneficial for improving ZT, and the compromise design of RLs should be carefully considered to advance ZT.
Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System
Authors: Micera Silvestro , Menciassi Arianna , Cianferotti Luisella , Gruppioni Emanuele , Lionetti Vincenzo 
Published: April 2024

AbstractImplantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re‐)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long‐term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed‐loop control algorithms to successfully realize this approach are highlighted. It is believed that these new “organ neuroprostheses” are going to become more and more valuable and very effective solutions in the years to come.
Teicoplanin‐Decorated Reduced Graphene Oxide Incorporated Silk Protein Hybrid Hydrogel for Accelerating Infectious Diabetic Wound Healing and Preventing Diabetic Foot Osteomyelitis
Authors: Bakadia Bianza Moise , Zheng Ruizhu , Qaed Ahmed Abeer Ahmed , Shi Zhijun , Babidi Bakamona Lyna , Sun Tun , Li Ying , Yang Guang 
Published: April 2024

AbstractDeveloping hybrid hydrogel dressings with anti‐inflammatory, antioxidant, angiogenetic, and antibiofilm activities with higher bone tissue penetrability to accelerate diabetic wound healing and prevent diabetic foot osteomyelitis (DFO) is highly desirable in managing diabetic wounds. Herein, the glycopeptide teicoplanin is used for the first time as a green reductant to chemically reduce graphene oxide (GO). The resulting teicoplanin‐decorated reduced graphene oxide (rGO) is incorporated into a mixture of silk proteins (SP) and crosslinked with genipin to yield a physicochemically crosslinked rGO‐SP hybrid hydrogel. This hybrid hydrogel exhibits high porosity, self‐healing, shear‐induced thinning, increased cell proliferation and migration, and mechanical properties suitable for tissue engineering. Moreover, the hybrid hydrogel eradicates bacterial biofilms with a high penetrability index in agar and hydroxyapatite disks covered with biofilms, mimicking bone tissue. In vivo, the hybrid hydrogel accelerates the healing of noninfected wounds in a diabetic rat and infected wounds in a diabetic mouse by upregulating anti‐inflammatory cytokines and downregulating matrix metalloproteinase‐9, promoting M2 macrophage polarization and angiogenesis. The implantation of hybrid hydrogel into the infected site of mouse tibia improves bone regeneration. Hence, the rGO‐SP hybrid hydrogel can be a promising wound dressing for treating infectious diabetic wounds, providing a further advantage in preventing DFO.
Membrane Fusion Liposomes Deliver Antifibrotic and Chemotherapeutic Drugs Sequentially to Enhance Tumor Treatment Efficacy by Reshaping Tumor Microenvironment
Authors: Jia Nan , Wang Qi , Li Wenpan , Chen Dawei , Hu Haiyang 
Published: April 2024

AbstractThe intricate tumor microenvironment in triple‐negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor‐associated fibroblasts (TAFs). Nanoparticle‐based therapies, especially “all‐in‐one” nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these “all‐in‐one” nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules. This study prepared cell membrane fusion liposomes (TAFsomes and CCMsomes) to load FDA‐approved antifibrotic drug pirfenidone (PFD/TAFsomes) and antitumor drug doxorubicin (DOX/CCMsomes). These liposomes can specifically target TAFs cells and tumor cells, and combined administration can effectively inhibit TAFs activity, reshape the tumor microenvironment (TME), and significantly enhance the tumor chemotherapy efficacy. Combined drug delivery defeats “all‐in‐one” liposomes (DOX/PFD/Liposomes, DOX/PFD/TAFsomes, and DOX/PFD/CCMsomes) by flexibly adjusting the drug delivery ratio. Moreover, an asynchronous delivery strategy that optimizes the administration schedule not only further improves the therapeutic effect, but also amplifies the effectiveness of α‐PD‐L1 immunotherapy by modulating the tumor immune microenvironment. This delivery strategy provides a personalized treatment approach with clinical translation potential, providing new ideas for enhancing the therapeutic effect against solid tumors such as TNBC.
Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice
Authors: Wu Chengling , Xie Jingyu , Yao Qingxin , Song Yilin , Yang Gucheng , Zhao Jie , Zhang Ruijia , Wang Ting , Jiang Xingyu , Cai Xinxia , Gao Yuan 
Published: April 2024

AbstractThe precise delivery of anti‐seizure medications (ASM) to epileptic loci remains the major challenge to treat epilepsy without causing adverse drug reactions. The unprovoked nature of epileptic seizures raises the additional need to release ASMs in a spatiotemporal controlled manner. Targeting the oxidative stress in epileptic lesions, here the reactive oxygen species (ROS) induced in situ supramolecular assemblies that synergized bioorthogonal reactions to deliver inhibitory neurotransmitter (GABA) on‐demand, are developed. Tetrazine‐bearing assembly precursors undergo oxidation and selectively self‐assemble under pathological conditions inside primary neurons and mice brains. Assemblies induce local accumulation of tetrazine in the hippocampus CA3 region, which allows the subsequent bioorthogonal release of inhibitory neurotransmitters. For induced acute seizures, the sustained release of GABA extends the suppression than the direct supply of GABA. In the model of permanent damage of CA3, bioorthogonal ligation on assemblies provides a reservoir of GABA that behaves prompt release upon 365 nm irradiation. Incorporated with the state‐of‐the‐art microelectrode arrays, it is elucidated that the bioorthogonal release of GABA shifts the neuron spike waveforms to suppress seizures at the single‐neuron precision. The strategy of in situ supramolecular assemblies‐directed bioorthogonal prodrug activation shall be promising for the effective delivery of ASMs to treat epilepsy.
Sensitized Triplet–Triplet Annihilation in Nanostructured Polymeric Scintillators Allows for Pulse Shape Discrimination
Authors: Hu Xueqian , Rigamonti Davide , Villa Irene , Pollice Luca , Mauri Michele , Molin Andrea Dal , Tardocchi Marco , Meinardi Francesco , Weder Christoph , Monguzzi Angelo 
Published: April 2024

AbstractScintillating materials emit light when exposed to ionizing radiation or particles and are used for the detection of nuclear threats, medical imaging, high‐energy physics, and other usages. For some of these applications, it is vital to distinguish neutrons and charged particles from γ‐rays. This is achievable by pulse shape discrimination (PSD), a time‐gated technique, which exploits that the scintillation kinetics can depend on the nature of the incident radiation. However, it proves difficult to realize efficient PSD with plastic scintillators, which have several advantages over liquid or crystalline scintillating materials, including mechanical robustness and shapeability. It is shown here that sensitive and rapid PSD is possible with nanostructured polymer scintillators that consist of a solid polymer matrix and liquid nanodomains in which an organic dye capable of triplet–triplet annihilation (TTA) is dissolved. The liquid nature of the nanodomains renders TTA highly efficient so that delayed fluorescence can occur at low energy density. The nanostructured polymer scintillators allow discriminating α particles, neutrons, and γ‐rays with a time response that is better than that of commercial scintillators. Exploiting that the liquid nanodomains can facilitate energy transfer processes otherwise difficult to realize in solid polymers, an auxiliary triplet sensitizer is incorporated. This approach further increases the scintillator's sensitivity toward α particles and neutrons and other high‐energy processes where localized interactions are involved.
Crack‐Resistant and Tissue‐Like Artificial Muscles with Low Temperature Activation and High Power Density
Authors: Jiang Zhen , Tran Bach H. , Jolfaei Maryam Adavoudi , Abbasi Burhan Bin Asghar , Spinks Geoffrey M. 
Published: April 2024

AbstractConstructing soft robotics with safe human–machine interactions requires low‐modulus, high‐power‐density artificial muscles that are sensitive to gentle stimuli. In addition, the ability to resist crack propagation during long‐term actuation cycles is essential for a long service life. Herein, a material design is proposed to combine all these desirable attributes in a single artificial muscle platform. The design involves the molecular engineering of a liquid crystalline network with crystallizable segments and an ethylene glycol flexible spacer. A high degree of crystallinity can be afforded by utilizing aza‐Michael chemistry to produce a low covalent crosslinking density, resulting in crack‐insensitivity with a high fracture energy of 33 720 J m−2 and a high fatigue threshold of 2250 J m−2. Such crack‐resistant artificial muscle with tissue‐matched modulus of 0.7 MPa can generate a high power density of 450 W kg−1 at a low temperature of 40 °C. Notably, because of the presence of crystalline domains in the actuated state, no crack propagation is observed after 500 heating–cooling actuation cycles under a static load of 220 kPa. This study points to a pathway for the creation of artificial muscles merging seemingly disparate, but desirable properties, broadening their application potential in smart devices.
All‐Round Passivation Strategy Yield Flexible Perovskite/CuInGaSe2 Tandem Solar Cells with Efficiency Exceeding 26.5%
Authors: Tang Liting , Zeng Li , Luo Jun , Wang Wuji , Xue Zhuo , Luo Zekai , Yan Hui , Gong Junbo , Wang Sheng , Li Jianmin , Xiao Xudong 
Published: April 2024

AbstractThe perovskite/Cu(InGa)Se2 (CIGS) tandem solar cells (TSCs) presents a compelling technological combination poised for the next generation of flexible and lightweight photovoltaic (PV) tandem devices, featuring a tunable bandgap, high power conversion efficiency (PCE), lightweight flexibility, and enhanced stability and durability. Over the years, the imperative to enhance the performance of wide bandgap (WBG) perovskite solar cells (PSCs) has grown significantly, particularly in the context of a flexible tandem device. In this study, an all‐round passivation strategy known as Dual Passivation at Grains and Interfaces (DPGI) is introduced for WBG PSCs in perovskite/CIGS tandem structures. The implementation of DPGI is tailored to improve film crystallinity and passivate defects across the solar cell structure, leading to a substantial performance enhancement for WBG PSCs. Subsequently, both rigid and flexible tandem devices are assembled. Impressively, a fully flexible 4T perovskite/CIGS TSCs is successfully fabricated with a PCE of 26.57%, making it the highest value in this field and highlighting its potential applications in the next generation of flexible lightweight PV tandem devices.