bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferrostatin-1 Ameliorates Liver Dysfunction via Reducing Iron in Thioacetamide-induced Acute Liver Injury in Mice
Authors: Jiang Hui , Zhang Xinyu , Yang Wanping , Li Meiqi , Wang Guohua , Luo Qianqian 
Published: April 2022

Background and Aims: Hepatic iron overload always leads to oxidative stress, which has been found to be involved in the progression of liver disease. However, whether iron disorder is involved in acute liver disease and the further molecular mechanisms remain unclear.Methods: A mice model of acute liver injury (ALI) was established via intraperitoneal injection of thioacetamide (TAA) (250 mg/kg/day) for 3 consecutive days. Ferrostatin-1 (Fer-1) was administered intraperitoneally (2.5 μM/kg/day) starting 3 days before TAA treatment. Deferoxamine (DFO) was intraperitoneally injected (200 mg/kg/day) with TAA treatment for 3 days. We further observed the effect of Fer-1 on TAA model with high-iron diet feeding. ALI was confirmed using histological examination and liver function activity. Moreover, expressions of iron metabolism and ferroptosis proteins were measured by Western blot analysis.Results: The study revealed that the iron accumulation and ferroptosis contributed to TAA-induced ALI pathogenesis. TAA induced prominent inflammation and vacuolar degeneration in the liver as well as liver dysfunction. In addition, protein expression of the cystine/glutamate antiporter SLC7A11 (xCT) and glutathione peroxidase 4 (GPX4) was significantly decreased in the liver, while transferrin receptor 1 (TfR1), ferroportin (Fpn) and light chain of ferritin (Ft-L) expression levels were increased after TAA exposure. As the same efficiency as DFO, pre-administration of Fer-1 significantly decreased TAA-induced alterations in the plasma ALT, AST and LDH levels compared with the TAA group. Moreover, both Fer-1 and DFO suppressed TfR1, Fpn and Ft-L protein expression and decreased iron accumulation, but did not affect xCT or GPX4 expression in the liver. Both Fer-1and DFO prevented hepatic ferroptosis by reducing the iron content in the liver. Furthermore, Fer-1 also reduced iron and reversed liver dysfunction under iron overload conditions.Conclusion: These findings indicate a role of TAA-induced iron accumulation and ferroptosis in the pathogenesis of ALI model. The effect of Fer-1 was consistent with that of DFO, which prevented hepatic ferroptosis by reducing the iron content in the liver. Thus, Fer-1 might be a useful reagent to reverse liver dysfunction and decreasing the iron content of the liver may be a potential therapeutic strategy for ALI.
Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity
Authors: Jiang Jin-Jin , Zhang Guo-Fu , Zheng Jia-Yi , Sun Ji-Hu , Ding Shi-Bin 
Published: April 2022

Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism.Methods: C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. In vitro, steatotic L-02 cells was used to study the potential mechanism.Results: We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the in vivo results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells.Conclusion: Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.
Sub-Analysis of CYP-GUIDES Data: Assessing the Prevalence and Impact of Drug-Gene Interactions in an Ethnically Diverse Cohort of Depressed Individuals
Authors: Crutchley Rustin D. , Keuler Nicole 
Published: April 2022

Introduction: Minority groups are underrepresented in pharmacogenomics (PGx) research. Recent sub-analysis of CYP-GUIDES showed reduced length of stay (LOS) in depressed patients with CYP2D6 sub-functional status. Our primary objective was to determine whether PGx guided (G) versus standard treatment (S) influenced LOS among different race/ethnic groups. Secondary objectives included prevalence of drug-gene interactions (DGIs) and readmission rates (RAR).Methods: Retrospective sub-analysis of CYP-GUIDES data comprising CYP2D6 phenotypes was reclassified using standardized CYP2D6 genotype to phenotype recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG). The Mann-Whitney test was used to determine differences in LOS between groups G and S and Kruskal Wallis test to compare LOS among different race/ethnic groups. Logistic regression was used to determine covariates associated with RAR.Results: This study included 1,459 patients with 67.3% in G group (n = 982). The majority of patients were White (57.5%), followed by Latinos (25.6%) and Blacks (12.3%). Although there were no differences in LOS between G and S groups, Latinos had significant shorter LOS than Whites (p = 0.002). LOS was significantly reduced by 5.6 days in poor metabolizers in group G compared to S (p = 0.002). The proportion of supra functional and ultra-rapid metabolizers (UMs) were 6 and 20.3% using CYP-GUIDES and CPIC/DPWG definitions, respectively. Prevalence of DGIs was 40% with significantly fewer DGIs in Blacks (p &lt; 0.001). Race/ethnicity was significantly associated with RAR (aOR 1.30; p = 0.003).Conclusion: A greater number of patients were classified as CYP2D6 UMs using CPIC/DPWG definitions as compared to CYP-GUIDES definitions. This finding may have clinical implications for using psychotropics metabolized by CYP2D6.
Chip-Scaled Ka-Band Photonic Linearly Chirped Microwave Waveform Generator
Authors: Brunetti Giuseppe , Armenise Mario N. , Ciminelli Caterina 
Published: April 2022

Synthetic aperture radar (SAR) systems employ a Linearly Chirped Microwave Waveform Generator (LCMWG) with large time–bandwidth product (TBWP), to provide a wide range resolution. Photonics has now been recognized as a disruptive approach to achieve high performance at bandwidth of few tens of gigahertz, with light and compact architectures, due to the typical photonics benefits, such as electromagnetic interference immunity, small power consumption, small footprint, and high immunity to vibration/shock and radiation. In this article, we report on the photonic generation of a high-frequency LCMW, with a large TBWP (102–103), using a chip-scaled architecture, based on a frequency-tunable optoelectronic oscillator (OEO) and a recirculating phase modulation loop (RPML). A new configuration of the OEO employing an ultrahigh Q-factor resonator has been conceived to allow the oscillator working in Ka band at 40 GHz or even more, with very low phase noise. Key building block of the RPML is a phase modulator driven by an engineered parabolic split waveform. The ultra-large pulse compression rate (PCR) &gt;&gt; 102, together with large signal purity, was also obtained, making the proposed architecture particularly suitable for SAR systems with large range resolution demand, such as Earth surveillance and monitoring.
Accurate Calculation of FFR Based on a Physics-Driven Fluid‐Structure Interaction Model
Authors: Xi Xiaolu , Liu Jincheng , Sun Hao , Xu Ke , Wang Xue , Zhang Liyuan , Du Tianming , Liu Jian , Li Bao 
Published: April 2022

Background: The conventional FFRct numerical calculation method uses a model with a multi-scale geometry based upon CFD, and rigid walls. Therefore, important interactions between the elastic vessel wall and blood flow are not routinely considered. Changes in the resistance of coronary microcirculation during hyperaemia are likewise not typically incorporated using a fluid–structure interaction (FSI) algorithm. It is likely that both have resulted in FFRct calculation errors.Objective: In this study we incorporated both the influence of vascular elasticity and coronary microcirculatory structure on FFR, to improve the accuracy of FFRct calculation. Thus, in this study, a physics-driven 3D–0D coupled model including fluid–structure interaction was established to calculate accurate FFRct values.Methods: Based upon a novel geometric multi-scale modeling technology, a FSI simulation approach was used. A lumped parameter model (0D) was used as the outlet boundary condition for the 3D FSI coronary artery model to incorporate physiological microcirculation, with bidirectional coupling between the two models.Results: The accuracy, sensitivity, specificity, and both positive and negative predictive values of FFRDC calculated based upon the coupled 3D–0D model were 86.7, 66.7, 84.6, 66.7, and 91.7%, respectively. Compared to the calculated value using the basic CFD model (MSE = 5.9%, accuracy rate = 80%), the FFRCFD calculated based on the coupled 3D–0D model has a smaller MSE of 1.9%.Conclusion: The physics-driven coupled 3D–0D model that incorporates fluid–structure interactions not only consider the influence of the elastic vessel wall on blood flow, but also provides reliable microvascular resistance boundary conditions for the 3D FSI model. This allows for a calculation that is based upon conditions that are closer to the physiological environment, and thus improves the accuracy of FFRct calculation. It is likely that more accurate information will provide an enhanced recommendation regarding percutaneous coronary intervention (PCI) in the clinic.
Return to Work and Work Productivity During the First Year After Cancer Treatment
Authors: So Serana Chun Yee , Ng Danielle Wing Lam , Liao Qiuyan , Fielding Richard , Soong Inda , Chan Karen Kar Loen , Lee Conrad , Ng Alice Wan Ying , Sze Wing Kin , Chan Wing Lok , Lee Victor Ho Fun , Lam Wendy Wing Tak 
Published: April 2022

ObjectivesWorking-age cancer patients face barriers to resuming work after treatment completion. Those resuming work contend with reduced productivity arising from persisting residual symptoms. Existing studies of return to work (RTW) after cancer diagnosis were done predominantly in Western countries. Given that employment and RTW in cancer survivors likely vary regionally due to healthcare provision and social security differences, we documented rates and correlates of RTW, work productivity, and activity impairment among Chinese cancer survivors in Hong Kong at one-year post-treatment.MethodsOf 1,106 cancer patients assessed at six-months post-cancer treatment (baseline), 593 previously worked; detailed work status, psychological distress (HADS), physical symptom distress (MSAS-SF), supportive care needs (SCNS-SF34-C), health-related quality of life (SF12), and illness perception (B-IPQ) were assessed. Six months later (follow-up), work productivity and activity impairment were assessed (WPAI; n = 402). Descriptive analyses examined RTW rate. Fully adjusted regressions determined RTW, work productivity, and activity impairment predictors.ResultsAt baseline, 39% (232/593) were working, 26% (153/593) on sick leave, and 35% (208/593) were unemployed. Compared to patients returning to work, unemployed participants were older, likely manual/service-oriented workers, and had lower family income, chemotherapy, fewer unmet health system and information needs, poorer physical functioning, and negative illness perceptions. Sick leave participants were likely service-oriented workers, who had head and neck cancer, chemotherapy, and poor physical functioning. At FU, baseline depressive symptoms, physical symptom distress, and negative illness perceptions predicted presenteeism and work productivity loss; gynecological cancer, fewer unmet health system and information needs, and greater unmet sexuality needs predicted absenteeism; physical symptom distress, negative illness perception, and poor physical functioning predicted activity impairment.ConclusionCancer survivors who had more physically demanding jobs and poorer physical functioning delayed RTW. Unmanaged physical symptom and psychological distress hindered work productivity.
Defining the Exposome Using Popular Education and Concept Mapping With Communities in Atlanta, Georgia
Authors: Lebow-Skelley Erin , Young Lynne , Noibi Yomi , Blaginin Karla , Hooker Margaret , Williamson Dana , Tomlinson Martha Scott , Kegler Michelle C. , Pearson Melanie A. 
Published: April 2022

IntroductionThe exposome concept provides a framework to better incorporate the environment into the study of health and disease and has been defined by academics to encompass all lifetime exposures including toxicants, diet, and lifestyle choices. However, initial applications of the exposome concept have been less apt at measuring social determinants of health, focusing primarily on conventional environmental exposures and lifestyle choices that do not reflect the complex lived experience of many communities. To bring community voice into the exposome concept, the HERCULES Exposome Research Center and its Stakeholder Advisory Board co-developed the Exposome Roadshow. We present and discuss the resulting community-exposome definition to inform and improve exposome research.Materials and MethodsFour communities from distinct areas across metro-Atlanta participated in separate 2-day Exposome Roadshow workshops with concept mapping. Aligned with a popular education approach in which community knowledge is used to work collectively for change, concept mapping provided a systematic method to collect and visualize community members' knowledge and create a shared understanding to take action. Community members brainstormed, sorted, and rated their responses to the prompt: “What in your environment is affecting your and your community's health?” Responses were analyzed and visually depicted by concept maps consisting of separate but interrelated clusters of ideas. Community members discussed and validated the maps, selecting a final map illustrating their community's exposome.ResultsA total of 118 community members completed concept mapping. On average communities identified 7 clusters to define their exposome. The resulting concept maps offer a community definition of the exposome. Five major themes arose across all four communities: conventional environmental concerns, built environment, social relationships, crime and safety, and individual health and behaviors.DiscussionThe resulting community-exposome definition demonstrates the importance of expanding the scope of exposures beyond traditional environmental influences to include the lived experience of individuals and communities. While newer exposome definitions align more closely with this community definition, traditional exposome methods do not routinely include these factors. To truly capture the totality of lifetime exposures and improve human health, researchers should incorporate community perspectives into exposome research.
Specialized Biopsychosocial Care in Inpatient Somatic Medicine Units—A Pilot Study
Authors: Köbler Paul , Krauss-Köstler Eva K. , Stein Barbara , Ficker Joachim H. , Wilhelm Martin , Dechêne Alexander , Waller Christiane 
Published: April 2022

IntroductionSpecialized biopsychosocial care concepts are necessary to overcome the dualism between physical and psychosocial treatment in acute care hospitals. For patients with complex and chronic comorbid physical and mental health problems, neither standardized psychiatric/psychosomatic nor somatic care units alone are appropriate to their needs. The “Nuremberg Integrated Psychosomatic Acute Unit” (NIPA) has been developed to integrate treatment of both, psychosocial and physical impairments, in an acute somatic care setting.MethodNIPA has been established in inpatient internal medical wards for respiratory medicine, oncology and gastroenterology. One to two patients per ward are regularly enrolled in the NIPA treatment while remaining in the same inpatient bed after completion of the somatic care. In a naturalistic study design, we evaluated treatment effects by assessment of symptom load at admission and at discharge using the Patient Health Questionnaire (PHQ) and the Generalized Anxiety Disorder Scale-7 (GAD-7). Furthermore, we assessed the severity of morbidity using diagnosis data during treatment. At discharge, we measured satisfaction with treatment through the Patient Satisfaction Questionnaire (ZUF-8).ResultsData from 41 NIPA patients were analyzed (18–87 years, 76% female). Seventy-eight percent suffered from at least moderate depression and 49% from anxiety disorders. Other diagnoses were somatoform pain disorder, somatoform autonomic dysfunction, eating disorder and posttraumatic stress disorder. Hypertension, chronic lung diseases and musculoskeletal disorders as well as chronic oncological and cardiac diseases were the most common somatic comorbidities. Treatment resulted in a significant reduction of depressive mood (admission: M = 10.9, SD = 6.1, discharge: M = 7.6, SD = 5.3, d = 0.58, p = 0.001), anxiety (admission: M = 10.6, SD = 4.9, discharge: M = 7.3, SD = 4.1, d = 0.65, p&lt; 0.001) and stress (admission: M = 6.0, SD = 3.6, discharge: M = 4.1, SD = 2.5, d = 0.70, p&lt; 0.001). Somatic symptom burden was reduced by NIPA treatment (admission: M = 10.9, SD = 5.8, discharge: M = 9.6, SD = 5.5, d = 0.30), albeit not statistically significant (p = 0.073) ZUF-8 revealed that 89% reported large or full satisfaction and 11% partial dissatisfaction with treatment.DiscussionNIPA acute care is bridging the gap for patients in need of psychosocial treatment with complex somatic comorbidity. Further long-term evaluation will show whether psychosocial NIPA care is able to reduce the course of physical illness and hospital costs by preventing hospitalization and short-term inpatient re-admissions.
Evaluating the Price, Availability, and Affordability of Essential Medicines in Primary Healthcare Institutions: A Mixed Longitudinal and Cross-Sectional Study in Jiangsu, China
Authors: Wang Xiao , He Xuan , Ren Yuqin , Zhang Zhuolin , Cai Lele , Cao Zhaoliu , Li Xin 
Published: April 2022

ObjectiveThis study aimed to evaluate the price, availability, and affordability of essential medicines in primary healthcare institutions in Jiangsu Province.MethodsA mixed longitudinal and cross-sectional survey was conducted in primary healthcare institutions in Jiangsu based on the adjusted World Health Organization and Health Action International methodology. 45 essential medicines were collected from 30 primary healthcare institutions in Nanjing from 2016 to 2020. We also collected information on these medicines in 70 primary healthcare institutions across seven cities of Jiangsu in 2021. The availability, price, and affordability were compared with matched sets. Differences of availability between years and cities were further compared using Wilcoxon rank-sum test.ResultsIn Nanjing, the variation was significant of availability during the study period. The MPR was generally decreasing between 2016 and 2020, with the median price ratio (MPR) for lowest-priced generics (LPGs) ranging from 1.20 to 2.53 and originator brands (OBs) substantially above international levels. The median availability of generic medicines increased in 2018 and subsequently stabilized at around 55%, and the availability of originator medicines was low. There were no significant regional differences in prices across the sampled cities in Jiangsu, and the median MPR for LPGs was acceptable (1.23), while the median MPR for OBs was 8.54. The mean availability was different across regions (p &lt; 0.001), being higher in Nanjing (54.67%) and Nantong (56.22%), and lower in northern Jiangsu (about 35%). For LPGs, there was little difference in the proportion of medicines with low availability and high affordability (50.00% for urban residents and 40.48% for rural residents). For OBs, there were more than half of rural residents had low availability and low affordability of medicines (58.82%).ConclusionsIn terms of yearly changes, the prices of essential medicines have considerably decreased, and the availability of LPGs has slightly increased. However, the availability of medicines was found to be poor and there were regional differences in the availability and affordability of medicines among metropolitan and rural areas. Policy interventions targeting external factors associated with health resource allocation are essential and possible strategies include effective and efficient government investment mechanisms on primary healthcare.
The NASA EPIC/DSCOVR Ocean PAR Product
Authors: Frouin Robert , Tan Jing , Compiègne Mathieu , Ramon Didier , Sutton Marshall , Murakami Hiroshi , Antoine David , Send Uwe , Sevadjian Jeff , Vellucci Vincenzo 
Published: April 2022

The EPIC/DSCOVR observations of the Earth’s surface lit by the Sun made from the first Lagrange point several times during the day in spectral bands centered on 443, 551, and 680 nm are used to estimate daily mean photosynthetically available radiation (PAR) at the ice-free ocean surface. The PAR algorithm uses a budget approach, in which the solar irradiance reaching the surface is obtained by subtracting from the irradiance arriving at the top of the atmosphere (known), the irradiance reflected to space (estimated from the EPIC Level 1b radiance data), taking account of atmospheric transmission and surface albedo (modeled). Clear and cloudy regions within a pixel do not need to be distinguished, which dismisses the need for often-arbitrary assumptions about cloudiness distribution within a pixel and is therefore adapted to the relatively large EPIC pixels. A daily mean PAR is estimated on the source grid for each EPIC instantaneous daytime observation, assuming no cloudiness changes during the day, and the individual estimates are remapped and weight-averaged using the cosine of the Sun zenith angle. In the computations, wind speed, surface pressure, and water vapor amount are extracted from NCEP Reanalysis 2 data, aerosol optical thickness and Angström coefficient from MERRA-2 data, and ozone amount from EPIC Level 2 data. Areas contaminated by Sun glint are excluded using a threshold on Sun glint reflectance calculated using wind data. Ice masking is based on NSIDC near-real-time ice fraction data. The product is evaluated against in situ measurements at various locations and compared with estimates from sensors in polar and geostationary orbits (MODIS, AHI). Unlike with MODIS, the EPIC PAR product does not exhibit gaps at low and middle latitudes. Accuracy is satisfactory for long-term studies of aquatic photosynthesis, especially given the much larger uncertainties on the fraction of PAR absorbed by live algae and the quantum yield of carbon fixation. The EPIC daily mean PAR product is generated operationally on a Plate Carrée (equal-angle) grid with 18.4 km resolution at the equator and on an 18.4 km equal-area grid, i.e., it is fully compatible with the NASA Greenbelt OBPG ocean-color products. Data are available since the beginning of the DSCOVR mission (i.e., June 2015) from the NASA Langley ASDC website.