bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor
Authors: Rotbain Curovic Viktor , Houlind Morten B. , Hansen Tine W. , Eugen-Olsen Jesper , Laursen Jens Christian , Eickhoff Mie K. , Persson Frederik , Rossing Peter 
Published: April 2022

Background: Elevated soluble urokinase plasminogen activator receptor (suPAR) is highly associated with increased risk of diabetic complications. Dapagliflozin is a drug inhibiting the sodium-glucose co-transporter 2 in the kidney to decrease blood glucose, while also decreasing risk of kidney disease, heart failure, and death. Therefore, we have investigated suPAR as a monitor for treatment effect with dapagliflozin in diabetes.Methods: suPAR was measured in two double-blinded randomized clinical cross-over trials. The first trial investigated the effect of a single dose dapagliflozin 50 mg or placebo 12 h after intake, in individuals with type 1 diabetes and albuminuria. The second trial investigated the effect of a daily dose dapagliflozin 10 mg or placebo for 12 weeks, in individuals with type 2 diabetes and albuminuria. suPAR was measured in serum samples taken, in the acute trial, after treatment with dapagliflozin and placebo, and in the long-term trial, before and after treatment with dapagliflozin and placebo. Effect of dapagliflozin on suPAR levels were assessed using paired t-test.Results: 15 participants completed the acute trial and 35 completed the long-term trial. Mean difference in suPAR between dapagliflozin and placebo in the acute trial after 12 h was 0.70 ng/ml (95% CI: 0.66; 1.33, p = 0.49). In the long-term trial the mean difference was 0.06 ng/ml (95% CI -0.15; 0.27, p = 0.57).Conclusion: Based on our findings we conclude that suPAR is not a feasible marker to monitor the effect of treatment with dapagliflozin. Thus, a further search of suitable markers must continue.
Sodium Tanshinone IIA Sulfonate as a Potent IDO1/TDO2 Dual Inhibitor Enhances Anti-PD1 Therapy for Colorectal Cancer in Mice
Authors: Zhang Rongjie , Wang Yuanfeiyi , Liu Dan , Luo Qing , Du Peixin , Zhang Haiyan , Wu Wenshuang 
Published: April 2022

Although the antitumor efficacy of immune checkpoint blockade (ICB) has been proved in colorectal cancer (CRC), the results are unsatisfactory, presumably owing to the presence of tryptophan metabolism enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2). However, only a few dual inhibitors for IDO1 and TDO2 have been reported. Here, we discovered that sodium tanshinone IIA sulfonate (STS), a sulfonate derived from tanshinone IIA (TSN), reduced the enzymatic activities of IDO1 and TDO2 with a half inhibitory concentration (IC50) of less than 10 μM using enzymatic assays for natural product screening. In IDO1- or TDO2- overexpressing cell lines, STS decreased kynurenine (kyn) synthesis. STS also reduced the percentage of forkhead box P3 (FOXP3) T cells in lymphocytes from the mouse spleen cocultured with CT26. In vivo, STS suppressed tumor growth and enhanced the antitumor effect of the programmed cell death 1 (PD1) antibody. Compared with anti-PD1 (α-PD1) monotherapy, combined with STS had lower level of plasma kynurenine. Immunofluorescence assay suggested that STS decreased the number of FOXP3+ T cells and increased the number of CD8+ T cells in tumors. Flow cytometry analysis of immune cells in tumor tissues demonstrated an increase in the percentage of tumor-infiltrating CD8+ T cells. According to our findings, STS acts as an immunotherapy agent in CRC by inhibiting both IDO1 and TDO2.
Effect of Baicalein on the Pharmacokinetics of Cilostazol and Its Two Metabolites in Rat Plasma Using UPLC-MS/MS Method
Authors: Weng Qinghua , Chen Chaojie , Xiong Jianhua , Liu Ya-Nan , Pan Xinxin , Cui Ju , Cai Jian-Ping , Xu Ren-Ai 
Published: April 2022

This study aimed to explore the effect of baicalein on the pharmacokinetics of cilostazol (CLZ) and its two metabolites 3,4-dehydro cilostazol (3,4-CLZ) and 4′-trans-hydroxy cilostazol (4′-CLZ) in rats using a newly established ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Ticagrelor was used as an internal standard (IS), then cilostazol and its two metabolites were separated by means of a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using gradient elution method with 0.4 ml/min of flow rate. Acetonitrile as organic phase and water with 0.1% formic acid as aqueous phase constructed the mobile phase. Selective reaction monitoring (SRM) mode and positive ion mode were preferentially chosen to detect the analytes. Twelve SD rats were divided into two groups (n = 6) when CLZ was administered orally (10 mg/kg) with or without oral baicalein (80 mg/kg). The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied with the standards of United States Food and Drug Administration guidelines. In control group, AUC0-∞ and Cmax of CLZ were 2,169.5 ± 363.1 ng/ml*h and 258.9 ± 82.6 ng/ml, respectively. The corresponding results were 3,767.6 ± 1,049.8 ng/ml*h and 308.6 ± 87.9 ng/ml for 3, 4-CLZ, 728.8 ± 189.9 ng/ml*h and 100.3 ± 51.3 ng/ml for 4′-CLZ, respectively. After combination with baicalein, AUC0-∞ and Cmax of CLZ were 1.48, 1.38 times higher than the controls. Additionally, AUC0-∞ and Cmax were separately decreased by 36.12 and 19.54% for 3,4-CLZ, 13.11 and 44.37% for 4′-CLZ. Baicalein obviously alters the pharmacokinetic parameters of CLZ, 3,4-CLZ and 4′-CLZ in rats. These results suggested that there was a potential drug-drug interaction between baicalein and CLZ. Therefore, it must raise the awareness when concomitant use of CLZ with baicalein, the dosage regimen of CLZ should be taken into consideration, if this result is confirmed in clinical studies.
Highly Efficient Metasurface Polarization Converter at Far-Infrared Range
Authors: Tamim Ahmed Mahfuz , Hasan Md Mehedi , Faruque Mohammad Rashed Iqbal 
Published: April 2022

Controlling the polarization state is an efficient way to enhance the functionalities in sensing, imaging, and communication systems in the microwave and terahertz (THz) spectrum. This study proposed an anisotropic metasurface and numerically explained it as a highly efficient polarization conversion using far-infrared frequency. Structural design, optimization, and results examination of the metasurface are performed using the CST microwave studio electromagnetic simulator. The metasurface was developed surrounding the two individual arrow-shaped metal resonators with two bar resonators on the opposite angular side of the arrow. Aluminum (Al) was used as a metallic resonator, while gallium arsenide (GaAs) was as the substrate. The interference theory was used to describe the co-polarized and cross-polarized reflectance coefficients, where two different mediums and interference layers were considered along with the reflected and transmitted wave. The polarization conversion efficiency yielded over 90% from 282.9 to 302.3 µm (0.987–1.062 THz) and 558.78 to 676.7 µm (0.442–0.537 THz) indicating multiple resonances at 286.7, 298.25, 586.1, and 689.55 µm. In conclusion, the performances and diverse characteristics of the designed metasurface demonstrated potential applications in the far-infrared spectrum as an efficient polarization converter application.
The Clinical Efficacy of Personalized Embryo Transfer Guided by the Endometrial Receptivity Array/Analysis on IVF/ICSI Outcomes: A Systematic Review and Meta-Analysis
Authors: Liu Zhenteng , Liu Xuemei , Wang Meimei , Zhao Huishan , He Shunzhi , Lai Shoucui , Qu Qinglan , Wang Xinrong , Zhao Dongmei , Bao Hongchu 
Published: April 2022

Objective: To assess the prevalence of displaced window of implantation (WOI) in infertile women, and the clinical utility of personalized embryo transfer (pET) guided by the endometrial receptivity array/analysis (ERA) on IVF/ICSI outcomes.Methods: The protocol was registered at Prospero: CRD42020204237. We systematically searched all published English literature related to the prevalence of WOI displacement and ongoing pregnancy rate/live birth rate in the overall good-prognosis infertile patients (GPP) and/or repeated implantation failure (RIF) patients undergoing IVF/ICSI-ET cycles after ERA test until August 2021.Result(s): 11 published studies were enrolled in the final analysis. The estimate of the incidence of WOI displacement based on ERA was 38% (95%CI 19–57%) in GPP and 34% (95%CI 24–43%) in RIF, respectively. There was no difference in OPR/LBR between patients undergoing routine ET without ERA test and those who following pET with ERA (39.5 vs. 53.7%, OR 1.28, p = 0.49, 95%CI 0.92–1.77, I2 = 0%) in relative GPP. Notably, the meta-analysis revealed that OPR/LBR of patients with RIF undergoing pET who had non-receptive ERA increased to the level of to those undergoing sET with receptive ERA (40.7 vs.49.6%, OR 0.94, p = 0.85, 95%CI 0.70–1.26, I2 = 0%).Conclusion: Considering the approximately one third of infertile women could suffered from displaced WOI, the ERA test emerged as a promising tool. Although the present meta-analysis demonstrates that patients with general good-prognosis may not benefit from ERA, pET guided by ERA significantly increases the chances of pregnancy for non-receptive patients with RIF of endometrial origin.
The Relationship Between Negative Life Events and Internet Addiction Disorder Among Adolescents and College Students in China: A Systematic Review and Meta-Analysis
Authors: Wang Jun , Hao Qing-hong , Tu Yang , Wang Yang , Peng Wei , Li Hui , Zhu Tian-min 
Published: April 2022

ObjectiveInternet Addiction Disorder (IAD) has become a social problem. Literature suggests that negative life events can cause numerous problematic behaviors and part of them will result in IAD. However, there is a lack of evidence that elucidates the association between negative life events and IAD. Thereby, we performed a comprehensive analysis to further document the relationship between negative life events and IAD among adolescents and college students in China.MethodsWe searched ten electronic databases for relevant articles. We extracted correlation coefficient (r) values from each study and calculated 95% confidence interval (95% CI) after applying Fisher’s z. A random-effect or fixed-effect model was applied to analyze the data. Heterogeneity was examined using I2 statistics and the Cochran’s Q statistics.ResultsA total of 31 studies were involved in this meta-analysis. Positive correlation was observed between negative life events and IAD. The subtype interpersonal relationship of negative life events was closely associationed with IAD.ConclusionThere were significant positive association between negative life events and IAD. The findings can be used to guide IAD interventions.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/#recordDetails].
Prevention of Unhealthy Weight, Disordered Eating, and Poor Body Image in Children. Perspectives From Norwegian Parents and Healthcare Professionals
Authors: Fiskum Charlotte , Riiber Åshild , Eik-Nes Trine Tetlie 
Published: April 2022

BackgroundChildhood obesity (ChO) and eating disorders are on the rise, with concerning effects on health. Early prevention is essential as interventions after problems arise are costly and with a low success rate. In Norway, prevention of ChO has been largely weight-centered, without desired effects. Confident Body, Confident Child (CBCC) is a universal program aimed at preventing ChO, disturbed eating, and body image problems through a health-centered intervention for parents of children between 2 and 6 years. The current study is part of a cultural adaptation and translation of CBCC into Norwegian.MethodsFocus groups with parents (n = 16) and professionals (n = 11) were held around healthy eating, activity, and body image, with an emphasis on possible barriers for prevention as well as approaches considered helpful. The interviews were analyzed using interpretative phenomenological analysis.ResultsParents and professionals described parental stress connected to high standards, conflicting information, and parental comparison. A narrowing sense of normality around healthy living was described with little flexibility resulting in “all-or-nothing” thinking. Parents were anxious to say or do the wrong thing when regulating children's food intake and when faced with comments about appearance. Parents and professionals described parental concern around children not eating enough, and professionals described an increase in parents using food as regulation. Both parents and professionals expressed that having a child with overweight was tied to a sense of failure and shame. Interventions related to overweight seemed to increase stress and shame, further complicating follow-up. As an alternative, parents and professionals expressed a desire for interventions with normalizing information around “good-enough” parenting related to food and weight.DiscussionThe described fear of doing something wrong and lack of flexibility is interpreted within a stress-sensitive understanding, where stress and shame can influence parents toward mobilizing action or disengagement, presenting as dichotomous behaviors of “all-or-nothing”.ConclusionInterventions that can normalize parental concerns in a non-moralizing way may reduce stress and shame. CBCC addresses all the major concerns raised in this study, providing parents with evidence-based information they can implement into everyday life. The Norwegian cultural adaptation added extra emphasis on normalization and shame-reduction.
Mapping the Research on Health Policy and Services in the Last Decade (2009–2018): A Bibliometric Analysis
Authors: Zhao Linyan , Zhao Yang , Du Jian , Desloge Allissa , Hu Zhiyong , Cao Gaofang 
Published: April 2022

BackgroundHealth policy and services is a continuously evolving field of research that can inform prevention and control efforts for a variety of health conditions. The “Healthy China” strategy reflects the demand to formulate health policy that suits China's national needs and goals. Applying bibliometric analysis to grasp the general situation of health policy and services research globally will be conducive to informing China's designated health plans and initiatives.MethodA bibliometric analysis of 58,065 articles on “Health Policy and Services” topics was conducted. The document type was restricted to journal articles that were published in the Web of Science database between the time parameter of January 1, 2009 to December 31, 2018. Data was collected on indicators such as the annual number of publications in the field of health policy and services, the country where the publication is issued, the publication organization, the source journal, the frequency of citations, research hotspots, and academic areas.ResultsThe overall number of articles published in Web of Science on health policy and services research has increased over time. The United States has the largest number of articles in the field. The institution with the highest number of citations in the field is Harvard University and the journal with the most published articles in the field is Health Affairs. Research hotspots in the health policy and services field include topics such as “HIV Infections,” “Primary Health Care,” “Delivery of Health Care,” and “Health Services Accessibility.”ConclusionExperts in the field of health policy and services globally are dedicated to researching the most effective ways to improve people's health and living standards. There is a certain gap in the depth of health policy and services research between China and developed countries and regions such as Europe or America. China must learn from foreign experience to conduct meaningful and informative research that can aid in the formulation of multi-dimensional health policies in specific areas such as environmental infectious diseases, where attention is needed in areas beyond the medical and health system.
Examining the Impacts of the Coronavirus Pandemic and Social Distancing on the Health of People With Mobility Disabilities
Authors: Goddard Kelsey Shinnick , Schulz Jonathan , Nzuki Isaac , Hall Jean P. 
Published: April 2022

ObjectiveTo understand the effects of the coronavirus pandemic on the health and participation of people with mobility disabilities living in the community.MethodsParticipants responded to a survey designed to assess the effects of the coronavirus pandemic on their health and access to health care. Participants identified if various life situations were worsened, unchanged, or improved during the pandemic. Participants could provide further information on their improved or worsened lived experience in open-ended questions.ResultsA total of 39 people with mobility disabilities responded to the survey. Results indicate that many experienced a worsening of life situations related to health, including access to medications, health care services, and transportation.ConclusionsResults show that many experiences were caused by the lack of appropriate policies, rather than the pandemic itself. Therefore, there is a need to modify pandemic preparedness plans and other policies to meet the needs of people with disabilities.
Aging Leads to Increased Monocytes and Macrophages With Altered CSF-1 Receptor Expression and Earlier Tumor-Associated Macrophage Expansion in Murine Mesothelioma
Authors: Duong Lelinh , Pixley Fiona J. , Nelson Delia J. , Jackaman Connie 
Published: April 2022

Increased cancer incidence occurs with the emergence of immunosenescence, highlighting the indispensability of the immune system in preventing cancer and its dysregulation with aging. Tumor-associated macrophages (TAMs) are often present in high numbers and are associated with poor clinical outcomes in solid cancers, including mesothelioma. Monocytes and macrophages from the bone marrow and spleen can respond to tumor-derived factors, such as CSF-1, and initiation of the CSF-1R signaling cascade results in their proliferation, differentiation, and migration to the tumor. Age-related changes occur in monocytes and macrophages in terms of numbers and function, which in turn can impact tumor initiation and progression. Whether this is due to changes in CSF-1R expression with aging is currently unknown and was investigated in this study. We examined monocytes and macrophages in the bone marrow and spleen during healthy aging in young (3–4 months) and elderly (20–24 months) female C57BL/6J mice. Additionally, changes to these tissues and in TAMs were examined during AE17 mesothelioma tumor growth. Healthy aging resulted in an expansion of Ly6Chigh monocytes and macrophages in the bone marrow and spleen. CSF-1R expression levels were reduced in elderly splenic macrophages only, suggesting differences in CSF-1R signaling between both cell type and tissue site. In tumor-bearing mice, Ly6Chigh monocytes increased with tumor growth in the spleen in the elderly and increased intracellular CSF-1R expression occurred in bone marrow Ly6Chigh monocytes in elderly mice bearing large tumors. Age-related changes to bone marrow and splenic Ly6Chigh monocytes were reflected in the tumor, where we observed increased Ly6Chigh TAMs earlier and expansion of Ly6Clow TAMs later during AE17 tumor growth in the elderly compared to young mice. F4/80high TAMs increased with tumor growth in both young and elderly mice and were the largest subset of TAMs in the tumor. Together, this suggests there may be a faster transition of Ly6Chigh towards F4/80high TAMs with aging. Amongst TAM subsets, expression of CSF-1R was lowest in F4/80high TAMs, however Ly6Clow TAMs had higher intracellular CSF-1R expression. This suggests downstream CSF-1R signaling may vary between macrophage subsets, which can have implications towards CSF-1R blockade therapies targeting macrophages in cancer.
Smart Self-Coherent Optical Communication for Short Distances
Authors: Nadimi Goki Pantea , Imran Muhammad , Cavaliere Fabio , Potì Luca 
Published: April 2022

We proposed and investigated a high-performance, energy-efficient, and low-cost self-homodyne coherent detection transmission (SHCDT) system for the 5G access network segment assuring high capacity and light digital signal processing (DSP) at the same time, avoiding the local oscillator for detection. The system implementation is based on a code-based spectral shaping at the transmitter and carrier extractor at the receiver. In the self-homodyne coherent system, a continuous wave carrier is transmitted together with the modulated signal. After transmission, at the receiver, the carrier is extracted and used as a local oscillator (LO) to prevent frequency offset with respect to the transmitted signal and phase noise, resulting in a decrease in the digital signal processing (DSP) complexity. Transmission results indicate that even a low portion of the residual local oscillator (LO) on the transmitted signal at the receiver side can lead to an increase in the signal-to-noise ratio (OSNR) penalty. Consequently, applying a proper technique to separate the unmodulated carrier and the modulated signal is the key to the system’s performance. We evaluated the self-homodyne coherent system performance through numerical analysis and experimental validation. The performance of the proposed self-coherent system, using a narrow bandwidth Fabry–Perot filter for optical carrier extraction, is evaluated experimentally on a 28 Gbaud dual-polarization 16QAM transmission system considering different code block lengths for signal spectral shaping through bit-error-rate (BER) measurements.
Photovoltaics-Driven Power Production Can Support Human Exploration on Mars
Authors: Abel Anthony J. , Berliner Aaron J. , Mirkovic Mia , Collins William D. , Arkin Adam P. , Clark Douglas S. 
Published: April 2022

A central question surrounding possible human exploration of Mars is whether crewed missions can be supported by available technologies using in situ resources. Here, we show that photovoltaics-based power systems would be adequate and practical to sustain a crewed outpost for an extended period over a large fraction of the planet’s surface. Climate data were integrated into a radiative transfer model to predict spectrally-resolved solar flux across the Martian surface. This informed detailed balance calculations for solar cell devices that identified optimal bandgap combinations for maximizing production capacity over a Martian year. We then quantified power systems, manufacturing, and agricultural demands for a six-person mission, which revealed that photovoltaics-based power generation would require <10 t of carry-along mass, outperforming alternatives over ∼50% of Mars’ surface.