bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Shenfu Injection for Severe Pneumonia in the Elderly: A Systematic Review and Meta-Analysis Based on Western and Eastern Medicine
Authors: Shi Shihua , Wang Fei , Chen Bonan , Pan Jie , Luo Dan , Pei Caixia , Huang Demei , Wang Xiaomin , Wang Yilan , Shen Zherui , Li Weihao , Wu Yongcan , He Yacong , Wang Zhenxing 
Published: August 2022

Background: Although increasing clinical trials studying Shenfu injection (SFI) comprising panaxoside 0.8 mg/ml extracted from Panax ginseng C.A. Mey. and aconitine 0.1 mg/ml extracted from Aconitum carmichaeli Debeaux for elderly patients with severe pneumonia on biomarkers associated with COVID-19 progression are emerging, there is no evidence-based evaluation for the effect of SFI on elderly severe pneumonia.Objectives: To evaluate the effect of SFI on elderly patients with severe pneumonia providing hints for treating critical COVID-19, we conducted a systematic review and meta-analysis.Methods: Nine databases, namely, PubMed, EMBASE, Web of Science, Science Direct, Google Scholar, Wanfang, Chongqing VIP Database, CNKI, and SinoMed were used to search clinical trials reporting the effect of SFI as an adjuvant for elderly severe pneumonia on outcomes of interest. Primary outcomes were total effective rate, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mortality, and safety. Secondary outcomes were predictors associated with COVID-19 progression. Duplicated or irrelevant articles with unavailable data were excluded. Cochrane Collaboration’s tool was used to evaluate the risk of bias by two reviewers independently. All data were analyzed by Rev Man 5.4. Continuous variables were shown as weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence intervals (95% CI), whereas dichotomous data were calculated as the risk ratio (RR) with 95% CI.Results: We included 20 studies with 1, 909 participants, and the pooled data showed that compared with standard control, SFI could improve the total effective rate (RR = 1.25, 95% CI = 1.14–1.37, and n = 689), APACHE II score (WMD = −2.95, 95% CI = −3.35, −2.56, and n = 809), and predictors associated with COVID-19 progression (brain natriuretic peptide, creatine kinase, stroke volume, cardiac output, left ventricular ejection fraction, cardiac index, sE-selectin, von Willebrand factor, activated partial thromboplastin time, platelet counts, D-Dimer, procalcitonin, and WBC count). SFI may reduce mortality (RR = 0.52, 95% CI = 0.37–0.73, and n = 429) and safety concerns (RR = 0.29, 95% CI = 0.17–0.51, and n = 150) for elderly severe pneumonia.Conclusion: SFI as an adjuvant may improve the total effective rate, APACHE II score, gas exchange, and predictors associated with COVID-19 progression, reducing mortality and safety concerns for elderly patients with severe pneumonia.
Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
Authors: Cao Peng , Guo Wei , Wang Jun , Wu Sanlan , Huang Yifei , Wang Yang , Liu Yani , Zhang Yu 
Published: August 2022

The purposes of this study were to identify physiological and genetic factors that contributed to variability of pemetrexed (PEM) exposure and to optimize the dosing regimens for Chinese non-small cell lung carcinoma patients. A prospective population pharmacokinetics (PPK) research was performed in this population. The PEM concentrations of 192 plasma samples from 116 in-hospital patients were detected. All patients were genotyped for polymorphisms. The PPK model of PEM was developed. The pharmacokinetic behavior of PEM was described by a two-compartment model with first-order elimination. The population typical values were as follows: clearance (CL) 8.29 L/h, intercompartmental clearance (Q) 0.10 L/h, central volume of distribution (V1) 18.94 L and peripheral volume of distribution (V2) 5.12 L. Creatinine clearance (CrCl) was identified as a covariate to CL, and ERCC1 (rs3212986) and CYP3A5 (rs776746) gene polymorphisms as covariates to Q. By using empirical body surface area (BSA)-based dosing strategy, PEM exposure decreased with the elevation of CrCl. Contrarily, CrCl-based dosing strategy exhibited a satisfactory efficacy of achieving the target PEM exposure. BSA-based dosing regimen in current clinic practice is not suitable to achieve the target exposure in PEM chemotherapy of Chinese NSCLC patients. Alternatively, renal function-based dosing strategy is suggested.
Alpiniae oxyphyllae fructus possesses neuroprotective effects on H2O2 stimulated PC12 cells via regulation of the PI3K/Akt signaling Pathway
Authors: Li Ruolan , Wang Lingyu , Zhang Qing , Duan Huxinyue , Qian Die , Yang Fei , Xia Jun 
Published: August 2022

Backgroud: Alzheimer’s disease (AD) is a typical neurodegenerative disease, which occurs in the elderly population. Alpiniae oxyphyllae Fructus (AOF) is a traditional Chinese medicine that has potential therapeutic effect on AD, but the mechanism behind it is unclear.Methods: Firstly, the main chemical components of AOF were identified by LC-MS, while the main active ingredients and targets were screened by TCMSP database. At the same time, AD-related target proteins were obtained using Genecards and OMIM databases. PPI was constructed by cross-linking AOF and AD targets, and GO enrichment analysis and KEGG pathway enrichment analysis were performed to identify the relevant biological processes and signaling pathways. Finally, based on the H2O2-stimulated PC12 cell, flow cytometry, WB and immunofluorescence experiments were performed to verify the protective effect of AOF on AD.Results: We identified 38 active ingredients with 662 non-repetitive targets in AOF, of which 49 were potential therapeutic AD targets of AOF. According to the GO and KEGG analysis, these potential targets are mainly related to oxidative stress and apoptosis. The role of AOF in the treatment of AD is mainly related to the PI3K/AKT signaling pathway. Protocatechuic acid and nootkatone might be the main active ingredients of AOF. In subsequent experiments, the results of CCK-8 showed that AOF mitigated PC12 cell damage induced by H2O2. Kits, flow cytometry, and laser confocal microscopy indicated that AOF could decrease ROS and increase the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), while AOF could also increase mitochondrial membrane potential (MMP), thereby inhibiting apoptosis. Finally, immunofluorescence and WB results showed that AOF inhibited the expression of BAX and caspase-3 in PC12 cells, and promoted the expression of Bcl-2. At the same time, the phosphorylation levels of PI3K and Akt proteins were also significantly increased.Conclusion: This study suggests that AOF had the potential to treat AD by suppressing apoptosis induced by oxidative stress via the PI3K/Akt pathway.
Habitat radiomics analysis of pet/ct imaging in high-grade serous ovarian cancer: Application to Ki-67 status and progression-free survival
Authors: Wang Xinghao , Xu Chen , Grzegorzek Marcin , Sun Hongzan 
Published: August 2022

Purpose: We aim to develop and validate PET/ CT image-based radiomics to determine the Ki-67 status of high-grade serous ovarian cancer (HGSOC), in which we use the metabolic subregion evolution to improve the prediction ability of the model. At the same time, the stratified effect of the radiomics model on the progression-free survival rate of ovarian cancer patients was illustrated.Materials and methods: We retrospectively reviewed 161 patients with HGSOC from April 2013 to January 2019. 18F-FDG PET/ CT images before treatment, pathological reports, and follow-up data were analyzed. A randomized grouping method was used to divide ovarian cancer patients into a training group and validation group. PET/ CT images were fused to extract radiomics features of the whole tumor region and radiomics features based on the Habitat method. The feature is dimensionality reduced, and meaningful features are screened to form a signature for predicting the Ki-67 status of ovarian cancer. Meanwhile, survival analysis was conducted to explore the hierarchical guidance significance of radiomics in the prognosis of patients with ovarian cancer.Results: Compared with texture features extracted from the whole tumor, the texture features generated by the Habitat method can better predict the Ki-67 state (p &lt; 0.001). Radiomics based on Habitat can predict the Ki-67 expression accurately and has the potential to become a new marker instead of Ki-67. At the same time, the Habitat model can better stratify the prognosis (p &lt; 0.05).Conclusion: We found a noninvasive imaging predictor that could guide the stratification of prognosis in ovarian cancer patients, which is related to the expression of Ki-67 in tumor tissues. This method is of great significance for the diagnosis and treatment of ovarian cancer.
A Wars2 mutant mouse shows a sex and diet specific change in fat distribution, reduced food intake and depot-specific upregulation of WAT browning
Authors: Mušo Milan , Bentley Liz , Vizor Lucie , Yon Marianne , Burling Keith , Barker Peter , Zolkiewski Louisa A. K. , Cox Roger D. , Dumbell Rebecca 
Published: August 2022

Background: Increased waist-to-hip ratio (WHR) is associated with increased mortality and risk of type 2 diabetes and cardiovascular disease. The TBX15-WARS2 locus has consistently been associated with increased WHR. Previous study of the hypomorphic Wars2V117L/V117L mouse model found phenotypes including severely reduced fat mass, and white adipose tissue (WAT) browning, suggesting Wars2 could be a potential modulator of fat distribution and WAT browning.Methods: To test for differences in browning induction across different adipose depots of Wars2V117L/V117L mice, we measured multiple browning markers of a 4-month old chow-fed cohort in subcutaneous and visceral WAT and brown adipose tissue (BAT). To explain previously observed fat mass loss, we also tested for the upregulation of plasma mitokines FGF21 and GDF15 and for differences in food intake in the same cohort. Finally, to test for diet-associated differences in fat distribution, we placed Wars2V117L/V117L mice on low-fat or high-fat diet (LFD, HFD) and assessed their body composition by Echo-MRI and compared terminal adipose depot weights at 6 months of age.Results: The chow-fed Wars2V117L/V117L mice showed more changes in WAT browning marker gene expression in the subcutaneous inguinal WAT depot (iWAT) than in the visceral gonadal WAT depot (gWAT). These mice also demonstrated reduced food intake and elevated plasma FGF21 and GDF15, and mRNA from heart and BAT. When exposed to HFD, the Wars2V117L/V117L mice showed resistance to diet-induced obesity and a male and HFD-specific reduction of gWAT: iWAT ratio.Conclusion: Severe reduction of Wars2 gene function causes a systemic phenotype which leads to upregulation of FGF21 and GDF15, resulting in reduced food intake and depot-specific changes in browning and fat mass.
OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
Authors: Man Yuncheng , An Ran , Monchamp Karamoja , Sekyonda Zoe , Kucukal Erdem , Federici Chiara , Wulftange William J. , Goreke Utku , Bode Allison , Sheehan Vivien A. , Gurkan Umut A. 
Published: August 2022

Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up to 1% volume fraction; ektacytometry detected no significant change in Elongation Index (EI), while the OcclusionChip showed significant differences in Occlusion Index (OI). OcclusionChip detected a significant increase in OI in RBCs from an individual with sickle cell trait (SCT) and from a subject with SCD who received allogeneic hematopoietic stem cell transplant (HSCT), as the sample was taken from normoxic (pO2:159 mmHg) to physiologic hypoxic (pO2:45 mmHg) conditions. Oxygen gradient ektacytometry detected no difference in EI for SCT or HSCT. These results suggest that the single cell-based OcclusionChip enables detection of sickle hemoglobin (HbS)-related RBC abnormalities in SCT and SCD, particularly when the HbS level is low. We conclude that the OcclusionChip is complementary to the population based ektacytometry assays, and providing additional sensitivity and capacity to detect modest abnormalities in red cell function or small populations of abnormal red cells.
Sheep recombinant IGF-1 promotes organ-specific growth in fetal sheep
Authors: Stremming J , White A , Donthi A , Batt DG , Hetrick B , Chang EI , Wesolowski SR , Seefeldt MB , McCurdy CE , Rozance PJ , Brown LD 
Published: August 2022

IGF-1 is a critical fetal growth-promoting hormone. Experimental infusion of an IGF-1 analog, human recombinant LR3 IGF-1, into late gestation fetal sheep increased fetal organ growth and skeletal muscle myoblast proliferation. However, LR3 IGF-1 has a low affinity for IGF binding proteins (IGFBP), thus reducing physiologic regulation of IGF-1 bioavailability. The peptide sequences for LR3 IGF-1 and sheep IGF-1 also differ. To overcome these limitations with LR3 IGF-1, we developed an ovine (sheep) specific recombinant IGF-1 (oIGF-1) and tested its effect on growth in fetal sheep. First, we measured in vitro myoblast proliferation in response to oIGF-1. Second, we examined anabolic signaling pathways from serial skeletal muscle biopsies in fetal sheep that received oIGF-1 or saline infusion for 2 hours. Finally, we measured the effect of fetal oIGF-1 infusion versus saline infusion (SAL) for 1 week on fetal body and organ growth, in vivo myoblast proliferation, skeletal muscle fractional protein synthetic rate, IGFBP expression in skeletal muscle and liver, and IGF-1 signaling pathways in skeletal muscle. Using this approach, we showed that oIGF-1 stimulated myoblast proliferation in vitro. When infused for 1 week, oIGF-1 increased organ growth of the heart, kidney, spleen, and adrenal glands and stimulated skeletal myoblast proliferation compared to SAL without increasing muscle fractional synthetic rate or hindlimb muscle mass. Hepatic and muscular gene expression of IGFBPs one to three was similar between oIGF-1 and SAL. We conclude that oIGF-1 promotes tissue and organ-specific growth in the normal sheep fetus.
The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication
Authors: Devaux Christian Albert , Raoult Didier 
Published: August 2022

Cases of coronavirus disease 2019 (COVID-19) have been reported worldwide. However, one epidemiological report has claimed a lower incidence of the disease in people living at high altitude (&gt;2,500 m), proposing the hypothesis that adaptation to hypoxia may prove to be advantageous with respect to SARS-CoV-2 infection. This publication was initially greeted with skepticism, because social, genetic, or environmental parametric variables could underlie a difference in susceptibility to the virus for people living in chronic hypobaric hypoxia atmospheres. Moreover, in some patients positive for SARS-CoV-2, early post-infection ‘happy hypoxia” requires immediate ventilation, since it is associated with poor clinical outcome. If, however, we accept to consider the hypothesis according to which the adaptation to hypoxia may prove to be advantageous with respect to SARS-CoV-2 infection, identification of the molecular rational behind it is needed. Among several possibilities, HIF-1 regulation appears to be a molecular hub from which different signaling pathways linking hypoxia and COVID-19 are controlled. Interestingly, HIF-1α was reported to inhibit the infection of lung cells by SARS-CoV-2 by reducing ACE2 viral receptor expression. Moreover, an association of the rs11549465 variant of HIF-1α with COVID-19 susceptibility was recently discovered. Here, we review the evidence for a link between HIF-1α, ACE2 and AT1R expression, and the incidence/severity of COVID-19. We highlight the central role played by the HIF-1α signaling pathway in the pathophysiology of COVID-19.
Study protocol of a randomized controlled trial of motivational interviewing-based intervention to improve adherence to continuous positive airway pressure in patients with obstructive sleep apnea syndrome: The MotivAir study
Authors: Rapelli Giada , Pietrabissa Giada , Angeli Licia , Manzoni Gian Mauro , Tovaglieri Ilaria , Perger Elisa , Garbarino Sergio , Fanari Paolo , Lombardi Carolina , Castelnuovo Gianluca 
Published: August 2022

ObjectiveThis study aims to evaluate the effectiveness of the MotivAir program—a phone-based intervention based on Motivational Interviewing (MI) principles and techniques—in enhancing adherence to Continuous Positive Airway Pressure (CPAP) therapy among patients with Obstructive Sleep Apnea Syndrome (OSAS).MethodsA multicenter randomized controlled trial (RCT) design with random allocation at the level of the individual will be conducted to compare the impact of the experimental program (usual care plus MI) with a control group receiving usual care only in improving selected clinical and psychological parameters in the patients. A minimum sample of 80 participants (40 patients per group) will be recruited in each center according to the inclusion criteria. After the initial screening, participants will be randomly assigned to either the experimental group or the control condition. The program will last 180 days and will be delivered by a trained nurse. The impact of the MotivAir program on selected primary (adherence to CPAP in terms of average hours of usage per night and the Apnea-Hypopnea Index, AHI) and secondary (motivation, perceived competence, quality of life, sleepiness) outcomes will be measured at baseline, and after 1-, 3-, and 6-month from CPAP initiation.DiscussionParticipants are expected to show an increased level of adherence to CPAP and to acquire the skills and self-confidence necessary to deal with the psychological consequences of their chronic condition.
A nurse-led, telephone-based patient support program for improving adherence in patients with relapsing-remitting multiple sclerosis using interferon beta-1a: Lessons from a consumer-based survey on adveva® PSP
Authors: Barello Serena , Paolicelli Damiano , Bergamaschi Roberto , Cottone Salvatore , D'Amico Alessandra , Annibali Viviana , Paolillo Andrea , Bosio Caterina , Panetta Valentina , Graffigna Guendalina 
Published: August 2022

BackgroundEvidence suggests that organizational models that provide care interventions including patient support programs may increase patient adherence to multiple sclerosis (MS) therapies by providing tailored symptom management, informational support, psychological and/or social support, lifestyle changes, emotional adjustment, health education, and tailored coaching, thus improving patients' overall quality of life across the disease course.ObjectiveThe main objective of this study was to describe MS patients' self-reported experience of a nurse-led, telephone-based PSP and to explore its potential role in improving disease and therapy management skills.MethodsSurvey data were analyzed from a subset of patients relapsing–remitting MS (RRMS) using interferon beta-1a already registered in the adveva® PSP from three Italian multiple sclerosis centers with a consolidated experience in RRMS disease, treatment management, and PSP programs.ResultsIn total, 244 patient data at baseline were analyzed, of which 115 had a follow-up of at least 6 months. Results from this study provide an early view into the role of this PSP in improving the patients reported overall experience regarding disease management and injectable therapy, thus potentially ameliorating treatment adherence and decreasing health care cost. Moreover, study findings confirm the role of providing a patient-focused support by addressing non-medication-related topics in the PSP consultations. Indeed, patients involved in the adveva® PSP program reported a better psychological status in the follow up as demonstrated by an increased optimism regarding their future, tolerance of disease uncertainty, and their perceived ability to benefit from external help and social support (informal caregivers).ConclusionsAs such, it is reasonable to conclude that the involvement in the adveva® PSP and the PSP's assistance in guiding patients on proper treatment self-management techniques is of great value to patients as it might contribute to improving engagement in their health care journey in terms of perceived self-care skills, emotional coping toward the future and the unpredictability of the disease course and their general attitudes toward the injection itself, involving pain tolerance.
Association between fundamental motor skills and executive function in preschool children: A cross-sectional study
Authors: Han Xiaowei , Zhao Meiling , Kong Zhe , Xie Jun 
Published: August 2022

ObjectiveThe main purpose of this study was to explore the association between early fundamental motor skills (FMS) and executive function (EF) in preschool children.MethodsA total of 394 young children (4.07 ± 0.76 years) were evaluated. The FMS and EF were evaluated using the Test of Gross Motor Development-2 (TGMD-2) and the NIH Toolbox Cognition Battery (NTCB), respectively.ResultsTotal FMS score was moderately and positively correlated with total EF score (r = 0.33, p &lt; 0.001) and was a significant predictor of total EF score (β = 0.37, p &lt; 0.001). Specifically, locomotor skills were significant predictors of inhibition control (β = 0.21, p &lt; 0.001), working memory (β = 0.18, p &lt; 0.01), and cognitive flexibility (β = 0.24, p &lt; 0.001), while object control skills were only significant predictors of inhibition control (β = 0.17, p &lt; 0.01).ConclusionFMS were significantly and positively correlated with EF and were significant predictors of EF. Early childhood policymakers, preschool teachers, and researchers should take these connections seriously and implement appropriate complex motor intervention programs in future teaching to stimulate the development of both motor and higher-order cognitive skills in preschool children.