bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid
Authors: Li Ke , Yu Xiu-Hua , Maskey Anish R. , Musa Ibrahim , Wang Zhen-Zheng , Garcia Victor , Guo Austin , Yang Nan , Srivastava Kamal , Dunkin David , Li Jun-Xiong , Guo Longgang , Cheng Yung-Chi , Yuan Haoliang , Tiwari Raj , Li Xiu-Min 
Published: January 2023

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect.Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity.Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p &lt; 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p &lt; 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p &lt; 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p &lt; 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of −44.73kJ/mol.Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.
Proton-pump inhibitor use amongst patients with severe hypomagnesemia
Authors: Seah Sherry , Tan Yen Kheng , Teh Kevin , Loh Wann Jia , Tan Pei Ting , Goh Leng Chuan , Malakar Roy Debajyoti , Aw Tar Choon , Lau Chin Shern , Dhalliwal Trishpal , Kui Swee Leng , Kam Jia Wen , Khoo Joan , Tay Tunn Lin , Tan Eberta , Au Vanessa , Soh Shui Boon , Zhang Meifen , King Thomas F. , Gani Linsey , Puar Troy H. 
Published: January 2023

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors.Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia.Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (&lt;0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17–2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05–7.00), low BMI (OR, 0.90; 95% CI: 0.86–0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29–2.98), renal impairment (OR, 3.85; 95% CI: 2.58–5.75), and diuretic use (OR, 1.68; 95% CI: 1.09–2.61).Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.
A pharmacist-led medication review service with a deprescribing focus guided by implementation science
Authors: Alaa Eddine Nada , Schreiber James , El-Yazbi Ahmed F. , Shmaytilli Haya , Amin Mohamed Ezzat Khamis 
Published: January 2023

Background: Little research addressed deprescribing-focused medication optimization interventions while utilizing implementation science. This study aimed to develop a pharmacist-led medication review service with a deprescribing focus in a care facility serving patients of low income receiving medications for free in Lebanon followed by an assessment of the recommendations’ acceptance by prescribing physicians. As a secondary aim, the study evaluates the impact of this intervention on satisfaction compared to satisfaction associated with receiving routine care.Methods: The Consolidated Framework for Implementation Research (CFIR) was used to address implementation barriers and facilitators by mapping its constructs to the intervention implementation determinants at the study site. After filling medications and receiving routine pharmacy service at the facility, patients 65 years or older and taking 5 or more medications, were assigned into two groups. Both groups of patients received the intervention. Patient satisfaction was assessed right after receiving the intervention (intervention group) or just before the intervention (control group). The intervention consisted of an assessment of patient medication profiles before addressing recommendations with attending physicians at the facility. Patient satisfaction with the service was assessed using a validated translated version of the Medication Management Patient Satisfaction Survey (MMPSS). Descriptive statistics provided data on drug-related problems, the nature and the number of recommendations as well as physicians’ responses to recommendations. Independent sample t-tests were used to assess the intervention’s impact on patient satisfaction.Results: Of 157 patients meeting the inclusion criteria, 143 patients were enrolled: 72 in the control group and 71 in the experimental group. Of 143 patients, 83% presented drug-related problems (DRPs). Further, 66% of the screened DRPs met the STOPP/START criteria (77%, and 23% respectively). The intervention pharmacist provided 221 recommendations to physicians, of which 52% were to discontinue one or more medications. Patients in the intervention group showed significantly higher satisfaction compared to the ones in the control group (p &lt; 0.001, effect size = 1.75). Of those recommendations, 30% were accepted by the physicians.Conclusion: Patients showed significantly higher satisfaction with the intervention they received compared to routine care. Future work should assess how specific CFIR constructs contribute to the outcomes of deprescribing-focused interventions.
Cardiovascular risk assessment in periodontitis patients and controls using the European Systematic COronary Risk Evaluation (SCORE) model. A pilot study.
Authors: Kosho Madeline X. F. , Verhelst Alexander R. E. , Teeuw Wijnand J. , Gerdes Victor E. A. , Loos Bruno G. 
Published: January 2023

Aim: To investigate the use of the European SCORE model in a dental setting by exploring the frequency of a ‘high’ and ‘very high’ 10-year CVD mortality risk in patients with and without periodontitis. The secondary aim was to investigate the association of SCORE with various periodontitis parameters adjusting for remaining potential confounders.Material and methods: In this study, we recruited periodontitis patients and non-periodontitis controls, all aged ≥40 years. We determined the 10-year CVD mortality risk per individual with the European Systematic Coronary Risk Evaluation (SCORE) model by using certain patient characteristics and biochemical analyses from blood by finger stick sampling.Results: In total, 105 periodontitis patients (61 localized, 44 generalized stage III/IV) and 88 non-periodontitis controls were included (mean age: 54.4 years). The frequency of a ‘high’ and ‘very high’ 10-year CVD mortality risk was 43.8% in all periodontitis patients and 30.7% in controls (p = .061). In total, 29.5% generalized periodontitis patients had a ‘very high’ 10-year CVD mortality risk, compared to 16.4% in localized periodontitis patients and 9.1% in controls (p = .003). After adjustment for potential confounders, the total periodontitis group (OR 3.31; 95% CI 1.35–8.13), generalized periodontitis group (OR 5.32; 95% CI 1.90–14.90), lower number of teeth (OR .83; 95% CI .73–1.00) and higher number of teeth with radiographic bone loss ≥33% (OR 1.06; 95% CI 1.00–1.12) were associated with a “very high” SCORE category. In addition, various biochemical risk markers for CVD were more frequently elevated in periodontitis compared to controls (e.g., total cholesterol, triglycerides, C-reactive protein).Conclusion: The periodontitis group as well as the control group had a sizable frequency of a ‘high’ and ‘very high’ 10-year CVD mortality risk. The presence and extent of periodontitis, lower number of teeth and higher number of teeth with bone loss ≥33% are significant risk indicators for a ‘very high’ 10-year CVD mortality risk. Therefore, SCORE in a dental setting can be a very useful tool to employ for primary and secondary prevention of CVD, especially among the dental attenders who have periodontitis.
Xylem anatomical responses of Larix Gmelinii and Pinus Sylvestris influenced by the climate of Daxing’an mountains in Northeastern China
Authors: Farooq Taimoor Hassan , Yasmeen Sumaira , Shakoor Awais , Nawaz Muhammad Farrakh , Rashid Muhammad Haroon U. , Ahmad Sarir , Rasheed Majeeda , Li He , Li Qian 
Published: January 2023

Wood anatomy and plant hydraulics play a significant role in understanding species-specific responses and their ability to manage rapid environmental changes. This study used the dendro-anatomical approach to assess the anatomical characteristics and their relation to local climate variability in the boreal coniferous tree species Larix gmelinii (Dahurian larch) and Pinus sylvestris var. mongolica (Scots pine) at an altitude range of 660 m to 842 m. We measured the xylem anatomical traits (lumen area (LA), cell wall thickness (CWt), cell counts per ring (CN), ring width (RW), and cell sizes in rings) of both species at four different sites Mangui (MG), Wuerqihan (WEQH), Moredagha (MEDG) and Alihe (ALH) and investigated their relationship with temperature and precipitation of those sites along a latitude gradient. Results showed that all chronologies have strong summer temperature correlations. LA extremes were mostly associated with climatic variation than CWt and RWt. MEDG site species showed an inverse correlation in different growing seasons. The correlation coefficient with temperature indicated significant variations in the May-September months at MG, WEQH, and ALH sites. These results suggest that climatic seasonality changes in the selected sites positively affect hydraulic efficiency (increase in the diameter of the earlywood cells) and the width of the latewood produced in P. sylvestris. In contrast, L. gmelinii showed the opposite response to warm temperatures. It is concluded that xylem anatomical responses of L. gmelinii and P. sylvestris showed varied responses to different climatic factors at different sites. These differences between the two species responses to climate are due to the change of site condition on a large spatial and temporal scale.
Technology supports me: Perceptions of the benefits of digital technology in adolescents
Authors: Bitto Urbanova Laura , Madarasova Geckova Andrea , Dankulincova Veselska Zuzana , Capikova Silvia , Holubcikova Jana , van Dijk Jitse P. , Reijneveld Sijmen A. 
Published: January 2023

BackgroundTechnology plays a significant role in the lives of adolescents. Our knowledge is predominantly based on research exploring the risks associated with it, but adolescents also feel that technology supports their lives. This has received less consideration. Therefore, we aim to examine how adolescents perceive the benefits of digital technology.MethodsWe used qualitative data collected as part of the international Health Behaviour in School-Aged Children study. We conducted online, semi-structured interviews with 15 Slovak adolescents who came from three different types of secondary schools based on their graduation systems (mean age: 15.33; 20% boys). The data were analyzed using consensual qualitative research and thematic analysis.ResultsWe identified five main themes based on the comments of adolescents: 1. I know (source of information, formal and non-formal education); 2. I can (smart device, helpful tool); 3. I am connected/included (social interactions); 4. I have my comfortable place (leisure time, creating my alternative world); and 5. I work on my future (self-development).ConclusionAdolescents perceived digital technology as mostly supportive and a helpful tool in their lives. The potential benefits of digital technology should be better reflected in public perception and policy, as the societal debate is mostly dominated by perceived disadvantages and risks.
Causal discovery replicates symptomatic and functional interrelations of posttraumatic stress across five patient populations
Authors: Pierce Benjamin , Kirsh Thomas , Ferguson Adam R. , Neylan Thomas C. , Ma Sisi , Kummerfeld Erich , Cohen Beth E. , Nielson Jessica L. 
Published: January 2023

IntroductionApproximately half of individuals with posttraumatic stress disorder (PTSD) may meet criteria for other psychiatric disorders, and PTSD symptoms are associated with diminished health and psychosocial functioning. However, few studies examine the longitudinal progression of PTSD symptoms concurrent with related symptom domains and functional outcomes, such that may neglect important longitudinal patterns of symptom progression beyond PTSD specifically.MethodsTherefore, we used longitudinal causal discovery analysis to examine the longitudinal interrelations among PTSD symptoms, depressive symptoms, substance abuse, and various other domains of functioning in five longitudinal cohorts representing veterans (n = 241), civilians seeking treatment for anxiety disorders (n = 79), civilian women seeking treatment for post-traumatic stress and substance abuse (n = 116), active duty military members assessed 0–90 days following TBI (n = 243), and civilians with a history of TBI (n = 43).ResultsThe analyses revealed consistent, directed associations from PTSD symptoms to depressive symptoms, independent longitudinal trajectories of substance use problems, and cascading indirect relations from PTSD symptoms to social functioning through depression as well as direct relations from PTSD symptoms to TBI outcomes.DiscussionOur findings suggest PTSD symptoms primarily drive depressive symptoms over time, tend to show independence from substance use symptoms, and may cascade into impairment in other domains. The results have implications for refining conceptualization of PTSD co-morbidity and can inform prognostic and treatment hypotheses about individuals experiencing PTSD symptoms along with co-occurring distress or impairment.
Tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as first-line therapy for advanced non-squamous non-small cell lung cancer
Authors: Liang Xueyan , Chen Xiaoyu , Li Huijuan , Li Yan 
Published: January 2023

Background and objectiveTislelizumab is a programmed cell death protein-1 (PD-1) inhibitor. Tislelizumab plus chemotherapy as first-line option for advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy alone, resulted in significantly prolonged survival outcomes; however, evidence regarding its relative efficacy and cost is lacking. We aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy compared with that of chemotherapy alone, from the health care perspective in China.MethodsA partitioned survival model (PSM) was used for this study. The survival data were obtained from the RATIONALE 304 trial. Cost-effectiveness was defined as incremental cost-effectiveness ratio (ICER) less than the willingness to pay (WTP) threshold. Incremental net health benefits (INHB), incremental net monetary benefits (INMB), and subgroup analyses were also assessed. Sensitivity analyses were further established to assess the model stability.ResultsCompared with chemotherapy alone, tislelizumab plus chemotherapy increased by 0.64 quality-adjusted life-years (QALYs) and 1.48 life-years, and yielded an increase of $16,631 in cost per patient. The INMB and INHB were $7,510 and 0.20 QALYs at a WTP threshold of $38,017/QALY, respectively. The ICER was $26,162/QALY. The outcomes were most sensitive to the HR of OS for tislelizumab plus chemotherapy arm. The probability of tislelizumab plus chemotherapy being considered cost-effective was 87.66% and &gt;50% in most of the subgroups at the WTP threshold of $38,017/QALY. At the WTP threshold of $86,376/QALY, the probability achieved 99.81%. Furthermore, the probability of tislelizumab plus chemotherapy being considered cost-effective in subgroups of patients with liver metastases and PD–L1 expression ≥50% were 90.61 and 94.35%, respectively.ConclusionTislelizumab plus chemotherapy is likely to be cost-effective as a first-line treatment for advanced non-squamous NSCLC in China.
Pooled prevalence and determinants of antenatal care visits in countries with high maternal mortality: A multi-country analysis
Authors: Chilot Dagmawi , Belay Daniel Gashaneh , Ferede Tigist Andargie , Shitu Kegnie , Asratie Melaku Hunie , Ambachew Sintayehu , Shibabaw Yadelew Yimer , Geberu Demiss Mulatu , Deresse Melkamu , Alem Adugnaw Zeleke 
Published: January 2023

BackgroundComplications during pregnancy and childbirth are the leading causes of maternal and child deaths and disabilities, particularly in low- and middle-income countries. Timely and frequent antenatal care prevents these burdens by promoting existing disease treatments, vaccination, iron supplementation, and HIV counseling and testing during pregnancy. Many factors could contribute to optimal ANC utilization remaining below targets in countries with high maternal mortality. This study aimed to assess the prevalence and determinants of optimal ANC utilization by using nationally representative surveys of countries with high maternal mortality.MethodsSecondary data analysis was done using recent Demographic and Health Surveys (DHS) data of 27 countries with high maternal mortality. The multilevel binary logistic regression model was fitted to identify significantly associated factors. Variables were extracted from the individual record (IR) files of from each of the 27 countries. Adjusted odds ratios (AOR) with a 95% confidence interval (CI) and p-value of ≤0.05 in the multivariable model were used to declare significant factors associated with optimal ANC utilization.ResultThe pooled prevalence of optimal ANC utilization in countries with high maternal mortality was 55.66% (95% CI: 47.48–63.85). Several determinants at the individual and community level were significantly associated with optimal ANC utilization. Mothers aged 25–34 years, mothers aged 35–49 years, mothers who had formal education, working mothers, women who are married, had media access, households of middle-wealth quintile, richest household, history of pregnancy termination, female household head, and high community education were positively associated with optimal ANC visits in countries with high maternal mortality, whereas being rural residents, unwanted pregnancy, having birth order 2–5, and birth order &gt;5 were negatively associated.Conclusion and recommendationsOptimal ANC utilization in countries with high maternal mortality was relatively low. Both individual-level factors and community-level factors were significantly associated with ANC utilization. Policymakers, stakeholders, and health professionals should give special attention and intervene by targeting rural residents, uneducated mothers, economically poor women, and other significant factors this study revealed.
A bibliometric analysis of inflammatory bowel disease and COVID-19 researches
Authors: Wang Fangfei , Xie Jinliang , Xiong Huifang , Xie Yong 
Published: January 2023

BackgroundPatients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19.MethodsPublications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite.ResultsA total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were “management”, “impact”, “vaccination”, and “receptor”. The following keywords represented research frontiers: “depression”, “the quality of life of IBD patients”, “infliximab”, “COVID-19 vaccine”, and “second vaccination”.ConclusionsOver the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as “depression”, “the quality of life of IBD patients”, “infliximab”, “COVID-19 vaccine”, and “second vaccination” were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.