bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review
Authors: Leong Bin Abdullah Mohammad Farris Iman , Singh Darshan 
Published: September 2021

Background: Kratom or Mitragyna speciosa (Korth.) has received overwhelming attention recently due to its alleged pain-relieving effects. Despite its potential therapeutic value, kratom use has been linked to many occurrences of multiorgan toxicity and cardiotoxicity. Accordingly, the current narrative review aimed to provide a detailed account of kratom’s adverse cardiovascular effects and cardiotoxicity risk, based on in vitro studies, poison center reports, coroner and autopsy reports, clinical case reports, and clinical studies.Methods: An electronic search was conducted to identify all research articles published in English from 1950 to 2021 using the major research databases, such as Google Scholar, Web of Science, PubMed, Scopus, Mendeley, EMBASE, Cochrane Library, and Medline. We then analyzed the literature’s discussion of adverse cardiovascular effects, toxicity, and mortality related to kratom use.Results: Our findings revealed that, although in vitro studies have found kratom preparations’ most abundant alkaloid—mitragynine—to cause a prolonged QTc interval and an increased risk of torsades de pointes, a clinical study examining humans’ regular consumption of kratom did not report such a risk. However, this latter study did show that regular kratom use could induce an increased QTc interval in a dose-dependent manner. A few case reports also highlighted that kratom consumption is associated with ventricular arrhythmia and cardiopulmonary arrest, but this association could have ensued when kratom was co-administered with another substance. Similarly, analyses of national poison data showed that kratom’s most common adverse acute cardiovascular effects include tachycardia and hypertension. Meanwhile, coroner and autopsy reports indicated that kratom’s cardiovascular sequelae encompass coronary atherosclerosis, myocardial infarction, hypertensive cardiovascular disease, left ventricular hypertrophy, cardiac arrhythmia, cardiomegaly, cardiomyopathy, focal band necrosis in the myocardium, and myocarditis. Given the available data, we deduced that all cardiac eventualities reported in the literature could have been compounded by polysubstance use and unresolved underlying medical illnesses.Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion, and further studies are still necessary to address this issue.
Fascin-1 is Highly Expressed Specifically in Microglia After Spinal Cord Injury and Regulates Microglial Migration
Authors: Yu Shuisheng , Cheng Li , Tian Dasheng , Li Ziyu , Yao Fei , Luo Yang , Liu Yanchang , Zhu Zhenyu , Zheng Meige , Jing Juehua 
Published: September 2021

Recent research indicates that after spinal cord injury (SCI), microglia accumulate at the borders of lesions between astrocytic and fibrotic scars and perform inflammation-limiting and neuroprotective functions, however, the mechanism of microglial migration remains unclear. Fascin-1 is a key actin-bundling protein that regulates cell migration, invasion and adhesion, but its role during SCI has not been reported. Here, we found that at 7–14 days after SCI in mice, Fascin-1 is significantly upregulated, mainly distributed around the lesion, and specifically expressed in CX3CR1-positive microglia. However, Fascin-1 is not expressed in GFAP-positive astrocytes, NeuN-positive neurons, NG2-positive cells, PDGFRβ-positive cells, or blood-derived Mac2-positive macrophages infiltrating into the lesion core. The expression of Fascin-1 is correspondingly decreased after microglia are specifically depleted in the injured spinal cord by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. The upregulation of Fascin-1 expression is observed when microglia are activated by myelin debris in vitro, and microglial migration is prominently increased. The inhibition of Fascin-1 expression using small interfering RNA (siRNA) markedly suppresses the migration of microglia, but this effect can be reversed by treatment with myelin. The M1/M2-like polarization of microglia does not affect the expression of Fascin-1. Together, our results suggest that Fascin-1 is highly expressed specifically in microglia after SCI and can play an important role in the migration of microglia and the formation of microglial scars. Hence, the elucidation of this mechanism will provide novel therapeutic targets for the treatment of SCI.
Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone
Authors: Kumar Shashank , Prajapati Kumari Sunita , Shuaib Mohd , Kushwaha Prem Prakash , Tuli Hardeep Singh , Singh Atul Kumar 
Published: September 2021

In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2–62 µM while in vivo efficacy was studied in the range of 20–500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-κB, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.
Cost-Effectiveness of Short-Course Radiation Plus Temozolomide for the Treatment of Newly Diagnosed Glioblastoma Among Elderly Patients in China and the United States
Authors: Chen Jigang , Tong Xin , Han Mingyang , Zhao Songfeng , Ji Linjin , Qin Yongkai , He Zilong , Pan Yuesong , Wang Chunhui , Liu Aihua 
Published: September 2021

Background: Glioblastoma multiforme (GBM) is a fatal type of brain tumor with a high incidence among elderly people. Temozolomide (TMZ) has proven to be an effective chemotherapeutic agent with significant survival benefits. This study aimed to evaluate the economic outcomes of radiotherapy (RT) and TMZ for the treatment of newly diagnosed GBM in elderly people in the United States (US) and China.Methods: A partitioned survival model was constructed for RT plus TMZ and RT alone among patients with methylated and unmethylated tumor status. Base case calculations and one-way and probabilistic sensitivity analyses were performed. Life-years, quality-adjusted life-years (QALYs), costs (in 2021 US dollars [$] and Chinese Yuan Renminbi [¥]), and incremental cost-effectiveness ratios (ICERs) were calculated.Results: RT plus TMZ was found to be associated with significantly higher costs and QALYs in all groups. Only US patients with methylated status receiving RT plus TMZ had an ICER ($89358.51) less than the willingness-to-pay (WTP) threshold of $100000 per QALY gained when compared with receiving RT alone. When the WTP threshold ranged from $100000 to $150000 from the US perspective, the probability of RT plus TMZ being cost-effective increased from 80.5 to 99.8%. The cost of TMZ must be lower than ¥120 per 20 mg for RT plus TMZ to be cost-effective among patients with methylated tumor status in China.Conclusion: RT plus TMZ was not cost-effective in China, and a reduction in the TMZ price was justified. However, it is highly likely to be cost-effective for patients with methylated tumor status in the US.
A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings
Authors: Gatti Milo , Cojutti Pier Giorgio , Campoli Caterina , Caramelli Fabio , Corvaglia Luigi Tommaso , Lanari Marcello , Pession Andrea , Ramirez Stefania , Viale Pierluigi , Pea Federico 
Published: September 2021

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings.Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, &lt;12 h; quasi-optimal, between 12–24 h; acceptable, between 24–48 h; suboptimal, &gt;48 h).Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases.Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios.
Controlled Ovarian Hyperstimulation Protocol in Infertile Patients During the COVID-19 Pandemic
Authors: Li Fei , Zhang HuiXia , Shi WeiYi , Wu YiFang , Tian Ye , Guo YiHong , Jin HaiXia , Li Gang 
Published: September 2021

Objectives: To explore the appropriate controlled ovarian hyperstimulation (COH) protocols in infertility patients who received the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments during the COVID-19 pandemic.Materials and Methods: This retrospective cohort study evaluated the efficiency of the early follicular-phase long-acting GnRH-agonist long (EFLL) protocol (a new protocol developed by Chinese clinicians), prolonged pituitary down-regulation of EFLL protocol (Pro-EFLL), and the GnRH-ant protocol for couples meeting the study criteria between February 2020 and June 2020 who were treated by the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic, and compared the pregnancy rates and miscarriage rates per fresh transfer cycle, number of retrieved oocytes, endometrial thickness on the day of hCG injection and the number of fertilized oocytes, mature oocytes, fertilized oocytes, and transferable embryos among the three protocols.Results: We found that the prolonged pituitary down-regulation during the COVID-19 pandemic by utilizing a full-dose of GnRH-a administrated in infertility patients were no differences in clinical outcomes than other protocols, The prolonged pituitary down-regulation protocol and EFLL protocol were associated with a higher Endometrial thickness on the day of hCG injection (12.67 ± 2.21 vs. 12.09 ± 2.35 vs. 10.79 ± 2.38, P &lt; 0.001), retrieved oocytes (14.49 ± 6.30 vs. 15.02 ± 7.93 vs. 10.06 ± 7.63, P &lt; 0.001), mature oocytes (11.60 ± 5.71 vs. 11.96 ± 6.00 vs. 7.63 ± 6.50, P &lt; 0.001), fertilized oocytes (9.14 ± 5.43 vs. 8.44 ± 5.34 vs. 5.42 ± 5.20, P &lt; 0.001), and transferable embryos (4.87 ± 2.96 vs. 6.47 ± 5.12 vs. 3.00 ± 3.28 vs. P &lt; 0.001) in the GnRH-antagonist protocol.Conclusion: We recommend that patients start Gn injections 33–42 days after a pituitary downregulated full dose (3.75 mg) of gonadotropin-releasing hormone agonist during the COVID-19 pandemic, even a delay of 2–4 weeks does not affect the implantation rate. The study can provide a more detailed estimate and clinical management strategies for infertile couples during the COVID-19 pandemic.
The Estimated Effect of Physicians' Advice for Smoking Cessation and Assumed Tobacco Retail Price Increase on Smoker's Intention to Quit in Shanghai, China: A Cross-Sectional Study
Authors: Wang Ruiping , Gao Xiangjin , Qiang Yan , Yang Qiong , Li Xiaopan , Li Bin 
Published: September 2021

Background: Tobacco consumption produces a heavy disease burden worldwide, and tobacco price increase, an advertisement for tobacco-induced harm, graphic warning labels on cigarette packages and advice of physicians for quitting are policies that have been proved as effective smoking cessation measures. But evidence on the estimated effect of advice of physicians for quitting and assumed tobacco retail price increase on smoking cessation intention among smokers is still limited in China.Methods: From January to April of 2021, we recruited 664 current smokers in Songjiang district of Shanghai by a multistage sampling design. We implemented a logistic regression analysis to calculate the odds ratio (OR) and 95% confidence interval (CI) to explore how smoking cessation intention would be influenced by the assumed tobacco retail price increase as well as advice of physicians for quitting, and used the paired tabulation method to identify the salient tobacco control measures among smokers as well.Results: A total of 664 current smokers included 548 males (82.53%), with an average smoking duration of 22.50 years (SD: 11.52 years). About 68.79 and 43.67% of current smokers reported smoking cessation intention due to advice of physicians for quitting and the assumed tobacco retail price increase, respectively. Logistic regression analysis indicated that female smokers (OR = 2.85 and 4.55), smokers with previous smoking cessation attempt (OR = 3.71 and 3.07), longer smoking duration (OR = 2.26 and 2.68), lower smoking intensity (OR = 1.82 and 1.69), and heavier tobacco burdens (OR = 1.67 and 2.22) had the higher intention of smoking cessation both due to advice of physicians for quitting and due to assumed tobacco price increase, respectively. Meanwhile, the advice of physicians for quitting was more effective and acceptable (over 80%) than the assumed tobacco price increase for inducing smokers to consider quitting in Shanghai.Conclusions: Smokers have a high intention of smoking cessation in Shanghai, and the advice of physicians for quitting is a potentially more salient tobacco control measure than the assumed tobacco retail price increase. Incorporating smoking duration, intensity, personal burden as well as noncommunicable disease (NCD) status of smokers into the implementation of tobacco control measures is beneficial for descending smoking prevalence.
Cardiovascular Disease in the Peruvian Andes: Local Perceptions, Barriers, and Paths to Preventing Chronic Diseases in the Cajamarca Region
Authors: Sanchez-Samaniego Giuliana , Hartinger Stella M. , Tallman Paula S. , Mäusezahl Daniel 
Published: September 2021

Objectives: Public health interventions can be improved by understanding peoples’ explanatory models of disease. We explore awareness and perceptions of cardiovascular diseases (CVD) and options for preventative actions in young adults living in rural Andean communities.Methods: We used convenience sampling to select 46 men and women from communities in Cajamarca (Peru). Subjects participated in eight focus groups where they discussed their understanding and perceived causes of CVD as well as barriers and pathways to healthy lifestyles.Results: Fresh foods, physical activity, unpleasant emotions, and healthcare access were cited as important determinants of healthy lifestyles. Barriers to healthy diets included lacking nutritional knowledge, fluctuating food prices, and limited access to foodstuffs. Women felt particularly vulnerable to CVD and identified gendered barriers to manage stress and engage in sports. Low health literacy, poor doctor-patient relationships, and long distances prevented participants from fully accessing healthcare.Conclusion: CVD prevention interventions should consider local knowledge of these diseases and of healthy lifestyles, and harness ongoing programmes that have successfully promoted good nutrition in children and pregnant women. In concert with public-private parterships, governments should include disease prevention interventions for the entire family.
Exploration of the Temperature Sensing Ability of La2MgTiO6:Er3+ Double Perovskites Using Thermally Coupled and Uncoupled Energy Levels
Authors: Vu Thi Hong Quan , Bondzior Bartosz , Stefańska Dagmara , Dereń Przemysław J. 
Published: September 2021

This work aimed to explore the temperature-sensing performance of La2MgTiO6:Er3+ double perovskites based on thermally coupled and uncoupled energy levels. Furthermore, the crystal structure, chemical composition, and morphology of the samples were investigated by powder X-ray diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy, respectively. The most intense luminescence was observed for the sample doped with 5% Er3+. The temperature-dependent emission spectra of La2MgTiO6:5% Er3+ were investigated in the wide range of 77–398 K. The highest sensitivity of the sample was equal to 2.98%/K corresponding to the thermally coupled energy level 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 as compared to 1.9%/K, obtained for the uncoupled energy level 2H11/2 → 4I15/2 and 2H9/2 → 4I15/2. Furthermore, the 300 K luminescent decay profiles were analyzed using the Inokuti–Hirayama model. The energy transfer among Er3+ ions was mainly regulated by the dipole–dipole mechanism. The critical transfer distance R0, critical concentration C0, energy transfer parameter Cda, and energy transfer probability Wda were 9.81 Å, 2.53×1020 ions·cm−3, 5.38×10−39 cm6·s−1, and 6020 s−1, respectively.
Combined Anticancer Effect of Sulfated Laminaran from the Brown Alga Alaria angusta and Polyhydroxysteroid Glycosides from the Starfish Protoreaster lincki on 3D Colorectal Carcinoma HCT 116 Cell Line
Authors: Malyarenko Olesya S. , Malyarenko Timofey V. , Usoltseva Roza V. , Surits Valerii V. , Kicha Alla A. , Ivanchina Natalia V. , Ermakova Svetlana P. 
Published: September 2021

Colorectal cancer is one of the most frequent types of malignancy in the world. The search for new approaches of increasing the efficacy of cancer therapy is relevant. This work was aimed to study individual, combined anticancer effects, and molecular mechanism of action of sulfated laminaran AaLs of the brown alga Alaria angusta and protolinckiosides A (PL1), B (PL2), and linckoside L1 (L1) of the starfish Protoreaster lincki using a 3D cell culture model. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), soft agar, 3D spheroids invasion, and Western blotting assays were performed to determine the effect and mechanism of the action of investigated compounds or their combinations on proliferation, colony formation, and the invasion of 3D HCT 116 spheroids. AaLs, PL1, PL2, and L1 individually inhibited viability, colony growth, and the invasion of 3D HCT 116 spheroids in a variable degree with greater activity of linckoside L1. AaLs in combination with L1 exerted synergism of a combined anticancer effect through the inactivation of protein kinase B (AKT) kinase and, consequently, the induction of apoptosis via the regulation of proapoptotic/antiapoptotic proteins balance. The obtained data about the efficacy of the combined anticancer effect of a laminaran derivative of brown algae and polyhydroxysteroid glycosides of starfish open up prospects for the development of new therapeutic approaches for colorectal cancer treatment.
Практики здорового способу життя Церкви адвентистів сьомого дня в Україні
Authors: Kuryliak Valentyna 
Published: September 2021

Розглянуто особливості філософії та практик реалізації принципів здорового способу життя Церквою адвентистів сьомого дня в Україні. Встановлено, що соціальні та культурні зміни, спричинені отриманням Україною статусу незалежності, сприяли відкриттю санаторіїв, пансіонатів, центрів здоров’я вірянами релігійної конфесії адвентистів. Констатовано, що починаючи з 1991 р. адвентисти загалом проводили короткострокові оздоровчі програми та виставки, однак із часом перелаштувалися на західну систему надання послуг на базі постійно діючих оздоровчих установ. Окреслено філософію та практики реалізації здорового способу життя Церквою адвентистів сьомого дня в Україні в контексті роботи медичних, санаторних та оздоровчих закладів, які безпосередньо належать цій релігійній організації. Практична новизна дослідження заснована на матеріалах інтерв’ювання керівників закладів здоров’я, які безпосередно були дотичними до створення медичних установ та реалізації різноманітних адвентистських програм по здоров’ю. Вивлено, що представники інших протестантських та православних конфесій, які відвідували бази відпочинку, змінювали свою думку щодо адвентизму та адвентистів, що, своєю чергою, сприяло створенню атмосфери релігійної терпимості та толерантного ставлення один до одного. Діяльність оглянутих центрів здоров’я, санаторіїв та пансіонатів в основному реалізовує місію Церкви адвентистів сьомого дня, а самі виконавці (персонал) вбачають у профілактиці захворювань та реабілітації пацієнтів свій вклад у служіння Богу. Крім того, в діяльності закладів, які ми дослідили, особлива увага приділяється навчанню принципам здорового способу життя, правильного харчування, водолікування тощо. Визначено, що в основу процесу реалізації програм по здоров’ю покладено принципи християнської етики, якими намагаються керуватися керівники та персонал, вбачаючи у цьому виконання місії Христа на землі, особливо у сфері відновлення та профілактики здоров’я відвідувачів санаторіїв.