bluuebunny/crossref_metadata_2025 huggingface dataset:
Entrepreneurial Willingness, Practice, and Management Path of College Graduates in a Green Development Environment
Authors: Ma Fei
Published: September 2022

Before entrepreneurial behavior occurs, individual personality traits have a very important impact on the formation of entrepreneurial willingness. The purpose of this research is to explore the entrepreneurial intention, practice, and management path of college graduates in a green development environment. In this study, three dimensions of green entrepreneurial traits (risk propensity, ecological values, and social responsibility) and three dimensions of green entrepreneurial motivation (fame and fortune motive, spiritual motive and responsibility motive, and green entrepreneurial intention) are determined, and a questionnaire is compiled. Then, the questionnaire survey data of college graduates is collected, and a structural equation model is constructed. The influence of risk tendency, ecological values, and social responsibility on green entrepreneurship motivation is studied in turn, and the influence of fame and fortune motive, spiritual motive, and responsibility motive on green entrepreneurship willingness is explored. Finally, the mediating role of the three dimensions of green entrepreneurial motivation in the influence of green entrepreneurial traits on green entrepreneurial willingness is tested. The study finds that the average score of families with entrepreneurial experience was 4.0526. The average score of families without entrepreneurial experience was 3.6463, and the significance index was at the level of 0.001. The same results as previous scholars have appeared, that is, students with entrepreneurial family background have stronger (green) entrepreneurial willingness. Green entrepreneurship creates green value through green products or services, drives green consumption, leads green values, and contributes to the sustainable development of society and ecology.
MiR-522-3p Targets Transcription Factor 4 to Overcome Cisplatin Resistance of Gastric Cells
Authors: Ma Guofeng , Xue Wen , Ni Jie , Tao Ran
Published: September 2022

Gastric cancer (GC) is a malignancy originating from gastric epithelial tissue. Chemoresistance to cisplatin (DDP) often leads to chemotherapy failure in GC. Previously, miR-522 was found to be associated with chemoresistance in GC cells. Thus, we attempted to clarify miR-522-3p’s role underlying chemoresistance of GC cells. RT-qPCR measured the miR-522-3p levels in untreated and DDP-treated AGS cells. RT-qPCR and Western blotting detected transcription factor 4 (TCF4) mRNA and protein levels in GC cells. AGS and AGS/DDP cell proliferation were detected by the colony formation assay. Flow cytometry analysis detected AGS and AGS/DDP cell apoptosis. Bioinformatics and dual luciferase reporter assays predicted and verified the relationship between miR-522-3p and TCF4. Rescue experiments further clarified the regulatory patterns of miR-522-3p/TGF4 in GC cells. miR-522-3p presented a downregulation in GC cells and was positively affected by DDP. TCF4 presented elevation in GC cells and was negatively affected by DDP. Mechanistically, miR-522-3p targeted TCF4 to suppress TCF4 gene expression. miR-522-3p overexpression suppressed GC cell proliferation and resistance to DDP and GC cell apoptosis was facilitated. TCF4 overexpression facilitated GC cell proliferation and resistance to DDP while repressing GC cell apoptosis. TCF4 elevation rescued changes in GC cell proliferation, apoptosis, and chemoresistance due to miR-522-3p overexpression. To sum up, miR-522-3p suppresses GC cell malignancy and resistance to DDP via targeting TCF4. Our research may provide a new biomarker for GC diagnosis and a novel direction for GC chemotherapy.
A Cross-Border e-Commerce Cold Chain Supply Inventory Planning Method Based on Risk Measurement Model
Authors: Liu Yingjun
Published: September 2022

Inventory planning results are less reliable when the statistical problem of supply chain risk factors is not considered. In conjunction with the risk measurement model, a cross-border e-commerce cold chain supply inventory planning method is proposed to effectively address the aforementioned issues. This paper aims to define the fundamental elements of the supply chain network, determine the supply chain's imbalance range, and develop a risk measurement model and also to calculate the ordering cost and storage cost, the storage cost, the cross-border e-commerce imbalance index based on the risk measurement model, the node imbalance, the dynamic programming algorithm for the imbalance node, and the identification method for the cross-border e-commerce supply chain imbalance node. Taking inventory strategy into account, the optimization model of distribution node location and the node importance evaluation system are developed. The planning of cold chain supply inventory for cross-border e-commerce is studied based on an optimized management inventory. The experimental results indicate that the throughput of the research method is between 1000 and 2500 Mbps, that the overall fluctuation range and delay are small, and that the inventory turnover rate has been significantly increased, thereby satisfying the requirements of engineering materials inventory management.
SMAC-Based WSN Protocol-Current State of the Art, Challenges, and Future Directions
Authors: Amengu Angelina Ankah , Abdulai Jamal-Deen , Katsriku Ferdinand Apietu , Adu-Manu Kofi Sarpong
Published: September 2022

Wireless Sensor Networks (WSNS) have become an indispensable tool in this epoch of technological advancements, particularly for progress made in the Internet of things. Wireless sensor nodes are deployed to collect and transmit vital data from the environment to a base station for analysis. Nevertheless, the limited battery power of the sensor nodes is rapidly drained when they stay awake for an extended period. Research has shown that significant sources of energy dissipation of sensor nodes are idle listening, packet collision, control overhead, and overhearing. One optimal solution is employing a low duty cycle mac protocol, particularly the sensor mac (SMAC) protocol. It is essential to have a detailed knowledge of the challenges identified in SMAC and solutions suggested to mitigate these challenges and the future directions. In this paper, we review techniques in SMAC protocols implemented in WSNS. In particular, we provide highlights of recent developments in the schemes used in SMAC for mitigating the challenges in SMAC and present research gaps in SMAC protocol. Finally, we discuss open issues that need to be addressed to advance the design and implementation of SMAC in WSN applications.
Research on Design of Extensible Mobile Flood Control Wall in Underground
Authors: Su Chen , Yuan Zhiwei
Published: September 2022

The current natural environment is unpredictable with heavy rains and floods happening from time to time. In order to ensure the safety of underground workers, infrastructure, and rail transit, a mobile and expandable underground flood control wall was optimized and designed. The use of mortise-and-tenon structure splicing and modular extension design effectively increases the stability and useable area of the flood wall. The finite element analysis software was used to simulate and study the force of each component under combined loads, such as static water, dynamic water, and impact, to analyze the stability performance of the assembly such as anti-sliding, anti-tilting, and internal stress. The verification results show that when the designed and studied underground flood control wall equipment is fully deployed, the maximum stress is 220.762 MPa, and the maximum offset distance is 32.334 mm, which are all within the safe range. It provides innovative ideas for the optimization of the related flood control wall structure.
IRF2 Destabilizes Oncogenic KPNA2 to Modulate the Development of Osteosarcoma
Authors: Xia Shuchi , Ma Yiqun
Published: September 2022

Osteosarcomas (OS) are the most common primary malignant bone tumor. Emerging evidence revealed that karyopherin alpha 2 (KPNA2) was strongly associated with the tumorigenesis and development of numerous human cancers. The aim of the present study was to investigate the expression pattern, biological functions, and underlying mechanism of KPNA2 in OS. Bioinformatics TFBIND online was applied to forecast transcription factor (TF) binding sites in the promoter region of KPNA2. The expression profile of KPNA2 in OS tissues were firstly assessed. CCK8, colony formation, wound healing, and Transwell assays were used to assess cell viability, proliferation, and migration in vitro, and in vivo experiments were performed to explore the effects of KPNA2 and interferon regulatory factor-2 (IRF2) on tumor growth. Furthermore, the correlation between IRF2 and KPNA2 was investigated using chromatin immunoprecipitation (ChIP), RT-qPCR, western blot, and dual-luciferase assays. KPNA2 was obviously upregulated, while IRF2 decreased significantly in OS tissues and cell lines, as well as negatively correlated with each other. KPNA2 removal remarkably suppressed OS cell growth, migration, invasion in vitro, and tumor growth in vivo, while IRF2 knockdown exerts an opposing effect. IRF2 binds to the KPNA2 promoter to modulate the malignant phenotypes of OS cells by regulating epithelial-to-mesenchymal transition (EMT). The present study demonstrated that KPNA2 performed the oncogenic function, possibly regulating tumor development through EMT. Importantly, it was confirmed that IRF2 serves as a potential upstream TF of KPNA2 involved in the regulation of EMT progress in OS.
Orai1 Inhibitors as Potential Treatments for Pulmonary Arterial Hypertension
Authors: Masson Bastien , Le Ribeuz Hélène , Sabourin Jessica , Laubry Loann , Woodhouse Emily , Foster Richard , Ruchon Yann , Dutheil Mary , Boët Angèle , Ghigna Maria-Rosa , De Montpreville Vincent Thomas , Mercier Olaf , Beech David J. , Benitah Jean-Pierre , Bailey Marc A. , Humbert Marc , Montani David , Capuano Véronique , Antigny Fabrice
Published: September 2022

Background:

Pulmonary arterial hypertension (PAH) is characterized by progressive distal pulmonary artery (PA) obstruction, leading to right ventricular hypertrophy and failure. Exacerbated intracellular calcium (Ca
2+
) signaling contributes to abnormalities in PA smooth muscle cells (PASMCs), including aberrant proliferation, apoptosis resistance, exacerbated migration, and arterial contractility. Store-operated Ca
2+
entry is involved in Ca
2+
homeostasis in PASMCs, but its properties in PAH are unclear.

Methods:

Using a combination of Ca
2+
imaging, molecular biology, in vitro, ex vivo, and in vivo approaches, we investigated the roles of the Orai1 SOC channel in PA remodeling in PAH and determined the consequences of pharmacological Orai1 inhibition in vivo using experimental models of pulmonary hypertension (PH).

Results:

Store-operated Ca
2+
entry and Orai1 mRNA and protein were increased in human PASMCs (hPASMCs) from patients with PAH (PAH-hPASMCs). We found that MEK1/2 (mitogen-activated protein kinase kinase 1/2), NFAT (nuclear factor of activated T cells), and NFκB (nuclear factor-kappa B) contribute to the upregulation of Orai1 expression in PAH-hPASMCs. Using small interfering RNA (siRNA) and Orai1 inhibitors, we found that Orai1 inhibition reduced store-operated Ca
2+
entry, mitochondrial Ca
2+
uptake, aberrant proliferation, apoptosis resistance, migration, and excessive calcineurin activity in PAH-hPASMCs. Orai1 inhibitors reduced agonist-evoked constriction in human PAs. In experimental rat models of PH evoked by chronic hypoxia, monocrotaline, or Sugen/hypoxia, administration of Orai1 inhibitors (N-{4-[3,5-bis(Trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-4-methyl-1,2,3-thiadiazole-5-carboxamide [BTP2], 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline [JPIII], or 5J4) protected against PH.

Conclusions:

In human PAH and experimental PH, Orai1 expression and activity are increased. Orai1 inhibition normalizes the PAH-hPASMCs phenotype and attenuates PH in rat models. These results suggest that Orai1 should be considered as a relevant therapeutic target for PAH.
DATA- AND KNOWLEDGE-DRIVEN SMART CITY STRATEGIES: RESEARCH ON IMPLEMENTATION CHALLENGES OF LOCAL GOVERNMENTS IN TURKEY
Authors: ÖZDEMİR Akın
Published: September 2022

The present study sought an answer to the question, “What kind of challenges do local governments in Turkey confront while implementing data- and knowledge-driven smart city strategies?”. It seems noteworthy to explore tacit links between such implementation challenges through a field study employing an exploratory design. Thanks to the original theoretical framework enriched with empirical findings, this research is expected to bring practical and theoretical contributions to the smart city literature. The data were gathered through face-to-face, semi-structured interviews with 23 personnel of Sakarya Metropolitan Municipality (SMM), which has become the very first local government in Turkey to have introduced a smart city strategy and action plan. In this field research employing a single case, the content analysis technique was utilized to interpret the findings. Accordingly, SMM is faced with basically data-driven difficulties such as data security, poor technological and physical infrastructure, insufficient budget and high costs, dubious legal regulations and bureaucracy, resistance to change, lack of human resources and high turnover, and digital divide while implementing its smart city strategy.
Understanding the Policies of the brics Countries in R2P Cases: An English School Perspective
Authors: Tüzgen Nilay , Gök Gonca Oğuz
Published: September 2022

This article’s main aim is to evaluate the position of brics ‘as a group’ towards the Responsibility to Protect (r2p) norm by locating it in the framework of the English School’s pluralist versus solidarist debate. It traces the pluralist and solidarist elements in brics discourses and decisions towards r2p by scrutinising the content of the ten brics summit declarations between 2011 and 2020 and the voting of brics members on UN Security Council resolutions regarding seven cases involving atrocity crimes (Syria, Yemen, Mali, Ivory Coast, Central African Republic, South Sudan, Libya) discussed at the UN Security Council. The article argues that although there is an obvious quantitative increase in brics common pluralist agenda, they do not demonstrate group solidarity in practice and have not yet socialised to act as a group on the r2p as a key norm of global governance. Therefore, their position as a group towards r2p could best be framed as ‘Charter solidarism’ in principle per se, not in practice.
Education In The Scottish Parliament
Authors: Redford Morag
Published: September 2022

Preamble

This paper follows on from the previous bulletin (Redford 2021), which covered the education remit of the Parliament’s Education and Skills Committee between February and August 2021. The following bulletin covers the education remit of the Education, Children and Young People Committee from September 2021 to January 2022.
The Lichen Flora on Quercus in the Tamentout Forest of Algeria
Authors: BELGUIDOUM AMINA , LOGRADA TAKIA , RAMDANI MESSAOUD
Published: September 2022

Lichens are major components of forest ecosystems. However, their accurate identification at species level is often difficult, especially in poorly investigated areas. The objective of this study is an inventory of epiphytic lichens in the Tamentout Forest on three types of phorophytes, Quercus faginea, Q. suber and Q. ilex. In this region, 68 epiphytic lichen species have been identified, belonging to 23 families and 36 genera. The specific richness on the three phorophytes was different. Quercus suber, the dominant phorophyte, supports the highest number of species compared to Q. faginea, and Q. ilex. An analysis of growth forms shows that all are represented in the study area. However, crustose and foliose lichens are the most common ones. As a result of our inventory, we report Parmeliella testacea new to Algeria, and list 20 lichen species now protected by Algerian legislation.
Disability and Australian higher education: The case for an Accessible model of disability support
Authors: Pitman Tim , Brett Matt
Published: September 2022

This article explores a century and a half of supporting students with disabilities in Australian higher education, spanning the introduction of mass public education legislation in 1872 through to 2022. The article documents the transition from a paradigm in which disability was not integral to universal public instruction to systemic approaches to provision of reasonable adjustments. This transition has opened opportunities for persons with disabilities in some regards yet impedes full inclusion in others. Theoretically, we draw upon multiple paradigms of disability to explore how disability support has evolved in the Australian higher education sector, including ‘charitable’, ‘inspiration porn’, ‘medical’, ‘social’, ‘prosthetic’ and ‘ecological’ models. We offer qualitative and quantitative examples across time to illustrate these evolving paradigms. We then explore an alternative model of disability, which we define as an ‘Accessible’ model of disability support.
Exposure to Death and Bereavement: An Analysis of the Occupational and Psychological Wellbeing of Funeral and Mortuary Operators
Authors: Guidetti Gloria , Grandi Annalisa , Converso Daniela , Colombo Lara
Published: September 2022

Confronting death and suffering represent central work-related contents in the funeral industry occupations. Despite past research evidence on the role of psychosocial risks, a positive side of the relationship with death exposure has also been highlighted. To expand research on these topics, the aim of the present study was to analyze the role of death exposure in affecting funeral and mortuary operators’ wellbeing. Analysis of variance was performed on 201 questionnaires to analyze differences between work exposure. Workers always/very often exposed to death through sight or manipulation of bodies showed better psychological and occupational wellbeing compared to those not at all/very rarely committed with these tasks. Those who interacted very frequently with the bereaved showed better psychological and occupational wellbeing, compared to those who were never/very rarely committed with these relational tasks. Insights on the role of death and suffering exposure and information for occupational health practitioners are discussed.
Underchallenged and overly bored: Why rigor is important in the middle school classroom
Authors: Tinkel Dani
Published: September 2022

Middle schools often struggle to provide students with the necessary academic rigor to promote academic growth. Many students experience academic stagnation when schools fail to provide appropriate academic services. Dani Tinkel’s article examines how the limited priorities of middle school inadvertently promote disengagement and underachievement and what schools can do to ensure that all middle school students have opportunities to be cognitively challenged, including through programs like Advancement Via Individual Determination (AVID) and the Schoolwide Enrichment Model (SEM), by providing a vision for a balanced middle school experience.
Reaching for consensus about preschool curricula
Authors: Reid Jeanne L. , Kagan Sharon Lynn
Published: September 2022

The need for equitable access to high-quality preschool has recently gained unprecedented attention. As states and districts strive to expand access while promoting quality, curriculum quality has emerged as a critical component of preschool programs that promote young children’s learning. Yet many educators make curricular decisions with insufficient guidance on what constitutes curricular quality. Indeed, deep divisions in the field are evident regarding how to define quality in preschool curricula. Jeanne L. Reid and Sharon Lynn Kagan explore the areas of consensus and disagreement among early education leaders. They argue that — using guidance from a study at the National Academies of Sciences, Engineering, and Medicine and drawing from international models of curriculum frameworks — the field can move toward consensus on what constitutes a high-quality curriculum and thus help to fulfill the promise of equitable access to high-quality preschool.
Policy Solutions: The case for democratic reforms in urban school districts
Authors: Collins Jonathan E.
Published: September 2022

The voices of students of color often are left out of discussions of urban school reform conversations when they should be central to reform efforts. Jonathan Collins suggests looking at democratic reform as an avenue to bring those voices forward. Participatory budgeting, for example, introduces students to the idea that they could decide how money is spent at their schools. This allows them to shape their environment and address the problems they see as most pressing.
Backtalk: Educate, don’t erase
Authors: Pittinsky Todd L.
Published: September 2022

When hate-fueled acts of vandalism or violence happen, school leaders’ impulse is often to sweep them away as quickly as possible. Todd Pittinsky encourages them to use these incidents as opportunities to educate. Students and community members may not be aware of the antisemitism and other forms of hate within their own communities and going public can serve as a wake-up call. Creating educational events in response can give students a sense of empowerment.
Comparative Population Pharmacokinetic‐Pharmacodynamic Analysis for Piroxicam‐β‐Cyclodextrin and Piroxicam
Authors: Wang Dan , Miller Raymond , Zheng Jenny , Hu Chuanpu
Published: September 2022

Piroxicam (Feldene®) is indicated for osteoarthritis and rheumatoid arthritis but not analgesia due to its delayed onset of pain relief. Piroxicam‐β‐cyclodextrin (PBCD) was developed for pain indication by virtue of the increased absorption rate of piroxicam. Forty‐eight patients received a single dose of PBCD or Feldene (10, 20, and 40 mg) in a randomized study, and piroxicam plasma concentration and pain relief were measured. The purpose of the study was to investigate the PK‐PD relationship of piroxicam, determine the optimal dose, and evaluate the effect of increased absorption rate on analgesic effect of piroxicam for the pain model studied. The pharmacokinetic data were best described by a two‐compartment model with first‐order absorption. The absorption rate of PBCD (5/h) was faster than Feldene (1.41/h). Pain relief was found to be increasing with drug concentration in a hypothetical effect compartment (Emax model). The estimated half‐life of the equilibration between plasma and effect site was about 2.34 hours. Monte Carlo simulation showed that the time when at least 50% of the patients have a 75% probability of achieving meaningful pain relief (pain intensity difference (PID ≥ 1) for PBCD and Feldene at a dose of 20 mg was about 0.5 and 1.5 hours, respectively. PBCD demonstrated an advantage with an onset of pain relief 1 hour earlier than Feldene.
The Effect of Telmisartan on the Steady‐State Pharmacokinetics of Digoxin in Healthy Male Volunteers
Authors: Stangier Joachim , Su Chung‐An P. F. , Hendriks Maarten G. C. , van Lier Jan J. , Sollie Frans A. E. , Oosterhuis Berend , Jonkman Jan H.G.
Published: September 2022

A multiple‐dose, open‐label, two‐period, crossover randomized study was conducted in 12 healthy male volunteers to investigate the effect of multiple‐dose telmisartan on the steady‐state pharmacokinetics of digoxin. On day 1 of a 7‐day medication period, subjects received a loading dose of digoxin 0.5 mg in the morning, followed by an evening dose of digoxin 0.25 mg, either alone or together with telmisartan 120 mg administered in the morning. On the subsequent 6 days, either digoxin 0.25 mg or digoxin 0.25 mg together with telmisartan 120 mg was administered once daily in the morning. Each 7‐day medication period was separated by a washout period of ≥ 14 days. A steady‐state plasma concentration‐time profile was assessed for digoxin during each period and for telmisartan during the period with the combined treatment. Multiple‐dose telmisartan administered with digoxin resulted in higher serum digoxin concentrations than those observed after digoxin given alone. Geometric mean AUC144–168, Cmax, and Cmin values for digoxin when given in combination with telmisartan were higher by 22%, 50%, and 13%, respectively, compared with values when given alone. However, the 90% confidence interval for the geometric mean of Cmin was within the predefined 80% to 125% range of no interaction. During combination medication, digoxin tmax was shorter and Cmax/AUC144–168 increased, suggesting that the rise in digoxin Cmax may be due to more rapid drug absorption. Study medications were well tolerated, with the incidence, nature, and intensity of adverse events being similar during both medication periods. Also, no changes in vital signs or clinical laboratory tests were observed during the study. Although there was some evidence for a pharmacokinetic interaction between digoxin and telmisartan found in this study, the safety and tolerability of digoxin were unaffected by concurrent administration of telmisartan in the study population. Since any symptoms of overdose are related only to steady state and not peak concentrations and due to the fact that there was a lack of effect on serum trough levels of digoxin in this study, it is unlikely that the findings have any clinical relevance. The magnitude of increase in digoxin concentrations is comparable with increases observed with administration of calcium antagonists, carvedilol, ACE inhibitors such as captopril, and antiarrhythmic drugs such as amiodarone, quinidine, and propafenone. Monitoring of serum digoxin concentrations should be considered when patients first receive telmisartan and in the event of any changes in telmisartan dose.
Crossover Trials Should Not Be Used to Test One Treatment against Another Treatment with a Totally Different Chemical Class/Mode of Action
Authors: Cleophas Ton J.
Published: September 2022

Comparisons of treatments with totally different chemical class/mode of action are at risk of a negative correlation between treatment responses. The crossover design is flawed when correlation between treatment responses is negative. The objective of this study is to assess whether this flaw is prevalent in the literature. Fourteen randomized controlled crossover studies were assessed for correlation levels in relation to their type of treatment comparison. Correlation coefficient (r) was calculated using the t‐statistic: p‐values were turned into t‐values for the degrees of freedom, and r was calculated using the formula for the pooled standard error of the mean (SEM): (pooled SEM)2 = SEM12 + SEM22 − 2 r SEM1•SEM2. Crossover studies comparing treatments with totally different chemical class/mode of action were frequently negative, and this was obviously due to their correlation between treatment responses' being negative. Crossover studies comparing similar treatments frequently had a positive correlation, and this added extra sensitivity in the treatment comparison; 27% of the crossover hypertension studies compared completely different treatments, and they should not have been performed in the form of a crossover study. The author's conclusion was that crossover trials should not be used to test one treatment against another treatment with a totally different chemical class/mode of action. Crossover trials are particularly sensitive to compare treatments from one chemical class with one mode of action. It is hoped that this work affects the design of future crossover trials.
Celecoxib Does Not Affect the Antiplatelet Activity of Aspirin in Healthy Volunteers
Authors: Wilner Keith D. , Rushing Margaret , Walden Catherine , Adler Rebecca , Eskra James , Noveck Robert , Vargas Ramon
Published: September 2022

Celecoxib is a novel cyclooxygenase‐2‐specific inhibitor for the management of acute pain, primary dysmenorrhea, and the signs and symptoms of arthritis. This double‐blind, placebo‐controlled study in 16 healthy volunteers evaluated whether celecoxib alters the effect of concomitant aspirin on platelet function. Volunteers received celecoxib (400 mg/day) or placebo for 4 days. On day 5, they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo. Thromboxane and platelet aggregation response to adenosine 5′‐diphosphate (ADP), collagen, and arachidonic acid were measured before the first dose of celecoxib or placebo (baseline) and before dosing and 2 and 8 hours postdose on day 5. There was no significant difference in thromboxane inhibition between the two groups (percent inhibition: placebo 99.4%, celecoxib 99.0%; p = 0.555). There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP, collagen, or arachidonic acid between the groups. Therefore, these data indicate that celecoxib does not alter the effects of aspirin on platelet function.
The Effect of Erythromycin and Clarithromycin on the Pharmacokinetics of Intravenous Digoxin in Healthy Volunteers
Authors: Tsutsumi Kimiko , Kotegawa Tsutomu , Kuranari Masae , Otani Yasukiyo , Morimoto Takuya , Matsuki Shunji , Nakano Shigeyuki
Published: September 2022

Several case reports have suggested an interaction between digoxin and macrolide antibiotics. The authors investigated the effect of erythromycin and clarithromycin on the pharmacokinetics of intravenously administered digoxin (0.5 mg) in healthy subjects. Nine male subjects participated in three studies (digoxin alone, digoxin with erythromycin, and digoxin with clarithromycin). Subjects took erythromycin (800 mg per day) or clarithromycin (400 mg per day) on the day before digoxin dosing and during the kinetic study. Neither of the macrolides affected serum digoxin concentration‐time curves. However, more than 1.3‐fold increases in urinary digoxin excretions were observed during erythromycin and clarithromycin coadministration compared with digoxin alone. There were significant differences in renal clearance between macrolide coadministration and the control condition (digoxin alone: 98.4 ml/min; digoxin with erythromycin: 137.3 ml/min; digoxin with clarithromycin: 133.6ml/min). In conclusion, neither erythromycin nor clarithromycin has a significant effect on serum digoxin disposition after an intravenous administration. Renal digoxin excretion is not inhibited but rather enhanced by both macrolides.
Single‐Dose Pharmacokinetics of Nizatidine (Axid®) in Children
Authors: Abdel‐Rahman Susan M. , Johnson Franklin K. , Manowitz Neil , Holmes Gregory B. , Kearns Gregory L.
Published: September 2022

The pharmacokinetics of nizatidine following a single 5.0 mg/kg oral dose given as an extemporaneous liquid formulation in apple juice was examined in 12 healthy children (8.0 +− 2.4 years, 30.7 +− 8.4 kg). Nizatidine and N‐desmethylnizatidine were quantitated by HPLC/MS from five postdose blood samples taken over a 12‐hour period. The apparent terminal elimination rate constant for nizatidine in the pediatric subjects (0.58 +− 0.8 h−1) was virtually identical to that (0.54 +− 0.13 h−1) previously reported from adult studies. When corrected for an estimated 30% reduction in nizatidine oral bioavailability observed in adults upon coingestion of the drug with other fruit/vegetable juices, nizatidine pharmacokinetic parameter estimates (e.g., Cmax' CL/F, Vss/F) in our pediatric subjects were similar to those previously reported in adults who were administered dimensionally similar (e.g., approximately 4 mg/kg) solid oral doses of the drug. Examination of the mean area under the curve (i.e., AUC0–∞) for nizatidine and N‐desmethylnizatidine suggested an approximate 15% metabolic conversion of the parent drug. Finally, nizatidine plasma concentrations in pediatric patients following a single 5.0 mg/kg oral dose exceeded the EC50 value of the drug for gastric acid suppression determined from adult studies for approximately 6 hours.
Drugs Released for Clinical Use
Authors: de HAEN PAUL
Published: September 2022

This listing includes new single chemical entities and preparations, duplicate single products, and combination products that have been made available for clinical use by the U.S. Food and Drug Administration during the period from February 21 to April 20, 1971. This information is taken from the manufacturer's package insert or brochure, which should be consulted for further details on indications, dosage, contraindications, and adverse reactions.
Pharmacokinetics and Pharmacodynamics of Famotidine in Infants
Authors: James Laura P. , Marotti Tonya , Stowe Cindy D. , Farrar Henry C. , Taylor Bonnie J. , Kearns Gregory L.
Published: September 2022

The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5‐mg/kg infusion of famotidine, timed serum (n = 6), urine (24‐hour collection), and repeated measurements of gastric pH were obtained. The mean ± standard deviation maximum plasma concentration (Cmax) was 640.66 ± 250.66 ng/mL, the elimination half‐life (t1/2β) was 10.51 ± 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 ± 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 ± 0.061 L/hr/kg and 0.093 ± 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2β, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24‐hour sampling point. In this study, the t1/2β of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.
Absolute Bioavailability and Dose Proportionality of Oral Ganciclovir after Ascending Multiple Doses in Human Immunodeficiency Virus (HIV)‐Positive Patients
Authors: Jung Donald , Griffy Kay , Wong Rodney , Colburn Wayne , Hulse Jim
Published: September 2022

This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open‐label, randomized, four‐treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5‐mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24‐hour time interval. Mean steady‐state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 μg/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady‐state area under the concentration‐time curve (AUC0–24) for the 6,000 mg/day oral regimen approached that of the single‐dose intravenous regimen. There was a proportional increase in AUC0–24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.
Preliminary Evaluation of Progestins as Inducers of Cytochrome P450 3A4 Activity in Postmenopausal Women
Authors: Tsunoda Shirley M. , Harris Robert Z. , Mroczkowski Patrick J. , Benet Leslie Z.
Published: September 2022

The effects of intramuscularly and orally administered medroxyprogesterone acetate on cytochrome P450 3A4 (CYP3A4) activity were investigated in twelve postmenopausal women in a randomized, crossover study. Unbound prednisolone clearance and the erythromycin breath test were used as markers of CYP3A4 activity. After 2 months of intramuscular progestin therapy, unbound prednisolone clearance increased by 25% in five of six subjects. Similarly, after intramuscular progestin therapy, results from the erythromycin breath test showed a 23% mean increase in CYP3A4 activity. In contrast, 2 months of oral progestin therapy had no effect on prednisolone pharmacokinetics or erythromycin metabolism. These results suggest that parenterally but not orally administered progestins may induce or activate the CYP3A4 enzyme system, leading to an increased metabolism of many CYP3A4 substrates.
A Review of Potential Cardiovascular Uses of Intravenous Glucagon Administration
Authors: White C. Michael
Published: September 2022

Glucagon is a counter‐regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta‐1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta‐blocker overdose and has evidence for use in verapamil and imipramine overdose as well. Glucagon has been used as adjunctive therapy in shock situations and heart failure but is inferior to catecholamines. An interesting potential indication for glucagon is in treating postcountershock asystole.
A Comparison of the Pharmacokinetics and Tolerability of Riluzole after Repeat Dose Administration in Healthy Elderly and Young Volunteers
Authors: Liboux Aimé Le , Cachia Jean‐Paul , Kirkesseli Stéphane , Gautier Jean‐Yves , Guimart Colette , Montay Guy , Peeters Pierre A. M. , Groen Edwin , Jonkman Jan H. G. , Wemer Johannes
Published: September 2022

The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender‐ and weight‐matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender. The mean terminal elimination half‐life (t1/2), however, was statistically significant between elderly and young subjects. Riluzole was well tolerated upon repeat dose administration. Headache was the most frequent adverse event reported, and there was no overt difference in the type, frequency, or severity of adverse events between elderly and young volunteers or between genders. In conclusion, these results indicate that no dosage adjustments of riluzole are required in the elderly.
Assessment of the Potential Pharmacokinetic and Pharmacodynamic Interactions between Erythromycin and Argatroban
Authors: Tran Jonathan Q. , Di Cicco Robert A. , Sheth Sunita B. , Tucci Marcella , Peng Lana , Jorkasky Diane K. , Hursting Marcie J. , Benincosa Lisa J.
Published: September 2022

Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers in an open‐label, crossover study with a 5‐day washout between regimens. Argatroban 1 μg/kg/min was infused alone for 5 hours (regimen A) and again on day 6 of a 7‐day oral regimen of 500 mg erythromycin four times daily (regimen B). Serial blood samples for the determination of activated partial thromboplastin time (aPTT) and argatroban concentrations were collected for up to 48 hours following infusion. Mean values for argatroban area under the concentration‐time curves (AUC0 — inf), maximum concentration (Cmax), and half‐life (t1/2) were similar between regimens. Mean aPTT values were not affected significantly by the concomitant administration of argatroban and erythromycin compared to argatroban alone. No serious adverse events or bleeding episodes occurred during the study. These results suggest that oxidative metabolism by CYP3A4/5 is unlikely to be an important in vivo elimination pathway for argatroban. Therefore, coadministration of CYP3A4/5 inhibitors should not require a modification in the dosage of argatroban.
Pharmacokinetics of a Recombinant Modified Amino Terminal Fragment of Bactericidal/Permeability‐Increasing Protein (rBPI21) in Healthy Volunteers
Authors: Bauer Robert J. , Wedel Nancy , Havrilla Nancy , White Mark , Cohen Albert , Carroll Stephen F.
Published: September 2022

Phase I pharmacokinetic and safety studies were conducted in healthy volunteers with rBPI21, a recombinant protein derived from the amino terminal domain of human bactericidal/permeability‐increasing protein. rBPI21 was administered as a 30‐minute infusion at doses of 0.25 to 4 mg/kg or as a 24‐ to 48‐hour infusion at doses of 2 to 8 mg/kg. For the 30‐minute infusions, the clearance of rBPI21 decreased with increasing dose from 8.4 mL/min/kg at 0.25 mg/kg to 3.3 mL/min/kg at 4 mg/kg. For rBPI21 infused over 24 to 48 hours the clearance was 10 to 11 mL/min/kg. The concentration‐time profile of rBPI21 was well described by a three‐compartmental model with parallel first‐order and Michaelis‐Menten (saturable) elimination. This model for the clearance of rBPI21 has been useful in estimating starting doses for therapeutic clinical trials.
How family socioeconomic status, peer behaviors, and school-based intervention on healthy habits influence adolescent eating behaviors
Authors: Moreno-Maldonado Concepción , Ramos Pilar , Moreno Carmen , Rivera Francisco
Published: September 2022

Psychologists in schools can play an important role in developing policies and programs to promote healthy eating habits. This study analyses the contributions of family socioeconomic status, peer influence (schoolmates’ food consumption), and school-based nutrition interventions to explain adolescent eating behaviors. Data were obtained from the 2014 Health behaviour in school-aged children survey in Spain, with a sample of 6,851 adolescents (11- to 16-years-old). The results suggest that school-based healthy-eating programs could improve by considering parental education level and by implementing interventions focused on the peer social network. Policies that limit access to unhealthy products in schools – rather than simply offering healthy foods alongside unhealthy products – could be more effective.
Social-emotional classroom climate and academic achievement for Chinese elementary students: The roles of convergent and divergent thinking
Authors: Cheng Li , Zhang Xiaowei , Lin Junqi , Dong Yan , Zhang Jiatong , Tong Zhuo
Published: September 2022

This study aims to explore the effects of the social-emotional classroom climate on academic achievement in mathematics and literature for elementary students in grades 3 through 6. The research specifically focuses on the indirect role of creative thinking (convergent and divergent thinking). Structural equation modeling techniques were used to examine data collected from 1365 Chinese elementary students. The results indicate that in mathematics and literature classrooms, (1) the social-emotional climate had a positive effect on school achievement, and (2) divergent and convergent thinking play indirect roles between social-emotional climate and academic achievement. The findings suggest that elementary students’ positive perception of social-emotional classroom climate, including the perceptions of teacher support and student cohesiveness, can promote divergent and convergent thinking and ultimately contribute to the output of academic achievement in mathematics and literature.
Correlation of maternal dietary intake with breast milk composition and infant growth
Authors: Mexitalia Maria , Ardian Rendy Yoga , Pratiwi Rina , Panunggal Binar
Published: September 2022

Background: Maternal dietary intake during the period of lactation has an impact on infants growth. Macronutrients in breast milk are affected by several factors such as maternal dietary intake and maternal nutritional status. This study aims to prove the association between maternal protein and fat intake with the composition of breast milk and growth of infants (age 0–6 months). Methods: Prospective study was conducted for 6 months in 41 mother-infant pairs who were exclusively breastfed, and visited to hospitals or health centres. The mothers age is <40 years old with normal and single pregnancy. The breast milk was collected and analyzed using Human Milk Analyzer. Results: There was a negative correlation between maternal protein intake and breast milk composition at 3 months old infants ( p = 0.042), between fat intake with HAZ score at 2 weeks ( p = 0.048), and between protein intake with HAZ score at 3 months ( p = 0.049). Finally, there was a significant increase in WAZ and HAZ score in all sample groups. Although the maternal protein intake of our subjects were only at 83% of Indonesian's RDA average, the protein composition of breast milk and the growth of the infants was sufficient. Conclusion: There is correlation between maternal dietary intake with the composition of breastmilk and infant growth. Even though the calories and protein intake of the mother is lower than the RDA, the breast milk is still sufficient for the growth of infants aged 0–6 months who are exclusively breastfed.
Sex workers’ peer support during the COVID-19 pandemic: Lessons learned from a study of a Portuguese community-led response
Authors: De Jesus Moura Joana , Pinto Marta , Oliveira Alexandra , Andrade Maria , Vitorino Sérgio , Oliveira Sandra , Matos Roberta , Maria Margarida
Published: September 2022

To respond to the consequences felt by the COVID-19 pandemic, a community-led intervention was developed by the Portuguese national Movement of Sex Workers. With this exploratory study, we aimed to document their work and analyze their perceptions of this impact. To do so, we interviewed them individually, between May and August of 2020. Additionally, we analysed an Excel Sheet that contained the needs assessment and the support provided by the Movement. The content analysis of both suggests that the impact of the pandemic might have been exacerbated by the social inequalities caused by the prostitution stigma and characteristics such as gender, migration status, race, and socioeconomic status. This study calls for the inclusion of sex workers’ voices in the design of policies and responses related to the commerce of sex. The consolidation of a Portuguese Movement of Sex Workers is also noted.
Avoidance of Overt Precipitation and Patient Harm Following Errant Y‐Site Administration of Calcium Chloride and Parenteral Nutrition Compounded With Sodium Glycerophosphate
Authors: Anderson Collin , Stidham Chanelle , Boehme Sabrina , Cash Jared
Published: September 2022

Calcium phosphate precipitates present 1 of many challenges associated with parenteral nutrition (PN) compounding. Extensive research has led to the establishment of solubility curves to guide practitioners in the prescription and preparation of stable PN. Concurrent dosing of intravenous products via y‐site administration with PN can alter the chemical balance of the solution and modify solubility. Medications containing calcium or phosphate should not be administered in the same line as PN, due to the high potential for precipitation. Herein a case is reported from a pediatric cardiac intensive care unit where a physician ordered the administration of calcium chloride. The bedside nurse added the calcium chloride intermittent infusion as a y‐site administration with the patient’s PN. The patient’s PN had been compounded with sodium glycerophosphate, temporarily available in the United States during a sodium phosphate shortage. The patient did not experience any observable adverse effects from the y‐site administration with PN. Following this event, the scenario was replicated to investigate any precipitation risk associated with the y‐site administration. Additionally, a separate PN solution containing sodium phosphate rather than glycerophosphate was compounded and used in a laboratory setting to demonstrate the potential for harm had the patient’s PN been compounded with an inorganic phosphate source. This replication of the error demonstrates the additional safety gained in relation to precipitation risk when PN solutions are compounded with sodium glycerophosphate in place of sodium phosphate.