bluuebunny/crossref_metadata_2025_split huggingface dataset:
The design, synthesis, pharmacokinetic and pharmacodynamic evaluation of acyloxyalkyl-substituted T705 prodrugs
Authors: Li Xingzhou , Zhang Tianhong , Zhong Wu 
Published: October 2019

Background:
The pharmacokinetic properties of T705 are not optimal for the development of new drugs.

Objective:
To improve the pharmacokinetic properties of T-705, structure modification of T-705 was conducted using a prodrug strategy.

Method:
The acidic amide H atom (N4-H) of T705 was attempted to be replaced with acyloxyalkyl groups following the prodrugs development strategy for carboxylic acids, and the resulting compounds were investigated whether could work as prodrugs and contribute to improving the pharmacokinetic properties of the parent compound T705 in vivo.

Results:
4-acyloxyalkyl-T705 (4a–e), did act as prodrugs in vivo. 4-iso-butyryloxymethyl-T705 (4a) and 4-acetoxymethyl-T705 (4b) could significantly improve the plasma concentration and systemic exposure for T705, compound 4a displayed non inferior anti-influenza activities, compared with its parent drug T705.

Conclusion:
Our prodrugs development strategy for T705 is feasible, which may serves as a reference to prodrugs development of similar heterocyclic amides compounds.
Pharmacokinetics of Picroside I, II, III, IV in Rat Plasma by UPLCMS/ MS
Authors: Xie Haili , Lu Xiaojie , Jin Weiqiang , Zhou Hua , Chen Dongxin , Wang Xianqin , Zhou Yunfang 
Published: October 2019

Background:
Modern pharmacological studies show that rhizoma coptidis has protective
effects on the liver, gallbladder, kidney, cerebral ischemia-reperfusion, local hypoxia injury, antiinflammatory,
bone injury, nerve cells and myocardial cells. The effective components have been isolated
from picroside I, II, III and IV.

Introduction:
A selective and sensitive ultra-performance liquid chromatography electrospray ionization
tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed for the simultaneous
quantitative determination of picroside I, II, III and IV in rat plasma to aid the pharmacokinetics studies.

Method:
Sprague-Dawley (SD) rats were orally administered with 10 mg/kg, intravenously injected
with 1 mg/kg for the mixture of picroside I, II, III and IV. The biological samples were collected at
0.083 3 h, 0.25 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h. A UPLC BEH C18 column (2.1 mm×50 mm,
1.7 μm) was used for chromatographic separation with the mobile phase consisting of acetonitrile and
0.1% formic acid by gradient elution. The flow rate was 0.4 mL/min. Multiple reaction monitoring
(MRM) transitions were m/z 491.1→147.1 for picroside I, m/z 511.1→234.9 for picroside II, m/z
537.3→174.8 for picroside III and m/z 507.3→163.1 for picroside IV in negative ion mode.

Result:
The inter-day precision was less than 13%, the intra-day precision was less than 15%. The
accuracy ranged from 89.4% to 111.1%. Recovery was higher than 79.1%, and the matrix effect ranged
from 96.2% to 109.0%.

Conclusion:
The sensitive, rapid and selective UPLC-MS/MS method can be applied to the pharmacokinetic
study of picroside I, II, III and IV in rats.
Mechanism of a Novel Camptothecin-Deoxycholic Acid Derivate Induced Apoptosis against Human Liver Cancer HepG2 Cells and Human Colon Cancer HCT116 Cells
Authors: Xiao Linxia , Xu Jialin , Weng Qi , Zhou Leilei , Wang Mengke , Liu Miao , Li Qingyong 
Published: October 2019

Background:Camptothecin (CPT) is known as an anticancer drug in traditional Chinese medicine. However, due to the lack of targeting, low solubility, and instability of CPT, its therapeutic applications are hampered. Therefore, we synthesized a series of CPT-bile acid analogues that obtained a national patent to improve their tumour-targeting chemotherapeutic effects on liver or colon cancers. Among these analogues, the compound G2 shows high antitumor activity with enhanced liver targeting and improved oral absorption. It is significant to further investigate the possible anticancer mechanism of G2 for its further clinical research and application.Objective:We aimed to unearth the anticancer mechanism of G2 in HepG2 and HCT116 cells.Methods:Cell viability was measured using MTT assay; cell cycle, Mitochondrial Membrane Potential (MMP), and cell apoptosis were detected by flow cytometer; ROS was measured by Fluorescent Microplate Reader; the mRNA and protein levels of cell cycle-related and apoptosis-associated proteins were examined by RT-PCR and western blot, respectively.Results:We found that G2 inhibited cells proliferation of HepG2 and HCT116 remarkably in a dosedependent manner. Moreover, G2-treatment led to S and G2/M phase arrest in both cells, which could be elucidated by the change of mRNA levels of p21, p27 and Cyclin E and the increased protein level of p21. G2 also induced dramatically ROS accumulated and MMP decreased, which contributed to the apoptosis through activation of both the extrinsic and intrinsic pathways via changing the genes and proteins expression involved in apoptosis pathway in both of HepG2 and HCT116 cells.Conclusion:These findings suggested that the apoptosis in both cell lines induced by G2 was related to the extrinsic and intrinsic pathways.
MDM2-p53 Interaction Inhibitors: The Current State-of-Art and Updated Patent Review (2010-Present)
Authors: Rusiecki Rafał , Witkowski Jakub , Jaszczewska-Adamczak Joanna 
Published: October 2019

Background:Mouse Double Minute 2 protein (MDM2) is a cellular regulator of p53 tumor suppressor (p53). Inhibition of the interaction between MDM2 and p53 proteins is a promising anticancer therapy.Objective:This updated patent review is an attempt to compile the research and achievements of the various researchers working on small molecule MDM2 inhibitors from 2010 to date. We provide an outlook into the future for therapy based on MDM2 inhibition by presenting an overview of the most relevant patents which have recently appeared in the literature.Methods:Literature and recent patents focusing on the anticancer potential of MDM2-p53 interaction inhibitors and its applications have been analyzed. We put the main emphasis on the most perspective compounds which are or were examined in clinical trials.Results:Literature data indicated that MDM2 inhibitors are therapeutically effective in specific types of cancer or non-cancer diseases. A great number of patents and research work around new MDM2- p53 interaction inhibitors, possible combinations, new indications, clinical regimens in previous years prove that this targeted therapy is in the scope of interest for many business and academic research groups.Conclusion:Novel MDM2 inhibitors thanks to higher potency and better ADME properties have shown effectiveness in preclinical and clinical development however the final improvement of therapeutic potential for MDM2 inhibitors might depend on the useful combination therapy and exploring new cancer and non-cancer indications.
Gender Dysphoria, Eating Disorders and Body Image: An Overview
Authors: Milano Walter , Ambrosio Paola , Carizzone Francesa , De Biasio Valeria , Foggia Giuseppina , Capasso Anna 
Published: October 2019

Background::Gender dysphoria is a clinical condition in which a state of inner suffering, stress and anxiety is detected when biological sex and a person's gender identity do not coincide. People who identify themselves as transgender people are more vulnerable and may have higher rates of dissatisfaction with their bodies which are often associated with a disorderly diet in an attempt to change the bodily characteristics of the genus of birth and, conversely, to accentuate the characteristics of the desired sexual identity.Aim::The purpose of this work is to examine the association between dissatisfaction with one's own body and eating and weight disorders in people with gender dysphoria.Results::Gender dysphoria and eating disorders are characterized by a serious discomfort to the body and the body suffers in both conditions. The results of our study suggest that rates of pathological eating behaviors and symptoms related to a disordered diet are high in patients with gender dysphoria and that standard screening for these symptoms must be considered in both populations at the time of evaluation and during the course of the treatment.Conclusions::In light of this evidence, clinicians should always investigate issues related to sexuality and gender identity in patients with eating disorders, to develop more effective prevention measures and better strategies for therapeutic intervention..
Synthetic Methods and Antimicrobial Perspective of Pyrazole Derivatives: An Insight
Authors: Kumar Harish , Bansal Kushal Kumar , Goyal Anju 
Published: October 2019

Background:
Due to newly emerging microbial infections and the development of resistance
against cutting-edge therapeutics, innovative and robust medicinal agents are required.
Small ring heterocycles, such as pyrazole and its derivatives have been acknowledged to possess
myriad biological properties and the presence of pyrazole in clinics like celecoxib, phenylbutazone
(anti-inflammatory), CDPPB (antipsychotic), rimonabant (anti-obesity), antipyrine, difenamizole
(analgesic), fipronil (broad-spectrum insecticidal), betazole (H2-receptor agonist) and fezolamide
(antidepressant) drugs has proven the pharmacological perspective of pyrazole nucleus.

Objectives:
The current review paper aimed at a recent update made on novel methodologies
adopted in the synthesis of pyrazole derivatives with the emphasis on antibacterial (DNA gyrase
inhibition) and antifungal activities.

Methods:
Pyrazole is one of the major tools to be investigated in drug design and discovery. Many
studies have been reported by researchers that have claimed the significant biological potential of
these derivatives. However, numerous studies on pyrazoles compounds shown to exhibit potential
antifungal and antibacterial activities, the focus has also been made on DNA gyrase inhibition.
Additionally, some important patents granted to this heterocyclic nucleus related to antimicrobial
potential are also addressed appropriately.

Results:
DNA gyrase is a promising biotarget yet to be explored against a number of medicinal agents.
The present work provides valuable insight into synthetic methods and antibacterials/antifungal significance
of pyrazoles in general as well as new inhibitors of DNA gyrase in particular.

Conclusion:
The manuscript constitutes a valuable reference which advocates candidature of pyrazoles
as a potential therapeutic alternative as antibacterial and antifungal agent.
Effectiveness and Safety of Single Percutaneous Peribulbar Block Using Magnesium Sulphate as an Adjuvant to Local Anesthetics Versus the Standard Peribulbar Block for Strabismus Surgery in Adults
Authors: Sherif Norhan Aly , Mohamad Mayada Khairy , Taher Sameh Galal , Hannon Ahmed Abdou , Salem Hesham Mohamed 
Published: October 2019

Background:Peribulbar anesthesia in ophthalmic surgeries is limited by delayed and/or incomplete orbital akinesia and inadequate operative and postoperative analgesia.Objective:The aim of this study was to assess the safety and effectiveness of a single percutaneous peribulbar block technique with 100 mg magnesium sulphate added to the local anesthetics used compared with the standard peribulbar block technique in adult strabismus surgery.Methods:A total of 54 consecutive patients undergoing strabismus surgery were included in the study. They were divided into two equal groups (27 patients each). In group I, 1 ml (100 mg/ml) magnesium sulphate added to a mixture of 2 ml lidocaine 2%, 2 ml bupivacaine 0.5% and 1 ml hyaluronidase (150 units/ml) was administered through a single percutaneous peribulbar injection with a short (1 inch) needle, while in group II, a mixture of 1 ml saline added to 2 ml lidocaine 2%, 2 ml bupivacaine 0.5% and 1 ml hyaluronidase (150 units/ml) was administered using the standard peribulbar block technique. The collected data included patient's baseline characteristics, perioperative and early postoperative outcomes and follow-up data.Results:The elapsed time before the onset of anesthesia and akinesia of the globe was significantly shorter in group I compared with group II (1.9 ± 0.7vs.3.9 ± 1.0 min,p< 0.001; 2.3 ± 0.7vs.4.4 ± 1.2 min,p< 0.001 respectively), and the duration of anesthesia was significantly longer in group I compared with group II (180.0 ± 0.0vs.43.0 ± 8.5 min,p< 0.001). The median VAS pain score was significantly lower in group I compared with group II (1.0vs. 4.0,p< 0.001), and the patient's satisfaction was significantly higher in group I compared with group II (100.0%vs. 25.9%,p< 0.001).Conclusion:Co-administration of 100 mg magnesium sulphate with the local anesthetics was effective and safe. It achieved suitable conditions to start surgery rapidly. Further, it improved the quality of operative conditions and patient satisfaction.
ACTIVATING EFL LEARNERS BY INTEGRATING TEAM-BASED LEARNING WITH COLLABORATIVE STRATEGIC READING
Authors: Maming Khadijah 
Published: October 2019

Team-Based Learning (TBL) is one of active learning strategies that build on individuals’ strengths by allowing them to collaborate and work as a team to achieve common learning objectives. TBL is a cooperative learning strategy was introduced to encourage students become active learners rather than be passive recipients of information. It is generally based on the principle that students working together as a cohesive team are able to achieve higher levels of learning. The lecturer’s role essentially is as facilitator. In order to activate the participation of EFL learners in classroom and improve their reading comprehension ability, the researcher conducted a research to find out good impacts of TBL integrated with Collaborative strategic reading toward the English Education Department students in Indonesia as EFL learners. The researcher applied quasi-experimental method. The students started reading activity by previewing the text, click (what vocabulary the students understand), clunk (what vocabulary the students don’t understand), getting the gist, wrapping up and done cooperatively. The conclusion of this research showed that TBL integrated with Collaborative strategic reading can activate the participation of EFL learners in classroom and improve their reading comprehension ability. It also had better achievement than the students taught by conventional learning. Keywords: team-based learning, collaborative strategic reading, EFL, active learning
Effectiveness of Upper Limb Wearable Technology for Improving Activity and Participation in Adult Stroke Survivors: Systematic Review
Authors: Parker Jack , Powell Lauren , Mawson Susan 
Published: October 2019

BackgroundWith advances in technology, the adoption of wearable devices has become a viable adjunct in poststroke rehabilitation. Upper limb (UL) impairment affects up to 77% of stroke survivors impacting on their ability to carry out everyday activities. However, despite an increase in research exploring these devices for UL rehabilitation, little is known of their effectiveness.ObjectiveThis review aimed to assess the effectiveness of UL wearable technology for improving activity and participation in adult stroke survivors.MethodsRandomized controlled trials (RCTs) and randomized comparable trials of UL wearable technology for poststroke rehabilitation were included. Primary outcome measures were validated measures of activity and participation as defined by the International Classification of Functioning, Disability, and Health. Databases searched were MEDLINE, Web of Science (Core collection), CINAHL, and the Cochrane Library. The Cochrane Risk of Bias Tool was used to assess the methodological quality of the RCTs and the Downs and Black Instrument for the quality of non RCTs.ResultsIn the review, we included 11 studies with collectively 354 participants at baseline and 323 participants at final follow-up including control groups and participants poststroke. Participants’ stroke type and severity varied. Only 1 study found significant between-group differences for systems functioning and activity (P≤.02). The 11 included studies in this review had small sample sizes ranging from 5 to 99 participants at an average (mean) age of 57 years.ConclusionsThis review has highlighted a number of reasons for insignificant findings in this area including low sample sizes and the appropriateness of the methodology for complex interventions. However, technology has the potential to measure outcomes, provide feedback, and engage users outside of clinical sessions. This could provide a platform for motivating stroke survivors to carry out more rehabilitation in the absence of a therapist, which could maximize recovery.Trial RegistrationPROSPERO CRD42017057715; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=57715
Elements of Social Convoy Theory in Mobile Health for Palliative Care: Scoping Review
Authors: Portz Jennifer D , Elsbernd Kira , Plys Evan , Ford Kelsey Lynett , Zhang Xuhong , Gore M Odette , Moore Susan L , Zhou Shuo , Bull Sheana 
Published: October 2019

Background
Mobile health (mHealth) provides a unique modality for improving access to and awareness of palliative care among patients, families, and caregivers from diverse backgrounds. Some mHealth palliative care apps exist, both commercially available and established by academic researchers. However, the elements of family support and family caregiving tools offered by these early apps is unknown.

Objective
The objective of this scoping review was to use social convoy theory to describe the inclusion and functionality of family, social relationships, and caregivers in palliative care mobile apps.

Methods
Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines, a systematic search of palliative care mHealth included (1) research-based mobile apps identified from academic searches published between January 1, 2010, and March 31, 2019 and (2) commercially available apps for app stores in April 2019. Two reviewers independently assessed abstracts, app titles, and descriptions against the inclusion and exclusion criteria. Abstracted data covered app name, research team or developer, palliative care element, target audience, and features for family support and caregiving functionality as defined by social convoy theory.

Results
Overall, 10 articles describing 9 individual research-based apps and 22 commercially available apps were identified. Commercially available apps were most commonly designed for both patients and social convoys, whereas the majority of research apps were designed for patient use only.

Conclusions
Results suggest there is an emerging presence of apps for patients and social convoys receiving palliative care; however, there are many needs for developers and researchers to address in the future. Although palliative care mHealth is a growing field, additional research is needed for apps that embrace a team approach to information sharing, target family- and caregiver-specific issues, promote access to palliative care, and are comprehensive of palliative needs.
Læreres opplevelse av muligheter i skole-hjem-samarbeidet
Authors: Faugstad Randi , Jenssen Eirik Sørnes 
Published: October 2019

Denne studien undersøker Hvordan lærere opplever deres muligheter til å etablere et godt skole-hjem-samarbeid. Studien bygger på intervju av ti lærere ved fire skoler som uttrykker sine synspunkter på egne muligheter, sine utfordringer og sitt handlingsrom i dette samarbeidet.
Studien viser at lærerne i stor utstrekning utvikler sitt skole-hjem-samarbeid ut fra egne erfaringer og oppfatninger, og at de finner lite støtte i strukturer og rutiner ved skolene. Et funn er at foreldremøte og utviklingssamtalene er preget av formaliteter som synes å stå i veien for et reelt foreldresamarbeid.
English abstract
English title: Teachers experiences of their opportunities in school-home cooperation
Teachers experiences of their opportunities in school-home cooperation This study investigates How teachers experience their opportunities to establish a good school-home cooperation. The study is based on interviews with ten teachers at four primary schools in which the teachers relate their experiences of opportunities for and challenges of establishing collaboration between the school and the home, as well as their professional place within this collaboration.
The study has shown that, to a great extent, the teachers have developed their own practices of dealing with school-home cooperation. The teachers seem to receive little support from structures and routines within the schools. One finding is that the teachers’ meetings with parents and parent-teacher conferences are largely characterized by formalities that seem to hinder a genuine collaboration.
PENGARUH KONDISI TANAH TANAM TERHADAP PRODUKSI RIMPANG DAN AMILUM GARUT (Maranta arundinacea L. )
Authors: H. Hardjo Popy 
Published: October 2019

Garut/larut (Maranta arundinacea L.) termasuk familia Marantaceae yang membentuk rimpang (rhizoma) dan diolah menjadi amilum Marantae di mana mempunyai banyak kegunaan mulai untuk bahan makanan sampai sebagai bahan industri dan ramuan obat-obatan.
Kondisi lingkungan tumbuh dan daerah perakaran sangat berpengaruh terhadap pertumbuhan dan produksi tanaman garut. Oleh karena itu diteliti pengaruh kondisi tanah sawah dan tegal terhadap pertumbuhan tanaman garut saat berumur 10 bulan serta produksi rimpang dan amilumnya saat panen 12 bulan.
Pertumbuhan vegetatif tanaman garut di sawah lebih baik dari pada di tegal, dan sejalan dengan produksi rimpang serta rendemen amilum lebih besar di sawah dibandingkan di tegal.
Kondisi tanah daerah perakaran baik tanah sawah maupun tegal tidak mempengaruhi kadar amilum maupun kadar lembab amilum.
História da Educação Agrícola no Brasil: educação do campo versus educação ruralista | The History of Agricultural Education in Brazil: Countryside education versus landholder education
Authors: Molina Rodrigo Sarruge 
Published: October 2019

O objetivo desta pesquisa foi discutir a docência e a educação no meio rural brasileiro à luz da História, evidenciando projetos antagônicos que disputaram a hegemonia educacional e produtiva no campo. Resultante das pesquisas de pós-doutorado, a análise é amparada na teoria e na metodologia materialista histórica dialética e está inserida na área de Fundamentosda Educação e de suas subáreas: “História da educação” e da “Educação do campo”. O principal resultado do estudo aponta um dualismo histórico e estrutural da Educação Agrícola brasileira, em que a classe dominante ruralista impôs dois projetos: de um lado, uma educação elitista mais teórica, gerencial e de capatazia destinada aos filhos dos fazendeiros e aos seus gerentes; e, de outro, uma educação mais prática, “proletária” e alienada aos trabalhadores “braçais” agrícolas, o que refletiu na formação de professores e nos sistemas educacionais. Hoje, o meio rural conta com uma inovação, a “educação do campo”, que propõe romper com esse dualismo histórico por meio de uma solução libertadora, a qual defende os interesses dos “povos da terra”; nessa perspectiva, os camponeses, os ribeirinhos, os caiçaras, os indígenas e os demais trabalhadores rurais são os protagonistas de seu futuro.