bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Different Thermal Stimuli on Improving Microcirculation in the Contralateral foot
Authors: Ren Weiyan , Xu Liqiang , Zheng Xuan , Pu Fang , Li Deyu , Fan Yubo
Published: August 2020

Backgroud: The lower extremities of the body often suffer from impaired microcirculation, particularly in the elderly or people with underlying conditions such as diabetes. Especially for people suffering from peripheral vascular diseases, skin lesions or wearing an external fixator in one side of limbs, direct contact treatments are not suitable for them to improve microcirculation. Heating the contralateral limb has been reported to improve blood flow in the impaired limb. However, its effect on microvascular responses has not been previously investigated. Thus, the aim of this study was to explore how heating by warm bath and infrared radiation affects the circulations in the contralateral foot. Twelve healthy adults participated in this study and were randomly assigned to either placing the left foot in a warm bath or exposing it to infrared radiation every other day. The temperature (Temp) and skin blood flow (SBF) in the second metatarsal head of the contralateral foot were measured before and after the intervention. Results: The results showed that both Temp (Bath: from 29.05±3.56 °С to 31.03±4.14 °С; Infrared: from 29.98±3.86 °С to 31.07±3.92 °С) and SBF (Bath: from 62.26±48.12 PU to 97.76±63.90 PU; Infrared: from 63.37±39.88 PU to 85.27±47.62 PU) in the contralateral foot were significantly increased after heating in both tests (P<0.05). However, the increase in contralateral SBF lasted 5 minutes after heating in a warm bath, but only lasted for 1 minute after infrared exposure. Moreover, the increase in Temp from the baseline in the first minute of the Recovery stage was significantly greater when using the warm bath than infrared radiation. Conclusions: The results of this study show that both heating methods are the effective at increasing contralateral Temp and SBF, but the warm bath has a stronger residual thermal effect.
Investigation of Isothermal Treatment on the Structural, Microstructure and Physical Properties of Li2O-Al2O3-SiO2 Glass-Ceramic
Authors: Lutpi Husniyah Aliyah , Mohamad Hasmaliza , Abdullah Tuti Katrina
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
Cannabis Use Among Patients Attending A Methadone Maintenance Treatment Clinic In Nairobi, Kenya
Authors: Ngarachu Elizabeth Wambui , Kiburi Sarah Kanana , Owiti Frederick R. , Kangethe Rachel N.
Published: August 2020

Background: Cannabis use is common among patients with opioid use disorder receiving methadone treatment. Research has shown that cannabis use during methadone treatment may impact negatively on treatment outcome. This study aimed at determining the prevalence and pattern of cannabis use and the associated socio-demographic characteristics among patients on methadone treatment. Methods: This was a retrospective study of 984 patients on methadone therapy at a methadone maintenance treatment clinic in Nairobi, Kenya. Data on socio-demographic characteristics and drug use patterns based urine drug screens was collected from patients’ files. Data was analyzed using SPSS for windows version 23.0. Results: Prevalence of cannabis use was 84.8% at baseline and 62.8% during follow up. Polysubstance use pattern was observed with heroin, cannabis and benzodiazepines being the commonest drugs. Majority of cannabis users were male (88.1%), aged 28-37 years (42.2%), unemployed (74.3%), had low level of education (87.7%) and single (72.4%). Cannabis use was associated with loss to follow up (p<0.001). Females were more likely to drop out of treatment and less likely to stop using cannabis during follow up compared to males. Sociodemographic factors associated with reduced risk for cannabis use were; being in older age group 48-57 years (OR 0.51, 95%CI, 0.30-0.87, p=0.013) and university education (OR 0.15, 95%CI, 0.05-0.69, p=0.005) while being in age group 18-27 years and being married were associated with increased risk for cannabis use (OR 2.62,95%CI, 1.78-3.86,p=0.001 and OR 1.50, 95%CI, 1.7-2.10,p=0.021 respectively). Conclusion: There is a prevalence of cannabis use among patients in receiving methadone treatment in Kenya is similar. In addition, cannabis use was associated with loss to follow up and sociodemographic characteristics. Cannabis use screening and targeted interventions for management should be incorporated in methadone treatment programs to improve outcomes for patients on methadone. Key words : cannabis, opioid use disorder, methadone maintenance treatment, Kenya
Dietary Curcumin Supplement Promotes Browning and Energy Expenditure in Postnatal Overfed Rats
Authors: Zhu Xiaolei , Du Susu , Yan Qinhui , Min Cuiting , Zhou Nan , Zhou Wei , Li Xiaonan
Published: August 2020

Background: Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure and induces white adipose tissue (WAT) gain throughout life. The aim of this study is to investigate the effect of curcumin (CUR) on thermogenesis and WAT browning in postnatal overfed rats.Methods and results: Litter sizes were adjusted to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. After weaning, the SL rats were fed with a standard diet (SL) or a diet supplemented with 1% (SL1%CUR) or 2% (SL2%CUR) CUR for ten weeks. At postnatal 13 weeks, SL rats with 1% or 2% CUR supplement had lower body weight and less WAT gain, had increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, increased respiratory exchange ratio (RER) and heat production were consistent with the expression of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not of the SL1% CUR rats. In addition, 2% CUR dietary supplement enhanced the serum norepinephrine (NE) levels in SL rats, which was accompanied by upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.Conclusion: Dietary CUR supplement attenuates body weight gain and metabolic disorders of SL rats. The beneficial effects were probably induced by promoting browning of SAT and energy expenditure, and it was more effective in SL with 2% CUR supplement.
Liver-transplantation-corrected coagulation dysfunction and neurological impairment in patients with argininemia
Authors: Cui Bin , Sun Li-Ying , Wei Lin , Qu Wei , Zeng Zhi-Gui , Liu Ying , Tan Yu-Le , Wang Jun , Zhu Zhi-Jun
Published: August 2020

Background

Argininemia is a rare disease caused by inborn errors of metabolism. Advances in diagnosis and treatment have increased the number of patients receiving effective management. Argininemia is characterized by progressive spastic paraplegia, mental retardation, failure to thrive and irritability, and patients with coagulopathy are paid more attention. We studied the changes in coagulation dysfunctions and neurodevelopment in patients with argininemia before and after liver transplantation(LT).
Methods

The data in this study were obtained from the Liver Transplantation Center of Beijing Friendship Hospital, Capital Medical University between January 2015 and November 2019. We identified data related to argininemia in all patients diagnosed with urea cycle disorder, and extracted the details on coagulation, liver function, neurodevelopmental outcomes, histopathological and morphological examination, and other clinical presentations. The patients were followed up by telephone and/or in the clinic.
Results

Nine patients with argininemia diagnosed by tandem mass spectrometry and symptoms, and confirmed by gene sequencing. The symptoms deteriorated after dietary restriction in all patients with argininemia. Coagulopathy manifested before surgery, and no significant correlation was detected with plasma ammonia concentration. The coagulation dysfunction was completely resolved and progressive neurological impairment was prevented in seven patients with LT.
Conclusions

Coagulation dysfunctions are common manifestations of patients with
The Pathological Features and Prognoses of Intraductal Papillary Mucinous Neoplasm and Mucinous Cystic Neoplasm After Surgical Resection: A Single Institution Series
Authors: Li Yuqiong , Zhu Zhongfei , Peng Lisi , Jin Zhendong , Sun Liqi , Song Bin
Published: August 2020

Background: Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) represent the tumors with malignant transformation potential. The objective of the study was to verify their pathological characteristics, prognoses, and recurrence factors. Methods: 218 IPMNs and 27 MCNs resected at a single institution were included. The demographic, preoperative, histopathological and follow-up data of the patients were recorded and analyzed. Results: Of the 218 IPMN and 27 MCN patients, 93 (42.7%) and 8 (29.6 %) cases were malignant, respectively. IPMNs occurred in older patients compared with MCN patients (median 63 years vs 54 years, P<0.0001) and MCNs occurred exclusively in females (100%). Of the overall study cohort, the pathological specimens presented peripheral invasion in 37 (15.1%) patients and incisal margin invasion was observed in 46 (18.8%) patients. After a median follow-up of 34 months, 37(14.9%) patients relapsed. The 1, 3, 5 -year overall survival rate (OS) and diseases-free survival (DFS) rate for IPMNs were 98.75%, 98.75%, 97.5%, and 85.7%, 81.1%, 80.6%; and for MCNs the rates were 95.7%, 95.7%, 95.7%, and 91.3%%, 87.0%, 87.0%, respectively. There were four independent risk factors associated with recurrence: pathological diagnoses with malignancy (Odds rate, OR=3.65), presence of oncocytic type for IPMN (OR=1.69), peripheral invasion (OR=12.87) and incisal margin invasion (OR=1.99). Conclusions: IPMNs and MCNs are indolent tumors with favorable prognoses after surgical resection in terms of their relatively high OS and DFS rate. Patients with malignant pathological-related diagnoses should accept strict tumor surveillance in view of their higher risk of recurrence.
CircTP63 Promotes Hepatocellular Carcinoma Progression by Sponging miR-155-5p and Upregulating ZBTB18
Authors: Wang Jiantao , Che Jinbiao
Published: August 2020

Background: Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet still lacking biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.Methods: qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18. Results: circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression. Conclusion: Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of CircRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.
miRNA-24 Down-Regulates Endothelial Nitric Oxide Synthase Expression and Inhibits Endothelial Cell Tube Formation
Authors: Luo Xuelan , Chen Wei , Qin Yuwang , Gan Na , Lvy Dongning , Liu Zhenguo , Ou Hesheng
Published: August 2020

Background: This study is to investigate the effects of miR-24 on expression of eNOS and Sp1, the proliferation, migration, and tube formation abilities of human umbilical vein endothelial cells (HUVECs). Results: After transfection with miR-24 overexpression plasmid or anti-miR-24, miR-24 was successfully over-expressed or inhibited. Compared with the control group, the HUVEC proliferation and cell number in the miR-24 high expression group was significantly decreased. Moreover, for the miR-24 high expression group, the cell motility was slower, and the migrating cells were significantly decreased by 61.20%, with very few capillaries in the Matrigel assay. Furthermore, the mRNA and protein expression levels of eNOS were decreased by 44.44% and 47.00 %, respectively. Meanwhile, the mRNA and protein levels of Sp1 were significantly decreased by 34.88% and 68.00%, respectively. In the miR-24 interference group, the above indexes were decreased compared with control group, while significantly increased compared with the miR-24 high expression group, especially concerning the number of branches and the tube length. Moreover, the Sp-1 and eNOS mRNAs were found to be the direct targets of miR-24 by a luciferase reporter system.Conclusion: Over-expression of miR-24 significantly suppresses cell proliferation, migration, and tube formation ability of HUVECs, via regulating eNOS expression. The transcription factor Sp1, a target of miR-24, might contribute to the eNOS expression regulation and the inhibiting effects on HUVECs.
Designing a Wellness-Based Tourism Model for Sustainable Rural Development
Authors: Esfandiari Hossein , Choobchian Shahla
Published: August 2020

Wellness tourism, which is a fast-growing sector in the tourism industry, is a sub-branch of health tourism. In this type of tourism, tourists travel to get rid of the stresses of their daily life and rejuvenate without medical intervention and supervision. These tourists usually have no specific physical illness; rather, they are interested in enjoying the healing nature of other areas. These people travel to use the natural facilities available at the destination. These facilities, which may include favorable climate, hot springs, pristine nature of rural areas, and so on, are provided to tourists so that they can relax. The present study is a non-experimental survey in which the structural equation modeling method (AMOS22) is used to analyze the data. The statistical population was composed of the tourists visiting the natural attractions of Sarab County, Iran. The data collection instrument was a questionnaire whose validity was confirmed by a panel of experts. To measure the reliability of the research instrument, 30 copies of the questionnaire were completed by some wellness tourists in Sarein Township, Ardabil province in Iran. The results confirmed the good reliability of the questionnaire. Also, the average variance extracted (AVE) and composite reliability (CR) calculated for the studied variables were greater than 0.5 and 0.7, respectively. The results showed that among the studied factors, the location of the place had the greatest impact on choosing a wellness-based tourism destination. Also, among the different dimensions of wellness, the physical aspect was the most prominent dimension in choosing this kind of tourism. The research contributes approaches to developing wellness tourism in Iran in particular and in the world in general. Based on these approaches and strategies, effective steps would be taken to reduce life stress and move towards improving quality of life in the COVID-19 conditions.
Regime equations development for the design of Egyptian sandy canals
Authors: Arafa Ahmed A. , AboulAtta Nahla M. , El-Samman Tarek A. , Saad Neveen Y.
Published: August 2020

The construction of the High Aswan Dam in Egypt led to reducing the solids suspension in water from more than 3,500 p.p.m. to less than 100 p.p.m. As the regime of Egyptian canals has been changed completely after the construction of the High Aswan Dam, the previous derived equations are not applicable any more, and using them leads to a shortage in the carrying capacity of the canals. In the current study, extensive field measurements have been carried out on 15 stable Egyptian canals, which cover various discharges of irrigation canals with sandy soils starting from 5 m3/s to 50 m3/s and d50 ranging from 0.196 to 0.538 mm. Then, applicable regime relationships for designing stable sandy channels were determined. The new equations are useful for designing new stable canals and redesigning unstable canals within the same range. The new regime equations were verified by using the HEC- RAS program. Finally, sensitivity analysis has been performed in order to investigate the effect of changing the deduced parameters on the discharge.
Recent Advances in Curcumin Treated Non-Small Cell Lung Cancers: An Impetus of Pleiotropic Traits and Nanocarrier Aided Delivery
Authors: Malik Parth , Malik Parth , Hoidal John R. , Hoidal John R. , Mukherjee Tapan K. , Mukherjee Tapan K.
Published: August 2020

Characterized by the abysmal 18% five year survival chances, non-small cell lung cancers (NSCLCs) claim more than half of their sufferers within the first year of being diagnosed. Advances in biomedical engineering and molecular characterization have reduced the NSCLC diagnosis via timid screening of altered gene expressions and impaired cellular responses. While targeted chemotherapy remains a major option for NSCLCs complications, delayed diagnosis, and concurrent multi-drug resistance remain potent hurdles in regaining normalcy, ultimately resulting in relapse. Curcumin administration presents a benign resolve herein, via simultaneous interception of distinctly expressed pathological markers through its pleiotropic attributes and enhanced tumor cell internalization of chemotherapeutic drugs. Studies on NSCLC cell lines and related xenograft models have revealed a consistent decline in tumor progression owing to enhanced chemotherapeutics cellular internalization via co-delivery with curcumin. This presents an optimum readiness for screening the corresponding effectiveness in clinical subjects. Curcumin is delivered to NSCLC cells either (i) alone, (ii) in stoichiometrically optimal combination with chemotherapeutic drugs, (iii) through nanocarriers, and (iv) nanocarrier co-delivered curcumin and chemotherapeutic drugs. Nanocarriers protect the encapsulated drug from accidental and non-specific spillage. A unanimous trait of all nanocarriers is their moderate drug-interactions, whereby native structural expressions are not tampered. With such insights, this article focuses on the implicit NSCLC curative mechanisms viz-a-viz, free curcumin, nanocarrier delivered curcumin, curcumin + chemotherapeutic drug and nanocarrier assisted curcumin + chemotherapeutic drug delivery.
Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with Clinical Insight
Authors: Ray Suman K. , Meshram Yamini , Mukherjee Sukhes
Published: August 2020

Cancer immunotherapy endeavours in harnessing the delicate strength and specificity of the immune system for therapy of different malignancies, including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include the administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies, including colorectal carcinoma in a recent decade. Despite the considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect the therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review, we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.
Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients
Authors: Lagoutte-Renosi Jennifer , Flammang Mylène , Chirouze Catherine , Beck-Wirth Geneviève , Bozon Fabienne , Brunel Anne-Sophie , Drobacheff-Thiebaut Marie-Christine , Foltzer Adeline , Hustache-Mathieu Laurent , Kowalczyk Jakub , Michel Catherine , Davani Siamak , Muret Patrice
Published: August 2020

Background:

Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that
exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now
makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently
no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate
to tenofovir alafenamide.

Objective:

Our study aimed to evaluate the effects on renal function and lipid profile of a switch
from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management.

Methods:

Demographic, clinical and biological data was recorded from a retrospective clinical cohort
study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir
alafenamide. A descriptive analysis of the study population, with a comparison of biological
parameters using the paired Student t test for paired data was performed.

Results:

From January 2016 to January 2019, a total of 103 patients were included. There was no
significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine,
p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total
cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients
received lipid-lowering therapy after switching.

Conclusion:

In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide,
lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to
monitor lipid parameters after this switch, despite the absence of an official recommendation.
Emerging Trends in the Long-Acting Antiretroviral Therapy: Current Status and Therapeutic Challenges
Authors: Labh Rajpushpa , Gupta Rachna
Published: August 2020

Antiretroviral drug therapy has significantly improved the prognosis and life expectancy
of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral
regimens generally require adherence to life-long, daily dosing, to keep viral multiplication
under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance
against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and
lymph nodes leads to the build-up of viral reservoirs in these sites. To combat some of these challenges
and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the
arsenal, in the fight against HIV. Few long-acting preparations have been approved, and several
others are in various clinical and preclinical stages of development. However, long-acting formulations
also have their share of clinical issues like limited drug distribution, long term adverse drug
reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological
premises are being tested to mitigate some of these problems. One such promising approach involves
nanotechnological methods, which are being used to develop ultra-long acting formulations
and drug delivery systems, targeting tissues with residual HIV concentration. Long-Acting Slow Effective
Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug
modifications to design preparations with tailor-made favorable pharmacokinetics and wider
drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards
eliminating the disease.
Evaluating the Risks of Systemic Maternal Ivermectin Exposure During Pregnancy in Human and Vertebrate Animals: A Scoping Review
Authors: Westlake Camille S. , Aronoff David M.
Published: August 2020

Background:

Ivermectin is widely used for the treatment of neglected tropical diseases
associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy.
However, the United States FDA classification and current distribution protocols limit
ivermectin treatment in pregnant women because antepartum safety has not been well-established.

Objective:

We conducted a scoping review to address the question of what is known from both human
and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy.

Methods:

We searched PubMed for adverse outcomes related to systemic ivermectin exposure in
human and vertebrate animal pregnancies, including English-language primary articles from 1900 -
2019.

Results:

We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate
animal studies of interest. One prospective randomized, controlled trial investigating the safety
of systemic ivermectin exposure during pregnancy and four retrospective human studies did not
identify a significant association with adverse birth outcome metrics. Out of the three human case
reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal
death. A retrospective cross-sectional study concluded a positive association between onchocerciasis
and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse
pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack
of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse
pregnancy outcomes.

Conclusion:

Further research is warranted to address safety concerns regarding the use of
ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten
maternal-child health.
A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors
Authors: Zeytün Ebru , Altıntop Mehlika D. , Sever Belgin , Özdemir Ahmet , Ellakwa Doha E. , Ocak Zeynep , Ciftci Halil I. , Otsuka Masami , Fujita Mikako , Radwan Mohamed O.
Published: August 2020

Background:

After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved,
and several promising candidates are in various stages of clinical evaluation.

Objectives :

Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new
thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML).

Methods:

New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line.
Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other
leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic
effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its
selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory
effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the
ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module
of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p.

Results:

4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed
antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 μM similar to imatinib (IC50=
6.84±1.11μM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells.
Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity
index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound
2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the
strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17μM). According to molecular
docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase, forming
significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's
rule of five and Jorgensen's rule of three.

Conclusion:

Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.
A Review of the Potential Receptors of Migraine with a Special Emphasis on CGRP to Develop an Ideal Antimigraine Drug
Authors: Naduchamy Krishna P. , Parthasarathy Varadarajan
Published: August 2020

Background and Objective:

Migraine is a neurovascular syndrome associated with unilateral, throbbing headache accompanied with nausea, vomiting and photo/phonophobia. Several proteins are involved in the etiopathogenesis of migraine headache. The aim of the present review is to give an insight into the various target proteins involved in migraine headache pertaining to the development of a potential anti-migraine drug molecule. Proteins/receptors such as serotonin (5-HT), Calcitonin Gene Related Peptide (CGRP), Transient Receptor Potential Vanilloid (TRPV1), cannabinoid, glutamate, opioid and histamine receptors play various roles in migraine. The nature of the proteins, their types, binding partner membrane proteins and the consequences of the reactions produced have been discussed. The studies conducted on animals and humans with the above mentioned target proteins/receptors and the results obtained have also been reviewed.

Conclusion:

Calcitonin Gene Related Peptide (CGRP), a G protein coupled receptor (GPCR) significantly contributed to the progression of migraine. CGRP antagonist inhibits the release of CGRP from trigeminal neurons of trigeminal ganglion. Based on the study results, the present review suggests that the inhibition of CGRP receptor might be a successful way to treat migraine headache. Currently, researchers across the world are focussing their attention towards the development of novel molecules to treat migraine headache by targeting CGRP receptor which can be attributed to its specificity among the several proteins involved in migraine.
Role of Erlotinib in Influencing the Quality of Life of Cancer Patients
Authors: Purohit Deepika , Pandey Parijat
Published: August 2020

Background::

Cancer is one of the significant causes of morbidity and mortality in patients globally. Lung cancer,
among other cancers, remains to be one of the principal causes of deaths in both men and women. The most common
type of lung cancer is the non-small-cell lung cancer (NSCLC). Apart from lung cancer, pancreatic cancer is also one of
the common cancers currently.

Objective::

The assessment of QoL in erlotinib-treated patients can also prove to be very useful in the establishment of this
drug as the main treatment option for the patients with pancreatic and lung cancer.

Methods::

Therapies that target EGFR-mediated signalling are the latest keystones for treating these two types of cancers.
They comprise of two main treatment modalities: firstly, against the extracellular fields, that include monoclonal antibodies
and secondly, mechanisms that create interferences in the signalling pathways, primarily the small molecule tyrosine
kinase inhibitors.

Results::

Quality of life (QoL) is one of the key advantages in erlotinib therapy over chemotherapy.

Conclusion::

The present review reports the role of erlotinib in improving the quality of life of cancer patients especially
in NSCLC and pancreatic cancers. The studies or trials establishing the relations between erlotinib and QoL are discussed
in detail in this review.
The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate
Authors: Wardhani Shinta Oktya , Susianti Hani , Rahayu Puji , Yueniwati Yuyun
Published: August 2020

Background:

The failure of imatinib therapy in patients with chronic myeloid leukemia
(CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported
to occur earlier in the progression of CML.

Objective:

The study aimed to assess the association between the level of LSC and treatment response
among CML patients treated with imatinib mesylate.

Methods:

A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided
into two groups, response and non-response group. To assess the level of LSC, flow cytometry
was conducted conforming with BD Bioscience. The association and effect estimates were determined
using multiple logistic regression.

Results and Discussion:

A total of 29 response and non-response CML patients treated with imatinib
therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels
of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure
among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed
significantly higher in the non-response group compared to the response group among CML patients
treated with imatinib.

Conclusion:

Our study reveals that the elevated level of LSC is considered as an important factor to
predict the failure of imatinib therapy among CML patients.
Educación en Arquitectura: Transiciones hacia el Desarrollo Sostenible
Authors: Castellanos Tuirán Alexandra Isabel , Martínez-Osorio Pedro Arturo
Published: August 2020

Se analizan tres aspectos relativos a la Educación en Arquitectura, con el fin de encontrar puntos en común y convergencias: el desarrollo social de la cultura occidental, desde el punto de vista ambiental; la evolución de la Educación en occidente, desde la aparición de las primeras teorías modernas; y el proceso evolutivo de la formación en Arquitectura desde la perspectiva histórica y epistemológica. Se reflexiona sobre la relación de estos temas, desde una visión crítica de la enseñanza de la Arquitectura, una disciplina en la que muchas veces ha de pensarse que estos aspectos transitan por caminos divergentes.
Uso intraluminal de stent de nitinol Dual para colapso completo de tráquea en un maltés: reporte de caso
Authors: De Lavalle-Galvis Rodrigo Jose , Pinzón D José , Mendoza D Ariel , Ramos R Amanda , Guzmán Jorge , Oviedo S Teresa , De la Puente Mario
Published: August 2020

Anamnesis: paciente canino, maltés, femenino, castrado, 4 años y 5 Kg. de peso El motivo principal de consulta fue tos y dificultad respiratoria grave. Hallazgos clínicos y de laboratorio: Durante la evaluación clínica, el paciente presentó cianosis, estridor inspiratorio y espiratorio severo, tos en graznido especialmente después de una emoción. Se realizó un examen a través de una broncoscopia, que reveló una disminución dinámica en el diámetro de la luz traqueal, un colapso severo en las porciones cervicales y torácicas. Enfoque de tratamiento: Debido a la gravedad del colapso traqueal, se decidió la implantación de un stent de nitinol. La elección del stent es fundamental; Fue necesario realizar una medición del diámetro y la longitud de la tráquea para minimizar los efectos secundarios y los rechazos. La tráquea presentó variabilidad del diámetro a nivel torácico por esta razón se decidió utilizar un stent dual, el stent se colocó en observación directa utilizando un broncoscopio pediátrico. Conclusión: Presentamos un caso en el que se usó un stent dual, indicado en casos en que el diámetro de la tráquea varía, obteniendo excelentes resultados ya que se ajustó a los diferentes diámetros traqueales que el paciente presentó en los niveles cervical y torácico.
Online Health Information Seeking by Parents for Their Children: Systematic Review and Agenda for Further Research
Authors: Kubb Christian , Foran Heather M
Published: August 2020

Background

Parents commonly use the internet to search for information about their child’s health-related symptoms and guide parental health-related decisions. Despite the impact of parental online health seeking on offline health behaviors, this area of research remains understudied. Previous literature has not adequately distinguished searched behaviors when searching for oneself or one`s child.

Objective

The purpose of this review is to examine prevalences and associated variables of parent-child online health information seeking; investigate parents’ health-related online behavior regarding how they find, use, and evaluate information; and identify barriers and concerns that they experience during the search. Based on this analysis, we develop a conceptual model of potentially important variables of proxy online health information seeking, with a focus on building an agenda for further research.

Methods

We conducted a comprehensive systematic literature review of the PsycINFO, JMIR, and PubMed electronic databases. Studies between January 1994 and June 2018 were considered. The conceptual model was developed using an inductive mixed methods approach based on the investigated variables in the study sample.

Results

A total of 33 studies met the inclusion criteria. Findings suggest that parents worldwide are heavy online users of health-related information for their children across highly diverse circumstances. A total of 6 studies found high parental health anxiety, with prevalences ranging from 14% to 52%. Although parents reported wishing for more guidance from their pediatrician on how to find reliable information, they rarely discussed retrieved information from the web. The conceptual model of proxy online health information seeking includes 49 variables.

Conclusions

This systematic review identifies important gaps regarding the influence of health-related information on parents’ health behavior and outcomes. Follow-up studies are required to offer parents guidance on how to use the web for health purposes in an effective way, as well as solutions to the multifaceted problems during or after online health information seeking for their child. The conceptual model with the number of studies in each model category listed highlights how previous studies have hardly considered relational variables between the parent and child. An agenda for future research is presented.
Work-Related and Personal Factors Associated With Mental Well-Being During the COVID-19 Response: Survey of Health Care and Other Workers (Preprint)
Authors: Evanoff Bradley A , Strickland Jaime R , Dale Ann Marie , Hayibor Lisa , Page Emily , Duncan Jennifer G , Kannampallil Thomas , Gray Diana L
Published: August 2020

BACKGROUND

The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19).

OBJECTIVE

The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being.

METHODS

All faculty, staff, and postdoctoral fellows of a university, including its medical school, were invited in April 2020 to complete an online questionnaire measuring stress, anxiety, depression, work exhaustion, burnout, and decreased well-being. We examined associations between these outcomes and factors including work in high-risk clinical settings and family/home stressors.

RESULTS

There were 5550 respondents (overall response rate of 34.3%). Overall, 34% of faculty and 14% of staff (n=915) were providing clinical care, while 61% of faculty and 77% of staff were working from home. Among all workers, anxiety (prevalence ratio 1.37, 95% CI 1.09-1.73), depression (prevalence ratio 1.28, 95% CI 1.03-1.59), and high work exhaustion (prevalence ratio 1.24, 95% CI 1.13-1.36) were independently associated with community or clinical exposure to COVID-19. Poor family-supportive behaviors by supervisors were also associated with these outcomes (prevalence ratio 1.40, 95% CI 1.21-1.62; prevalence ratio 1.69, 95% CI 1.48-1.92; and prevalence ratio 1.54, 95% CI 1.44-1.64, respectively). Age <40 years and a greater number of family/home stressors were also associated with these poorer outcomes. Among the subset of clinicians, caring for patients with COVID-19 and working in high-risk clinical settings were additional risk factors.

CONCLUSIONS

Our findings suggest that the pandemic has had negative effects on the mental health and well-being of both clinical and nonclinical employees. Mitigating exposure to COVID-19 and increasing supervisor support are modifiable risk factors that may protect mental health and well-being for all workers.
A Design of Oral Appliance for Obstructive Sleep Apnea (Preprint)
Authors: Belkhode Vikram , Nimonkar Sharayu , Godbole Surekha , Nimonkar Pranali
Published: August 2020

BACKGROUND

As per the current epidemiological studies, the prevalence of obstructive sleep apnea (OSA) among the adult population is very high. Oral appliances (OA) has emerged as the most recommended alternative treatment option for mild to moderate OSA.

OBJECTIVE

The objective of this article is to develop a new design of OA named “customized maxillary oral appliance”, for managing moderate obstructive sleep apnea (OSA) syndrome.

METHODS

The design proposed in this clinical technique is first of its kind that is fabricated on the maxillary arch. Customized maxillary oral appliance is developed by combining the principles of the three most popular OA’s used in OSA, namely soft palate lifters, tongue retaining devices, and mandibular advancement devices.

RESULTS

A new design of OA for the maxillary arch is proposed for managing moderate OSA.

CONCLUSIONS

Given the potential impact of OSA on general and mental health and the side effects of existing appliances there is a need for a new remedy to be introduced in the field of sleep medicine. This novel design can provide a new therapeutic op¬tion for patients with moderate OSA.

CLINICALTRIAL

Trial Registration: CTRI/2020/07/026936 Registered 31 July 2020, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=90265.33636
WOMB CONTROL IN TONI MORRISON’S BELOVED
Authors: Fatmasari Yuniar
Published: August 2020

This study reveals the ideological strategies the dominant takes to exploit Black enslaved women’s womb experienced by the characters in Toni Morrison’s Beloved as well as their resistance. Written in 1987, the novel is set eight years after the end of the Civil War in time painful experiences during slavery era are still there in the mind of ex-enslaved Black women and men. The novel narrates the past through personal life experiences presented by Sethe and Baby Suggs. During slavery era, their bodies are not merely used to work in the plantation area but since they are women, their wombs are valuable commodity providing advantages and profit to the masters. To make it possible, the dominant function ideological strategies to control the Black enslaved women’s wombs. Therefore, this study tries to explore how the ideological strategies are practiced in the novel. According to Collins, creating negative images such as mammy, breeder woman, and jezebel addresses to the bodies of Black enslaved women belongs to ideological strategy which is more powerful compared to theeconomic and politic strategy. Each image covers dominant interest to control Black women’s womb under new-progressive capitalism in United States. The result of the study shows that those three images works effectively to control the Black enslaved women, even nowadays, those images are still there in the body of young generation of Black women and provide another form of womb’scontrol. However, the study as well finds out that the resistance toward the oppression is also varied. Self-definition is presumed to be a fundamental element to the journey of internalized oppression to the ‘free mind’ which eventually leads to the action of resistance. With this self-definition, Blackwomen begin to deny the existed negative images controlling their wombs.
MEMBACA GENDER DALAM KONTEKS POSTMEMORY
Authors: Kumalasari Isti
Published: August 2020

Judul Buku The GeneraTion of PosTmemory: WriTinG and Visual CulTure afTer The holoCausT | Pengarang: Marianne HirscH | Penerbit: coluMbiauniversity Press | Tahun: 2012. Halaman: 305
HASRAT NANO RIANTIARNO DALAM CERMIN CINTA: KAJIAN PSIKOANALISIS LACANIAN
Authors: Manik Ricky Aptifive
Published: August 2020

Literary works known as authors’ desire manifestation.  In its history, a desire comes from the feeling of the lack of subject.  Writing a literary work becomes an effort to hide it.  The effort can be seen through an author’s point of view on ego ideal in his works.  Novel of Cermin Cinta is chosen as a sample in order to search what and how Nano Riantiarno’s desires are.  The aim is to find out the reflecting of Nano’s ego ideal.  This study uses Lacanian Psychoanalysis (PL).  Metaphor and metonymy will be used through PL in looking deeply the signs of Nano’s desire in Cermin Cinta.  This study finds out that a desire of becoming a writer and an artist has guided Nano unconsciously to other symbolic signs, such as being a ‘tough’,  ‘consistent’, ‘determined’, ‘diligent’ writer, etc. His effort in setting up a theatre community where he becomes the characters writer and director which was reached from the images of Rendra, Putu Wijaya, Arifin C. Noor, and Teguh Karya becomes his desire about the ontological intactness for his identity.  Besides, ‘Freedom’ becomes  ‘object a’ of Nano to get jouissance for himself.