bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP46 inhibits cell proliferation in lung cancer through PHLPP1/AKT pathway
Authors: Wang Wei , Chen Meng , Xu Hailing , Lv Dongqing , Zhou Suna , Yang Haihua 
Published: March 2020

Abstract
Background: USP46 has been shown to function as tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers remains unknown. This study was aimed to investigate the role of USP46 in lung cancer tumorigenesis, and to identify the underlying mechanism. Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western Blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from lung cancer patients. The functional role of USP46 in regulating proliferation in lung cancer cells were examined by cell proliferation assay, radiation assay, genetic overexpression and knock down and chemical inhibition of relevant genes. The underlying mechanisms were investigated in multiple lung cancer cell line models by co-immunoprecipitation and ubiquitination assays. Results: This study identified strong downregulation of USP46 and PHLPP1 expression in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under normal growth conditions and during radiation induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. The effect of USP46 knock down on lung cancer cell proliferation was significantly reversed by exposure to radiation and AKT inhibition. Conclusions: USP46 is down-regulated in lung cancer, and it suppresses proliferation of lung cancer cells by inhibiting PHLPP1/AKT pathway. AKT inhibition slows proliferation of USP46 down-regulated lung cancer cells exposed to radiation suggesting a potential therapeutic avenue for USP46 down-regulated lung cancer through a combination of radiation and AKT inhibitor treatment.
Nanovesicular Photodynamic Clinical Treatment of Resistant Plantar Warts
Authors: Fadel Maha , Kassab Kawser , Samy Nevien , Abdelfadeel Doaa , Yassin Ghada , Nasr Maha 
Published: March 2020

Background:
Photodynamic therapy which involves the use of photosensitizer molecule activated
by a light source was proven very promising for the treatment of dermatological diseases, especially
the resistant ones such as recalcitrant Plantar Warts (PW).

Objective:
However, its efficacy is hindered by the poor permeation of the photosensitizer molecule
required to initiate skin photo-induced effects.

Methods:
In this manuscript, the efficiency of the nano-vesicular system (transfersomes) as a potential
topical drug delivery system for the photosensitizer methylene blue (MB) was investigated following
clinical Photodynamic Therapy (PDT) in patients suffering from PW.

Results:
Results revealed that MB transfersomal gel displayed a higher complete healing percentage for
the lesions compared to the free MB gel (86.67% versus 53.57%) achieved at a lower number of treatment
sessions (2.2 versus 4.14). Patients reported no signs of pain or inflammation, with no recurrence
of the lesions during the follow up period of 8 months.

Conclusion:
PDT using transfersomal MB is an effective and safe therapeutic modality for the treatment
of PW.
Novel and Predictive QSAR Model for Steroidal and Nonsteroidal 5α- Reductase Type II Inhibitors
Authors: Mando Huda , Hassan Ahmad , Gharaghani Sajjad 
Published: March 2020

Background:
In this study, a novel quantitative structure activity relationship
(QSAR) model has been developed for inhibitors of human 5-alpha reductase type II, which are
used to treat benign prostate hypertrophy (BPH).

Methods:
The dataset consisted of 113 compounds-mainly nonsteroidal-with known inhibitory
concentration. Then 3D structures of compounds were optimized and molecular structure descriptors
were calculated. The stepwise multiple linear regression was used to select descriptors
encoding the inhibitory activity of the compounds. Multiple linear regression (MLR) was used to
build up the linear QSAR model.

Results:
The results obtained revealed that the descriptors which best describe the activity were
atom type electropological state, carbon type, radial distribution function (RDF), barysz matrix
and molecular linear free energy relation. The suggested model could achieve satisfied square correlation
coefficient of R2 = 0.72, higher than of many previous studies, indicating its superiority.
Rigid validation criteria were met using external data with Q2 ˃ 0.5 and R2 = 0.75, reflecting the
predictive power of the model.

Conclusion:
The QSAR model was applied for screening botanical components of herbal preparations
used to treat BPH, and could predict the activity of some, among others, making reasonable
attribution to the proposed effect of these preparations. Gamma tocopherol was found to be an active
inhibitor, in consistence with many previous studies, anticipating the power of this model in
the prediction of new candidate molecules and suggesting further investigations.
Studies on Structures and Functions of Kinases leading to Prostate Cancer and Their Inhibitors
Authors: Nagappa Anantha N. , Bhatt Shvetank , Kanoujia Jovita 
Published: March 2020

Background:Cancer is the uncontrolled growth of abnormal cells in any part of the body. These abnormalities in the cells make them cancer cells, malignant cells, or tumour cells. These cells can infiltrate normal body tissues. Prostate Cancer begins when cells in the prostate gland start to grow out of control.Introduction:According to the National Cancer Institute, an estimated 20 percent of men experience Prostate Cancer in their lifetimes. Prostate Cancer can be divided into castration sensitive or hormone- sensitive Prostate Cancer (CSPC or HSPC) and castration-resistant Prostate Cancer (CRPC). Different therapies showed potential for the treatment of Prostate Cancer in that androgen receptor antagonist, cytochrome p17 inhibitors, radiation therapy, brachytherapy, surgical removal of the gland, androgen deprivation therapy and LnRH antagonists are some of the important ones. Despite various available treatment options in our understanding of the biological basis of Prostate Cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Several Tyrosine kinase inhibitors (TKIs) have been evaluated in the preclinical setting in Advanced Prostate Cancer. TKIs are small drug molecules that work by competitive ATP inhibition at the catalytic binding site of tyrosine kinase. This results in complete inhibition of the catalytic activity of certain enzymes. If chosen correctly, TKIs can target and inhibit critical, mutated pathways important for the development, progression and metastasis of Prostate Cancer. The review focuses on various tyrosine kinase drug targets and their chemical structure to discuss the mechanism and pathways in the treatment of Prostate Cancer.Methods:The method adopted for the study was mainly based on the secondary search through a systematic literature review. Targets discussed in this review include the epidermal growth factor family (EGFR), vascular endothelial growth factor family (VEGF) receptor, c-Src family kinases (Proto-oncogene tyrosine-protein kinase) (c-Src), platelet-derived growth factor (PDGF) and cmesenchymal- epithelial transition factor (c-Met), which showed some promising results in various studies.Results:Even with the strong scientific rationale for many TKIs in the treatment of Prostate Cancer, the clinical trial experience showed some negative results in advanced phases. However, despite various challenges, the validation studies targeting kinases hold great potential in Prostate Cancer. Given the success of kinase inhibitors across multiple other cancer types, it is likely that this drug class will eventually improve outcomes in Prostate Cancer.Conclusion:Modifications in structures and certain other aspects of TKIs may make these agents promising for the treatment of Prostate Cancer.
Exploration of Diosmin to Control Diabetes and Its Complications-an In Vitro and In Silico Approach
Authors: Dubey Kushagra , Dubey Raghvendra , Gupta Revathi , Gupta Arun 
Published: March 2020

Background:
Diosmin is a flavonoid obtained from the citrus fruits of the plants. Diosmin has blood lipid lowering activities, antioxidant activity, enhances venous tone and microcirculation, protects capillaries, mainly by reducing systemic oxidative stress.

Objective:
The present study demonstrates the potential of Diosmin against the enzymes aldose reductase,
α-glucosidase, and α-amylase involved in diabetes and its complications by in vitro evaluation
and reverse molecular docking studies.

Methods:
The assay of aldose reductase was performed by using NADPH as starting material and
DL-Glyceraldehyde as a substrate. DNS method was used for alpha amylase inhibition and in alpha
glucosidase inhibitory activity p-nitrophenyl glucopyranoside (pNPG) was used as substrate. The
reverse molecular docking studies was performed by using Molegro software (MVD) with grid resolution
of 30 Å.

Result:
Diosmin shows potent inhibitory effect against aldose reductase (IC50:333.88±0.04
μg/mL), α-glucosidase (IC50:410.3±0.01 μg/mL) and α-amylase (IC50: 404.22±0.02 μg/mL) respectively.
The standard drugs shows moderate inhibitory activity for enzymes. The MolDock
Score of Diosmin was -224.127 against aldose reductase, -168.17 against α-glucosidase and -
176.013 against α-amylase respectively, which was much higher than standard drugs.

Conclusion:
From the result it was concluded that diosmin was a potentially inhibitor of aldose reductase, alpha amylase and alpha glucosidase enzymes then the standard drugs and it will be helpful in the management of diabetes and its complications. This will also be benevolent to decrease the socio economical burden on the middle class family of the society.
The Citrus Flavanone Hesperetin Induces Apoptosis in CTCL Cells via STAT3/Notch1/NFκB-Mediated Signaling Axis
Authors: Kottaiswamy Amuthavalli , Kizhakeyil Atish , Padmanaban Abirami M. , Mirza Fathima B. , Vijay Venkatesh R. , Lee Pin S. , Verma Navin K. , Kalaiselvan Parkavi , Samuel Shila 
Published: March 2020

Background:
Hesperetin is a natural compound known for its cholesterol-lowering effect and a wide
range of pharmacological activities.

Objectives:
Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell
lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL).

Methods:
The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by
MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis
were performed using flow-cytometry and immunoblotting.

Results:
Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant
decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular
treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin
caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved
caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated
the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65.

Conclusion:
This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL
cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel
class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.
Local Knowledge for Global Actions: The role of traditional ecological knowledge in climate change adaptation
Authors: Hosen Nadzirah , Nakamura Hitoshi 
Published: March 2020

The scale of climate change put indigenous people at higher risk than the others. Nonetheless, due to their intimate knowledge of their land, traditional ecological knowledge (TEK) held by the indigenous peoples may be the key to combating climate change. This article aims to explain the role that TEK plays in adapting to climate change. Document review included grey literature alongside peer-reviewed literature and project websites related to indigenous knowledge in climate change adaptation. The findings show that TEK not only helps indigenous people cope with environmental and climate pressures, but the knowledge system fosters resilience of socio-ecological systems.Keywords: climate change adaptation; traditional knowledge; traditional ecological knowledge; resilienceeISSN: 2398-4287 © 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.DOI: https://doi.org/10.21834/e-bpj.v5i13.2059
Enhancement of Neurocognitive Assessments Using Smartphone Capabilities: Systematic Review
Authors: Templeton John Michael , Poellabauer Christian , Schneider Sandra 
Published: March 2020

Background
Comprehensive exams such as the Dean-Woodcock Neuropsychological Assessment System, the Global Deterioration Scale, and the Boston Diagnostic Aphasia Examination are the gold standard for doctors and clinicians in the preliminary assessment and monitoring of neurocognitive function in conditions such as neurodegenerative diseases and acquired brain injuries (ABIs). In recent years, there has been an increased focus on implementing these exams on mobile devices to benefit from their configurable built-in sensors, in addition to scoring, interpretation, and storage capabilities. As smartphones become more accepted in health care among both users and clinicians, the ability to use device information (eg, device position, screen interactions, and app usage) for subject monitoring also increases. Sensor-based assessments (eg, functional gait using a mobile device’s accelerometer and/or gyroscope or collection of speech samples using recordings from the device’s microphone) include the potential for enhanced information for diagnoses of neurological conditions; mapping the development of these conditions over time; and monitoring efficient, evidence-based rehabilitation programs.

Objective
This paper provides an overview of neurocognitive conditions and relevant functions of interest, analysis of recent results using smartphone and/or tablet built-in sensor information for the assessment of these different neurocognitive conditions, and how human-device interactions and the assessment and monitoring of these neurocognitive functions can be enhanced for both the patient and health care provider.

Methods
This survey presents a review of current mobile technological capabilities to enhance the assessment of various neurocognitive conditions, including both neurodegenerative diseases and ABIs. It explores how device features can be configured for assessments as well as the enhanced capability and data monitoring that will arise due to the addition of these features. It also recognizes the challenges that will be apparent with the transfer of these current assessments to mobile devices.

Results
Built-in sensor information on mobile devices is found to provide information that can enhance neurocognitive assessment and monitoring across all functional categories. Configurations of positional sensors (eg, accelerometer, gyroscope, and GPS), media sensors (eg, microphone and camera), inherent sensors (eg, device timer), and participatory user-device interactions (eg, screen interactions, metadata input, app usage, and device lock and unlock) are all helpful for assessing these functions for the purposes of training, monitoring, diagnosis, or rehabilitation.

Conclusions
This survey discusses some of the many opportunities and challenges of implementing configured built-in sensors on mobile devices to enhance assessments and monitoring of neurocognitive functions as well as disease progression across neurodegenerative and acquired neurological conditions.
Methodological Challenges in Web-Based Trials: Update and Insights From the Relatives Education and Coping Toolkit Trial
Authors: Robinson Heather , Appelbe Duncan , Dodd Susanna , Flowers Susan , Johnson Sonia , Jones Steven H , Mateus Céu , Mezes Barbara , Murray Elizabeth , Rainford Naomi , Rosala-Hallas Anna , Walker Andrew , Williamson Paula , Lobban Fiona 
Published: March 2020

International Registered Report Identifier (IRRID)
RR2-10.1136/bmjopen-2017-016965
Youth Experiences With Referrals to Mental Health Services in Canada: Protocol for a Web-Based Cross-Sectional Survey Study
Authors: Lal Shalini , Starcevic Danielle Joanna , Fuhrer Rebecca 
Published: March 2020

Background
Youth mental health is an important public health concern affecting low-, middle-, and high-income countries, and many young people in need of mental health services do not receive the care they need when they need it. An early step in accessing mental health care is the referral process, yet most of the research done on pathways to care has focused on clinical populations (eg, first-episode psychosis) recruited from mental health care settings. There has been limited research attention on the experiences of referral to mental health services from the perspectives of youth recruited from the general population who may or may not have received the services they need.

Objective
This study aims to investigate the experiences that youth between the ages of 17 and 30 years have with referrals to mental health services and to better understand their perspectives on the use of technology to facilitate referrals.

Methods
This study will use a cross-sectional, Web-based survey design. A convenience sample of 400 participants from 3 Canadian provinces (Quebec, Ontario, and British Columbia), between the ages of 17 and 30 years, will be recruited via Facebook and will be invited to complete a Web-based survey anonymously. A questionnaire including a series of quantitative and qualitative questions will ask participants about their sociodemographic characteristics, past experiences with referral and access to mental health services, and opinions about using technology to facilitate the referral process.

Results
Participant recruitment is planned to be initiated by early January 2020 and is estimated to be completed by May 2020. Data will be analyzed using descriptive statistics and logistic regression or chi-square tests for quantitative data, and descriptive content analysis will be used for the qualitative data.

Conclusions
The results of this study can help inform the improvement of referral policies and procedures in youth mental health service delivery. A better understanding of young people’s perspectives on referral processes and their opinions on how these processes can be improved are essential to providing appropriate and timely access to mental health care.

International Registered Report Identifier (IRRID)
PRR1-10.2196/16945
SMS Text Messages for Parents for the Prevention of Child Drowning in Bangladesh: Acceptability Study
Authors: Hossain Md Mosharaf , Mani Kulanthayan , Mat Min Ruhani 
Published: March 2020

Background
In many cases, greater use is being made of mobile phone text messages as a means of communication between patients and health care providers in countries around the world.

Objective
We studied the use of mobile phones and the factors related to the acceptability of text messages for parents for the prevention of child drowning in Bangladesh.

Methods
From a randomized controlled trial involving 800 parents, 10% (80/800) were selected, and socioeconomic status, mobile phone use, and acceptability of SMS text messages for drowning prevention were measured. Participants with at least one child under 5 years of age were selected from rural areas in Rajshahi District in Bangladesh. Mobile phone–based SMS text messages were sent to the participants. Multivariate regression was used to determine the factors related to the acceptability of text messages for the prevention of child drowning in Bangladesh.

Results
The acceptability of SMS text messages for the prevention of child drowning in Bangladesh was significantly lower among women (odds ratio [OR] 0.50, 95% CI 0.12-1.96, P=.02) than among men, lower for parents older than 30 years (OR 0.17, 95% CI 0.14-1.70, P=.01) compared to parents younger than 30 years, higher among parents who had an education (OR 1.63, 95% CI 1.11-5.80, P=.04) than among illiterate parents, and higher among parents with a monthly household income over 7000 Bangladeshi Taka (approximately US $82.54; OR 1.27, 95% CI 1.06-1.96, P=.05) than among parents whose monthly income was less than 7000 Bangladeshi Taka.

Conclusions
The high percentage of mobile phone use and the acceptability of SMS text messages for parents for the prevention of child drowning are encouraging, in terms of identifying the best strategy for using such technologies, and deserve further evaluation.
Exploring the Vast Choice of Question Prompt Lists Available to Health Consumers via Google: Environmental Scan
Authors: Tracy Marguerite Clare , Shepherd Heather L , Patel Pinika , Trevena Lyndal Jane 
Published: March 2020

Background
There is increasing interest in shared decision making (SDM) in Australia. Question prompt lists (QPLs) support question asking by patients, a key part of SDM. QPLs have been studied in a variety of settings, and increasingly the internet provides a source of suggested questions for patients. Environmental scans have been shown to be useful in assessing the availability and quality of online SDM tools.

Objective
This study aimed to assess the number and readability of QPLs available to users via Google.com.au.

Methods
Our environmental scan used search terms derived from literature and reputable websites to search for QPLs available via Google.com.au. Following removal of duplicates from the 4000 URLs and 22 reputable sites, inclusion and exclusion criteria were applied to create a list of unique QPLs. A sample of 20 QPLs was further assessed for list length, proxy measures of quality such as a date of review, and evidence of doctor endorsement. Readability of the sample QPL instructions and QPLs themselves was assessed using Flesch Reading Ease and Flesch-Kincaid Grade Level scores.

Results
Our environmental scan identified 173 unique QPLs available to users. Lists ranged in length from 1 question to >200 questions. Of our sample, 50% (10/20) had a listed date of creation or update, and 60% (12/20) had evidence of authorship or source. Flesch-Kincaid Grade Level scores for instructions were higher than for the QPLs (grades 10.3 and 7.7, respectively). There was over a 1 grade difference between QPLs from reputable sites compared with other sites (grades 4.2 and 5.4, respectively).

Conclusions
People seeking questions to ask their doctor using Google.com.au encounter a vast number of question lists that they can use to prepare for consultations with their doctors. Markers of the quality or usefulness of various types of online QPLs, either surrogate or direct, have not yet been established, which makes it difficult to assess the value of the abundance of lists. Doctor endorsement of question asking has previously been shown to be an important factor in the effectiveness of QPLs, but information regarding this is not readily available online. Whether these diverse QPLs are endorsed by medical practitioners warrants further investigation.