bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies for Targeting KRAS: A Challenging Drug Target
Authors: Wadood Abdul , Ajmal Amar , Rehman Ashfaq Ur 
Published: May 2022

Abstract:
In the developed world, cancer is the most common cause of death. Among the 36 human genes of
the RAS family, KRAS, NRAS, and HRAS play a prominent role in human cancer. KRAS belongs to the Ras
superfamily of proteins and is a small GTPase signal transduction protein. Among the RAS isoform, KRAS is
the dominant mutant that induces approximately 86% of the RAS mutations. The most frequently mutated
KRAS isoform is KRAS4B. About 90% of pancreatic cancer, 30-40% of colon cancer, and 15 to 20% of lung
cancers are caused by mutations KRAS4B isoform. Liver cancer, bladder cancer, breast cancer, and myeloid
leukaemia are also caused by mutations in KRAS but are rare. The FDA has recently approved sotorasib for the
treatement of KRASG12C-mutated advanced non-small cell lung cancer (NSCLC) patients. However, no FDAapproved
drugs are available for other KRAS-driven cancer. As the KRAS proteins lack a druggable pocket accessible
to the chemical inhibitors, the cancer-causing mutant proteins are almost identical to their essential
wild-type counterparts. Therefore, they are considered undruggable. The new insights into the structure and
function of RAS have changed this understanding and encouraged the development of many drug candidates.
This review provides information about the different strategies for targeting KRAS, a challenging drug target
that might be valuable for the scientific community.
Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats
Authors: Marín-Prida Javier , Liberato José Luiz , Llópiz-Arzuaga Alexey , Stringhetta-Padovani Karina , Pavón-Fuentes Nancy , Leopoldino Andréia Machado , Cruz Osmany Guirola , González Ignacio Hernández , Pérez Mariela León , Camins Antoni , Ferreira dos Santos Wagner , Uyemura Sergio Akira , Pardo-Andreu Gilberto L. , Pentón-Rol Giselle 
Published: May 2022

Background:Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options.Objective:This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis.Methods:Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis of NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed.Results:C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurological deficit in a dose-dependent manner, and improved the exploratory activity of I/R rats. This biliprotein inhibited NOX2 expression, a crucial NADPH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-β) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats.Conclusion:These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.
Fungal Metabolites: A Potential Source of Antidiabetic Agents with
Particular Reference to PTP1B Inhibitors
Authors: Deshmukh Sunil Kumar , Agrawal Shivankar , Gupta Manish K. 
Published: May 2022

Abstract:
Diabetes is a growing health concern worldwide because it affects people of all age
groups and increases the risk of other diseases such as renal impairment and neural and cardiovascular
disorders. Oral hypoglycemic drugs mainly control diabetes; however, their associated side effects
limit their use in patients with other complications. PTP1B is a viable drug target to explore
new antidiabetic drugs. PTP1B acts as a negative regulator of the insulin-signaling pathway, and
therefore, PTP1B inhibitors display antihyperglycemic activity. Several classes of compounds from
natural and synthetic sources act as PTP1B inhibitors. Fungi are comprehensive in their diversity and
recognized as a valuable source for therapeutically active molecules. In recent years, researchers
have reported diverse classes of fungal secondary metabolites as potent PTP1B inhibitors. Some
metabolites such as 6-O-methylalaternin, fumosorinone A, nordivaricatic acid, and the divarinyl
divarate showed good activity and can be taken forward as a lead to develop novel PTP1B inhibitors
and antidiabetic drugs. Therefore, the present review focuses on the fungal metabolites identified in
the last five years possessing PTP1B inhibitory activity. A total of 128 metabolites are reviewed.
Their fungal species and source, chemical structure, and activity in terms of IC50 are highlighted.
The Role of VEGF Family in Lipid Metabolism
Authors: Zhou Yan , Zhu Xueping , Wang Huan , Duan Chenglin , Cui Hanming , Shi Jingjing , Shi Shuai , Yuan Guozhen , Hu Yuanhui 
Published: May 2022

Abstract:
The vascular endothelial growth factor (VEGF) family plays a major role in tumors and
ophthalmic diseases. However, increasingly more data reported its potential in regulating lipids.
With its biological functions mainly expressed in lymphatic vessels, some factors in the families,
like VEGF-A and VEGF-C, have been proved to regulate intestinal absorption of lipids by affecting
chylous ducts. Other effects, including regulating lipoprotein lipase (LPL), endothelial lipase (EL),
and recombinant syndecan 1 (SDC1), have also been confirmed. However, given the scant-related
studies, further research should be conducted to examine the concrete mechanisms and provide
pragmatic ways to apply them in the clinic. The VEGF family may treat dyslipidemia in specific
ways that are different from common methods and concurrently contribute to the treatment of other
metabolic diseases, like diabetes and obesity.
Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives
against Pathogens of Clinical Importance
Authors: Juliana Martins Francislene , Savacini Sagrillo Fernanda , Josianne Vinturelle Medeiros Rafaelle , Gonçalves de Souza Alan , Rodrigues Pinto Costa Amanda , Silva Novais Juliana , Alves Miceli Leonardo , Campos Vinícius , Marie Sá Figueiredo Agnes , Claudia Cunha Anna , Lidmar von Ranke Natalia , Lamim Bello Murilo , Abrahim-Vieira Bárbara , De Souza Alessandra , Ratcliffe Norman , da Costa Santos Boechat Fernanda , Cecília Bastos Vieira de Souza Maria , Rangel Rodrigues Carlos , Carla Castro Helena 
Published: May 2022

Background:
Microbial resistance has become a worldwide public health problem, and may lead to morbidity and mortality in affected patients.

Objective:
Therefore, this work aimed to evaluate the antibacterial activity of quinone-4-oxoquinoline derivatives.

Method:
These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and by in silico assays.

Results:
The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities, and in some cases were more active than commercially available reference drugs. These compounds also inhibited bacterial adhesion and the assays revealed seven non-hemolytic derivatives. The derivatives seem to cause damage to the bacterial cell membrane and those containing the carboxyl group at the C-3 position of the 4-quinolonic nucleus were more active than those containing a carboxyethyl group.

Conclusion:
The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding pocket on the DNA gyrase enzyme.
Natural Antioxidants as Additional Weapons in the Fight against Malarial
Parasite
Authors: Virendra Sharma Arvind , Sahu Chandrakant , Kumar Ankur , Chawla Pooja Abrol 
Published: May 2022

Background:
All currently available antimalarial drugs are developed from natural prod-uct lineages that may be traced back to herbal medicines, including quinine, lapachol, and artemis-inin. Natural products that primarily target free radicals or reactive oxygen species, play an im-portant role in treating malaria.

Objective:
This review analyses the role of antioxidative therapy in treating malaria by scavenging or countering free radicals and reviews the importance of natural plant extracts as antioxidants in oxidative therapy of malaria treatment.

Methods:
The search for natural antioxidants was conducted using the following databases: Re-searchGate, ScienceDirect, Google Scholar, and Bentham Science with the keywords malaria, reac-tive oxygen species, natural antioxidants, and antiplasmodial.

Conclusion:
This study reviewed various literature sources related to natural products employed in antimalarial therapy directly or indirectly by countering/scavenging reactive oxygen species pub-lished between 2016 till date. The literature survey made it possible to summarize the natural prod-ucts used in treating malaria, emphasizing botanical extracts as a single component and in associa-tion with other botanical extracts. Natural antioxidants like polyphenols, flavonoids, and alkaloids, have a broad range of biological effects against malaria. This review is pivoted around natural anti-oxidants obtained from food and medicinal plants and explores their application in restraining reac-tive oxygen species (ROS). We anticipate this article will provide information for future research on the role of antioxidant therapy in malaria infection.
The Role of Mitochondria-Targeting miRNAs in Intracerebral Hemorrhage
Authors: Gareev Ilgiz , Beylerli Ozal , Liang Yanchao , Lu Enzhou , Ilyasova Tatiana , Sufianov Albert , Sufianova Galina , Shi Huaizhang , Ahmad Aamir , Yang Guang 
Published: May 2022

Abstract:
Non-traumatic intracerebral hemorrhage (ICH) is the most common type of hemorrhagic
stroke, most often occurring between the ages of 45 and 60. Arterial hypertension (AH) is most often
the cause of ICH, followed by atherosclerosis, blood diseases, inflammatory changes in cerebral
vessels, intoxication and vitamin deficiencies. Cerebral hemorrhage can occur by diapedesis or as a
result of a ruptured vessel. AH is difficult to treat, requires surgery and can lead to disability or
death. One of the important directions in the study of the pathogenesis of ICH is mitochondrial dysfunction
and its regulation. The key role of mitochondrial dysfunction in AH and atherosclerosis, as
well as in the development of brain damage after hemorrhage, has been acknowledged. MicroRNAs
(miRNAs) are a class of non-coding RNAs (about 18-22 nucleotides) that regulate a variety of biological
processes including cell differentiation, proliferation, apoptosis, etc., primarily through gene
repression. There is growing evidence to support dysregulated miRNAs in various cardiovascular
diseases, including ICH. Further, the realization of miRNAs within mitochondrial compartment has
challenged the traditional knowledge of signaling pathways involved in the regulatory network of
cardiovascular diseases. However, the role of miRNAs in mitochondrial dysfunction for ICH is still
under-appreciated, with comparatively much lesser studies and investigations reported, than those in
other cardiovascular diseases. In this review, we summarize the up-to-date findings on the published
role miRNAs in mitochondrial function for ICH, and the potential use of miRNAs in clinical settings,
such as potential therapeutic targets and non-invasive diagnostic/prognostic biomarker tools.
Nanotechnological Advances for Nose to Brain Delivery of Therapeutics to
Improve the Parkinson Therapy
Authors: Khatri Dharmendra K. , Preeti Kumari , Tonape Shivraj , Bhattacharjee Sheoshree , Patel Monica , Shah Saurabh , Singh Pankaj K. , Srivastava Saurabh , Gugulothu Dalapathi , Vora Lalitkumar , Singh Shashi B. 
Published: May 2022

Abstract:
Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment
to the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's
disease (PD). About the nature of drugs and other potential molecules, they impose unavoidable doserestricted
limitations eventually leading to the failure of therapy. However, many advancements in
formulation technology and modification of delivery approaches have been successful in delivering the
drug to the brain in the therapeutic window. The nose to the brain (N2B) drug delivery employing the
nanoformulation, is one such emerging delivery approach, overcoming both classical drug formulation
and delivery-associated limitations. This latter approach offers increased bioavailability, greater patient
acceptance, lesser metabolic degradation of drugs, circumvention of BBB, ample drug loading along
with the controlled release of the drugs. In N2B delivery, the intranasal (IN) route carries therapeutics
firstly into the nasal cavity followed by the brain through olfactory and trigeminal nerve connections
linked with nasal mucosa. The N2B delivery approach is being explored for delivering other biologicals
like neuropeptides and mitochondria. Meanwhile, this N2B delivery system is associated with critical
challenges consisting of mucociliary clearance, degradation by enzymes, and drug translocations
by efflux mechanisms. These challenges finally culminated in the development of suitable surfacemodified
nano-carriers and Focused- Ultrasound-Assisted IN as FUS-IN technique which has expanded
the horizons of N2B drug delivery. Hence, nanotechnology, in collaboration with advances in the
IN route of drug administration, has a diversified approach for treating PD. The present review discusses
the physiology and limitation of IN delivery along with current advances in nanocarrier and
technical development assisting N2B drug delivery.
Melatonin Receptor Agonists for the Prevention of Delirium: An Updated
Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Maneeton Narong , Maneeton Benchalak , Kongsaengdao Subsai , Likhitsathian Surinporn , Woottiluk Pakapan , Kawilapat Suttipong , Srisurapanont Manit 
Published: May 2022

Background:
Although a previous review illustrated the efficacy of melatonin receptor
agonists (MRAs) in preventing delirium, some recent randomized controlled trials (RCTs) did not
confirm these effects.

Objectives:
This study systematically reviewed the efficacy, acceptability, and tolerability of MRAs
for delirium prevention.

Materials and Methods:
We searched electronic databases, including Scopus, PubMed, CINAHL,
and Controlled Trials Register, from their inception to February 20, 2022. The primary efficacy
outcome was delirium incidence rate after MRA administration; relative risks (RRs), overall discontinuation,
and discontinuation due to adverse events are also presented.

Results:
The overall pooled incidence rates of delirium in MRA-treated and placebo-treated groups
were significantly different with RR (95% CI)=0.66(0.52, 0.84, ), I2=59%. Similarly, the incidence
rate was significantly lower in the melatonin-treated group than in the placebo-treated group [RR
(95% CI) =0.65 (0.49, 0.88), I2=65%]. Unfortunately, incidence rates were not significantly different
between ramelteon-treated and placebo-treated groups [RR (95% CI) =0.67 (0.42, 1.08),
I2=50%]. The pooled incidence rate of delirium in either melatonin or ramelteon-treated groups was
not significantly different from the placebo-treated group in elderly patients. The pooled incidence
rate of delirium was significantly lower in the melatonin-treated group than in the benzodiazepinetreated
group.

Conclusion:
Based on this review, melatonin could prevent delirium with a small effect size. However,
ramelteon did not show efficacy in preventing delirium. Additionally, neither melatonin nor
ramelteon individually showed effectiveness in preventing delirium in elderly patients. Therefore,
using MRAs to prevent delirium in clinical practice should be cautious. However, future welldefined
and large sample size studies could verify these findings.
Physical Activity and its Associated Factors among Pregnant Sudanese
Women in Eastern Sudan
Authors: Munder Omer , Ishag Mohamed , Ahmed Abdel B.A. , ALhabardi Nadiah , Hassan Bahaeldin , Adam Ishag 
Published: May 2022

Background:
Moderate physical activity (PA) during pregnancy (> 150 min/week) is
beneficial to mothers and their growing fetuses. There are no published data on PA during pregnancy
in Sudan.

Methods:
A cross-sectional study was conducted to assess the level of PA among pregnant Sudanese
women and to determine its associated factors. Sociodemographic and obstetric variables
were gathered through a questionnaire, and PA was assessed by the Pregnancy Physical Activity
Questionnaire (PPAQ). The scores were compiled, the participants were classified according to the
intensity and type of PA, and logistic regression analysis was performed.

Results:
Five hundred women with a median (interquartile range) age of 27.0 (9.0) years were enrolled.
The majority (88.4%) were housewives, more than half (53.6%) were overweight, and just
over a quarter (25.8%) were obese. The sedentary activity was reported by 367 women (73.4%).
The most energy (29.54 ± 9.62 metabolic equivalent task h/week; 83.75%) was spent during household
and caregiving activities. While there was no association with age, parity, education, gestational
age, and PA, overweight (adjusted odds ratios (AOR) = 2.38, 95% confidence interval (CI) =
1.27-4.45) and obesity (AOR = 3.07, 95% CI = 1.56-6.02) were associated with PA.

Conclusions:
This study demonstrated that the majority of Sudanese pregnant women had a sedentary
lifestyle. Most of the energy was spent during household and caregiving activities. Overweight
and obese pregnant women were more likely to be physically active. Health education about the importance
of prenatal PA is needed in Sudan.
The Engagement Challenge: Feasibility and Acceptability of Cognitive Remediation for Teenagers in the Care of Youth
Protection Services
Authors: Thibaudeau Elisabeth , R.-Mercier Alexandra , Wykes Til , Reeder Clare , Guay Karianne , Nadeau Danielle , Dufour Geneviève , Cella Matteo , Cellard Caroline 
Published: May 2022

Background:
History of childhood maltreatment is recognized as an important
risk factor for the development of mental health and cognitive difficulties. Cognitive
difficulties are associated with impairments in everyday functioning in different domains
such as school or work. To date, no study has evaluated the feasibility and acceptability of
cognitive remediation therapy (CRT) for teenagers with a history of childhood
maltreatment.

Objective:
The objective was to assess the acceptability and feasibility of the CIRCuiTS
program for teenagers in youth protection services and to explore the preliminary effect
on clinical and neuropsychological outcomes.

Methods:
Ten participants were first assessed with clinical and neuropsychological
measures. They then received a mean of 16 CRT sessions with the CIRCuiTS program
adapted for teenagers. The same measures as a baseline were repeated directly after the
end of treatment, as well as 3-months and 1-year post-treatment. Descriptive statistics
were used to assess feasibility and acceptability, while the preliminary effect of
CIRCuiTS was assessed with Reliable Change Indices (RCIs).

Results:
CIRCuiTS was considered acceptable by both participants and therapists for the
attractiveness of the program, its easiness of use and understanding, and its cultural
adaptability. However, the feasibility was limited, with only 50% of participants having
completed CIRCuiTS. This was mostly explained by contextual factors. RCIs revealed
significant improvements in several neuropsychological domains, as well as a decline in
other domains.

Conclusion:
This pilot study highlights challenges that must be addressed to promote
engagement with CRT for teenagers in the care of youth protection services.
Working with Schools to Support Trans Youth: Seen, Safe and
Supported
Authors: Baum Joel 
Published: May 2022

Background:
As one of the primary places of socialization for a young
person, school is a critical part of any transgender student’s life. Mental health
providers can play a fundamental role supporting these vulnerable young people as
they navigate the hallways and classrooms of their schools.

Objective:
This article provides mental health personnel with information and
resources for supporting transgender youth in the school setting.

Method:
Some general principles for working effectively with educational
institutions serving transgender youth are provided. In addition, three critical tools
are introduced for maximizing conditions for a successful experience at school for
these students.

Results:
Educational institutions have adopted a range of specific structures found
effective in anticipating and managing various issues a transgender child may
encounter at school. These include structured approaches for initial discussions
with school officials about a child’s gender, and Gender Support Plans and Gender
Communication Plans designed to codify ways a school will support a student
around their emerging gender status. Awareness of these resources will help mental
health providers effectively partner with patients and their families as they navigate
educational institutions.

Conclusion:
For many transgender and other gender diverse students, the day-today
tumult of school can be a source of great anxiety and concerns that they have
no control over their circumstances. Using gender support and gender
communication plans can diminish these feelings. Mental health providers must
have a firm understanding of these plans and their implementation to provide the
necessary support for gender diverse students.
Sensorless Control of Permanent Magnet Linear Synchronous Motor
Based On Double Sliding Mode
Authors: Wen Cheng , Lv Kailin , Zhao Qiankai , Li Mingwei , Wang Xin , Zhao Xingqiao 
Published: May 2022

Background & Objective:
This document presents a dual sliding mode vector control
method to estimate speed and position of Permanent Magnet Linear Synchronous Motor
(PMLSM).

Methods:
Firstly, the motor simulation model is built based on the mathematical model of PMLSM.
For the sake of solving the problems of the jitter and position angle deviation in the traditional
SMO, the inverse hyperbolic tangent function is used and the software phase-locked loop algorithm
is introduced, and the gain of exponential approach rate is improved to change the real-time, so as to
eliminate the problems of high-frequency jitter and angle deviation. Secondly, global fractional order
integral sliding mode control (GFOISMC) is used to replace PI control to eliminate jitter and
improve the robustness to load disturbance. Finally, the dynamic performance of the system under
constant speed no-load and constant speed sudden load is simulated.

Results:
The simulation result proves a proposed dual sliding mode control strategy combining the
improved SMO and GFOISMC that can effectively reduce the jitter and improve robustness.

Conclusion:
In this paper, two sensorless control strategies are compared and their robust performance
is studied. The two control scheme is simulated in the MATLAB/Simulink environment.