bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation
Authors: Sadiq Idris Zubairu 
Published: December 2021

:Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free radicals ultimately leads to oxidative stress causing oxidation and damage to significant macromolecules in the living system and essentially disrupting signal transduction pathways and antioxidants equilibrium. At lower concentrations, ROS serves as “second messengers,” influencing many physiological processes in the cell. However, higher concentrations beyond cell capacity cause oxidative stress, contributing to human pathologies such as diabetes, cancer, Parkinson’s disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, and Alzheimer’s disease. Signaling pathways such as NF-κB, MAPKs, PI3K/Akt/ mTOR, and Keap1-Nrf2- ARE modulate the detrimental effects of oxidative stress by increasing the expression of cellular antioxidant defenses, phase II detoxification enzymes, and decreased production of ROS. Free radicals such as H2O2 are indeed needed for the advancement of the cell cycle as these molecules influence DNA, proteins, and enzymes in the cell cycle pathway. In the course of cell cycle progression, the cellular redox environment becomes more oxidized, moving from the G1 phase, becoming higher in G2/M and moderate in the S phase. Signals in the form of an increase in cellular pro-oxidant levels are required, and these signals are often terminated by a rise in the amount of antioxidants and MnSOD with a decrease in the level of cyclin D1 proteins. Therefore, understanding the mechanism of cell cycle redox regulation will help in the therapy of many diseases
Association of Dietary Prebiotic Consumption with Reduced Risk of
Alzheimer’s Disease in a Multiethnic Population
Authors: Gu Yian , Nishikawa Mia , Brickman Adam M. , Manly Jennifer J. , Schupf Nicole , Mayeux Richard P. 
Published: December 2021

Objective:
This study aimed to investigate the association between dietary prebiotic intake
and risk for Alzheimer’s disease (AD).

Methods:
This longitudinal study includes 1,837 elderly (≥65 years) participants of a multi-ethnic
community-based cohort study who were dementia-free at baseline and had provided dietary information
from food frequency questionnaires. Total daily intake of fructan, one of the best-known
prebiotics, was calculated based on consumption frequency and fructan content per serving of 8
food items. The associations of daily fructan intake with AD risk were examined using a Cox proportional
hazards model, adjusted for cohort recruitment wave, age, gender, race/ethnicity, education,
daily caloric intake, and APOE genotype. Effect modification by race/ethnicity, APOE genotype,
and gender was tested by including an interaction term into the Cox models, as well as by
stratified analyses.

Results:
Among 1,837 participants (1,263 women [69%]; mean [SD] age = 76 [6.3] years), there
were 391 incident AD cases during a mean follow-up of 7.5 years (13736 person-years). Each additional
gram of fructan intake was associated with 24% lower risk for AD ((95% CI)=0.60-0.97; P
=0.03). Additional adjusting for smoking, alcohol consumption, and comorbidity index did not
change results materially. The associations were not modified by race/ethnicity, gender, and APOE
genotype, although stratified analyses showed that fructan intake was significantly associated with
reduced AD risk in Hispanics but not in non-Hispanic Blacks or Whites.

Conclusion:
Higher dietary fructan intake is associated with a reduced risk of clinical Alzheimer’s
disease among older adults.
Olfactory Function, Genetic Predisposition, and Cognitive Performance in
Chinese Adults
Authors: Yang Xianyi , Si Jing , Lin Shuchun , Zhou Xiaofeng , Zhang Hui , Sun Zhonghan , Pu Yanni , Li Qian , Qiu Jiange , Wang Lin , Song Chunhua , Yuan Changzheng , Wang Xiaofeng , Zheng Yan 
Published: December 2021

Objective:
The objective of this study is to examine the association of olfactory function
and genetic predisposition of Alzheimer’s disease (AD) with cognitive performance in adults.

Methods:
A total of 2049 Chinese adults from Rugao Longevity and Ageing Study (RuLAS,
n=1460, mean age 78 years) and Central China Cohort (CCC, n=589, mean age 48 years) were included
in this study. A standard interview-based survey, clinical information, and blood samples
were collected in both cohorts. Olfactory function in terms of olfactory identification was measured
by the brief version of the Chinese Smell Identification Test consisted of 18 full points. Cognitive
performance was measured by the Chinese version of the Mini-mental State Examination. A
genetic risk score (GRS) was calculated from 5 single nucleotide polymorphisms, which were robustly
related to Alzheimer’s disease in Caucasians and cognitive performance in our Chinese population.

Results:
In the pooled analyses, participants at the lowest quartile of olfactory function had significantly
higher odds of cognitive impairment (adjusted odds ratio [95% CI] =1.45 [1.00 to 2.09], Ptrend
=0.005), and such association was stronger among participants with a stronger genetic predisposition
of Alzheimer’s disease (β coefficient±SE, -0.06±0.03 in participants with a lower GRS vs.
-0.19±0.05 in those with a higher GRS, respectively, Pinteraction=0.01). Similar associations were observed
in RuLAS (P-trend=0.06) and in CCC (P-trend<0.001).

Conclusion:
In this study, a decreased olfactory function was associated with worse cognitive performance
in adults, especially among participants with a higher genetic risk of Alzheimer’s disease.
Further studies are warranted to evaluate the causal relationship between olfaction and cognitive
performance.
Does the Global Postural Re-Education Affect the Psychological and Postural
Aspects of Alzheimer Disease Patients? A Six Months Quasi-Experimental
Study
Authors: Todri Jasemin , Lena Orges , Todri Ardita , Fuentes Juan M. 
Published: December 2021

Objective:
To study the implementation of Global Postural Re-education as a rehabilitative alternative in residence facilities for seniors with Alzheimer, and to verify its effect on psychological and cognitive symptoms.

Methods:
A quasi-experimental design was employed using month-follow-up assessments at 1,3,
and 6 months respectively. Ninety elderly people participated in the composition of the study sample: 69 women and 21 men aged from 67 to 89 years (80.2 ±5.5), grouped in two phases: mild and
moderate, according to Alzheimer severity. Patients in both groups received the same treatment
twice a week for consecutively 24 weeks. Three follow-up medium-long term assessments were
performed at intervals of 1, 3, and 6 months. Outcome measures included Mini-Mental State Examination, Geriatric Depression Scale, Quality of Life in Alzheimer Disease, Barthel Index, and Tinetti Scale.

Results:
The severity of groups therapy interaction showed significant changes in four outcome
measures as cognition [F(1,88)=60.26; p=.000; partial η2= 0.406], depression [F(1,88)=8.24;
p=.005; partial η2= 0.086], life quality [F(1,88)= 10.45; p=.002; partial η2= 0.106] and equilibrium
[F(1,88)= 6.96; p=.010; partial η2= 0.073]. No changes were found for autonomy [F(1,88)= 1.10;
p=.297; partial η2= 0.012]. These changes between the two groups were observed at the sixth
month follow-up assessment.

Conclusion :
Global postural reeducation could be useful as a complementary rehabilitation treatment in Alzheimer patients.
The Expression of Glutaminases and their Association with Clinicopathological
Parameters in the Head and Neck Cancers
Authors: Basheer Haneen A. , Elsalem Lina , Salem Anwar , Tailor Artysha , Hunter Keith , Afarinkia Kamyar 
Published: December 2021

Background:
The increased glutamine metabolism is a characteristic feature of cancer
cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms,
GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated
for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced
clinicopathological parameters in head and neck cancers.

Method:
Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal
to metastatic were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following
analysis by two expert pathologists, we carried out a statistical analysis of the scores.

Results:
GLS1 and GLS2 were found to be upregulated at the protein level in head and neck tumours
compared to normal tissues, and this increased expression correlated positively (GLS1) and
negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms
based on tumor differentiation. Increased expression of GLS1 was associated with high
CD147 expression, and elevated GLS2 expression was associated with both high CD147 and high
HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly
associated with more advanced clinicopathological parameters.

Conclusion:
The increased expression of GLS1 and GLS2 may be explored as a new treatment for
head and neck cancers.
Potential Roles of α-amylase in Alzheimer’s Disease: Biomarker and Drug
Target
Authors: Yeong Keng Yoon , Chen Win Ning , Tang Kim San 
Published: December 2021

:
Alzheimer’s disease (AD), the most common form of dementia, is pathologically characterized
by the deposition of amyloid-β plaques and the formation of neurofibrillary tangles. In a neurodegenerative
brain, glucose metabolism is also impaired and considered as one of the key features
in AD patients. The impairment causes a reduction in glucose transporters and the uptake of glucose
as well as alterations in the specific activity of glycolytic enzymes. Recently, it has been reported
that α-amylase, a polysaccharide-degrading enzyme, is present in the human brain. The enzyme is
known to be associated with various diseases such as type 2 diabetes mellitus and hyperamylasaemia.
With this information at hand, we hypothesize that α-amylase could have a vital role in the
demented brains of AD patients. This review aims to shed insight into the possible link between the
expression levels of α-amylase and AD. Lastly, we also cover the diverse role of amylase inhibitors
and how they could serve as a therapeutic agent to manage or stop AD progression.
Extracting Atomic Contributions to Binding Free Energy Using Molecular
Dynamics Simulations with Mixed Solvents (MDmix)
Authors: Barril Xavier , Alvarez-Garcia Daniel , Schmidtke Peter , Cubero Elena 
Published: December 2021

Background:
Mixed solvents MD (MDmix) simulations have proved to be a useful and increasingly
accepted technique with several applications in structure-based drug discovery. One of the
assumptions behind the methodology is the transferability of free energy values from the simulated
cosolvent molecules to larger drug-like molecules. However, the binding free energy maps (ΔGbind)
calculated for the different moieties of the cosolvent molecules (e.g. a hydroxyl map for the ethanol)
are largely influenced by the rest of the solvent molecule and do not reflect the intrinsic affinity of the
moiety in question. As such, they are hardly transferable to different molecules.

Method:
To achieve transferable energies, we present here a method for decomposing the molecular
binding free energy into accurate atomic contributions.

Result:
We demonstrate with two qualitative visual examples how the corrected energy maps better
match known binding hotspots and how they can reveal hidden hotspots with actual drug design potential.

Conclusion:
Atomic decomposition of binding free energies derived from MDmix simulations provides
transferable and quantitative binding free energy maps.
Exploration of Luteolin as Potential Anti-COVID-19 Agent: Molecular
Docking, Molecular Dynamic Simulation, ADMET and DFT Analysis
Authors: Ansari Waseem Ahmad , Ahamad Tanveer , Khan Mohsin Ali , Khan Zaw Ali , Khan Mohammad Faheem 
Published: December 2021

Background:
Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic
respiratory disease with mild to severe pneumonia symptoms. No clinical antiviral agent is available so
far. However, several repurposing drugs and vaccines are being given to individuals or in clinical trials
against SARS-CoV-2

Objective:
The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of
SARS-CoV2 encoded proteins via utilizing computational tools.

Method:
Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference
drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic
(MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density
functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one
human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO
gap energy and other chemical descriptors analysis.

Results:
In the present study, Lut binds effectively in the binding pockets of spike glycoprotein (6VSB),
ADP phosphatase of NSP3 (6W02), and RNA dependent RNA polymerase (7AAP) protein receptors with
significant values of docking scores -7.00, -7.25, and -6.46 respectively as compared to reference drugs
remdesivir and nafamostat.

Conclusion::
Thus, Lut can act as a therapeutic agent and is orally safe for human consumption as predicted
by molecular modelling against SARS-CoV-2 in the treatment of COVID-19.
Comparison of General Dietary and Lifestyle Habits Before and During
COVID-19 among the Saudi Adult Population in Riyadh
Authors: ALkharashi Nouf A. 
Published: December 2021

Background:
During the initial outbreak of the global COVID-19 pandemic, there
were few effective evidence-based vaccines or treatments available, which led to many attempts
to find alternative options.

Objective:
This study aimed to compare the general dietary and lifestyle habits among the Saudi
adult population in Riyadh before and during COVID-19.

Methods:
This was a cross-sectional study targeting the Riyadh population from 16 May 2020 to
16 June 2020. The study was composed of a structured questionnaire that collected demographic
information (such as age, gender, place of residence, and health status), dietary habit information
(such as daily intake of certain foods, food frequency, number of meals/day, and number of
times drinking tea and coffee), lifestyle habit information (such as physical activity; sleep quality;
and time spent using the internet, social media, and electronic devices for fun or stress relief)
using Google forms. A total of 1193 participants aged over 18 years were included in the study.

Results:
During the COVID-19 period, a significant increase was observed in the number of
meals eaten daily, fruit and vegetable intake, the intake of sweets and cakes/biscuits, the number
of hours of sleep per day, and time spent on the internet and social media compared with the pre-
COVID-19 pandemic period. However, the amount of running exercise or physical activity was
found to be significantly reduced.

Conclusion:
In this study, we found that the dietary and lifestyle habits changed among Saudi
adults during the COVID-19 period. Similar large-scale studies should be undertaken in the future
to confirm the results of the study.
Therapeutic Benefits of Piper nigrum: A Review
Authors: Malviya Rishabha , Majumdar Banishree , Sharma Akanksha 
Published: December 2021

Abstract:
This manuscript aims to describe the various pharmacological activities of Piper
nigrum. Pepper is a common spice of the plant which is used as spice in preparation of various
foods. Pepper production is centered in Kerela, followed by Karnataka and Maharashtra in India.
Other big pepper-producing countries include Indonesia, Malaysia, Brazil, Vietnam, and Sri Lanka.
It has various pharmacological activities which is why it is used in the treatment of different diseases.
The manuscript mainly describes the antituberculosis, anticonvulsant, analgesic, antipyretic, anti-
inflammatory, antimicrobial, antioxidant, gastrointestinal and anticancer activities of Piper nigrum.
The manuscript also describes the various studies related to the pharmacological activities of
Piper nigrum. It is concluded from the manuscript that Piper nigrum has great efficacy in the treatment
of various diseases.
5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery
to Lung Cancer: In Vitro Investigations
Authors: Kumar Gourav , Gupta Rashmi , Vishwakarma Leena , Guleri Sunil Kant 
Published: December 2021

Background and Objective:
The study aimed to investigate the augmented cytotoxic effects of polymercoated
(poly-lactic-co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management
of lung cancer.

Materials and Methods:
In this study, several formulations were prepared using a double emulsion (water-oil-water)
method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment.

Results:
Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity
index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. Compared to others, the optimized
polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09±10.75%). The
percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles
(FGNPs), (PFGNPs) and 5-FU solution were 47.87±1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively,
over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of
PFGNPs on the A549 cells was 82.89% compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression
analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for
PFNPs.

Conclusion:
PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained
delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung
cancer with reduced toxicity and improved efficacy.
Pharmacogenomics of Antihypertensive Drugs in Brazil: Recent Progress
and Clinical Implications
Authors: Vecchia Genvigir Fabiana Dalla , Dagli-Hernandez Carolina , Hirata Thiago Dominguez Crespo , Zhou Yitian , Lauschke Volker M. , Hirata Mario Hiroyuki , Hirata Rosario Dominguez Crespo 
Published: December 2021

Background:
The available antihypertensive drugs are effective and well tolerated agents. However, only about half of patients with treated hypertension achieve appropriate blood pressure control. Genetic and non-genetic factors contribute to the interindividual variability of the therapeutic response.

Objective:
This review constitutes a comprehensive update of the pharmacogenomics of antihypertensive drugs and their clinical implications in Brazil.

Results:
Twenty-five studies explored the influence of gene variants on drug response in patients with primary, resistant, or gestational hypertension. Variants in BDKRB2, NOS3, PRKCA, and VEGFA influenced the response to enalapril in patients with primary hypertension. AGT and MMP2 variants were associated with a high risk of resistance to antihypertensive treatment, whereas NOS2 variants were related to low risk. Moreover, NAT2 slow acetylators showed an increased response to hydralazine in patients with resistant hypertension. HMOX1, NAMPT, MMP9, NOS3, and TIMP1 variants might be markers of drug responsiveness in hypertensive or preeclamptic pregnant women. Power and replication of studies, polygenic nature of the response to therapy, and treatment with multiple drugs were important challenges to identify genetic predictors of antihypertensive response in Brazil.

Conclusion:
Pharmacogenomic studies in Brazilian cohorts provide some evidence of variants, mainly in pharmacodynamics genes, which influence the response to antihypertensive drugs. However, some findings are limited by cohort size or therapeutic scheme and may be influenced by interactions with other genetic and non-genetic factors. Therefore, further investigations are needed to elucidate the contribution of pharmacogenomics to the efficacy and safety of antihypertensive therapy.
Numerical Analysis of Johnson-Cook Damage Model Parameters Effects
on the Cutting Simulation of AISI 1045
Authors: Sun Yong , Li Guohe , He Zhen , Kong Xiangcheng 
Published: December 2021

Background:
The failure model is an important basis for research on material failure
and fracture, and plays an important role in the finite element simulation of metal cutting. Johnson-
Cook damage model is widely used to predict the onset of damage to many materials. Its
damage evolution is controlled by five parameters.

Objective:
This study aimed to decrease the cost of damage parameters’ identification and find out
the damage parameters which have a great influence on the simulation results. This work can provide
assistance in the optimization and selection of constitutive model parameters.

Methods:
Suitable Johnson-Cook damage model parameters, which can be used in the metal cutting
simulation of AISI 1045 steel, are selected by comparing the simulation results and the experimental
results. The cutting process of AISI 1045 steel is simulated by changing the Johnson-
Cook damage parameters in the ABAQUS/Explicit.

Results:
The relevance of cutting force, feed force, cutting temperature, and deformation coefficient
with five Johnson-Cook damage parameters are determined.

Conclusion:
The finite element simulation results show that the Johnson-Cook damage model
parameters D2 and D3 have the biggest impact on the cutting simulation of AISI 1045 steel.
Meanwhile, different Johnson-Cook damage parameters would cause diverse changes in the simulation
results.
Implementation of an Expressive Writing Intervention for
Adolescents During Inpatient Psychiatric Hospitalization
Authors: Taniguchi Yuko , Schlief Mason , Bright Jered , Simon Sue , Leffler Jarrod M. 
Published: December 2021

BACKGROUND:
Given the high rates of mental health concerns and communication difficulties for adolescents a treatment intervention to allow for effective expression may be therapeutic. One of the leading writing practices is Pennebaker’s Expressive Writing (EW) intervention. EW involves individuals writing about their feelings and thoughts regarding negative life experiences. Benefits of EW include a reduction of psychological symptoms and doctor visits, and better adjustment.

OBJECTIVE:
To examine the role of using EW and creative writing as a group intervention for youth admitted to an inpatient psychiatric hospital (IPH)

METHODS:
The current study evaluated participant engagement in a 3-day EW activity facilitated by nurses and graduate students on the IPH unit under the supervision of the IPH unit nurse manager and course instructor. Participants included 23 youth between 12- and 18-years-old

RESULTS:
Of the 23 participants 49.69% discussed vivid descriptions of illness, 24.5% discussed negative emotions, 20.25% included casual explanation, 5.52% discussed polarized view, and 16.56% discussed their desires, wishes, and goals. The response rate of clinician’s review of the EW content included 58% of clinician’s coding was on the patient’s current state, 24% was on causal explanations, and 18% was on treatment options.

CONCLUSION:
The current EW intervention facilitated by nursing staff and graduate students in an IPH was found to be engaged in by participants and provide an additional therapeutic resource to participants. EW may foster patient communication with staff about their functioning, mental health concerns, and treatment needs.