bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust contact-constrained topology optimization considering uncertainty at the contact support
Authors: Schmidt Timo , Kriegesmann Benedikt , Seifried Robert 
Published: August 2023

Abstract

In this paper, the general framework for contact-constrained topology optimization of Strömberg and Klarbring [13] is extended to robust topology optimization. In doing so, a linear elastic design domain is considered and the augmented Lagrangian approach is used to model the unilateral contact. For topology optimization, the design space is parametrized with the SIMP-approach and the Sigmund’s filter is applied. Additionally, the robust framework considers uncertainties at the contact support such as deviations of the geometry of the contact surface and the friction coefficient. Both uncertainties are described by the first-order second-moment method which leads to minimal additional costs. In fact, only two addional linear equations must be solved to obtain the robust objective and its gradient with respect to the design variables. Having both the objective and the gradient, the design update is computed with the method of moving asymptodes. The robust framework is applied to 2D and 3D examples to prove its scalabiltiy for real-world applications.
Understanding the Molecular Basis for Enhanced Glutenase Activity of
Actinidin using Structural Bioinformatics
Authors: Puja Shivangi , Seth Shreya , Hora Rachna , Kaur Satinder , Mishra Prakash Chandra 
Published: August 2023

Background:
Management of gluten intolerance is currently possible only by consumption
of a gluten-free diet (GFD) for a lifetime. The scientific community has been searching for alternatives
to GFD, like the inclusion of natural proteases with meals or pre-treatment of gluten-containing
foods with glutenases. Actinidin from kiwifruit has shown considerable promise in digesting
immunogenic gliadin peptides compared to other plant-derived cysteine proteases.

Methods:
In this study, we aimed to understand the structural basis for the elevated protease action
of actinidin against gliadin peptides by using an in silico approach.

Results:
Docking experiments revealed key differences between the binding of gliadin peptide to
actinidin and papain, which may be responsible for their differential digestive action.

Conclusion:
Sequence comparison of different plant cysteine proteases highlights amino acid residues
surrounding the active site pocket of actinidin that are unique to this molecule and hence likely
to contribute to its digestive properties.
New Molecules of Importance in the Prevention and Treatment of
Acne: A Systematic Patent Review (2016-2020)
Authors: Calderón-Pardo Daniela Estefanía , Serafini Mairim Russo , Alves Izabel Almeida , Aragón Diana Marcela 
Published: August 2023

Background:
Acne is a highly prevalent disease that mainly affects the pilosebaceous
units associated with sebaceous glands, causing inflammatory skin lesions and affecting
the self-esteem, mental health, and quality of life of those who suffer from this
disease. Different treatments exist today to prevent, reduce, and improve symptoms; however,
over the years, there have been problems with bacterial resistance and slight effectiveness
with prolonged use.

Objective:
The purpose of this article is based on the review of patents of new products of
principal topical administration for the treatment of acne in recent years 2016-2020, to
evaluate and analyze novel synthetic molecules and semi-synthetics with potential therapeutic
and preventive in the acne treatment.

Methods:
A systematic review of patents was conducted through the official database of
the European Patent Office - Espacenet, where the search focused on the keywords: "acne
and bacteria" in the title or abstract. Only patents granted between the years 2016-2020
were included, with products having molecules with a synthetic and semi-synthetic origin,
without considering natural, biological products or those used as diagnostic means.

Results:
A total of 19 patents were selected, most with principally antimicrobial and antiinflammatory
action, where the reduction in the appearance of resistance by C. acnes is
verified, and its action is complemented by inhibiting the different pathophysiological
mechanisms that lead to the worsening of the disease.

Conclusion:
Novel approaches in the treatment and prevention of acne, mainly topically,
are focused on the reduction of bacterial resistance and irritation compared to current
treatments. The use of combined formulations provides better results with additional benefits,
improving treatment times and patient adherence.
Validation of novel catechol derivatives as potent Escherichia coli MetAP inhibitors using Molecular Docking and Molecular Dynamics Simulation
Authors: Chowdhury Abhishek , Laskar Monjur Ahmed , Panda Debashis , Choudhury Manabendra Dutta 
Published: August 2023

Background:
Urinary tract infections (UTIs) are the most common form of nosocomial
infection primarily caused by Escherichia coli. Complicated UTIs carry a higher risk of treatment
failure, recurrent infections, and increased morbidity. Methionine aminopeptidase (MetAP) has
gained tremendous importance as a bacterial drug target due to its role in cell growth and membrane integrity. However, the participation of metal-chelating residues and the occurrence of the
enzyme in the human body complicate the process of selecting a suitable inhibitor.

Aims:
This study aimed to find new molecules with more stable binding against urinary tract infection drug targets.

Objective:
The objective of this study was to find new molecules with more stable binding against
urinary tract infection drug targets using computational approaches.

Method:
The drug target was selected based on a literature study. Catechol derivatives were prepared and an ADME/T study was performed, followed by molecular docking and molecular dynamics.

Result:
The docking score of Met592 (-20.95) was found to be much better than that of known inhibitors (-12.88). The overall study on Rg signified that the ligand binding compels the respective
proteins to become more compact and less flexible in the case of Met592. Binding free energy
analysis also showed a better affinity for Met592 (-46.60) than the known inhibitor (-31.37).

Conclusion:
The increased binding score, good oral bioavailability, and better binding free energy
endorse the reliability of the ligand Met592, i.e., (R, E)-4-(4-(2-(((9H-purin-6-yl)amino)methyl)-
4,5-dimethylphenyl)thiazol-2-yl)-4-aminobut-2-enoic acid, as the probable drug candidate to treat
uropathogenic E. coli.
Preclinical Pharmacokinetics and CYP Modulation Activity of Chebulinic Acid: A
Potent Molecule Against Metabolic Disease
Authors: Biswas Arpon , Kumar Verma Sarvesh , Kumar Shiv , Mishra Tripti , Kumar Mukesh , Deb  Choudhury Abhijit , Agrawal Sristi , Sanap Sachin Nashik , Bisen Amol Chhatrapati , Mishra Anjali , Narender Tadigoppula , Bhatta Rabi Sankar 
Published: August 2023

Background:
Chebulinic acid (CA) is an active constituent of Terminalia chebula fruits with therapeutic
potential against multiple metabolic diseases, including dementia, benign prostate hyperplasia, and osteoporosis.

Objective:
The present work intends to explore the preclinical pharmacokinetics, including the absolute bioavailability
of CA and its influence on the gene expression of cytochrome P450 enzymes in the liver.

Methods:
Quantifying CA and probe drugs in vitro samples and preclinical serum samples of male SD rats were
performed using LC-MS/MS. The influence of CA on the hepatic CYPs and their gene expression was analyzed in
rat liver by quantitative real-time polymerase chain reaction.

Results:
The plasma protein binding was found to be 84.81 ± 7.70 and 96.34 ± 3.12, blood-to-plasma ratio of 0.62 ±
0.16 and 0.80 ± 0.23 at 1 μM and 10 μM concentrations, respectively. Again, the absolute oral bioavailability of CA
at 100 mg/kg was found to be 37.56 ± 7.3%. The in-vivo pharmacokinetic profile of probe drugs revealed CA to have
significant inducing effects on CYP1A2, 2C11, 2D2, and 2E1 after 14 days, which correlates to both in-vitro rat
microsomal data and gene expression results.

Conclusion:
Altogether, pharmacokinetic parameters reveal CA to have an affinity to distribute across different
extravascular tissues and induce rat liver CYP enzymes.
Research Progress of Neural Invasion in Pancreatic Cancer
Authors: Zhu Mengying , Luo Feng , Xu Bin , Xu Jian 
Published: August 2023

Abstract:
Pancreatic cancer is one of the highly malignant gastrointestinal tumors in humans, and
patients suffer from cancer pain in the process of cancer. Most patients suffer from severe pain in
the later stages of the disease. The latest studies have shown that the main cause of pain in patients
with pancreatic cancer is neuroinflammation caused by tumor cells invading nerves and triggering
neuropathic pain on this basis, which is believed to be the result of nerve invasion. Peripheral nerve
invasion (PNI), defined as the presence of cancer cells along the nerve or in the epineurial, perineural,
and endoneurial spaces of the nerve sheath, is a special way for cancer to spread to distant
sites. However, due to limited clinical materials, the research on the mechanism of pancreatic cancer
nerve invasion has not been carried out in depth. In addition, perineural invasion is considered
to be one of the underlying causes of recurrence and metastasis after pancreatectomy and an independent
predictor of prognosis. This article systematically reviewed the neural invasion of pancreatic
cancer through bioinformatics analysis, clinical manifestations and literature reviews
Separation of Channels Subserving Approach and Avoidance/Escape at
the Level of the Basal Ganglia and Related Brainstem Structures
Authors: Coizet Véronique , Tannir Racha Al , Pautrat Arnaud , Overton Paul G. 
Published: August 2023

Abstract:
The basal ganglia have the key function of directing our behavior in the context of events
from our environment and/or our internal state. This function relies on afferents targeting the main input
structures of the basal ganglia, entering bids for action selection at the level of the striatum or signals
for behavioral interruption at the level of the subthalamic nucleus, with behavioral reselection facilitated
by dopamine signaling. Numerous experiments have studied action selection in relation to inputs
from the cerebral cortex. However, less is known about the anatomical and functional link between
the basal ganglia and the brainstem. In this review, we describe how brainstem structures also
project to the main input structures of the basal ganglia, namely the striatum, the subthalamic nucleus
and midbrain dopaminergic neurons, in the context of approach and avoidance (including escape from
threat), two fundamental, mutually exclusive behavioral choices in an animal’s repertoire in which the
brainstem is strongly involved. We focus on three particularly well-described loci involved in approach
and avoidance, namely the superior colliculus, the parabrachial nucleus and the periaqueductal
grey nucleus. We consider what is known about how these structures are related to the basal ganglia,
focusing on their projections toward the striatum, dopaminergic neurons and subthalamic nucleus, and
explore the functional consequences of those interactions.
Ionic Liquid@ HT- Clay Combination for Baylis -Hillman Reaction and
Lactone Ceramide Analog Synthesis
Authors: Srivastava Vivek 
Published: August 2023

Abstract:
This study investigates the use of ionic liquids (ILs) immobilized on HT-clay as catalysts for
the Baylis-Hillman reaction. The catalytic system comprised three different types of ILs ([HIM]Im,
[BIM]Im, [EIM]Im) and exhibited high reactivity, and the B-H products were obtained in good yield,
which is superior to previously reported catalytic systems, whether they were heterogeneous or homogeneous.
The HT-clay immobilized with ILs also allowed for easy recovery from the reaction mass and
could be recycled for up to 7 consecutive runs with only a slight decrease in activity. Moreover, the
scope of our catalytic system was extended to synthesize biologically active lactone ceramide analogs
using the Baylis-Hillman reaction at room temperature with (S-) Garner aldehyde and methyl acrylate.
The synthesis was successful, and we obtained good yields of the desired products, highlighting the versatility
of the ionic liquid immobilized HT-clay catalytic system. This study demonstrates the potential of
ionic liquid immobilized HT-clay as a promising catalyst for various organic reactions. Our findings
emphasize the importance of developing efficient and environmentally friendly methods for synthesizing
valuable organic compounds. The results obtained from this study provide a significant contribution to
the ongoing research in the field of catalysis and will be useful for developing new approaches to the
synthesis of complex organic molecules.
Study of the Relationship Between Insulin Resistance, Iron Status Markers, and Body Weight in a Sample of Egyptian Population
Authors: Bahaaeldin Ahmed Mohamed , Hussein Magda Shoukry , Hashem Shaimaa Shaaban , Saleh Amr Mahmoud Mohamed 
Published: August 2023

Background:Iron plays a key role in the regulation of body iron homeostasis and is used as a clinical marker for iron deficiency (ID) and hemochromatosis. The idea that iron dysregulation may contribute to various metabolic diseases, such as obesity, insulin resistance, MetS, and T2DM, is a hot topic of discussion.Aim:The aim of this study is to investigate the relationship insulin resistance, iron status markers, and body weight in a sample of Egyptian population.Methods:Methods: A case control study was conducted on 90 subjects with age ranging from 18 to 70 years old from a diabetes outpatient clinic, and they were divided to three groups: Group I, non-obese- non-diabetic as the control group; Group II, obese-non-diabetic; and Group III, obese-diabetic.Results:In our study, there was no statistically significant difference between the three studied groups regarding the different iron parameters. Similarly, we found that neither HOMA-IR nor body weight had a significant correlation with iron status markers.:On the contrary, we detected significant positive correlations between the TIBC and the fasting blood glucose, between the serum iron and the LDL, between the TSAT and the systolic blood pressure, and between the HOMA-IR and hematocrit.Conclusion:Our study demonstrated no direct statistical significant relationship between the different iron parameters, obesity, and insulin resistance, either in the diabetic or non-diabetic subjects. This may be due to the complex metabolic dysregulation and the small number of the sample for future investigations.
An Identification of RET Inhibitor: A Computational Study
Authors: Verma Anil , Wadhwa Pankaj 
Published: August 2023

Introduction:
RET (Rearranged during transcription) kinase is one of the key targets for
anticancer drug development. Understanding the real mechanism of pharmacological action is aided
by the protein-ligand interaction. The purpose of this study is to find the most effective RET
inhibitors.

Methods:
Firstly, through a literature survey, we understood that tetrazole is useful nuclei to provide
anticancer activity. Hence, a molecule was drawn containing tetrazole ring using Chemdraw
16.0. This drawn compound was used to determine further ligands employing Zincpharmer. Then,
the 3D energy minimized structure of proposed ligands and positive control (selpercatinib and
pralsetinib) were drawn using Chem3D. Further, docking was performed for all the ligands with
phosphorylated RET kinase (PDB ID - 2IVU) using trial version of Molegro virtual docker 7.0.

Results:
Determined ligands were docked with the help of Molegro virtual Docker (MVD) 7.0
employing RET kinase (2ivu) as protein.

Conclusion:
Top 10 compounds were selected and their drug-like properties along with their oral
bioavailability were also determined. ZINC12180698, ZINC12180696, ZINC09616526, ZINC12180701,
ZINC09616182, ZINC09616145, ZINC17052231, ZINC17052262, ZINC12180700, and ZINC0961
6518 were among the top ten compounds that showed the strongest affinity for the target for RETmediated
cancer in this study.
Identification of Bioactive Compounds of Streptomyces spp. Isolated from
Qom Lake Sediments and Evaluation of its Antimicrobial Activity against
Pseudomonas aeruginosa
Authors: Pouryousef Forouz , Shakib Pegah , Issazadeh Khosro , Zolfaghari Mohammad Reza 
Published: August 2023

Background:
Marine sediments are rich sources for isolating active secondary metabolites
from microorganisms. Among the microorganisms, Actinomycetes are highly important due to the
production of various chemical compounds in a wide range of biological activities, such as antibacterial
activity. Streptomyces is the most important genera in the family of Actinomycetes. As a member
of this group, it has great potential in the production of secondary metabolites such as antibiotics, enzymes,
herbicides, anti-carcinogenic, and other useful compounds.

Objective:
This study aims to identify bioactive compounds of Streptomyces isolated from sediments
of the Salt Lake of Qom and to study their antimicrobial properties against standard strains of Pseudomonas
aeruginosa.

Methods:
In this study, 20 samples were collected from a depth of 5 to 15-20 cm of sediment in the
Salt Lake of Qom. Pure cultivations were then provided from these samples. This study used starch
casein agar (SCA) to isolate streptomyces, and 35 Streptomyces were isolated. The disc diffusion
method was used to explore the antimicrobial properties of Streptomyces against clinical strains of
Pseudomonas aeruginosa and strains standard of Pseudomonas aeruginosa PTCC 1310.

Results:
Seven strains, including SCA3 SCB1, SCB4, SCB8, SCC15, SCC18, and SCC28 strains, had antimicrobial
properties. In this study, the results show that SCC15 with the halo diameter of 17, 17, 15,
and 19 contains the best antibacterial properties against clinical strains 1, 2 and 3 of Pseudomonas aeruginosa
and Pseudomonas aeruginosa PTCC 1310. among the 16 peaks observed by GC/MS to identify
bioactive compounds of Streptomyces, it was found that Bis (2-ethyl hexyl) phthalate, with 69.06
percent, had the highest peak production, which reflects the importance of phthalates in microbial activities.

Conclusion:
According to the results, the Salt Lake of Qom was one of the sources of Streptomyces.
In addition, the isolated Streptomyces had antimicrobial properties against Pseudomonas aeruginosa
isolates. It was also found that phthalate was the most bioactive substance of Streptomyces isolated.
An Update on the Role of Circadian Rhythms in Sleep Disorders
Authors: Aziz Namra , Garg Vipin Kumar , Vinod Yadav Rupali , Gupta Arpit , Wal Ankita , Rathore Shruti , Wal Pranay 
Published: August 2023

Background:
The comprehension of the molecular, cellular, and biological mechanisms
that underlie the management of the sleep-wake cycle, as well as the effects of circadian disruption on
health and illness, has made significant strides.

Methods:
An extensive literature review was done from the standard databases such as Scopus, Elsevier,
and PubMed using standard keywords “Circadian rhythm”, and “sleep disorders”. In this section,
we examined circadian biology and provided adetailed description of the pathogenesis, clinical characteristics,
diagnosis, and management of the most typical Circadian rhythm sleep disorders (CRSDs)
seen in clinical practice.

Conclusion:
It can be concluded that the central circadian rhythm mechanism may be altered, or the
intrinsic circadian clock and the environment may not be in sync, to produce circadian rhythm sleep
disorders. As a consequence, we must focus on modifying our way of life in a constructive and
healthy way. Even while the lifestyle is based on personal preferences and identities, it is important to
examine it in isolation from its sociocultural environment.
Chemotherapy-Induced Peripheral Neuropathy Impacts Quality of Life
and Activities of Daily Living of Brazilian Multiple Myeloma Patients
Authors: de Miranda Drummond Paula Lana , dos Santos Roberta Márcia Marques , Silveira Lívia Pena , Malta Jéssica Soares , Moreira Reis Adriano Max , Costa Naiane Lima , de Paula e Silva Roberta Oliveira , Fagundes Evandro Maranhão , de Pádua Cristiane Aparecida Menezes 
Published: August 2023

Background:
Survival in multiple myeloma (MM) has improved in the past years with
the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced
peripheral neuropathy (CIPN) is associated with both drug classes affecting Health-
Related Quality of Life (HRQoL) and activities of daily living (ADL).

Objective:
We evaluated CIPN in MM patients to identify associated factors and impacts on
HRQoL and ADL.

Methods:
This is a cross-sectional study with Brazilian patients from public and private health services.
Patients were interviewed using validated tools to measure CIPN and HRQoL, along with
sociodemographic and clinical questions. Logistic regression was used to assess the association of
CIPN with sociodemographic, clinical, and HRQoL variables.

Results:
In total, 217 patients were eligible for the study. The median age was 67, 50.9%
were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health
services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide,
and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%)
had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL.
Numbness was the most common symptom (40.6%). CIPN was independently associated with education,
hospitalization, chemotherapy, side effects, disease symptoms, and global health status in
HRQoL.

Conclusion:
MM patients showed a high frequency of CIPN, which affected ADL and impaired
HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide
and bortezomib-based regimens should be performed to provide better treatment outcomes and
avoid permanent disabilities.
Comparison of Psychological Disorders During and After Pregnancies
Caused by Assisted Reproductive Treatments and Spontaneous
Pregnancies
Authors: Zargar Mahvash , Sayyah Mehdi , Nikbakht Roshan , Abdipour Zahra 
Published: August 2023

Introduction:
Mental disorders during pregnancy are one of the major public health
problems because of its effect on both mother and child, but the prevalence of psychiatric disorders
in infertile women is largely unknown to compare psychiatric disorders during and after
pregnancies with assisted reproductive therapies (ART) and spontaneous pregnancies.

Methods:
This cross-sectional study was conducted on pregnant women referring to midwifery
centers in Ahvaz City in 2022. Pregnant women were included in two groups of either pregnancy
caused by ART (n= 84) or spontaneous pregnancy (n= 256). The Symptom Checklist-90-R (SCL-
90-R) was used to assess psychiatric disorders during and after pregnancies.

Results:
A high percentage of women with spontaneous pregnancy (74.6%) and ART (91.7%) had
some degree of psychological disorders. The severity of psychological disorders in both groups
was higher during pregnancy than after pregnancy (p<0.001). The intensity of various psychological
disorders during and after pregnancy in the ART pregnancy group was significantly higher
than the control group (p<0.001). An increased risk of psychiatric disorders during pregnancy was
associated with the history of psychiatric disorders [odd ratio (OR): 12.393; P= 0.022], family history
of psychiatric disorders (OR:26.168; p<0.001), history of infertility (OR: 19.00; p<0.001),
primary infertility (OR: 12.714; P=0.004), infertility duration more than three years (OR: 43.424;
p<0.001), and frequency of embryo transfer (OR: 18.939; P=0.045).

Conclusion:
Psychiatric disorders were prevalent among pregnant women in the study area especially
in pregnant women with ART. Regular screening programs for mental health problem
should be included in an antenatal care service especially in this high-risk group.