bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychiatric Systemic Lupus Erythematosus: A Remaining Challenge
Authors: Mrak Daniel , Bonelli Michael , Radner Helga 
Published: May 2022

Abstract:
Systemic Lupus Erythematosus (SLE) is an autoimmune disease, which affects a wide range of organs with variable clinical features. Involvement of the nervous system is a challenging and multifaceted manifestation of the disease, presenting with a broad range of symptoms. Neuropsychiatric lupus (NPSLE) encompasses seven syndromes of the peripheral and 12 of the central nervous system, associated with a high disease burden. Despite advances in the management of SLE, NP manifestations still pose a challenge to clinicians. First, diagnosis and attribution to SLE is difficult due to the lack of specific biomarkers or imaging modalities. Second, therapeutic options are limited, and evidence is mainly based on case reports and expert consensus, as clinical trials are sparse. Moreover, no validated outcome measure on disease activity exists. Current recommendations for treatment include supportive as well as immunosuppressive medication, depending on the type and severity of manifestations. As NPSLE manifestations are increasingly recognized, a broader spectrum of therapeutic options can be expected.
Recursive Feature Elimination-based Biomarker Identification for Open
Neural Tube Defects
Authors: Ganjiwale Anjali , Karthik Kadhir Velu , Rajalingam Aruna , Shivashankar Mallaiah 
Published: May 2022

Background:
Open spina bifida (myelomeningocele) is the result of the spinal cord to close completely and is the second most common and severe birth defect. Open neural tube defects are multifactorial, and the exact molecular mechanism of the pathogenesis is not clear due to disease complexity for which prenatal treatment options remain limited worldwide. Artificial intelligence techniques like machine learning tools have been increasingly used in precision diagnosis.

Objective:
The primary objective of this study is to identify key genes for open neural tube defects using machine learning approach that provides additional information about myelomeningocele in order to obtain more accurate diagnosis.

Materials and methods:
Our study reports differential gene expression analysis from multiple datasets (GSE4182 and GSE101141) of amniotic fluid samples with open neural tube defects. The sample outliers in the datasets were detected using principal component analysis (PCA). We report a combination of the differential gene expression analysis with recursive feature elimination (RFE), a machine learning approach to get 4 key genes for open neural tube defects. The features selected were validated using five binary classifiers for diseased and healthy samples: Logistic Regression (LR), Decision tree classifier (DT), Support Vector Machine (SVM), Random Forest classifier (RF) and K-nearest neighbour (KNN) with 5-fold cross validation.

Results:
Growth Associated Protein 43 (GAP43), Glial fibrillary acidic protein (GFAP), Repetin (RPTN) and CD44 are the important genes identified in the study. These genes are known to be involved in axon growth, astrocyte differentiation in the central nervous system, post traumatic brain repair, neuroinflammation and inflammation linked neuronal injuries. These key genes represent a promising tool for further studies in diagnosis and early detection of open neural tube defects.

Conclusion:
These key biomarkers help in diagnosis and early detection of open neural tube defects, thus evaluating its progress and seriousness in diseases condition. This study strengthens previous literature sources of confirming these biomarkers linked with open NTD’s. Thus, among other prenatal treatment options present until now, these biomarkers help in early detection of open neural tube defects which provides success in both treatment and prevention of these defects in advance stage itself.
Potential Roles of 5-HT3 Receptor Antagonists in Reducing Chemotherapy-induced Peripheral Neuropathy (CIPN)
Authors: Satiamurthy Raajeswari , Yaakob Nor Syafinaz , Shah Noraida Mohamed , Azmi Norazrina , Omar Marhanis Salihah 
Published: May 2022

Abstract:
5-HT3 receptor antagonists corresponding to ondansetron, granisetron,
tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in
chemotherapy patients. However, current and previous studies reveal novel potentials of
those ligands in other diseases involving the nervous system, such as addiction,
pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and
cognitive function. This review gathers existing studies to support the role of 5-HT3
receptors in CIPN modulation. It has been reported that chemotherapy drugs increase
the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also
shown in pre-clinical and clinical studies that various neuropathic pains could be blocked
by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5-
HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review
suggests that future studies focus more on the 5-HT3 receptor antagonists and their
modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related
pain.
Investigation of the Anticancer Potential of 2-alkoxycarbonylallyl Esters Against Metastatic Murine Breast Cancer Line 4T1 Targeting the EGFR: A Combined Molecular Docking, QSAR, and Machine Learning Approach
Authors: Obadawo Babatunde Samuel , Oyeneyin Oluwatoba Emmanuel , Owolabi Taoreed Olakunle , Metibemu Damilohun Samuel , Ipinloju Nureni , Fagbohungbe Kehinde Henry , Modamori Helen Omonipo , Olatoye Victor Olanrewaju 
Published: May 2022

Background:The search for novel and potent anticancer drugs is imperative. This present study aims to unravel the mechanisms of action of 2-alkoxyecarbonyl esters using robust model(s) that can accurately predict the bioactivity of novel compounds. Twenty-four potential anticancer 2- alkoxycarbonylallyl ester compounds obtained from the literature were employed in building a 3D-QSAR model.Objectives:The objective of this study is to determine the predictive ability of the GFA-based QSAR models and extreme machine learning models and compare them. The lead compounds and newly designed compounds were docked at the active site of a human epidermal growth factor receptor (EGFR) kinase domain to determine their binding modes and affinity.Methods:QikProp program and Spartan packages were employed for screening compounds for druglikeness and toxicity. QSAR models were equally used to predict the bioactivities of these molecules using the Material Studio package. Molecular docking of the molecules at the active site of an EGFR receptor, 1M17, was done using Auto dock tools.Results:The model of choice, with r2pred (0.857), satisfied the recommended standard for a stable and reliable model. The low value of r2, Q2 for several trials and cRp2 (0.779 ≥ 0.5) and the high value of correlation coefficient r2 for the training set (0.918) and test set (0.849) provide credence to the predictability of the model. The superior inhibition of EGFR displayed by the lead compounds (20 and 21) with binding energies of 6.70 and 7.00 kcalmol-1, respectively, is likely due to the presence of double bonds and α-ester groups. ADMET screening showed that these compounds are highly druggable. The designed compounds (A and B) displayed better inhibition of EGFR.Conclusion:The QSAR model used here performed better than the Random Forest Regression model for predicting the bioactivity of these anticancer compounds, while the designed compounds (A and B) performed better with higher binding affinity than the lead compounds. Implementing the developed model would be helpful in the search for novel anticancer agents.
The Importance of Neglected and Underutilized Medicinal Plants from
South America in Modern Pharmaceutical Sciences
Authors: Shahrajabian Mohamad Hesam , Cheng Qi , Sun Wenli 
Published: May 2022

Abstract:
The world needs a paradigm change from the current views on many plants to secure future
food and nutrition. Many neglected and underutilized plants, specially medicinal and aromatic plants, are
nutrient dense, appropriate in diversifying diets, provide enough vitamins and micronutrients for people,
high resistant to diseases and pests, and can be adapted in many regions and of course with tremendous
pharmaceutical benefits. Many of the medicinal plant species which were common in traditional medicine
are still neglected and underutilized, especially in developing and under-developing countries. Lack of
attention to these plants means their potential medicinal properties are under exploited and underestimat- ed. The searches focused on publications from 1980 to July 2021 using PubMed, Google Scholar, Science
Direct, and Scopus databases. Review of the literature was carried out using the following keywords,
"medicinal plants", "neglected plants", "underutilized plants", "aromatic plants", "traditional medicine
science", and "South America". In this review article, the authors have focused on medicinal values of
Schinusterebinthifolius, Uncaria tomentosa, Phyllanthusamarus, Astrocaryum aculeatum, Croton cajucara,
Arrabidaea chica, Bauhinia forticata, Copaifera langsdorffii, Cordia verbenacea, Caesalpinia ferrea,
Salix alba L., Casearia sylvestris, Carapa guianensis, Costus spicatus, and Eugenia uniflora L., in
both modern and traditional science. Although many studies have evaluated the biological characteristics
of these plants, little has been done to identify and characterize its chemical components, which is certainly
a niche that requires to be further explored.
New 4-nitro-imidazole-N-glycinyl-hydrazones Designed as Trypanocidal
Analogues of Benznidazole
Authors: Fraga Carlos A.M. , de Alcântara Giulianna P. , Barbosa Juliana M.C. , Salomão Kelly , de Castro Solange L. , Wardell James L. , Low John N. , Wardell Solange M.S.V. , Carvalho Samir A. , da Silva Edson F. 
Published: May 2022

Background:
The drugs available for the treatment of Chagas disease are ineffective in its
chronic phase and produce many adverse effects, making the search for new drugs an urgent medical
need.

Objective:
This study aimed to design, synthesize, and evaluate the trypanocidal and cytotoxic profiles of
new 4-nitroimidazole prototypes.

Method:
The new compounds were synthesized in overall yields ranging from 31-to 52% through the
use of classical and reproducible methodologies. Their trypanocidal profile and cytotoxicity were assayed
against trypomastigote forms of T. cruzi and mammalian macrophages, respectively.

Results:
The best trypanocidal activity was evidenced in compounds that present lipophilic and electronegative
substituents, e.g. 4-chlorophenyl derivative (5), with an IC50 = 206.98 μM;

Conclusion:
The new benznidazole N-glycinyl-hydrazone analogues demonstrated a very significant
reduction in the trypanocidal activity compared to benznidazole, which seems to be related to the position
occupied by the nitro group in the imidazole ring.
QSAR Study on the Antitumor Activity of Novel 1,2, 3-Triazole Compounds
based on Topomer Comfa Method
Authors: Wei Qiu Lie , Xing Zhang , Jian Bo Tong 
Published: May 2022

Background:
The high mortality rate of cancer is endangering human health, and the research
and development of new anticancer drugs have the attention of scientists worldwide. Sulfonamides have
become the focus of anticancer drug research. 1,2,3-triazole compounds can inhibit the formation of a
variety of tumor cells. Based on the excellent antitumor activity exhibited by the 1,2,3-triazole compound
skeleton, the sulfonamide moiety in the sulfonamide structure can be introduced into the triazole compound
skeleton to obtain highly active anticancer drugs.

Methods:
The Topomer CoMFA method was used to study the three-dimensional quantitative structureactivity
relationship of 58 new 1,2,3-triazole compounds with sulfa groups, and a 3D-QSAR model was
obtained.

Results:
The cross-validation coefficient q2 is 0.545, the non-cross-correlation coefficient r2 is 0. 754, r_pred2 is 0.930, the optimal number of principal components N is 4, and the standard estimation error SEE is 0.319. These results show that the model has good internal and external forecasting capabilities. By searching for the R group in the Topomer search module and combining with the more active groups in the existing molecules, 6 new compounds with theoretically higher anti-HL-60 (leukemia cell line) activity are obtained.

Conclusion:
The prediction result of the Topomer CoMFA model is good, and the statistical verification
is effective. The prediction results of ADMET show that the 6 new compounds meet the drug requirements
and are expected to become potential anti-HL-60 inhibitors, providing guidance for the synthesis of
anti-tumor drugs.
QSAR and DFT Studies of Some Tacrine-Hydroxamate Derivatives as
Inhibitors of Cholinesterase (AChEs) in the Treatment of Alzheimer's Disease
Authors: Hammoudan Imad , Chtita Samir , Daoui Ossama , Elkhattabi Souad , Bakhouch Mohamed , El Yazidi Mohamed , Siddique Farhan , Riffi-Temsamani Driss 
Published: May 2022

Introduction:
This work was devoted to an in silico investigation conducted on twenty-eight
Tacrine-hydroxamate derivatives as a potential treatment for Alzheimer’s disease using DFT and QSAR
modeling techniques.

Methods:
The data set was randomly partitioned into a training set (22 compounds) and a test set (6 compounds).
Then, fourteen models were built and were used to compute the predicted pIC50 of compounds
belonging to the test set.

Results:
All built models were individually validated using both internal and external validation methods,
including the Y-Randomization test and Golbraikh and Tropsha's model acceptance criteria. Then, one
model was selected for its higher R², R²test, and Q²cv values (R² = 0.768, R²adj = 0.713, MSE = 0.304,
R²test=0.973, Q²cv = 0.615). From these outcomes, the activity of the studied compounds toward the main
protease of Cholinesterase (AChEs) seems to be influenced by 4 descriptors, i.e., the total dipole moment
of the molecule (μ), number of rotatable bonds (RB), molecular topology radius (MTR) and molecular
topology polar surface area (MTPSA). The effect of these descriptors on the activity was studied, in particular,
the increase in the total dipole moment and the topological radius of the molecule and the reduction
of the rotatable bond and topology polar surface area increase the activity.

Conclusion:
Some newly designed compounds with higher AChEs inhibitory activity have been designed
based on the best-proposed QSAR model. In addition, ADMET pharmacokinetic properties were carried
out for the proposed compounds, the toxicity results indicate that 7 molecules are nontoxic.
Exploration of Pharmacological Potential of Alpinetin
Authors: Singh Randhir , Singh Dhirendra 
Published: May 2022

Abstract:
Secondary metabolites found in plants are a natural source of bioactive chemicals.
These secondary metabolites are vital for the survival of plants and have a number of medicinal
properties, which can be utilised to treat human illnesses. Alpinetin (ALP) is one of the secondary
metabolites which belongs to the Flavonoid category of phytochemicals and is present in
Amomum subulatum Roxb's. Alpinetin has been found to possess antioxidant, anti-inflammatory,
anticancer, hepatoprotective and renoprotective activity, along with several other biological
properties. This review is focused on the exploration of the pharmacological activities of
Alpinetin. ALP is considered a prospective candidate for future clinical investigations due to the
number of therapeutic properties.
The Wider Considerations in Closing Chronic Disease Gaps – Focus on
Heart Failure and Implementation
Authors: Iyngkaran Pupalan , Hespe Charlotte , Hanna Fahad , Horowitz John D , Battersby Malcolm , Nelson Craig , Andrew Sharon , de Courten Maximilian P. 
Published: May 2022

Background:
Heart failure (CHF) is predominately a chronic disease. There are overlaps in HF and chronic disease research and care. Chronic disease and HF research is conducted with multiple goals. The overarching goal is “optimized patient outcomes at maximum cost-effectiveness”. Observations and patients, however, can come with many variables; thus, we see gaps in clinical translation. This document discusses an argument for three important gaps common to HF and chronic disease, i.e., screening, self-management, and patient-reported outcomes (PRO), and provides a glance of how it could fit into the evidence tree with a focus. Pertinent arguments for a framework for health services and models of care are provided as a prelude to future consensus.

Methodology:
1) A preliminary literature review to identify a taxonomy for cardiovascular research and 2) a review of the published literature describing the translation of research studies into clinical practice for cardiovascular disorders. We identified a spectrum from observational to large randomized controlled trials to post-marketing studies.

Results and Discussion:
Research design in context to the above gaps are discussed.We then propose 6 steps to facilitate this: 1) Research design; 2) Research application (translation) i. routine ii. challenges; 3. Transforming research to translational level; 4. Funding and infrastructure; 5. CCRE and collaboration; 6. Governance and cost-efficacy.

Conclusion:
1.	Implementation research is a neglected area that aims to link research findings to
improved patient outcomes, in an efficient and effective way.
2.	Skills required to perform implementation research include a complex interplay of factors.
3.	Ways to maximize translational impacts for chronic disease research to clinical practice are described in a CHF context.
Study of the Antihypertensive Effect of Laurus nobilis in Rats
Authors: Eddouks Mohamed , Bouadid Ismail , Amssayef Ayoub 
Published: May 2022

Aims:
The study aimed to study the antihypertensive activity of Laurus nobilis.

Background:
Laurus nobilis L. is used to treat hypertension in Morocco.

Objective:
The study was designed to investigate the effect of the aqueous extract leaves of Laurus
nobilis (AELN) on blood pressure.

Materials and Methods:
The antihypertensive and vasorelaxant activities of AELN were pharmacologically
investigated in normotensive and L-NAME-induced hypertensive rats. Thereafter,
blood pressure was evaluated, and the ex-vivo vasorelaxant activity of this extract was performed.

Results:
A considerable decrease in blood pressure parameters were observed in L-NAMEinduced
hypertensive rats treated with AELN. The extract induced a vasorelaxant effect on the
aorta precontracted with epinephrine or KCl by inhibiting extracellular Ca2+ entry.

Conclusion:
The study demonstrates that Laurus nobilis aqueous extract exhibits potent antihypertensive
and vasorelaxant activities via inhibiting Ca2+ entry.
Nyctanthes arbor-tristis Linn.: A Review on its Traditional Uses, Phytochemistry,
Pharmacological Activities, and Toxicity
Authors: Mouri Nusrat Jahan , Barua Antica , Junaid Md. , Shamsuddin Tahmida , Alam Muhammad Shaiful , Akter Rasheda , Sharmin Tania , Hosen S.M. Zahid 
Published: May 2022

Background:
Nyctanthes arbor-tristis Linn. (Oleaceae) is a traditional therapeutic plant, highly used in Ayurveda for a wide range of activities, such as anthelmintic, antipyretic, laxative, rheumatism, skin ailments, and sedative.

Aims of the review:
This review aims to furnish up-to-date details on botanical characterization, geographical distribution, traditional uses, phytochemical constituents, pharmacological activities, and toxicity of Nyctanthes arbor-tristis Linn. with the exploitation of future research on more curative treatments as well.

Methods:
The available information was reviewed using different e-tools, including PubMed (National Library of Medicine), ScienceDirect, Wiley, Elsevier, Springer. The scientific name is verified from 'The Plant 'List' (www.theplantlist.org) and 'Kew Royal Botanic 'Gardens' (mpns.kew.org).

Results:
Crude extracts and isolated compounds of Nyctanthes arbor-tristis Linn. have been found pharmacologically active as hepatoprotective, anti-leishmaniasis, antiviral, antifungal, antipyretic, antihistaminic, antimalarial, antibacterial, anti-inflammatory, antioxidant activities it was widely for intermittent fevers and arthritis treatment. The major classes of biologically active compounds are their iridoid, glucosides, essential oils, hydrocarbons, alkaloids, benzofurans, cyclohexylethanoid, fatty acids, sterols, and terpenoid.

Conclusions:
Phytochemical studies and Nyctanthes arbour-tristis Linn's pharmacological activities indicated it as a potential medicinal plant for various ailments. However, more research is crucial to investigate the mode of action of the plant's bioactive constituents and its therapeutic potential.
Aplikasi Dekomposisi Nilai Singlar Matriks Quaternion terhadap Perbaikan Citra Low dan High Pass Filtering
Authors: Wahyu Fibriyanti Regita Agustin , Karyati Karyati 
Published: May 2022

Dekomposisi nilai singular matriks quaternion (Quaternion Singular Value Decomposition/SVDQ) sangat berguna dalam pengolahan citra, seperti dalam kompresi ukuran gambar, eigen-images, dan perbaikan kualitas citra, khususnya perbaikan suatu citra low pass filtering dan high pass filtering. Tujuan penelitian ini adalah mengetahui bagaimana aplikasi dekomposisi nilai singular matriks quaternion pada perbaikan suatu citra low pass filtering dan high pass filtering, serta memberikan suatu aplikasi berbasis GUI MATLAB. Dasar dari dekomposisi nilai singular matriks quaternion didapatkan dengan menggunakan representasi terhadap matriks kompleks, dengan kata lain menggunakan isomorfisma matriks quaternion terhadap matriks kompleks. Hal itu bertujuan untuk mempermudah pendekomposisian matriks quaternion. Matriks quaternion tidak lepas dari nilai eigen matriks quaternion. Selanjutnya, nilai eigen matriks qauternion dapat dihitung menggunakan nilai eigen dari matriks kompleksnya. Melalui dekomposisi nilai singular matriks quaternion, diperoleh perbaikan citra low pass filtering dan high pass filtering yang hampir menyerupai citra aslinya. Untuk perbaikan citra low pass filtering berhenti pada dan untuk high pass filtering berhenti pada α=0,97.
Recommendations from Cochrane reviews for improving future trials on anesthesia and pain: a meta-research study
Authors: Runjic Renata , Plenkovic Mia , Pirosca Stefania , Clarke Mike , Treweek Shaun , Puljak Livia 
Published: May 2022

Background:
Cochrane systematic reviews (CSRs) have a section ‘Implications for research’ where authors make suggestions for improving future research. The authors of the present study assessed the prevalence and time dynamics of different recommendations in the CSRs about anesthesia and pain.
Methods:
The authors included all CSRs published by the Cochrane Anaesthesia Group and Cochrane Pain and Palliative Care Group before 17 July 2020. The authors analyzed recommendations for improving future research listed in the ‘Implications for research’ section of these CSRs and categorized recommendations for improvements.
Results:
They analyzed 370 reviews. Four categories of recommendations were present in more than 40% of the reviews. Most reviews recommended a larger sample size and better outcome choice, study design and choice of future intervention. These recommendations gradually increased in frequency in the Cochrane Pain and Palliative Care Group and mainly decreased in the Cochrane Anaesthesia Group.
Conclusion:
Recommendations from CSRs offer useful advice for trialists designing new trials.