bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into New Therapeutic Approaches for the Treatment and Management of
Polycystic Ovary Syndrome: An Updated Review
Authors: Bashir Rohina , Wani Imtiyaz Ahmad , Ganie Mohd. Ashraf 
Published: May 2022

Background:
Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive age women globally

Objective:
This review aims to facilitate an understanding of novel PCOS management approaches and highlights the results from relevant interventional studies from animal and human studies.

Methods:
Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.

Results:
According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulin sensitizing, anti-obesity, and restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.

Conclusion:
Exhaustive, multicentric and multiethnic studies are vital to generate a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data is warranted to corroborate the new therapeutics and direct health care resources accordingly.
Entanglement of Methylation Changes and cGAS-STING Signaling in
Non-Small-Cell Lung Cancer
Authors: Hao Fang 
Published: May 2022

Background:
cGAS-STING signaling has been primarily discovered as an important
DNA sensing machinery, bridging innate immunity and adaptive immunity. Beyond its antiviral
response, recent evidence expanded its complicated role in cancer therapy.

Methods:
UALCAN, The TCGA Wander, GEPIA, SMART, TIMER, Kaplan-Meier plotter,
TCGA Data, and cBioPortal were utilized in the investigation.

Results:
We evaluated the expression of four key molecules (MB21D1, TMEM173, TBK1, and
IRF3) in the cGAS-STING pathway and found that the TMEM173 gene was significantly downregulated
in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Not only
immunostimulatory cells but also regulatory T cells were triggered by the DNA sensing pathway.
With gene enrichment analysis, we revealed that cell cycle and mechanotransduction/cytoskeleton
signals were most closely connected with cGAS-STING signal alterations in non-small-cell lung
cancer (NSCLC). cGAS-STING signaling was robustly correlated with methylation changes, especially
histone H3K4 lysine demethylase KDM5s. Transient activation of cGAS-STING was found
to exert tumor surveillance effect, and inhibition of STING signaling co-opt elevated KDM5 demethylases
might inadvertently worsen clinical outcomes.

Conclusion:
cGAS-STING signaling and KDM5 demethylases have the potential to be used as
targets for evaluating an effective immune response in the tumor microenvironment.
MIL-101(Cr)-Functionalized TEDA-BAIL: An Efficient and Recyclable
Catalyst for the Synthesis of Pyrimido[4,5-b]quinolinetrione Derivatives
Authors: Mahmoudi Zohreh , Kabirifard Hassan , Ghasemzadeh Mohammad Ali 
Published: May 2022

Background:
In this study, a heterogeneous catalyst containing MIL-101(Cr) functionalized
TEDA-BAIL was used to carry out an efficient four-component reaction between aromatic aldehydes,
barbituric acid, dimedone, and aryl amines, resulting in the synthesis of a new class of pyrimido[
4,5-b]quinolinetrione derivatives.

Methods:
Pyrimido[4,5-b]quinolinetrione derivatives were synthesized through a one-pot fourcomponent
reaction between aromatic aldehydes, barbituric acid, dimedone, and aryl amines, in the
presence of triethylenediamine-based ionic liquid@MIL-101(Cr) composite as a catalyst under reflux
conditions. The TEDA-BAIL@MIL-101(Cr), which is a recyclable catalyst, was fully characterized
by Fourier transform infrared spectrophotometry (FT-IR), X-ray diffraction (XRD), scanning
electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) thermogravimetric analysis
(TGA), Brunauer-Emmett-Teller (BET) and Transmission electron microscopy (TEM).

Results:
Four-component synthesis of pyrimido[4,5-b]quinolinetriones was catalyzed by TEDABAIL@
MIL-101(Cr) with aromatic aldehydes, barbituric acid, dimedone, and aryl amines under
reflux conditions. The obtained experimental results revealed that the employed synthesis approach
is a simple method that offers several advantages, including sustainability, facile separation from the
reaction medium, and reusability of the catalyst after six consecutive runs without loss of activity.

Conclusion:
The presented method is an efficient synthesis route for the synthesis of pyrimido[4,5-
b]quinolinetriones in the presence of TEDA-BAIL@MIL-101(Cr) under reflux conditions. This procedure
provides multiple advantages, such as ease of execution, high yield, clean reaction conditions,
shorter reaction time, and catalyst sustainability.
The Functional Role of the Renin-Angiotensin System in Preeclampsia
Authors: Melaku Leta 
Published: May 2022

Abstract:
The renin-angiotensin system (RAS) is a signaling pathway that acts as a major regulator
in human physiology. To sidestep the major intimidations of low blood volume and low blood pressure,
the diverse actions of Ang II/ACE/AT1R can be viewed as a useful response in maintaining
homeostasis. The deleterious action of the Ang II/ACE/AT1R axis is endogenously counterbalanced
by ACE 2/Ang 1-7/MasR. Yet, over activation of the Ang II/ACE/AT1R axis may lead to hypertension.
Preeclampsia is characterized by hypertension with proteinuria or end-organ dysfunction after
20 weeks of gestation. The early-onset sort is more genuine and capable of high maternal and fetal
dismalness and mortality rates than the late-onset sort of preeclampsia. Various theories for the
pathogenesis of preeclampsia are, the exact underlying molecular mechanisms remain unclear but
are likely to be multifactorial. Later studies of RAS in preeclampsia have highlighted the need for
thorough research on this topic. There is an increase in the levels of circulating angiotensinogen during
the first 20 weeks of gestation. At the beginning of the pregnancy, there is an increment of prorenin
by 4 - 5 times. Renin synthesis in preeclampsia is suppressed. PE pregnant women have higher
levels of prorenin receptor expression in their placental tissue than normal pregnant women. AT1
receptor autoantibodies are also observed. Ang II is raised in normal pregnancies as a result of higher
levels of angiotensinogen and renin. Preeclampsia causes a decrease in angiotensin-(1-7) levels.
Aldosterone is also relatively low in pregnancies complicated by preeclampsia.
The Prevalence of Maternal and Newborn Morbidity Following a Repeat
Cesarean Section: Data From Zagazig University Hospital
Authors: Ali Ali El-Shabrawy , Badr Amira I. , Mohamed El-Behairy Manal , Noseir Wael Sabry 
Published: May 2022

Background and Objective:
Cesarean section (CS) is one of the most common obstetric procedures performed worldwide, and new research indicates that the frequency of CS is increasing. Maternal-fetal morbidity and death due to CS is a serious public health problem worldwide. Our study aimed to assess the impact of multiple cesarean sections (CSs) on mother-fetal morbidity.

Methods:
This cross-sectional study was performed on 165 women who underwent multiple repeated CSs in our clinic and met the criteria of inclusion by evaluating their records. All women were divided into 3 groups according to the number of CSs: 2nd (n = 111), 3rd (n = 44), and 4th/5th (n = 10). Maternal-neonatal outcomes; blood transfusion needs, adhesions, APGAR scores, and respiratory difficulties were investigated retrospectively.

Results:
Our results revealed that adhesion (60.6 %) was the most frequent maternal complication. The prevalence of thick adhesions decreased with the number of cesarean sections performed (70, 25, and 5 cases for the previous 2nd, 3rd, and 4 or more CS, respectively). There was no statistically significant difference between the groups in terms of adhesions, uterine rupture, bladder injury, endometritis, and wound infection. NICU admission (14.5 %), Low birth weight (3.6 %), and IUGR (3.03 %) were among the unfavorable fetal outcomes. There was a significant difference among the three studied groups regarding APGAR score, maternal age, and hospital stay, while a non-significance was found in birth weight and maternal adhesion.

Conclusion:
Our findings support our hypothesis that the likelihood of maternal complications rises as the number of CSs rises. The manner and time of delivery have a greater impact on infant outcome than the number of CSs. There is no clear absolute barrier for the number of CSs, however, 4 or more cesarean births were recognized as the essential level for the majority of outcomes. The number of CSs must be decreased to reduce the associated issues.
ECG for Cardiovascular Diseases Using Soft Computing Algorithms
Authors: Veer Karan , Mathur Prerak , Sharma Tanu 
Published: May 2022

Abstract:
Electrocardiogram (ECG) is widely used in the healthcare domain because of its usage as a diagnostics tool for several cardiovascular diseases. It becomes essential to study and analyse the ECG data with the help of classification techniques. In this review paper, a brief overview of ECG signal information is presented. Various approaches for diagnosing cardiovascular diseases have been discussed, along with the need for accurate ECG signal analysis. These approaches are mainly based on the principles of machine learning and deep learning. The advantages and limitations of these techniques in the detection of cardiovascular diseases are presented within the scope of future work. This study can be helpful for researchers in bridging the gap between current approaches and future techniques for the detection of arrhythmia conditions.
Drug-aggravated Bullous Pemphigoid in a 47-year-old Asian Woman -
A Case Report
Authors: Nelramachandrakumar Divyajayashree , Hariharan Haritha , Nagamanickam Senthilvel , Chander J. Sam Johnson Udaya 
Published: May 2022

Introduction:
Bullous pemphigoid is the most common chronic recurrent autoimmune
subepidermal blistering disorder most prevalent in the geriatric population. It varies widely in clinical
presentation ranging from tense bullae to intense generalized pruritus. It is immunologic in
origin with the presence of IgG antibodies.

Case Report:
A 47-year-old female presented to the hospital with complaints of blisters in the lower
limbs, which she self managed with neem oil, after which the blisters occurred over the body.
The patient also experienced blisters over both upper and lower limbs, gluteal region, painful generalized
ulcers, necrotic patches, multiple erythematous blisters, ulcer erosions over bilateral legs
and upper limbs with few lesions, which were foul-smelling and oozing. On the second day of admission,
the patient’s CRP and ESR levels were tested and the levels were 33.5 and 35 mm/hr, respectively.
The patient was treated with an injection of meropenem 1 g three times daily, dexamethasone
4 mg once daily, and ofloxacin 400 mg once daily. On the third day of admission, the patient
complained of leg swelling, and subsequently, D-Dimer levels were checked, which showed a
value of 5,740 and was treated with an injection of enoxaparin 40 mg for the same throughout the
course of the hospital stay A skin biopsy confirmed the diagnosis of bullous pemphigoid. The culture
test showed the growth of Klebsiella pneumonia and Acinetobacter baumani, which were resistant
to most of the antibiotics. The patient was managed appropriately with modalities including
antibiotics, anti-inflammatory agents, immunosuppressants, multivitamins, fluids, and albumin.
The patient responded well to the treatment without new lesions or fever spikes. There was the
presence of necrotic patches of old lesions alone at the time of discharge.

Conclusion:
This case report was done with the purpose of presenting an exemplary case of
bullous pemphigoid aggravated by the application of neem oil and emphasizing the inappropriate
use of folk medicine in an autoimmune disease like bullous pemphigoid.
Reactivity of 9-anilinoacridine Derivatives as Potent Anticancer
Agents: A DFT Approach
Authors: Sarmah Pubalee , Deka Ramesh Chandra 
Published: May 2022

Background:
Anticancer activity of 9-anilinoacridine derivatives has been well
reported. Although, the DNA-drug sequence-specific binding of these compounds may be
affected by the substituent(s) on the aniline ring, it is still unclear which substituent (NH2
or CH2–OH) on the anilino ring of the compound is the critical element. A good understanding
of chemical properties such as steric, lipophilic and electronic properties at the molecular
level may provide important background for mutagenic and carcinogenic properties.

Objectives:
The present study is an attempt to understand the reactive nature of some selected
9-anilinoacridine derivatives in both gas and solvent phases and to predict their anticancer
activity by QSAR analysis.

Methods:
Full geometry optimizations of all derivatives were carried out at gradient corrected
DFT using DMol3 program. We used DNP basis set in combination with BLYP to
study all the derivatives. The molecular mechanics parameters used for QSAR analysis
were calculated using Hyperchem software.

Results:
We found Compound (31) (R=COOC6H5) as the most stable compound and compound
(6) (R1= NO2) as the most reactive one in both gas and solvent phases. Fukui function
(f+) values of all the atoms showed that N10 is the most reactive atom in each of the molecule
which indicates that N10 is the preferred site for nucleophilic attack. The final QSAR
model with four parameters (electrophilicity, hardness, surface area, and molar refractivity)
is capable of predicting anticancer activity of the compounds against leukemic HL-60 cell
lines with r2 = 0.91 and 0.88 in both gas and solvent phases, respectively.

Conclusion:
The global and local reactivity descriptors, such as hardness, chemical potential,
electrophilicity index, Fukui function, and local philicity were calculated to understand
the reactive nature and reactive sites of the compounds. The comparative QSAR study
with the help of DFT and MM + techniques provides the importance of the selected descriptors
in predicting the activity of the selected derivatives.
Molecular Modelling and Docking Analysis of Filarial Targets by using New Lead Compounds identified fromPsoralea corylifoliaandMimusops elengi
Authors: A. Shobana , A.M. Priyadharshini , Manoharan Yogalakshmi , Bagavananthem Andavan Gowri Shankar 
Published: May 2022

Background:Psoralea corylifolia and Mimusops elengi could be a source of new bioactive compounds for treating filariasis Psoralea corylifolia and Mimusops elengi. Thediversity of these plants has been proved medicinally and phytochemically. These plants haveplayed an important role in ancient medicine for the treatments of various ailments and especially against many helminths.Methods:Psoralea corylifolia and Mimusops elengi could be a source of new bioactive compounds for treating filariasis. 20g of dried powder of Psoralea corylifolia and Mimusops elengi were extracted using a Soxhlet apparatus using various solvents like methanol, chloroform, acetone, and water for about 30 cycles and then concentrated using a rotary evaporator and stored at 4 °C in airtight containers. It is effective against Setaria cervi at 100 and 200 μg, respectively. In-vitro studies have been done for the respective compounds. Homology models of Glutathione S transferase, Chitinase, and Transglutaminase were constructed using MODELLER v9.20 (Accelrys).Results:The results from the in vitro studies were confirmed by TLC and GC MS analysis of the extracts, which showed the presence of different phytochemical compounds in the extracts. Among the compounds identified in GC MS, 7,10-Octadecadienoic acid, methyl ester, Pentadecanoic acid, 14-methyl-, methyl ester, 2-Nonadecanone2,4-dinitrophenylhydrazine, Aspidospermidin-17-ol, 1- acetyl-19,21-epoxy-15,16-dimethoxy-, 9- (2’,2’-Dimethylpropanihydrozano)-3,6 dichloro-2,7-bis- [2-(diethylamino)-ethoxy] fluorine, and 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca- 3,7,11,15-tetraenyl)-cyclohexanol were docked against crystallised bioactive compounds.Conclusion:As a result of this study, it was concluded that arresting these proteins will help in arresting the growth and multiplication of parasites, thus leading to the development of a new antifilarial drug.
SARS-CoV-2 Kerala Isolate Spike Protein Induces Cancer Proliferating
Markers for Lung and Breast Cancer: An In Silico Approach
Authors: Selvaraj Stalin , Chandrasekaran Deepak , Masimani Vinothini , Ravindrana Yazhiniv , Venugopal Gayathriv , Raghavendran Srikanth 
Published: May 2022

Background:
Coronavirus disease (COVID 19) has been emerging as a major threat to humans
all over the world. Severe Acute Respiratory Syndrome CoronaVirus 2 (nSARSCoV2) is the causative
agent for the disease resulting in severe acute respiratory illness. Earlier, it took several years to come up
with a vaccine or other sorts of treatments for viral diseases. But now with the advent of biotechnology
and development of bio-informatic tools, the process has been accelerated. The WHO reports 39,806,488
affected cases and 1,112,208 deaths till today all over the world (17 Oct 2020). nSARS CoV2 has a greater
influence on people with comorbidities mainly cancer.

Objective:
The study herein attempts to understand the binding affinity of the spike protein of the novel
coronavirus with the lung and breast cancer marker proteins by docking and ClusPro analysis.

Method:
The analysis was conducted in reference to hACE2 (human Angiotensin Converting Enzyme
2), the receptor of nSARS CoV2. Total 22 different marker proteins were analyzed using ClusPro.

Results:
BRCA1 (Breast Cancer type 1 susceptibility protein) and CXCR4 (a chemokine receptor belonging
to the G protein coupled receptor family) were found to exhibit higher binding affinities.-73.82
kcal/mol and -66.45 kcal/mol were the global energies they showed upon binding to S protein respectively.

Conclusion:
Therefore, novel SARSCoV2 has a higher chance of inducing cancer in non-cancerous individuals
and aids in cancer acceleration in cancer patients . This poses a threat to cancer patients and immunocompromised
individuals. The study can be exploited to identify the optimal drug delivery system
for novel SARS CoV2.
A Comprehensive Literature Search of Digital Health Technology Use in Neurological Conditions: Review of Digital Tools to Promote Self-management and Support
Authors: Spreadbury John Henry , Young Alex , Kipps Christopher Myles 
Published: May 2022

Background
The use of digital health technology to promote and deliver postdiagnostic care in neurological conditions is becoming increasingly common. However, the range of digital tools available across different neurological conditions and how they facilitate self-management are unclear.

Objective
This review aims to identify digital tools that promote self-management in neurological conditions and to investigate their underlying functionality and salient clinical outcomes.

Methods
We conducted a search of 6 databases (ie, CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, and the Cochrane Review) using free text and equivalent database-controlled vocabulary terms.

Results
We identified 27 published articles reporting 17 self-management digital tools. Multiple sclerosis (MS) had the highest number of digital tools followed by epilepsy, stroke, and headache and migraine with a similar number, and then pain. The majority were aimed at patients with a minority for carers. There were 5 broad categories of functionality promoting self-management: (1) knowledge and understanding; (2) behavior modification; (3) self-management support; (4) facilitating communication; and (5) recording condition characteristics. Salient clinical outcomes included improvements in self-management, self-efficacy, coping, depression, and fatigue.

Conclusions
There now exist numerous digital tools to support user self-management, yet relatively few are described in the literature. More research is needed to investigate their use, effectiveness, and sustainability, as well as how this interacts with increasing disability, and their integration within formal neurological care environments.
A Mixed Reality Cognitive Orthosis to Support Older Adults in Achieving Their Daily Living Activities: Focus Group Study With Clinical Experts
Authors: Yaddaden Amel , Spalla Guillaume , Gouin-Vallerand Charles , Briskie-Semeniuk Patricia , Bier Nathalie 
Published: May 2022

BackgroundMixed reality is an emerging technology that allows us to blend virtual objects into the actual user’s environment. This can be realized using head-mounted displays. Many recent studies have suggested the possibility of using this technology to support cognition in people with neurodegenerative disorders (NDs). However, most studies have explored improvements in cognition rather than in independence and safety during the accomplishment of daily living activities. Therefore, it is crucial to document the possibility of using mixed reality to support the independence of older adults in their daily lives.ObjectiveThis study is part of a larger user-centered study of a cognitive orthosis using pure mixed reality to support the independence of people living with NDs. This study aimed to explore (the difficulties encountered by older adults with NDs in their daily life to ensure that pure mixed reality meets their needs, (the most effective interventions with this population to determine what types of assistance should be provided by pure mixed reality technology, how the pure mixed reality technology should provide assistance to promote aging in place, and the main facilitators of and barriers to the use of this technology.MethodsWe conducted a descriptive, qualitative study. A total of 5 focus groups were completed with occupational therapists who had expertise in the disease and its functional impacts (N=29) to gather information. Each focus group met once for a 1-hour period. All sessions were held over a 3-month period. A semistructured interview guide was used. All group interviews were audiotaped with the consent of each participant to facilitate the data analysis. We conducted inductive qualitative analysis in four stages using a thematic analysis approach: full transcription of the audio recordings, first-order coding of the transcribed data, second-order coding from the first-order code list, and data reduction and matrix development.ResultsThe results suggested that the main difficulties encountered by this population were in remembering to complete tasks, initiating the tasks, and planning the tasks. Several interventions are used to improve the independence of this population, such as prevention, simplification or facilitation, adaptation, and compensation. The use of pure mixed reality in older adults with NDs to promote independence and safety at home is promising and may respond to several clinical functions identified by the participants. Finally, pure mixed reality has good potential for use in this population and involves certain facilitators and obstacles, such as resources, technical aspects, and social considerations.ConclusionsThe cognitive orthosis that will be developed in light of this study will act as a proof of concept for the possibility of supporting people with NDs using pure mixed reality.