bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis, and Molecular Docking Study of Novel 3-Cyanopyridine
Derivatives for the Anti-Cancer Drug Target Survivin Protein
Authors: Shen Li-Qun , Wu Ai-Qun , Lu Jia-Hao , Lai Wu-Ji , Jiang Li-He , Lei Fu-Hou 
Published: August 2022

Background:
Survivin is an important member of the antiapoptotic protein family and controls the
cell’s life cycle. Overexpression of survivin in tumor cells leads to inhibition of apoptosis, thus contributing
to cancer cell proliferation. The largest binding pocket in the survivin dimer was located in
the BIR domain. The key to the efficacy of 3-cyanopyridines was their surface interaction with the
survivin amino acid Ile74.

Method:
Through the optimization of the 3-cyanopyridine, 29 new compounds with a 3-
Cyanopyridine structure were designed, synthesized, and characterized by NMR, IR, and mass
spectrometry. The antitumor activity of the compounds in vitro was detected by the MTT method.

Results:
In vitro anti-tumor experiments showed that some compounds exhibited good anti-cancer
effects. The IC50 values of the compound 2-amino-6-(2,4-difluorophenyl)-4-(4-hydroxyphenyl) nicotinonitrile
(10n) against human liver cancer (Huh7), human glioma (U251), and human melanoma
(A375) cells were 5.9, 6.0 and 7.2 μM, respectively. The IC50 values of the compound 6-(2,4-difluorophenyl)-
4-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (9o) against Huh7,
U251 and A375 cells were 2.4, 17.5 and 7.2 μM, respectively, which were better than those of 10-
hydroxycamptothecin and 5-fluorouracil. Analysis of the results of molecular dynamics simulation
established that the BIR domain is the optimal binding site on the survivin protein, and the fingerprints
of the eight most active compounds and the molecular docking to the survivin protein are analyzed.

Conclusion:
3-Cyanopyridine is an excellent backbone for antitumor lead compounds, 10n and 9o,
as derivatives of 3-Cyanopyridine are excellent survivin protein-targeting inhibitors worthy of further
study. The key factor in inhibiting survivin protein through the action of amino acid Ile74.
Current Trends in Immuno-Oncology
Authors: Vanteddu Venkata Gangadhar , Sweta Bawari , Patel Tulsi Dipakbhai 
Published: August 2022

Abstract:
Surgery, radiation, chemotherapy, and targeted therapy were the four basic kinds of
cancer treatment until recently. Immuno-oncology (IO), or the concept that cancer cells were
damaged by activating the body's immune system, has emerged and is explained as a unique and
crucial method for treating different cancers over the last decade. The US Food and Drug Administration
and the European Medicines Agency both approved this newly recognized way of
treating cancer in 2020. Within IO, different therapeutic classes have arisen, which are the subject
of this article. Immune checkpoint inhibitors are currently the most well-known therapeutic
class of immuno-oncology medications due to their amazing ability to show efficacy in a variety
of tumor types. Biomarkers were tested for different tumors like gastrointestinal cancer, whole
Head, lower and upper part Neck cancer, and also cervical cancer by programmed death-ligand 1
(PD-L1) check point and their targets and are currently being utilized prior to treatment by using
Pembrolizumab. However, the significance of PD-L1 expression for immune check point reticence
therapy in other/different onco-cancer types remains unclear. Homogenized immuneoncology
drugs with regular therapy have been recently studied and clinical efficacy outcomes
have shown to be significantly improved. While IO agents are fast transforming the marketed
treatment for cancer patients, there are still a number of obstacles to overcome in terms of associating
their adverse effects and confirming those different healthcare systems, such as financing
these expensive therapies. In addition to cancer vaccines and chimeric antigen receptor T-cell
treatments, other IO drugs are in pipeline containing chimeric antigen receptor T-cell therapies;
earlier ones have their own set of toxicities and high cost related challenges.
Circular RNAs in Alzheimer’s Disease: A New Perspective of Diagnostic
and Therapeutic Targets
Authors: Vakili Omid , Asili Pooria , Babaei Zeinab , Mirahmad Maryam , Keshavarzmotamed Atoosa , Asemi Zatollah , Mafi Alireza 
Published: August 2022

Background:
Circular RNAs (circRNAs), as covalently closed single-stranded noncoding
RNA molecules, have been recently identified to involve in several biological processes, principally
through targeting microRNAs. Among various neurodegenerative diseases (NDs), accumulating evidence
has proposed key roles for circRNAs in the pathogenesis of Alzheimer’s disease (AD); although
the exact relationship between these RNA molecules and AD progression is not clear, they have been
believed to mostly act as miRNA sponges or gene transcription modulators through the correlating
with multiple proteins, involved in the accumulation of Amyloid β (Aβ) peptides, as well as tau protein,
as AD’s pathological hallmark. More interestingly, circRNAs have also been reported to play
diagnostic and therapeutic roles during the AD progression.

Objective:
The literature review indicated that circRNAs could essentially contribute to the onset and
development of AD. Thus, in the current review, the circRNAs’ biogenesis and functions are
addressed at first, and then the interplay between particular circRNAs and AD is comprehensively
discussed. Eventually, the diagnostic and therapeutic significance of these noncoding RNAs is briefly
highlighted.

Results:
A large number of circRNAs are expressed in the brain. Thereby, these RNA molecules are
noticed as potential regulators of neural functions in healthy circumstances, as well as in neurological
disorders. Moreover, circRNAs have also been reported to have potential diagnostic and therapeutic
capacities in relation to AD, the most prevalent ND.

Conclusion:
CircRNAs have been shown to act as sponges for miRNAs, thereby regulating the function
of related miRNAs, including oxidative stress, reduction of neuroinflammation, and the formation
and metabolism of Aβ, all of which developed in AD. CircRNAs have also been proposed as
biomarkers that have potential diagnostic capacities in AD. Despite these characteristics, the use of
circRNAs as therapeutic targets and promising diagnostic biomarkers will require further investigation
and characterization of the function of these RNA molecules in AD.
The Potential Role of Naringin and Naringenin as Nutraceuticals Against
Metabolic Syndrome
Authors: Massaro Luca , Raguzzini Anna , Aiello Paola , Valencia Débora Villaño 
Published: August 2022

Abstract:
Metabolic syndrome, an increasing problem in western society, is a cluster of conditions
that affect cardiovascular health, lipid and glucose management, increasing the risk of heart diseases,
stroke and diabetes. Bioactive flavonoids are a great resource of compounds with proven antiinflammatory
activities. Naringin, a natural flavanone found in citrus fruits, and its aglycone have
demonstrated to ameliorate obesity, dyslipidemia, and insulin resistance in animal models. The principal
mechanisms by which these flavonoids exert their action involve AMPK and PPARα up-regulation
and the down-regulation of genes involved in lipid metabolism. Although different studies
have been carried out to define the pharmacological effects of these flavonoids, their therapeutic use
is still limited.
The Influence of TNF-α, IL-6, TGF-β1, IFN-γ, IL-10 Polymorphisms on Predisposition
to Diabetes Mellitus among Jordanian Patients
Authors: Khdair Sawsan I. , Al-Naimat Ola S. , Jarrar Wassan , Al-Qerem Walid , Khudeir Feras A. 
Published: August 2022

Background:
Diabetes mellitus is a long-term disorder with high prevalence globally. It can be classified into two types: Type 1 diabetes and Type 2 diabetes mellitus. Diabetes mellitus is considered a multifactorial disorder in which genetic factors such as cytokines play a major role. Cytokines play a role is immune modulation and are associated with the development of diabetes mellitus. Single nucleotide polymorphisms in cytokines were studied extensively in different populations to determine their association with predisposition to diabetes mellitus. Objective: The aim of this study was to estimate the frequency of single nucleotide polymorphisms in the cytokine genes TNF-α, TGF-β, IL-6, IL-10, and INF-γ in 102 Jordanian diabetes mellitus patients in comparison to 50 controls and their association to diabetes mellitus susceptibility.

Objective:
The aim of this study was to estimate the frequency of single nucleotide polymorphisms in the cytokine genes TNF-α, TGF-β, IL-6, IL-10, and INF-γ in 102 Jordanian diabetes mellitus patients in comparison to 50 controls and their association to diabetes mellitus susceptibility.

Methods:
Analysis was performed using the highly specific polymerase chain reaction-sequence specific primers methodology

Results:
Our findings showed that the IL-10-1082 G/G genotype (P=0.02) and the TGF-β1 codon 25*G allele (P<0.01) may be considered risk factors for type 2 diabetes mellitus. In addition, the IFN- γ -874*A allele (P=0.04) seems to increase the predisposition to type 1 diabetes.

Conclusion:
Our study showed that the IL-10-1082 G/G genotype and TGF-β1 codon 25*G allele are associated with type 2 diabetes mellitus while the IFN- γ -874*A allele is associated with type 1 diabetes. Our findings may help in the early detection of diabetes mellitus which would in turn help in undergoing the needed preventative measures to delay the onset of diabetes mellitus
Effect of SGLT2 Inhibitors and Metformin on Inflammatory and Prognostic
Biomarkers in Type 2 Diabetes Patients
Authors: Cao Yang , Liang Ning , Liu Ting , Fang Jingai , Zhang Xiaodong 
Published: August 2022

Objective:
To assess the combined effect of Sodium-Glucose Transporter 2 Inhibitors (SGLT2i) and metformin treatment on inflammatory and prognostic biomarkers in patients with T2DM.

Methods:
Using the search terms “Sodium-Glucose Transporter 2 Inhibitors,” “Diabetes Mellitus, Type 2,” and “randomized controlled trial,” we screened the literature on PubMed, Cochrane Library, Embase, and Web of Science according to the inclusion and exclusion criteria. The studies selected were grouped to determine the combined effect of SGLT2i and metformin on inflammatory markers in patients with T2DM. Results were expressed using continuous variables, combined into weighted mean differences (WMD) and 95% confidence intervals (CI). The study was registered under the PROSPERO number CRD42022296480.

Results:
Meta-analysis showed that, compared with the control and metformin treatment groups, the SGLT2i coupled with metformin group was more effective in reducing C-reactive protein (CRP) (WMD, −0.185, 95% CI, −0.330 to −0.040, P < 0.05), tumor necrosis factor (TNF-α) (WMD, −0.628, 95% CI, −1.046 to −0.210, P < 0.05), uric acid (WMD, −0.653, 95% CI, −0.734 to −0.572, P < 0.05), leptin (WMD, −3.663, 95% CI, −4.812 to −2.515, P < 0.05), glycated hemoglobin (HbA1c) (WMD = −0.172, 95% CI, −0.255 to −0.089, P < 0.05)，and estimated glomerular filtration rate (eGFR)(WMD = 0.978, 95% CI (0.027, 1.928), P = 0.044). In parallel, we performed a Trial Sequential Analysis (TSA) of and the results showed reliable conclusions.

Conclusions:
SGLT2i combined with metformin reduced inflammation levels and significantly improved glycemic control and prognosis in patients with T2DM.
Transepithelial Corneal Cross-linking with Supplemental Oxygen in Keratoconus Treatment - Corneal Stromal Demarcation Line and Safety
Authors: Choo Jessica Qian Hui , Lim Li 
Published: August 2022

Purpose:
To evaluate the corneal stromal demarcation line and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen in progressive keratoconus treatment.

Methods:
This is a retrospective review of 25 patients with progressive keratoconus who underwent epithelial-on CXL with supplemental oxygen from December 2019 to February 2022. Outcomes measured include corneal stromal demarcation line depth, volume of cornea treated, endothelial cell count, best-corrected visual acuity, keratometric parameters and post-treatment adverse events.

Results:
25 eyes of 25 patients were included and mean age was 28.3 years. Mean follow-up period was 11.5 ± 1.39 months. Pre-operatively, mean ± standard deviation (SD) of K1, K2, Kmax and minimal corneal thickness were 45.9D ± 3.79D, 50.2D ± 4.83D, 57.5D ± 6.98D and 482.3um ± 36.8um respectively. There is no significant difference between pre and post-treatment corneal topographic parameters. There was improvement in BCVA post-treatment. The mean post-treatment corneal stromal demarcation line depth was 367.3 ± 89.8um. The volume of treated cornea including the central corneal epithelial thickness was 73.3 ± 4.39%. There was no reduction in endothelial cell count (ECC) post-procedure (pre-treatment mean ECC±SD: 2695.4 ± 224.5 cells/mm2, post-treatment ECC 2730.1 ± 252.0 cells/mm2, p-value = 0.33). Post-treatment corneal haze was mild and seen in 8 patients postoperatively. One patient developed a non-visual axis involving stromal infiltrate that resolved with topical broad-spectrum anti-microbials.

Conclusion:
Trans-epithelial CXL with supplemental oxygen for keratoconus treatment achieved comparable corneal stromal demarcation line depth comparable to that of conventional epithelial-off corneal cross-linking and had a similar safety profile.
The Rights of Unborn and Newborn Babies in Jordanian Arab Culture: Implications for Practice
Authors: Bawadi Hala , Al-Hamdan Zaid M. , Farhat Eshraq , Aldasoqi Khadeejeh Yousef , Alhammdan Mohammad , Jabaiti Samir 
Published: August 2022

Background:
Traditional patterns relating to how to handle the provision of culturally competent care for refugees are often challenging. Addressing the unique religious and cultural beliefs and norms of refugee parents during the childbirth process will alleviate their anxiety and feelings of alienation with respect to healthcare systems.

Objectives:
This paper aims to understand the meaning of Jordanian women’s beliefs and practices related to their foetuses and newborns and to facilitate the recognition by Western healthcare providers of these practices among immigrants and refugees.

Methods:
An interpretive phenomenological study was used to conduct an individual in-depth semi-structured interview with nine women.

Results:
Eight superordinate themes were identified: couple in legitimate relationship before conception, rejection of abortion, accepting the gender of the baby, guaranteeing that ‘Allah’ is the first word heard, rubbing the newborn’s palate with a date, choosing a meaningful name, ensuring circumcision for boys and showing gratitude to Allah.

Conclusion:
The attitudes of Jordanian women towards newborns’ rights and care are greatly influenced by their cultural and religious backgrounds. Capturing these attitudes and needs can inform the development of health education strategies and information resources. To enhance Muslim women’s engagement in maternal newborn health services, maternity staff should endeavour to create a trusting relationship with the childbearing women, which values their social, cultural and spiritual needs.
Calprotectin as a Serodiagnostic Marker for Bacterial Sepsis
Authors: Rezaei Faranak , Bakhshiani Zahra , Fouladi Saloomeh 
Published: August 2022

Introduction:
Since sepsis is a major global health problem, a rapid and correct diagnosis and the initiation of therapy are essential to improve the patient consequences. This study aimed to assess the serum levels of calprotectin and a more widely used sepsis biomarker in the patients with bacterial sepsis (BS).

Method:
Subjects were classified into BS group with the patients who met the sepsis criteria at the beginning of the study and the control group. We investigated the concentrations of biomarkers in 300 blood samples collected at admission from all patients hospitalized in the Fatemeh Al-Zahra Hospital, Najafabad, Isfahan in April 2019 and April 2020.

Results:
The microbial etiology in the BS group was confirmed in 35 patients (100%). The most frequently cultivated pathogens were Escherichia coli (n=11). The serum concentrations of calprotectin and CRP were significantly higher in the patients with BS (n= 35) than in the healthy controls (n= 20).

Conclusion:
Our results suggest that the serum level of calprotectin could have the substantial added value to manage BS which is a reliable biomarker of BS.
A Brief Overview of Invasive Fungal Infections in Immunocompromised Individuals
Authors: Pisote Deepak Kakasaheb , Menon Gowtham , Choure Rohit Lahurao 
Published: August 2022

Abstract:
Fungí is eukaryotic microorganisms that may spread and cause illness on the skin, subcutaneously,
and systemically. These infections can be invasive and difficult to identify at times. A patient
with a damaged immune system is more likely to get a fungal infection. Long-term chemotherapy,
organ transplantation, corticosteroid usage, or multidrug treatment all result in immunocompromised
people. Why do immunocompromised individuals need to be treated? The answer of this
query is that the immune system serves as an army for the human body, if it fails to protect it, foreign
particles such as bacteria, fungus, and viruses assault the body, causing the patient to become
immunocompromised. Candidiasis, aspergillosis, mucormycosis, and cryptococcal meningitis are
the most frequent invasive fungal diseases encountered in immunocompromised people. Patients afflicted
with invasive fungal infections have a significant death rate. As the number of immunocompromised
patients rises, so does the number of fungal infections. In this article, we took a quick look
at a few invasive fungal infections such as candidiasis, aspergillosis, and mucormycosis.
Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial
Authors: Dunn Abigail , Alvarez James , Arbon Amy , Bremner Stephen , Elsby-Pearson Chloe , Emsley Richard , Jones Christopher , Lawrence Peter , Lester Kathryn J , Majdandžić Mirjana , Morson Natalie , Perry Nicky , Simner Julia , Thomson Abigail , Cartwright-Hatton Sam 
Published: August 2022

Background
Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks.

Objective
This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms.

Methods
This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors.

Results
Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022.

Conclusions
The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety.

Trial Registration
ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933

International Registered Report Identifier (IRRID)
DERR1-10.2196/40707
Who Is Imam Mahdi, Prophesied In Other Religions, And From Holy Fatima lineage?
Authors: Khanghah Reza Rezaie 
Published: August 2022

Purpose: In this article, we will discuss the narrations and prophecies
that exist in Islam, both in Shia, Sunni and other religions regarding
Imam Mahdi. This article also attempts to deal with Holy Fatima and her
characteristics. Also, we will show that Imam Mahdi is mentioned not
only in other religions but also in other books. Also, this research was
conducted to answer and clarify three questions that stated in the
Introduction section.
Methods: We performed our methods in 4 stages: Identifying studies,
Selection of Studies, Collating Studies, Reporting results.
Results: According to Abrahamic religions, a person will reappear and
establish fairness and justice with the help of God, who is called Imam
Mahdi and based on the opinion of Christians, he is Christ. If the
Shiites, may Allah help them in His obedience, had fulfilled their
covenant with united hearts, then there would have been no delay in
meeting the Promised Saviour.
Conclusion: The concept of Imam Mahdi is universal and cannot just be
rejected. The appearance of Imam Mahdi will coincide with the coming
back of Jesus Christ. Imam Mahdi, with the assistance of the Messiah,
will ensure the completion and practical actualization of the mission of
the Prophet Muhammad. The Hidden Imam wrote to Abu-Omar Ameri: The
Prophet’s daughter (Holy Fatima) is a nice model for me. We hope this
article will take an important step in acquainting people with Imam
Mahdi and Jesus Christ and paving the ground for their reappearance.
Impact of a Novel Diabetes Prevention Intervention for Early Slow Weight Loss Responders among Adults with Prediabetes: An Adaptive Trial
Authors: Miller Carla K. , Nagaraja Haikady N. , Cheavens Jennifer , Fujita Kentaro , Lazarus Sophie 
Published: August 2022

<p> </p>
<p><strong>Objective:</strong> Some people are slower to respond during lifestyle interventions. An adaptive “rescue” intervention may improve outcomes among slow responders. The impact of a worksite “rescue” intervention for early slow responders was evaluated.</p>
<p><strong>Research Design and Methods:</strong> Employees ≥ 21 years old with prediabetes were stratified to intervention using a 2.5% weight loss (%WL) threshold at week 5. Outcomes were assessed at baseline and 4-months using mixed effect and linear regression models.</p>
<p><strong>Results:</strong> Significant improvement occurred in mean %WL, glycemia, total cholesterol, and triglycerides in the standard compared to adaptive (GLB+) intervention (all P ≤ 0.01). However, GLB+ also experienced significant reduction in %WL and glycemia (all P < 0.01). %WL at week 5 significantly predicted %WL at 4-months (P < 0.0001). Between-group difference of 4-month %WL was not significant for someone achieving 2.5%WL at week 5.</p>
<p><strong>Conclusions:</strong> Diabetes prevention programs should consider weight loss success following one month of treatment and offer a “rescue” intervention to early slow weight loss responders. </p>