bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies for Targeting CIB1: A Challenging Drug Target
Authors: Shahab Muhammad , Wadood Abdul , Zheng Guojun 
Published: August 2022

Abstract:
Breast cancer is a common malignancy in women and is a diverse disease. In women, 287,850 and in
males 2710 cases are reported in 2022 by WHO. Triple-negative breast cancer (TNBC), a subtype of breast
cancer that lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal
growth factor receptor 2 (HER2), accounted for 10-20% of all new cases discovered in the United States in
2017. Because calcium integrin-binding protein1 lacks a suitable pocket that could be used to create a chemical
inhibitor, and because the breast cancer-causing protein is nearly identical to its necessary wild-type counterpart,
it was thought to be druggable. The structure and function of the newly discovered calcium integrinbinding
protein1 have been improved, paving the way for the designing of several therapeutic candidates. Currently,
no FDA-approved drugs are available for CIB1-driven cancer. CIB1 has proven to challenge drug target
due to several factors, including the fact that the CIB1 protein is highly resistant to small inhibitors. This study
aimed to present various ways for targeting calcium integrin-binding protein1, which is an important target that
could be useful to scientists.
Machine Learning-based Virtual Screening for STAT3 Anticancer Drug Target
Authors: Wadood Abdul , Ajmal Amar , Junaid Muhammad , Rehman Ashfaq Ur , Uddin Reaz , Azam Syed Sikander , Khan Alam Zeb , Ali Asad 
Published: August 2022

Background:
Signal transducers and activators of the transcription (STAT) family is composed of
seven structurally similar and highly conserved members, including STAT1, STAT2, STAT3, STAT4,
STAT5a, STAT5b, and STAT6. The STAT3 signaling cascade is activated by upstream kinase signals and undergoes
phosphorylation, homo-dimerization, nuclear translocation, and DNA binding, resulting in the expression
of target genes involved in tumor cell proliferation, metastasis, angiogenesis, and immune editing. STAT3
hyperactivation has been documented in a number of tumors, including head and neck, breast, lung, liver, kidney,
prostate, pancreas cancer, multiple myeloma, and acute myeloid leukemia. Drug discovery is a timeconsuming
and costly process; it may take ten to fifteen years to bring a single drug to the market. Machine
learning algorithms are very fast and effective and commonly used in the field, such as drug discovery. These
algorithms are ideal for the virtual screening of large compound libraries to classify molecules as active or inactive.

Objective:
The present work aims to perform machine learning-based virtual screening for the STAT3 drug target.

Methods:
Machine learning models, such as k-nearest neighbor, support vector machine, Gaussian naïve Bayes,
and random forest for classifying the active and inactive inhibitors against a STAT3 drug target, were developed.
Ten-fold cross-validation was used for model validation. Then the test dataset prepared from the zinc database
was screened using the random forest model. A total of 20 compounds with 88% accuracy was predicted
as active against STAT3. Furthermore, these twenty compounds were docked into the active site of STAT3.
The two complexes with good docking scores as well as the reference compound were subjected to MD simulation.
A total of 100ns MD simulation was performed.

Results:
Compared to all other models, the random forest model revealed better results. Compared to the standard
reference compound, the top two hits revealed greater stability and compactness.

Conclusion:
In conclusion, our predicted hits have the ability to inhibit STAT3 overexpression to combat
STAT3-associated diseases.
The Therapeutic Potential of Targeting the Toll-like Receptor Pathway in Breast
Cancer
Authors: Toroghian Younes , Khayyami Reza , Hassanian Seyed Mahdi , Nassiri Mohammadreza , Ferns Gordon A. , Khazaei Majid , Avan Amir 
Published: August 2022

Abstract:
The toll-like receptor (TLR) signaling pathway plays a key role in inducing immune responses and were shown to be expressed in immune cells and tumor cells, and is involved in the progression of several malignancies including breast cancer. These findings provide a proof of the concept of targeting this pathway as a potential therapeutic option in the treatment of breast cancer. Moreover, there is a growing body of data showing the activation of TLRs in the tumor microenvironment and its dual function as anti-tumoral (dendritic T and natural killer cells activation) or pro-tumoral activity (cell proliferation, and drug resistance). Several agents have been developed for targeting of this pathway and one of these inhibitors, called Bacillus Calmette-Guerin (an agonist of TLR2 and TLR4), is recently being approved by FDA for immunotherapy of bladder cancer. This review summarizes the current knowledge of the mechanisms of action of TLR pathways in the development/progression of cancer for a better management of this disease.
Cancer Immunotherapy: Diverse Approaches and Obstacles
Authors: Sanatkar Seyed Amir , Heidari Arash , Rezaei Nima 
Published: August 2022

Abstract:
Cancer immunotherapy approaches have progressed significantly during the last decade due to the
significant improvement of our understanding of immunologic evasion of malignant cells. Depending on the
type, stage, and grade of cancer, distinct immunotherapy approaches are being designed and recommended;
each is different in efficacy and adverse effects. Malignant cells can adopt multiple strategies to alter the normal
functioning of the immune system in recognizing and eliminating them. These strategies include secreting different
immunosuppressive factors, polarizing tumor microenvironment cells to immunosuppressive ones, and
interfering with the normal function of the antigen processing machinery (APM). In this context, careful evaluation
of immune surveillance has led to a better understanding of the roles of cytokines, including IL-2, IL-12,
IL-15, interferon-α (IFN-α), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) in
cancer formation and their potential application in cancer immunotherapy. Additionally, monoclonal antibodies
(mAbs), adoptive cell therapy approaches, immune checkpoint blockade, and cancer vaccines also play significant
roles in cancer immunotherapy. Moreover, the development of clustered regularly interspaced short palindromic
repeats/CRISPR-associated protein 9 (CRISPR/CAS9) as an outstanding genome editing tool resolved
many obstacles in cancer immunotherapy. In this regard, this review aimed to investigate the impacts of different
immunotherapy approaches and their potential roles in the current and future roads of cancer treatment.
Whatever the underlying solution for treating highly malignant cancers is, it seems that solving the question is
nowhere near an achievement unless the precise cooperation of basic science knowledge with our translational
experience.
Feeding Pattern, Circadian Rhythm, and Immune Function: What do we know
about?
Authors: Estanislau Thiago Barros , Kruger Karsten , Rosa-Neto José Cesar , Padilha Camila S. , Gonçalves Daniela Caetano , Minuzzi Luciele Guerra , Lira Fábio Santos 
Published: August 2022

Abstract:
Feeding pattern is related to health status or chronic diseases, and this depends on the individual’s
eating habits. Feeding organized with the right time to start and end during the day, promotes an internal biological
rhythm, favoring molecular synchronization of the clock genes, which impose an effect on metabolism
and immune cells, creating a physiological response related to a healthy profile. On the other hand, a feeding
pattern disorganized, without the right time to start and end eating during the day, might lead to nonsynchronization
of the clock genes, a disruption condition, which is related to chronic diseases, such as obesity
and diabetes type 2. A strategy that should be adopted to favor molecular synchronization is time-restricted eating
(TRE), which can organize the initial and end of the eating patterns during the day. Our review points out
some cues that suggest TRE as an efficient strategy for healthy profile and can be a good intervention for the
treatment of chronic diseases.
Inhibitory Efficacy of Thiosemicarbazones for Carbonic Anhydrase II (Bovine and
Human) as a Target of Calcification and Tumorigenicity
Authors: Khan Majid , Halim Sobia Ahsan , Shafiq Zahid , Islam Muhammad , Shehzad Muhammad Tariq , Ibrar Aliya , Khan Farhan A. , Marraiki Najat , Uddin Jalal , Khan Ajmal , Al-Harrasi Ahmed 
Published: August 2022

Background:
Carbonic anhydrase II (CA-II) is associated with calcification, tumorigenicity, epilepsy,
osteoporosis, and several other physiological or pathological processes. CA-II inhibitors can be used to
reduce the intraocular pressure usually associated with glaucoma.

Objective:
In search for potent CA-II inhibitors, a series of thiosemicarbazone derivatives (3a-u) was synthesized.

Methods:
This series was evaluated against bovine and human carbonic anhydrase II (bCA-II and hCA-II) and
their docking studies were carried out.

Results:
In the preliminary screening, most of the compounds exhibited significant inhibition of bCA-II and
hCA-II. The predictive structure-activity relationship suggested that the thiosemicarbazide moiety plays a key
role in the inhibition of enzyme activity and substitution at R position and has a remarkable contribution to the
overall activity. The kinetic studies of the most active inhibitors of bCA-II (3d, 3e, 3l, 3f, and 3p) and hCA-II
(3g) were performed against bCA-II and hCA-II, respectively to investigate their mode of inhibition and dissociation
constants (Ki).

Conclusion:
Subsequently, (3e, 3f, 3l and 3p) were identified as competitive inhibitors of bCA-II with Ki values
of 5.02-14.70 μM, while (3d) as a noncompetitive inhibitor of bCA-II (Ki = 2.5 ± 0.015 μM), however, (3g)
demonstrated competitive inhibition of hCA-II with a Ki value of 5.95 ± 0.002 μM. The selectivity index
reflects that compound (3g) is more selective for hCA-II. The binding modes of these compounds with bCA-II
and hCA-II were investigated by structure-based molecular docking, and the docking results are in complete
agreement with the experimental findings.
Vernodalin Suppresses Tumor Proliferation and Increases Apoptosis of
Gastric Cancer Cells Through Attenuation of FAK/PI3K/AKT/mTOR and
MAPKs Signaling Pathways
Authors: Lin Nengming , Luo Ying , Zhang Dan , Hou Leping 
Published: August 2022

Background:
Gastric cancer (GC) is the most aggressive malignant tumor with limited treatment alternatives post metastasis. Vernodalin (VN) induced apoptosis has been reported in various types of human cancer cells. However, the precise molecular mechanisms underlying the anti-metastasis action of VN on GC cells are yet to be elucidated.

Objective:
In this study, we investigated the anti-metastatic and apoptotic effects of VN on SGC-7901 and AGS cells, with a purpose of gaining a deeper understanding of the anti-metastatic mechanisms of VN on gastric carcinoma. To attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by VN in GC cells.

Methods:
We employed VN and gastric cancer cells in experiments such as, MTT assay, apoptosis, MMP, DAPI, Rh-123, cell adhesion assay, and western blot analysis on GC SGC-7901 and AGS cells.

Result:
Our results revealed that VN inhibits the cell proliferation, adhesion, and metastasis and induces apoptosis of both GC cells. VN potentially reduced the protein expressions of MMP-2, MMP-9, and uPA, whereas intensified expressions of TIMP-1 and TIMP-2. Also, VN attenuates the expression of FAK, p-PI3K, p-AKT, p-mTOR, p-JNK, p-p38MAPK, and p-ERK. Thus, it is inferred that VN treatment reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/mTOR, and MAPKs signaling pathways. Our results confirm that VN prevented GC growth, invasion and metastasis and induce apoptosis in GC cells.

Conclusion:
Our findings suggest that VN is a potential natural therapeutic compound as a new remedy for GC chemotherapy treatment.
BCL11A Facilitates Cell Proliferation and Metastasis in Neuroblastoma via
Regulating the PI3K/Akt Signaling Pathway
Authors: Yuan Xiaojun , Jin Qianya , Chen Yanmin , Du Shibei , Xu Dongqing , Yue Juanqing , Cai Lei 
Published: August 2022

Purpose:
The study aims to access the value of B-cell lymphoma/leukemia 11A (BCL11A)
in the prognosis of patients with neuroblastoma (NB) and to explore its role and possible mechanism in
NB.

Methods:
Tumor specimens from 53 children with neuroblastoma were evaluated for the relationship
between BCL11A expression level and prognosis of NB patients. Online datasets like SEQC and Asgharzadeh
were analyzed to further check out the suppose.The role of BCL11A in the proliferation and
migration of NB cells was studied by functional experiments such as CCK8, colony formation, flow
cytometry, transwell and wound healing assay after knocking down BCL11A by small interfering RNA
(siRNA) in vitro. The protein makers of the potential pathways were tested by western blot.

Results:
High expression of BCL11A in NB patients was closely correlated with high-risk and poor prognosis. The proliferation and migration abilities of NB cell lines SK-N-BE(2) and IMR-32 were significantly impaired by silencing BCL11A. Downregulation of BCL11A expression level in NB cells inhibited the epithelial–mesenchymal transition (EMT) process and affected the PI3K/Akt signaling pathway.

Conclusion:
As a prognostic indicator of survival in NB patients, BCL11A might serve as a potential
therapeutic target. BCL11A played a regulatory role in cell proliferation, invasion, and migration in
NB, which may be through the PI3K/AKT signaling pathway and induce EMT.
BNT162b2 Elicited an Efficient Humoral Response Against Different
Strains of SARS-CoV-2 in People Living with HIV
Authors: Gidari Anna , Bastianelli Sabrina , Pierucci Sara , Busti Chiara , Sabbatini Samuele , Schiaroli Elisabetta , Benedetti Sara , Gamboni Giulia , Lanzi Alessandra , Francisci Daniela 
Published: August 2022

Background:
Vaccines have had a fundamental impact in containing the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. However, there are few efficacy data relating to frail patients, including the HIV-positive patient.

Objective:
This study evaluated the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) serum neutralization in People Living with HIV (PLWH) compared to a cohort of healthy volunteers both vaccinated with BNT162b2.

Methods:
A serum sample was then withdrawn 14-21 days after the second dose of the vaccine and a serum neutralization assay was performed on Vero-E6 cells. The experiments were performed using two strains of SARS-CoV-2 as 20A.EU1 and B.1.617.2.

Results:
PLWH on Antiretroviral Therapy (ART) showed a vaccine response comparable to the healthy subjects. No correlation between CD4 count or CD4/CD8 and neutralizing antibodies (NT-Abs) has been found. No differences in NT-Abs between patients with CD4 nadir above or under 200 cells/µl have been found. In both cohorts, vaccine-elicited serum better neutralized 20A.EU1 than B.1.617.2 strain.

Conclusion:
PLWH in ART and with good immuno-virological recovery showed a vaccine response comparable to that of healthy subjects and regardless of their immunological status at HIV infection diagnosis. However, larger studies are needed to confirm our results and to evaluate the vaccine response even in patients with low CD4 counts.
Antibody-drug Conjugates for Breast Cancer Treatment
Authors: Sheikh M. Saeed , Huang Ying 
Published: August 2022

Abstract:
The use of antibody-drug conjugates is expected to transform the management of human malignancy. Antibody-drug conjugates for cancer treatment are designed to deliver anticancer drugs to tumor cells. The main components of such conjugates are a monoclonal antibody that binds to a tumor antigen, an anticancer drug to inhibit tumor cell growth and a linker that serves to conjugate the anti-body and drug. The antibody-drug conjugates developed and approved for breast cancer treatment are ado-trastuzumab emtansine, (fam)-trastuzumab deruxtecan-nxki and sacituzumab govitecan. The mechanisms of action, clinical uses and toxic effects of these antibody-drug conjugates are discussed.
Effects of Acylhydrazone Derivatives on Experimental Pulmonary
Inflammation by Chemical Sensitization
Authors: de Lima Porto Ramos Katharina Rodrigues , da Silva Sandra Cabral , Marchand Pascal , Barreto Mota Fernanda Virgínia , de Assis Correia Julyanne Cunha , Gomes Silva Jéssica de Andrade , de Lima George Torres , Santana Marllon Alex , da Silva Moura Willian Charles , dos Santos Vanda Lúcia , Moura Ricardo Olímpio , da Silva Teresinha Gonçalves 
Published: August 2022

Background:
Chronic lung diseases are characterized by airway inflammation and
remodelling of the lung parenchyma that triggers considerable impairment of respiratory function.
Objective: In this study, two compounds belonging to the N-acylhydrazone class were evaluated,
aiming to identify new therapeutic agents for pulmonary inflammatory diseases.

Materials and Methods:
The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)-
acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was
evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma
and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity.

Results and Discussion:
The compounds did not show toxicity at the dose of 2,000 mg/kg, and no
animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10
mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage
by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and
JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing
the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell
migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference
drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in
animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it
was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing
mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively.

Conclusion:
Together, the results show that JR-12 and JR09-Bz showed promising activity against
airway inflammation, as well as low toxicity.
Developing a wood lathe machine with speed control and workers' anthropometry to increase the productivity of broom industry
Authors: Santosa I Gede 
Published: August 2022

To overcome the economic crisis in the current situation, the community in the village of Dawan Klungkung-Bali was encouraging small and medium-sized businesses, including the home industry sector, specifically the production of broom handles that made from leftover wood. The production process is quite simple where the worker utilized wooden chisels and hand grinders to create the broom handle. Even though the methods and tools are simple, it takes a long time to complete one broom handle. In addition, the process continued with the sanding process to smoothen the product, which caused the workers to quickly become fatigued due to the long duration of the bending down and pressing gestures. To address this issue, a wood lathe with speed control and height adjustment based on worker anthropometry was developed. This study was volunteered by ten workers that compared the workload of both traditional and proposed method. Workload is determined by measuring the worker's pulse with a pulse meter, skeletal muscle complaints that observed using the Nordic Body Map questionnaire, and worker productivity that calculated by dividing the number of broom handles produced per hour by the workload.
A Machine Learning Approach for Continuous Mining of Nonidentifiable Smartphone Data to Create a Novel Digital Biomarker Detecting Generalized Anxiety Disorder: Prospective Cohort Study
Authors: Choudhary Soumya , Thomas Nikita , Alshamrani Sultan , Srinivasan Girish , Ellenberger Janine , Nawaz Usman , Cohen Roy 
Published: August 2022

Background
Anxiety is one of the leading causes of mental health disability around the world. Currently, a majority of the population who experience anxiety go undiagnosed or untreated. New and innovative ways of diagnosing and monitoring anxiety have emerged using smartphone sensor–based monitoring as a metric for the management of anxiety. This is a novel study as it adds to the field of research through the use of nonidentifiable smartphone usage to help detect and monitor anxiety remotely and in a continuous and passive manner.

Objective
This study aims to evaluate the accuracy of a novel mental behavioral profiling metric derived from smartphone usage for the identification and tracking of generalized anxiety disorder (GAD).

Methods
Smartphone data and self-reported 7-item GAD anxiety assessments were collected from 229 participants using an Android operating system smartphone in an observational study over an average of 14 days (SD 29.8). A total of 34 features were mined to be constructed as a potential digital phenotyping marker from continuous smartphone usage data. We further analyzed the correlation of these digital behavioral markers against each item of the 7-item Generalized Anxiety Disorder Scale (GAD-7) and its influence on the predictions of machine learning algorithms.

Results
A total of 229 participants were recruited in this study who had completed the GAD-7 assessment and had at least one set of passive digital data collected within a 24-hour period. The mean GAD-7 score was 11.8 (SD 5.7). Regression modeling was tested against classification modeling and the highest prediction accuracy was achieved from a binary XGBoost classification model (precision of 73%-81%; recall of 68%-87%; F1-score of 71%-79%; accuracy of 76%; area under the curve of 80%). Nonparametric permutation testing with Pearson correlation results indicated that the proposed metric (Mental Health Similarity Score [MHSS]) had a colinear relationship between GAD-7 Items 1, 3 and 7.

Conclusions
The proposed MHSS metric demonstrates the feasibility of using passively collected nonintrusive smartphone data and machine learning–based data mining techniques to track an individuals’ daily anxiety levels with a 76% accuracy that directly relates to the GAD-7 scale.
Aprender, interpretar y actualizar
Authors: Rodriguez Suárez José Gregorio 
Published: August 2022

Coherence between faith professed and life lived is fundamental for religious experiencecredibility. For Christianity, Jesus’ lessons are paradigmatic. So, what is learned isinterpreted and updated by his disciples in their vital contexts. The objective of this paperis to propose a way to overcome individualism and forms of spirituality withoutencountering God, based on Jesus’ teaching in Luke 10:25-37. Since this is a qualitativedocumentary study a bibliographical review is made to address the topic from a biblical-theological approach. This paper shows partial results of PhD research in theology,concluding that love with words and actions is an ethical commitment to concrete serviceto others, as a manifestation of the authentic experience of God.