bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines as Potential Therapeutic Targets and their Role in the Diagnosis and
Prediction of Cancers
Authors: Uchendu Ikenna , Zhilenkova Angelina , Pirogova Yuliya , Basova Maria , Bagmet Leonid , Kohanovskaia Iana , Ngaha Yvan , Ikebunwa Obinna , Sekacheva Marina 
Published: November 2023

Abstract:
The death rate from cancer is declining as a result of earlier identification and more advanced treatments.
Nevertheless, a number of unfavourable adverse effects, including prolonged, long-lasting inflammation
and reduced immune function, usually coexist with anti-cancer therapies and lead to a general decline in
quality of life. Improvements in standardized comprehensive therapy and early identification of a variety of aggressive
tumors remain the main objectives of cancer research. Tumor markers in those with cancer are tumor-
associated proteins that are clinically significant. Even while several tumor markers are routinely used,
they don't always provide reliable diagnostic information. Serum cytokines are promising markers of tumor
stage, prognosis, and responsiveness to therapy. In fact, several cytokines are currently proposed as potential
biomarkers in a variety of cancers. It has actually been proposed that the study of circulatory cytokines together
with biomarkers that are particular to cancer can enhance and accelerate cancer diagnosis and prediction,
particularly via blood samples that require minimal to the absence of invasion. The purpose of this review
was to critically examine relevant primary research literature in order to elucidate the role and importance
of a few identified serum cytokines as prospective therapeutic targets in oncological diseases.
Efficacy and Safety of Atezolizumab Monotherapy or Combined Therapy with
Chemotherapy in Patients with Metastatic Triple-negative Breast Cancer: A
Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Alimohammadi Mina , Faramarzi Fatemeh , Mafi Alireza , Mousavi Tahoora , Rahimi Ali , Mirzaei Hamed , Asemi Zatollah 
Published: November 2023

Introduction::
Several successful attempts have been recorded with PD-L1 blockade via atezolizumab
monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative
breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating
the safety and efficacy of this promising strategy in patients with mTNBC.

Methods::
A comprehensive literature search was conducted using electronic databases to identify eligible
RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination
with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic
were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and
random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed
using CMA.

Results::
Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival
(PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy
indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better
OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia
was higher (51.9%) than other complications across atezolizumab therapy.

Conclusion::
Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab
therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%),
and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable
anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical
efficacy.
Insight into RNA-based Therapies for Ovarian Cancer
Authors: Keyvani Vahideh , Mahmoudian Reihaneh Alsadat , Mollazadeh Samaneh , Kheradmand Nahid , Ghorbani Elnaz , Khazaei Majid , Saeed Al-Hayawi Ibrahim , Hassanian Seyed Mahdi , Ferns Gordon A. , Avan Amir , Anvari Kazem 
Published: November 2023

Abstract:
Ovarian cancer (OC) is one of the most common malignancies in women and is associated with
poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated
the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach
has some challenges that include RNA degradation. To solve this critical issue, some novel delivery
systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased
therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper
provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential
benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach
to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key
oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize
cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary
tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens,
stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform
improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally,
off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization
of these therapeutics. Several preclinical and clinical researches have shown promising results in the
field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly
(ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to
PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting
tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian
cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian
cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds
great potential for improving patient outcomes. However, further research is needed to address challenges related
to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased
therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased
therapeutics have the potential to develop the management of ovarian cancer and provide new hope for
patients.
A Convenient Synthesis of Bis-(dihydro)caffeoylspermidines
Authors: He Lili , Sun Jian , Zhou Pengjuan , Ji Jingwen , Zhai Lijuan , Tang Dong , Ji Jinbo , Yang Haikang , Iqbal Zafar , Yang Zhixiang 
Published: November 2023

Abstract:
Caffeoyl spermidines are valuable alkaloids naturally existing in many plant species. These
alkaloids are characterized as pharmacologically important ingredients of many plant extracts used in
traditional medicines. Bis-caffeoylspermidine and bis-dihydrocaffeoylspermidine exhibit antioxidant,
anti-inflammatory, and enzyme inhibition properties that make them valuable natural sources of safer
therapeutic agents. However, the limited availability of these compounds in nature derives the attention
of synthetic chemists. Therefore, we synthesized bis-caffeoylspermidine and bisdihydrocaffeoylspermidine
using cheaper and commercially available starting materials in 97% and
86% overall yields, respectively. The synthetic scheme can be upgraded to the commercial-scale synthesis
of these compounds
CAD System Design for Pituitary Tumor Classification based on Transfer
Learning Technique
Authors: Gargya Sagrika , Jain Shruti 
Published: November 2023

Background::
A brain tumor is an asymmetrical expansion by cells inevitably emulating amid them. Image processing is a vibrant research area where the
handing out of the image in the medical field is an exceedingly tricky field. In this paper, an expert algorithm is suggested for the detection of
pituitary brain tumors from MR images.

Methods::
The preprocessing techniques (smoothing, edge detection, filtering) and segmentation techniques (watershed) are applied to the online data set. The
transfer learning technique is used as a classifier whose performance is measured in terms of classification accuracy. Resnet 50, Inception
V3VGG16, and VGG19 models are used as classification algorithms. The proposed model is validated using different machine learning techniques
considering hybrid features.

Results::
96% accuracy was obtained employing the Inception V3 model & 95% accuracy was attained using hybrid GLDS and GLCM features employing
Support Vector Machine algorithm while 93% was attained using Probabilistic Neural Network and k Nearest Neighbor techniques.

Conclusion::
Computer-aided systems gave much faster and more accurate results than image processing techniques.1.0% accuracy improvement was observed
while using Inception V3 over GLDS + GLCM + SVM and 2.1% accuracy improvement using GLDS + GLCM + SVM over GLDS + GLCM +
kNN.
Multidisciplinary Management of Aneurysmal Bone Cyst in Paediatric Patients:
A Case Report
Authors: Chilaca-Rosas Maria-Fatima , Salazar-Calderon David-Rafael , Contreras-Aguilar Manuel-Tadeo , Lezama Melissa-Garcia , Valadez Ernesto-Roldan 
Published: November 2023

Background::
The aneurysmal bone cyst is a benign neoplasm that tends to form the appearance of a mass with a bony septum that forms cavities with blood
inside. It is estimated to represent 1% of bone tumours and has an incidence of 0.14 per 100,000 people worldwide. Current publications have not
shown a multidisciplinary approach that can benefit patients, mainly in the functionality and quality of the management approach.

Objective::
Describe the multidisciplinary approach and the benefits of quality of life and functionality in this diagnosis.

Case presentation:
A paediatric patient was diagnosed with an aneurysmal bone cyst located in the cervical spine, which initially manifested with muscle pain,
enlargement of the posterior cervical region, and difficulty in performing arcs of movement. He was treated with multidisciplinary management
with surgery, embolisation, radiation, and bisphosphonate support.

Conclusion::
The purpose of approaching multidisciplinary management helped to improve the accompanying symptoms that prevented our patient from having
an active and quality life. However, more successful cases have not been reported to establish the best therapeutic protocol.
Application of the Static Headspace Method as a Tool for Rapid Control of
Fennel Seed Tea Vapors
Authors: Assami Karim , Meziane-Assami Dalila , Ghouila Zahia , Guerroudj Riad , Gacem Lazhar 
Published: November 2023

Background::
In recent years, there have been tensions surrounding the accessibility of
drugs at pharmacies. This situation has led people to turn to alternative medicine with increased use
of plants as medicines. Nevertheless, a good knowledge of the plant's chemical composition is necessary
for its proper use due to the presence of toxic products.

Objective::
The research objectives are to expand a novel use of the static headspace technique to
control the chemical composition of the vapor of fennel seed tea (Foeniculum vulgare Mill.) and also
constitute an attempt to develop a targeted qualitative analytical method for quality control and safety
assurance of a consumer product.

Methods::
This study qualitatively investigated the amount of estragole in fennel herbal tea vapour by
successful rehabilitation of the static headspace gas chromatography/mass spectrometry method. In
addition, an analysis is conducted on the total phenolic and flavonoid content in both tea and methanol
extract. Antioxidant activities of all extracts were measured and compared to Gallic acid.

Results::
The fennel seed tea showed total phenolic and flavonoid contents at 187.7 ± 17.1 GAE/100 g
and 133.8 ± 9.07 mg CE/100 g, respectively. Fennel seeds tea exhibited good DPPH anti-radical
action with an IC50 of 92.38 ± 10.64 mg/g. Even though studies on the total phenols, flavonoid contents,
and antioxidant activity of this herbal tea have all yielded positive outcomes, the application of
the static headspace method combined with gas chromatography and mass spectrometry indicated the
presence of estragole at 37.63 ± 3.77%. This compound was found at 80.67 ± 0.29% in the essential
oil.

Conclusion::
The application of this method has made it possible to reduce the handling time by
eliminating the extraction step and solvent use. The presence of estragole at an alarming level makes
it clear that employing plants as medicines must be regulated.
Deregulated MicroRNAs involved in P53 Signaling Pathway in Breast Cancer
with Focus on Triple-negative Breast Cancer
Authors: Naeimzadeh Yasaman , Heidari Zahra , Razban Vahid , Khajeh Sahar 
Published: November 2023

Background::
Breast cancer (BC), as a heterogenous disease, is the most common cancer among women worldwide. Triple-negative breast cancer (TNBC) is the
most aggressive and malignant subtype with a poor prognosis and a high rate of relapse and metastasis that is closely linked to
epithelial–mesenchymal transition (EMT). It is well-documented that miRNAs play oncogenic (oncomiR) or tumor-suppressive (TS-miR) roles in
controlling apoptosis (apoptomiR), differentiation, cell proliferation, invasion, migration, etc. Regarding the regulatory roles of miRNAs in the
expression levels of various genes, dysfunction or deregulated expression of these molecules can lead to various disorders, including various types
of cancers, such as BC. Many miRNAs have been identified with critical contributions in the initiation and development of different types of BCs
due to their influence on the p53 signaling network.

Objective::
The aim of this review was to discuss several important deregulated miRNAs that are involved in the p53 signaling pathway in BC, especially the
TNBC subtype. Finally, miRNAs’ involvement in tumor properties and their applications as diagnostic, prognostic, and therapeutic agents have
been elaborated in detail.

Results::
The miRNA expression profile of BC is involved in tumor-grade estrogen receptor (ER) and progesterone receptor (PR) expression, and other
pathological properties from luminal A to TNBC/basal-like subtypes via p53 signaling pathways.

Conclusion::
Developing our knowledge about miRNA expression profile in BC, as well as molecular mechanisms of initiation and progression of BC can help
to find new prognostic, diagnostic, and therapeutic biomarkers, which can lead to a suitable treatment for BC patients.
PEGylated Chitosan Biodegradable Nanoparticles Delivery of Salvia officinalis and Melissa officinalis for Enhanced Brain Targeting
Authors: Datta Sanjana , Gajbhiye Asmita , Patil Shailendra 
Published: November 2023

Background:
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the gradual decline of cognitive abilities, primarily caused by impairments in the cholinergic system. AD is diagnosed based on the presence of specific pathological features, in-cluding senile plaques, neurofibrillary tangles, and the loss of neurons and synapses. Despite on-going efforts, the etiology of AD remains unclear, and there is a significant lack of effective treatments to meet the medical needs of affected individuals. The complex nature of AD, involv-ing multiple factors, presents challenges in the development of potential therapies. Numerous ob-stacles hinder the achievement of optimal pharmacological concentration of promising molecules for AD treatment. These obstacles include the presence of the blood-brain barrier (BBB), which restricts the entry of therapeutic agents into the brain, as well as issues related to poor bioavaila-bility and unfavorable pharmacokinetic profiles. Unfortunately, many therapeutically promising compounds have failed to overcome these hurdles and demonstrate efficacy in treating AD.

Methods:
The PEGylated chitosan nanoconjugate was developed and evaluated for delivery of anti-Alzheimer natural extract of Salvia officinalis and Melissa officinalis to the brain. The nano-conjugates (S-PCN and M-PCN) were developed by ionic gelation technique.

Result:
The nanoconjugates (S-PCN and M-PCN) were evaluated for various optical and in-vitro parameters. MTT assay on UCSD229i-SAD1-1 human astrocytoma cells indicated IC50 values of 0.42, 0.49, 0.67, and 0.75 μM for S-PCN, M-PCN formulations, and free Salvia officinalis and Melissa officinalis extracts, respectively. The In vitro assessments using cell lines have confirmed the improved uptake and distribution of nanoconjugates compared to free extracts. These findings were validated through confocal microscopy and apoptosis assays, revealing a substantial in-crease in the accumulation of nanoconjugates within the brain. The targeting potential OF M- PCN over S-PCN was found to be 2-fold significant.

Conclusion:
Based on the findings, it can be inferred that biodegradable PEGylated chitosan nanoconjugates hold promise as effective nano-targeting agents for delivering anti-Alzheimer drugs to the brain. The incorporation of PEGylated chitosan nanoparticles in this approach demonstrates enhanced delivery capabilities, ultimately leading to improved therapeutic out-comes.
The Accuracy and Potential Racial and Ethnic Biases of GPT-4 in the Diagnosis and Triage of Health Conditions: Evaluation Study
Authors: Ito Naoki , Kadomatsu Sakina , Fujisawa Mineto , Fukaguchi Kiyomitsu , Ishizawa Ryo , Kanda Naoki , Kasugai Daisuke , Nakajima Mikio , Goto Tadahiro , Tsugawa Yusuke 
Published: November 2023

Background
Whether GPT-4, the conversational artificial intelligence, can accurately diagnose and triage health conditions and whether it presents racial and ethnic biases in its decisions remain unclear.

Objective
We aim to assess the accuracy of GPT-4 in the diagnosis and triage of health conditions and whether its performance varies by patient race and ethnicity.

Methods
We compared the performance of GPT-4 and physicians, using 45 typical clinical vignettes, each with a correct diagnosis and triage level, in February and March 2023. For each of the 45 clinical vignettes, GPT-4 and 3 board-certified physicians provided the most likely primary diagnosis and triage level (emergency, nonemergency, or self-care). Independent reviewers evaluated the diagnoses as “correct” or “incorrect.” Physician diagnosis was defined as the consensus of the 3 physicians. We evaluated whether the performance of GPT-4 varies by patient race and ethnicity, by adding the information on patient race and ethnicity to the clinical vignettes.

Results
The accuracy of diagnosis was comparable between GPT-4 and physicians (the percentage of correct diagnosis was 97.8% (44/45; 95% CI 88.2%-99.9%) for GPT-4 and 91.1% (41/45; 95% CI 78.8%-97.5%) for physicians; P=.38). GPT-4 provided appropriate reasoning for 97.8% (44/45) of the vignettes. The appropriateness of triage was comparable between GPT-4 and physicians (GPT-4: 30/45, 66.7%; 95% CI 51.0%-80.0%; physicians: 30/45, 66.7%; 95% CI 51.0%-80.0%; P=.99). The performance of GPT-4 in diagnosing health conditions did not vary among different races and ethnicities (Black, White, Asian, and Hispanic), with an accuracy of 100% (95% CI 78.2%-100%). P values, compared to the GPT-4 output without incorporating race and ethnicity information, were all .99. The accuracy of triage was not significantly different even if patients’ race and ethnicity information was added. The accuracy of triage was 62.2% (95% CI 46.5%-76.2%; P=.50) for Black patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for White patients; 66.7% (95% CI 51.0%-80.0%; P=.99) for Asian patients, and 62.2% (95% CI 46.5%-76.2%; P=.69) for Hispanic patients. P values were calculated by comparing the outputs with and without conditioning on race and ethnicity.

Conclusions
GPT-4’s ability to diagnose and triage typical clinical vignettes was comparable to that of board-certified physicians. The performance of GPT-4 did not vary by patient race and ethnicity. These findings should be informative for health systems looking to introduce conversational artificial intelligence to improve the efficiency of patient diagnosis and triage.
Experiences, Lessons, and Challenges With Adapting REDCap for COVID-19 Laboratory Data Management in a Resource-Limited Country: Descriptive Study
Authors: Ndlovu Kagiso , Mauco Kabelo Leonard , Makhura Onalenna , Hu Robin , Motlogelwa Nkwebi Peace , Masizana Audrey , Lo Emily , Mphoyakgosi Thongbotho , Moyo Sikhulile 
Published: November 2023

Background
The COVID-19 pandemic brought challenges requiring timely health data sharing to inform accurate decision-making at national levels. In Botswana, we adapted and integrated the Research Electronic Data Capture (REDCap) and the District Health Information System version 2 (DHIS2) platforms to support timely collection and reporting of COVID-19 cases. We focused on establishing an effective COVID-19 data flow at the national public health laboratory, being guided by the needs of health care professionals at the National Health Laboratory (NHL). This integration contributed to automated centralized reporting of COVID-19 results at the Ministry of Health (MOH).

Objective
This paper reports the experiences, challenges, and lessons learned while designing, adapting, and implementing the REDCap and DHIS2 platforms to support COVID-19 data management at the NHL in Botswana.

Methods
A participatory design approach was adopted to guide the design, customization, and implementation of the REDCap platform in support of COVID-19 data management at the NHL. Study participants included 29 NHL and 4 MOH personnel, and the study was conducted from March 2, 2020, to June 30, 2020. Participants’ requirements for an ideal COVID-19 data management system were established. NVivo 11 software supported thematic analysis of the challenges and resolutions identified during this study. These were categorized according to the 4 themes of infrastructure, capacity development, platform constraints, and interoperability.

Results
Overall, REDCap supported the majority of perceived technical and nontechnical requirements for an ideal COVID-19 data management system at the NHL. Although some implementation challenges were identified, each had mitigation strategies such as procurement of mobile Internet routers, engagement of senior management to resolve conflicting policies, continuous REDCap training, and the development of a third-party web application to enhance REDCap’s capabilities. Lessons learned informed next steps and further refinement of the REDCap platform.

Conclusions
Implementation of REDCap at the NHL to streamline COVID-19 data collection and integration with the DHIS2 platform was feasible despite the urgency of implementation during the pandemic. By implementing the REDCap platform at the NHL, we demonstrated the possibility of achieving a centralized reporting system of COVID-19 cases, hence enabling timely and informed decision-making at a national level. Challenges faced presented lessons learned to inform sustainable implementation of digital health innovations in Botswana and similar resource-limited countries.