bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation, Characterization, and Evaluation of Mesoporous Silica Nanoparticles in Enhancing Oral Bioavailability of Poorly Water-Soluble Drugs
Authors: Zhang Hong , Zuo Fanjiao , Wang Boyao , Qiu Xilong
Published: February 2024

Background:

Breviscapine (BVP) is one of the extracts of several flavonoids of Erigeron
breviscapus, which has been widely used in the treatment of cerebral infarction and its sequelae,
cerebral thrombus, coronary heart disease, and angina pectoris. But BVP has poor solubility.

Objective:

The objective of the study is to develop mesoporous silica nanoparticles (MSNs) that can
be loaded with a drug with poor water solubility. The MSNs, which were designed for oral administration,
enhanced both the dissolution rate and drug loading capacity.

Methods:

The use of MSNs as an oral drug delivery system was investigated by SEM, TEM, BETBJH,
XRD, FT-IR, and HPLC. Additionally, we examined the oral bioavailability of BVP loaded
onto MSNs and examined the cellular cytotoxicity of MSNs.

Results:

The results indicate that the oral bioavailability of BVP after loading onto MSNs was greater
than that of a marketed product. Furthermore, we studied the mechanism by which MSNs enhance
the oral absorption of BVP.

Conclusion:

MSNs have the potential to enhance the oral bioavailability of poorly water-soluble
drugs by accelerating the drug dissolution rate.
Effective Strategies in Designing Chitosan-hyaluronic Acid Nanocarriers: From Synthesis to Drug Delivery Towards Chemotherapy
Authors: Hong Long-Quy , Ho Thao N.T , Cu Son T. , Ngan Lien Tuyet , Tran Ngoc Quyen , Dang Tien T.
Published: February 2024

:

The biomedical field faces an ongoing challenge in developing more effective anti-cancer
medication due to the significant burden that cancer poses on human health. Extensive research has
been conducted on the utilization of natural polysaccharides in nanomedicine owing to their properties
of biocompatibility, biodegradability, non-immunogenicity, and non-toxicity. These characteristics
make them a potent drug delivery system for cancer therapy. The chitosan hyaluronic acid nanoparticle
(CSHANp) system, consisting of chitosan and hyaluronic acid nanoparticles, has exhibited
considerable potential as a nanocarrier for various cancer drugs, rendering it one of the most auspicious
systems presently accessible. The CSHANps demonstrate remarkable drug loading capacity,
precise control over drug release, and exceptional selectivity towards cancer cells. These properties
enhance the therapeutic effectiveness against cancerous cells. This article aims to provide a comprehensive
analysis of CSHANp, focusing on its characteristics, production techniques, applications, and
future prospects.
Intelligent Drug Delivery: Pioneering Stimuli-Responsive Systems to Revolutionize Disease Management- An In-depth Exploration
Authors: Kallepalli Badarinadh , Garg Unnati , Jain Neha , Nagpal Rohan , Malhotra Sakshi , Tiwari Triveni , Kaul Shreya , Nagaich Upendra
Published: February 2024

In recent years, there has been an escalating interest in stimuli-responsive drug delivery
systems (SRDDS) due to their ability to revolutionize the delivery of therapeutics. SRDDSs offer a
multitude of benefits in comparison to conventional drug delivery systems (DDS), including spatiotemporal
control of drug release, targeted delivery, and improved therapeutic efficacy. The development
of various classes of stimuli-responsive DDS, such as pH-responsive, temperature-responsive,
photo-responsive, redox responsive systems, has been propelled by advances in materials science,
nanotechnology, and biotechnology. These systems exploit specific environmental or physiological
cues to trigger drug release in a precisely controlled manner, making them highly promising for the
treatment of various diseases. In this review article, an in-depth exploration of the principles, mechanisms,
and applications of SRDDS in the context of diverse pathologies such as cancer, arthritis,
Alzheimer’s disease, atherosclerosis and tissue engineering has been provided. Furthermore, this
article delves into the discussion of recent patents, market overview and the progress of research in
clinical trials. Overall, this article underscores the transformative potential of SRDDS in enabling
personalized, precise, and effective drug delivery for the treatment of the above-mentioned diseases.
IR-780 Dye-based Targeting of Cancer-associated Fibroblasts Improves
Cancer Immunotherapy by Increasing Intra-tumoral T Lymphocytes
Infiltration
Authors: Yang Wei , Chen Zelin , Qu Langfan , Zhang Can , Chen Hongdan , Zheng Jiancheng , Chen Wanchao , Tan Xu , Shi Chunmeng
Published: February 2024

Background::

Immune-checkpoint inhibitors (ICIs) against programmed death
(PD)-1/PD-L1 pathway immunotherapy have been demonstrated to be effective in only a subset of
patients with cancer, while the rest may exhibit low response or may develop drug resistance after
initially responding. Previous studies have indicated that extensive collagen-rich stroma secreted
by cancer-associated fibroblasts (CAFs) within the tumor microenvironment is one of the key obstructions
of the immunotherapy for some tumors by decreasing the infiltrating cytotoxic T cells.
However, there is still a lack of effective therapeutic strategies to control the extracellular matrix
by targeting CAFs.

Methods::

The enhanced uptake of IR-780 by CAFs was assessed by using in vivo or ex vivo nearinfrared
fluorescence imaging, confocal NIR fluorescent imaging, and CAFs isolation testing. The
fibrotic phenotype down-regulation effects and in vitro CAFs killing effect of IR-780 were tested
by qPCR, western blot, and flow cytometry. The in vivo therapeutic enhancement of anti-PD-L1
by IR-780 was evaluated on EMT6 and MC38 subcutaneous xenograft mice models.

Results::

IR-780 has been demonstrated to be preferentially taken up by CAFs and accumulate in
the mitochondria. Further results identified low-dose IR-780 to downregulate the fibrotic phenotype,
while high-dose IR-780 could directly kill both CAFs and EMT6 cells in vitro. Moreover,
IR-780 significantly inhibited extracellular matrix (ECM) protein deposition in the peri-tumoral
stroma on subcutaneous EMT6 and MC38 xenografts, which increased the proportion of tumor-infiltrating
lymphocytes (TILs) in the deep tumor and further promoted anti-PD-L1 therapeutic efficacy.

Conclusion::

This work provides a unique strategy for the inhibition of ECM protein deposition in
the tumor microenvironment by targeted regulating of CAFs, which destroys the T cell barrier and
further promotes tumor response to PD-L1 monoclonal antibody. IR-780 has been proposed as a
potential therapeutic small-molecule adjuvant to promote the effect of immunotherapy.
Neuroinflammation in Glioblastoma: The Role of the Microenvironment
in Tumour Progression
Authors: Nóbrega Ana Helena Larangeira , Pimentel Rafael Sampaio , Prado Ana Paula , Garcia Jenifer , Frozza Rudimar Luiz , Bernardi Andressa
Published: February 2024

Glioblastoma (GBM) stands as the most aggressive and lethal among the main types of
primary brain tumors. It exhibits malignant growth, infiltrating the brain tissue, and displaying resistance
toward treatment. GBM is a complex disease characterized by high degrees of heterogeneity.
During tumour growth, microglia and astrocytes, among other cells, infiltrate the tumour microenvironment
and contribute extensively to gliomagenesis. Tumour-associated macrophages
(TAMs), either of peripheral origin or representing brain-intrinsic microglia, are the most numerous
nonneoplastic populations in the tumour microenvironment in GBM. The complex heterogeneous
nature of GBM cells is facilitated by the local inflammatory tumour microenvironment,
which mostly induces tumour aggressiveness and drug resistance. The immunosuppressive tumour
microenvironment of GBM provides multiple pathways for tumour immune evasion, contributing
to tumour progression. Additionally, TAMs and astrocytes can contribute to tumour progression
through the release of cytokines and activation of signalling pathways. In this review, we summarize
the role of the microenvironment in GBM progression, focusing on neuroinflammation. These
recent advancements in research of the microenvironment hold the potential to offer a promising
approach to the treatment of GBM in the coming times.
The Effects of Mesenchymal Stem Cells Loaded with Oncolytic
Coxsackievirus A21 on Mouse Models of Colorectal Cancer
Authors: Karbalaee Reza , Mehdizadeh Saber , Ghaleh Hadi Esmaeili Gouvarchin , Izadi Morteza , Kondori Bahman Jalali , Dorostkar Ruhollah , Hosseini Seyed Morteza
Published: February 2024

Background:

Cancer is a major cause of death worldwide. Colorectal cancer is the second
most common type. Additional treatments like chemotherapy and radiation therapy may be
recommended. Developing new techniques is vital due to drug resistance and a lack of targeted
therapies.

Objective:

In this study, the effects of mesenchymal stem cells (MSCs) loaded with oncolytic Coxsackievirus
A21 (CVA21) on a mouse model of CRC were investigated.

Methods:

The therapeutic potency of MSCs loaded with oncolytic CVA21 were evaluated in an
experimental mouse model of colorectal cancer which received an injection CT26 cells per mouse
subcutaneously. Splenocyte proliferation index, lactate dehydrogenase (LDH) assay, nitric oxide
(NO) production assessment, and cytokine assay (IFN-γ, IL-4, IL-10, and TGF-β) in the splenocyte
supernatant were all used to evaluate the impact of MSCs loaded with CVA21.

Results:

The results of this study showed that the treatment of a mouse model of colorectal cancer
with MSCs loaded with oncolytic CVA21 could significantly suppress the tumor growth, which
was accompanied by stimulation of splenocytes proliferation index, an increase of NO and LDH.
Also, MSCs loaded with oncolytic CVA21 increased the secretion of IFN-γ and decreased the secretion
of IL-4, IL-10, and TGF-β.

Conclusion:

The results of the current study suggest that MSCs loaded with oncolytic CVA21
therapy for the CRC mouse model may have some potential advantages. On the other hand, the results
of the study showed that, in addition to activating the acquired immune system, the use of
MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing level
of nitric oxide.
Brucine Inhibits Proliferation of Pancreatic Ductal Adenocarcinoma
through PI3K/AKT Pathway-induced Mitochondrial Apoptosis
Authors: Wu You , Zhang Fenglin , Xu Panling , Li Ping
Published: February 2024

Introduction:

The purpose of this research was to settle the role of brucine in pancreatic
ductal adenocarcinoma (PDAC) and the mechanisms involved.

Methods:

The findings of this study suggest that brucine exerts inhibitory effects on cell growth,
clonogenicity, and invasive potential of Panc02 and Mia Paca-2 cells. These effects may be linked
to an increase in apoptotic-prone cell population.

Results:

Gene sequencing data suggests that these effects are mediated through the induction of
apoptosis. Experimental evidence further supports the notion that brucine reduces mitochondrial
membrane potential and upregulates Bax expression while downregulating Bcl-2 expression. These
effects are believed to be a result of brucine-mediated suppression of PI3K/Akt activity, which
serves as a regulatory factor of mTOR, Bax, and Bcl-2. Suppression of PI3K activity enhances the
tumor-suppressing effects of brucine.

Conclusion:

Overall, these findings suggest that brucine has therapeutic potential as a remedy option
for PDAC.
Effect of Neoadjuvant Immunotherapy Combined with Chemotherapy on
Pulmonary Function and Postoperative Pulmonary Complications in
Esophageal Cancer: A Retrospective Study
Authors: Gao Yongyin , Zhang Hongdian , Qiu Yanli , Bian Xueyan , Wang Xue , Li Yue
Published: February 2024

Background:

Neoadjuvant immunotherapy, targeting the PD-1 or PD-L1, combined
with chemotherapy (NICT), can improve the radical resection and survival rates for locally advanced
EC. However, it may impair pulmonary function, and the effect of NICT on pulmonary
function and postoperative pulmonary complications in EC patients remains unknown. This study
aimed to investigate whether NICT can affect pulmonary functions and postoperative pulmonary
complications in EC patients.

Methods:

The study retrospectively recruited 220 EC patients who received NICT at the Department
of Esophageal Cancer in Tianjin Medical University Cancer Institute & Hospital from January
2021 to June 2022. Changes in pulmonary function before and after NICT were compared.
Logistic regression analysis was performed to analyze the correlations of pulmonary functions and
clinical characteristics with postoperative pulmonary complications, respectively.

Results:

The FEV1% pred, FVC, FVC% pred, and FEV1/FVC% significantly increased after
NICT, with a P-value of 0.018, 0.005, 0.001, and 0.036, respectively. In contrast, there was a significant
decline in the DLCO (8.92 ± 2.34 L before NICT vs. 7.79 ± 2.30 L after NICT; P < 0.05)
and DLCO% pred (102.97 ± 26.22% before NICT vs. 90.18 ± 25.04% after NICT; P < 0.05).
High DLCO and DLCO% pred at baseline levels were risk factors for DLCO reduction in EC patients
after NICT. Advanced age, smoking history, FEV1% pred after NICT, and FVC% pred baseline
and after therapy were risk factors for postoperative pulmonary complications, with a P-value
of 0.043, 0.038, 0.048, 0.034, and 0.004, respectively. Although the DLCO level decreased after
NICT, it did not increase the incidence of postoperative pulmonary complications.

Conclusion:

NICT may improve pulmonary ventilation function but also lead to a decrease in DLCO
and DLCO% pred in EC patients. Nevertheless, the decreased DLCO after NICT did not increase
the risk of postoperative pulmonary complications.
Unlocking the Pharmacological Potential of Benzimidazole Derivatives:
A Pathway to Drug Development
Authors: Monga Jyoti , Ghosh Niladry S. , Rani Isha , Singh Ranjit , Deswal Geeta , Dhingra Ashwani K. , Grewal Ajmer S.
Published: February 2024

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry.
They are heterocyclic compounds that have gained significance due to their diverse variety of
pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and
imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a
promising scaffold for drug development. Many biological actions of benzimidazole derivatives
have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular,
and anthelmintic properties. The mechanism of action of benzimidazole derivatives
varies with their chemical structure and target enzyme. This review has explored numerous methods
for producing benzimidazole derivatives as well as a broad range of pharmacological activities.
SAR investigations are also discussed in this review as they provide crucial details regarding
the essential structural qualities that benzimidazole derivatives must have in order to be biologically
active, which could aid in the rational design of new drug candidates.

:

Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical
drugs containing benzimidazole are anticipated to be available within the next ten
years as a result of the extensive therapeutic applications of benzimidazole and its derivatives.
This review inspired many researchers to develop more biologically active compounds bearing
benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we
concluded that 2-substituted benzimidazole was considered more extensively by researchers.
Effect of Intermittent Fasting on Lipid Profile, Anthropometric and
Hepatic Markers in Non-Alcoholic Fatty Liver Disease (NAFLD): A
Systematic Review
Authors: Castillo María Fernanda , Salgado-Canales Daniela , Arrese Marco , Barrera Francisco , Mikhailidis Dimitri P
Published: February 2024

Background::

The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is
lifestyle modification; this should accompany any pharmacological intervention. Intermittent fasting
(IF) has shown benefits over metabolic and cardiovascular parameters. Non-religious IF includes
Time-Restricted Feeding (TRF), Alternate-Day Fasting (ADF), and 5:2 IF interventions.

Objective::

To evaluate the effects of IF on anthropometric, liver damage, and lipid profile markers in
subjects with NAFLD.

Methods::

A bibliographic search was carried out according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed and Scopus databases.

Results::

Five studies involving 470 patients with NAFLD were included. In relation to anthropometric
markers, all the articles reported body weight reduction (2.48-7.63%), but only ADF and 5:2 IF
reported a body weight reduction >5%; also, all the articles reported fat mass reduction. Concerning
hepatic markers, all the articles reported a reduction in hepatic steatosis and alanine aminotransferase
activity, but no changes in fat-free mass and high-density lipoprotein cholesterol levels. There were
variable results on fibrosis, other liver enzymes, waist circumference and body mass index, as well as
the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol.

Conclusion::

Any form of IF could be potentially beneficial for NAFLD treatment and some associated
cardiometabolic parameters. However, it is necessary to evaluate the effects and safety of IF in
long-term studies involving a higher number of participants with different stages of NAFLD. The
effect of IF on NAFLD-associated vascular risk also needs evaluation.
Dynamic Linkages among HIV/AIDS, Health Expenditures, Environmental
Degradation, Life Expectancy, and Economic Growth: A Case of Eastern
Africa Countries
Authors: Govdeli Tuncer
Published: February 2024

Background:

Eastern African countries are among the countries with a very high
HIV/AIDS prevalence rate. High HIV/AIDS prevalence is a problem that has a detrimental effect
on the economic development of these countries. Previous studies have generally examined the
relationship of HIV/AIDS with life expectancy or economic growth. In this study, three different
models have been established and the relationship of HIV/AIDS with economic growth, health
expenditures, and life expectancy has been analyzed, and current econometric methods and policy
recommendations have been developed according to the results.

Objective:

The aim of this study was to investigate the relationship between health expenditure,
environmental degradation, life expectancy, HIV/AIDS, and economic growth.

Method:

Annual data from 9 Eastern African countries for the period of 2000-2019 were used.
Panel ARDL/PMG and Dumitrescu-Hurlin methods were used.

Results:

HIV/AIDS negatively affects economic growth and life expectancy, and positively affects
health expenditures. According to the causality results, HIV/AIDS is the cause of economic growth.
In addition, a bidirectional causal relationship has been found between HIV/AIDS and life expectancy.

Conclusion:

The main conclusion of the study is that HIV/AIDS plays a negative role in economic
growth and life expectancy. Further steps must be taken to prevent the further spread of HIV/AIDS,
which causes these factors to affect the well-being of the countries.
Human Immunodeficiency Virus-1 Drug Resistance Mutations in Iranian
Treatment-experienced Individuals
Authors: Bokharaei-Salim Farah , Khanaliha Khadijeh , Monavari Seyed Hamidreza , Kiani Seyed Jalal , Tavakoli Ahmad , jafari Ensieh , Chavoshpour Sara , Razizadeh Mohammad Hossein , Kalantari Saeed
Published: February 2024

Background:

Human immunodeficiency virus-1 infection still remains a global health
threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence
of drug-resistance mutations and treatment failure in HIV-infected patients persist.

Objective:

In this study, we investigated the development of drug resistance in HIV-1-infected individuals
receiving antiretroviral therapy for 6-10 years.

Methods:

In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received
antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1
viral load and drug-resistance mutations were assessed using molecular techniques.

Results:

The demographic and epidemiological characteristics of the participants were also analyzed:
Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which
indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between
viral load and CD4 count, as well as epidemiological factors, such as vertical transmission,
history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10
(83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed
against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse
transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment
were infected with CRF35_AD.

Conclusion:

Our study provides important insights into the characteristics and development of
drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran.
The findings underline the need for regular viral load monitoring, individualized treatment selection,
and targeted interventions to optimize treatment outcomes and prevent the further spread of
drug-resistant strains.
Feasibility of a Mobile Health Intervention for Providing a Continuum of
HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in
China
Authors: Zhu Zhihui , Lu Xiaoyan , Gao Pan , Wang Xiaodong , Hu Xuejiao , Xie Nianhua , Liu Cong , Zhao Yue , Zhao Yanqiu , Dai Zhen , Zhang Hongbo , Wang Jun , Sun Yehuan , Liu Tao , Sun Shufang , Yang Cui , Zaller Nickolas , Zhang Zhihua , Operario Don
Published: February 2024

Background:

Men who have sex with men (MSM) in China have a high risk for HIV
infection but experience suboptimal rates of HIV testing and service engagement due to various
social and structural barriers. We developed a mobile health (mHealth) intervention entitled
“WeTest-Plus” (WeTest+) as a user-centered “one-stop service” approach for delivering access to
comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention,
confirmatory testing, treatment, and care.

Objective:

The goal of the current study was to investigate the feasibility of WeTest+ to provide
continuous HIV services to high-risk MSM.

Methods:

Participants completed a 3-week pilot test of WeTest+ to examine acceptability, feasibility,
and recommendations for improvement. Participants completed a structured online questionnaire
and qualitative exit interviews facilitated by project staff. “Click-through” rates were assessed
to examine engagement with online content.

Results:

28 participants were included, and the average age was 27.6 years (standard deviation =
6.8). Almost all participants (96.4%) remained engaged with the WeTest+ program over a 3-week
observational period. The majority (92.9%) self-administered the HIV self-test and submitted
their test results through the online platform. Overall click-through rates were high (average
67.9%). Participants provided favorable comments about the quality and relevance of the
WeTest+ information content, the engaging style of information presentation, and the user-centered
features.

Conclusion:

This pilot assessment of WeTest+ supports the promise of this program for promoting
HIV self-testing and linkage to in-person services for MSM in China. Findings underscore the
utility of a user-centered approach to mHealth program design.
Mortality Risk Factors Among People Living with HIV Receiving
Second-line Antiretroviral Therapy in Rural China
Authors: Kang Qiujia , Pan Wanqi , Ma Yanmin , Wang Dongli , Jia Huangchao , Guo Huijun , Sang Feng , Xu Liran , Xu Qianlei , Jin Yantao
Published: February 2024

Background:

Second-line antiretroviral therapy (ART) was introduced in Henan
Province in 2009. The number of people living with human immunodeficiency virus (HIV) starting
this therapy is increasing.

Objective:

This study aimed to investigate the survival and factors affecting mortality among this
group.

Methods:

We conducted a retrospective cohort study of people living with HIV (PLHIV) who
switched to second-line ART between May 1, 2010, and May 1, 2016, using the Kaplan–Meier
method and Cox proportional hazards models.

Results:

We followed 3,331 PLHIV for 26,988 person-years, of whom 508 (15.3%) died. The
mortality rate was 1.88/100 person-years. After adjusting for confounding factors, we found being
a woman (hazard ratio (HR), 0.66; 95% confidence interval (CI) 0.55–0.79), > 50 years old (HR,
2.69; 95% CI, 2.03–3.56), single/widowed (HR, 1.26; 95% CI, 1.04–1.52), having > 6 years of education
(HR, 0.78; 95% CI, 0.65–0.94), Chinese medicine (HR, 0.75; 95% CI, 0.52–0.96), liver injury
(HR, 1.58; 95% CI, 1.19–2.10), and CD4+ T cell count <200 cells/μl (HR, 1.94; 95% CI,
1.47-2.55), or 200-350 cells/μl (HR, 1.37; 95% CI, 1.03–1.82) were associated with mortality
risk.

Conclusions:

We found lower mortality among PLHIV who switched to second-line ART than
most previous studies. The limitations of a retrospective cohort may, therefore, have biased the data,
and prospective studies are needed to confirm the results. Moreover, Chinese medicine combined
with second-line ART shows potential as a treatment for HIV.
A Brief Review on Recent Developments in Diels-alder Reactions
Authors: Chaudhary Manish , Shaik Shareef , Magan Muskan , Hudda Sharwan , Gupta Mukta , Singh Gurvinder , Wadhwa Pankaj
Published: February 2024

:

The [4+2] Diels-Alder cycloaddition has been widely used for the synthesis of six-member
scaffolds. In recent years, there have been significant developments in this area, including the
discovery and design of novel dienes and dienophiles with improved reactivity and selectivity.
These new building blocks can be used to develop diverse molecular structures with functional
group compatibility. Additionally, there is the use of catalytic systems and metal-mediated reactions
to enable asymmetric [4+2] cycloadditions, resulting in enantiomerically enriched products. Overall,
recent studies related to [4+2] Diels-Alder cycloaddition using numerous dienes, dienophiles,
and catalysts in different reaction conditions have significantly improved the efficiency, selectivity,
and versatility of the reaction, making it an increasingly important tool in the synthesis of complex
organic molecules as presented in this review. These advancements offer exciting possibilities for
the development of new methods and reagents for the construction of six-membered rings and the
synthesis of bioactive compounds.
Decoding the Mystery of Blood Cancer: Cause, Diagnosis, and Management
Authors: Sharma Raja , Kumar Satendra , Kaushik Niranjan , Singh Bahadur
Published: February 2024

:

Leukaemia, lymphoma, and myeloma are among the serious and frequently fatal conditions
that impact thousands of people each year. Genetics, environmental factors, and medical problems
can all affect the risk of developing blood cancer, however, the precise causes are still not entirely
known. Fatigue, unexpected weight loss, and frequent infections are examples of common
blood cancer symptoms. In the course of the diagnosis process, blood tests, imaging tests, and bone
marrow biopsies are frequently combined. Blood cancer therapies include chemotherapy, radiation
therapy, stem cell transplant, targeted therapy, and immunotherapy. Supportive care is also important
for managing symptoms and improving quality of life. Ongoing research is exploring new treatments
and therapies for blood cancer, as well as ways to improve supportive care and personalize treatment
plans. Blood cancer patients and their families have severe emotional and psychological effects that
must not be ignored. For improving outcomes and raising the general standard of living for people
affected by this condition, it is essential to address these needs.
Alterations of the Gut Microbiome and Metabolome Following: A Opportunity for Early Detection of Colorectal Cancer
Authors: Modarres Mehdi Pezeshgi , Habibi Mohammad Amin , Pashaei Mohammad Reza , Mohammadpour Yousef , Jazi Kimia , Ahmadpour Sajjad
Published: February 2024

:

Colorectal cancer (CRC) is a commonly diagnosed cancer responsible for numerous deaths
worldwide. In recent decades, technological advances implicated in considering the molecular pathways
underlying CRC pathogenesis. Several investigations have identified various mechanisms involved
in CRC and have paved the way for new therapeutics and early diagnosis. Gut microbiome
play a crucial role in intestinal inflammation and can be associated with colitis colorectal cancer. In
this review, we narrated the role of the microbiome population and their metabolome profile as a new
screening method for early detection of CRC.
No Correlation between Anti-drug Antibodies and Therapeutic Response
in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF
Blockers
Authors: Bouden Selma , Laadhar Lilia , Soua Jihene , Ben Messaoud Meriam , Rouached Leila , Ayadi Imene , Saidane Olfa , Ben Tekaya Aicha , Mahmoud Ines , Rekik Sonia , Sahli Srairi Héla , Tekaya Rawdha , Bellakhal Syrine , Fekih Monia , Abdelmoula Leila , Kallel Maryem
Published: February 2024

Introduction::

Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab
(IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases
such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However,
about 30% of patients do not respond to these treatments. This lack of response may be due to the
formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study
was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration
of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response.

Methods::

A cross sectional, multi-centric study was conducted, including patients with RA, SpA
or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels
were measured by an Enzyme Linked Immunosorbent assay (ELISA).

Results::

197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of
cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD.
The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA
(p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all
pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant
methotrexate significantly reduced immunogenicity.

Conclusion::

In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic
response in patients on TNF alpha antagonists. Other tracks more than immunogenicity
should be investigated to explain the loss of response to these biotherapies.
Mixed Connective Tissue Disease: The Two Cases Representing the Range
of this Illness
Authors: Parrey Ashaq Hussain , Koka Manzoor , Ismail Mohd
Published: February 2024

Introduction:

Mixed connective tissue disease (MCTD) is defined as a systemic rheumatic
disease characterized by the presence of high titer anti-U1 ribonucleoprotein (U1 RNP) antibodies
in combination with clinical features commonly seen in systemic lupus erythematosus
(SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA) and polymyositis (PM).

Case Presentation:

The annual incidence of MCTD is 1.9 per 100,000 adults. Any organ system
can be involved in MCTD however four clinical features that suggest the presence of MCTD
rather than another systemic rheumatic disease are Raynaud phenomenon with swollen hands or
puffy fingers, absence of severe kidney disease and central nervous system (CNS) disease at first
presentation generally, insidious onset of pulmonary hypertension and presence of autoantibodies
anti-U1 ribonucleoprotein (U1 RNP), especially antibodies to the 68 kD protein. MCTD, although
initially thought to be a disease with a benign course is not considered a valid argument at present.
This connective tissue disorder can present with life-threating organ involvement with rapid progression
of disease.

Conclusion:

We report two cases of MCTD, one with mild disease and another with life-threatening
illness, describing the range of severity at presentation of this disorder.
Severe Acro-osteolysis Mimicking Arthritis Mutilans in a Patient with
Primary Hyperparathyroidism: A Case Report
Authors: Sapundzhieva Tanya , Sapundzhiev Lyubomir , Klinkanov Kamen , Mitev Martin , Batalov Anastas
Published: February 2024

Background:

Primary hyperparathyroidism (PHPT) should be considered in the differential
diagnosis of a patient with suspected secondary osteoporosis, and severe osteoporosis with
multiple fractures is frequently the first clinical manifestation of the disease.

Case Presentation:

Mutilating arthritis (arthritis mutilans) can be part of the clinical presentation
of a number of rheumatic diseases, most commonly seen in psoriatic arthritis, rheumatoid arthritis,
and juvenile idiopathic arthritis, but also in systemic lupus, systemic sclerosis, and multicentric
reticulohistiocytosis. Evidence exists that subperiosteal and subchondral bone resorption, seen in
PHPT, could induce the so-called ‘osteogenic synovitis’, which could eventually lead to the development
of a secondary osteoarthritis with bone deformities.

Conclusion:

Here, we present a case report of a patient initially diagnosed with PHPT who presented
with mutilating arthritis of the finger joints and discuss whether the severe acro-osteolysis
is a manifestation of the endocrinopathy or whether there is a co-existing undiagnosed inflammatory
joint disease.
Reaction Time in Fibromyalgia Patients
Authors: Puri Basant K. , Lee Gary S. , Schwarzbach Armin
Published: February 2024

Background::

Fibromyalgia has unknown aetiology and is associated with reduced information processing speed and therefore prolonged reaction time. However, the processes underlying this are unknown.

Objectives::

First, to compare the reaction time in a cohort of fibromyalgia patients and a matched group of normal controls. Second, to assess whether detailed symptoms of pain and autonomic function, as well as measures of tinnitus, fatigue, daytime sleepiness and Mycoplasma pneumoniae infection are predictors of reaction time in fibromyalgia.

Methods::

The between-groups mean serial five-choice reaction time difference was assessed in a cohort of fibromyalgia patients and in a matched group of normal controls in an analytical casecontrolled study. With the mean serial five-choice reaction time as the dependent variable for the fibromyalgia group, a mixed stepwise multiple linear regression was performed with inputs relating to pain, dysautonomia, tinnitus, fatigue, daytime sleepiness and Mycoplasma pneumoniae infection.

Results::

The mean (standard error) serial five-choice reaction time for the fibromyalgia group was 448.4 (23.0) ms, compared with 386.3 (8.3) ms for the control group (p = 0.007). The final multiple linear regression model (p < 0.001; adjusted R2 = 0.772) contained 13 predictors: eight sensory pain and three affective pain parameters, and Mycoplasma pneumoniae IgG and IgA assay results.

Conclusion::

Certain sensory and affective pain parameters, as well as Mycoplasma pneumoniae infection, appear to be predictors of reaction time in fibromyalgia. Further research into the pathophysiological mechanisms by which they affect information processing is warranted and may shed light on the aetiology of fibromyalgia.
Insight into the Epidemiology of the Adult-onset Systemic Autoimmune
Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients
Authors: Attia Doaa H.S. , Mohamed Eman R. , Ismaeel Ahmed Y. , Suliman Yossra A. , Moneim Nermeen H.A. , Abdel Noor Rasha A.
Published: February 2024

Background/Objective:

Although systemic autoimmune rheumatic diseases (SARDs)
seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity
of data compared with the developed countries. Furthermore, most of the studies addressed a
particular disease. This work aimed to shed light on the relative frequency and epidemiology of
the different adult-onset SARDs in Egypt.

Methods:

This is a retrospective hospital-based study including six university hospitals providing
free health care services: Cairo, Alexandria, Tanta, Suez Canal, Beni-Suef and Assiut University
Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient
departments between January 2000 and December 2021 were retrospectively reviewed. Data
about the patient’s diagnosis, gender, age at disease onset, year of disease onset and residence
were collected.

Results:

The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus
(SLE), Behçet’s disease (BD) and spondyloarthropathies (SPA) represented the main SARDs
in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect
females; males are mainly affected by axial SPA and BD. There is an increasing incidence of
SARDs during the study period.

Conclusion:

The study revealed the high burden of SARDs in Egypt, helping better allocation of
economic resources for the management of diseases of the highest prevalence and those affecting
the young reproductive age groups. Increased public and medical staff awareness about SARDs is
recommended to help early referral of patients to rheumatologists and, hence, better estimation of
their epidemiology.
Management of Pulmonary Hypertension during Pregnancy
Authors: Matusov Yuri , Khan Adnan , Levian Candace , Ozimek John , Tapson Victor F.
Published: February 2024

:

Pregnancy in patients with pulmonary arterial hypertension (PAH) is a high-risk condition
associated with high morbidity and mortality. Patients with severe PAH are often advised
against pregnancy. Still, those patients who pursue pregnancy require a dedicated and multidisciplinary
approach since the progression of fetal growth will accompany significant hemodynamic
changes, which can be challenging for patients with a poorly functioning right ventricle. In this article,
we describe the approach to the unique cardiovascular, respiratory, hematologic, and social
challenges that pregnant patients with PAH face throughout pregnancy. We discuss the impact of
these physiologic changes on diagnostic studies commonly used in PAH and how to incorporate
diagnostic data in making the diagnosis and risk stratifying pregnant patients with PAH. The pharmacologic
challenges of pulmonary vasodilators in pregnancy are discussed as well. Pregnant patients
with PAH are at particularly high risk of mortality around the time of delivery, and we discuss
the multidisciplinary approach to the management of these patients, including the use of anesthesia,
inotropic support, type of delivery, and postpartum care, providing clinicians with a practical
approach to the management of this difficult condition.
Comparative Effectiveness of Oral Hypoglycemic Agents for Glycemic Control and Glycemic Variability in Patients with Type 2 Diabetes Mellitus: Using Flash Glucose Monitoring
Authors: Venkatachalapathy Poongothai , Mohandoss Karthik Kumar Dos Alagarswamy , Munisamy Murali , Sellappan Mohan
Published: February 2024

Aim:

The study aimed to compare the effectiveness of oral hypoglycemic agents
(OHAs) as monotherapy, dual and quadruple therapy for glycemic control (GC) and glycemic
variability (GV) in patients with type-2 diabetes (T2DM) using flash glucose monitoring system
(FGM).

Background:

Diabetes management largely relies on HbA1c monitoring. Glycemic variability
(GV) has been an evolving glycemic target for preventing complications related to type 2 diabetes
mellitus (T2DM).

Objective:

The purpose of the study was to compare glycemic control (GC) measures and glycemic
variability (GV) measures among study groups and to study the relationships between
GC and GV indices.

Methods:

Retrospectively, FGM data were collected from 50 T2DM patients. The patients were
classified based on prescribed number of OHAs as monotherapy [group 1: dipeptidyl peptidase-
4 (DPP-4) inhibitors (n=10), group 2: sodium-glucose co-transporter-2 (SGLT2) inhibitors
(n=10), group 3: sulphonylureas (n=10), group 4: dual therapy (n=10), and group 5: quadruple
therapy (n=10)]. Measures of GC and GV were evaluated.

Results:

Significant differences between study groups were observed in GC and GV measurements.
The SGLT2 inhibitors monotherapy group demonstrated optimal GC [eA1c (%): 6.5 ±
2.2; MBG: 140.80 ± 63.94; TIR: 60.60 ± 19.96] and GV (SD: 42.38 ± 34.57; CV: 27.85 ± 6.68;
MAGE: 96.76 ± 52.47; MODD: 33.96 ± 22.91) in comparison to other study groups. On using
Pearson correlation analysis, mean blood glucose (MBG) and mean amplitude of glycemic excursion
(MAGE) showed moderate correlation (r = 0.742)(r2 = 0.551), depicting distinct glucose
variabilities at the same mean blood glucose levels.

Conclusion:

The monotherapy group of SGLT2 inhibitors demonstrated glucose-lowering effects
with reduced glycemic variability. Hence, optimum glycemic control is associated with
decreased glycemic variability.
Therapeutic Interventions to Improve Static Balance in Type 2 Diabetes
Mellitus: A Systematic Review and Meta-Analysis
Authors: Marques Pedro Ana Cristina , Diógenes Campelo Bruna Larysse , Costa Souza Wellington , da Silva Sousa Fernanda Mello , da Rocha Rebeca Barbosa , Saura Cardoso Vinicius
Published: February 2024

Introduction:

Diabetes mellitus (DM) is a metabolic disorder characterized by an abnormal
increase in blood glucose levels resulting from insulin secretion and/or dysfunctional activity
that can lead to several serious complications in addition to decreased postural balance.

Objective:

This study aimed to identify and analyze the main interventions used to improve static
balance in patients with DM.

Methods:

For the selection of articles, a bibliographic search was performed using PubMed,
Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated
the effect of training on static balance in adults with type 2 DM were selected, and 34 studies
were included.

Results:

The search resulted in the identification of 2681 articles, and of these, 31 were eligible
for the study. The identified interventions were proprioceptive, aerobic, resistance training on
platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in
the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance
Scale score and balance index, and a reduction in the variables of postural sway.

Conclusion:

There are a variety of effective training methods for improving static balance, and
the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility
and/or financial cost.
Glycemic Control in Patients with Type 1 Diabetes: Comparison of Holidays
versus Schooldays
Authors: Al Hayek Ayman , Alwin Robert Asirvatham , Almonea Khuloud Ibrahim , Al Dawish Mohamed Abdulaziz
Published: February 2024

Background and Aims:

To examine the influence of school life in children and adolescents
with type 1 diabetes (T1D) by comparing the glycemic control and Ambulatory Glucose
Profile (AGP) between the holidays and schooldays.

Methods:

This is a retrospective study conducted on 147 patients with T1D (14-19 years) who
used an intermittently scanned Continuous Glucose Monitoring (isCGM) system to self-test their
glucose levels during the periods of school time and holiday time. A record was maintained of the
Continuous Glucose Monitoring (CGM) metrics i.e., Glucose Variability (GV) (%), mean Time in
Range (TIR), Time above Range (TAR), Time below Range (TBR), and average time period of
the hypoglycemic events during schooldays and the holidays.

Results:

The study revealed differences between the recorded values during the holidays and
schooldays, in % in target 70-180 mg/dL (38.2 vs 49.5; p = 0.039), mean glucose (194 vs 185; p =
0.048), frequency of low glucose events (9.2 vs 5.1; p = 0.036), mean duration of low glucose
levels (117 vs 65; p = 0.021), % TBR below 70 mg/dL (2.9 vs 1.45; p = 0.023), % TBR below 54
mg/dL (1.1 vs 0.51; p = 0.031), TAR 181-250 mg/dL (21.1 vs 16.5; p = 0.037) and TAR >250
mg/dL (8.9 vs 6.5; p=0.043). On comparing the HbA1c levels of the study population recorded
during the holidays (8.34%) with those recorded during the schooldays (8.13%), the HbA1c values
during the school days were observed to be lower; however, no significant changes were noted in
the HbA1c level between the holidays and schooldays. Concerning the FreeStyle Libre (FSL) scanning,
the frequency during the holidays (n=6.2) was significantly lower than during the schooldays
(n=9.5) (p=0.042).

Conclusion:

From the findings, it appears that children with T1D have good diabetes control during
schooldays rather than during the holidays. To improve their glucose control during the holidays,
these patients may also benefit from receiving greater attention and guidance.

result:

The study revealed crucial differences between the recorded values during the holidays and schooldays, in % in target 70-180 mg/dL (38.2 vs 49.5; p = 0.039), mean glucose (194 vs 185; p = 0.048), frequency of low glucose events (9.2 vs 5.1; p = 0.036), mean duration of low glucose levels (117 vs 65; p = 0.021),

conclusion:

From the findings, it appears that children with T1D have good diabetes control during schooldays rather than during the holidays. In order to improve their glucose control during the holidays, these patients may also benefit from receiving greater attention and guidance.
Progress in Cardiac Magnetic Resonance Feature Tracking for Evaluating
Myocardial Strain in Type-2 Diabetes Mellitus
Authors: Shen Li-Ting , Shi Rui , Yang Zhi-Gang , Gao Yue , Jiang Yi-Ning , Fang Han , Min Chen-Yan , Li Yuan
Published: February 2024

The global prevalence of type-2 diabetes mellitus (T2DM) has caused harm to human
health and economies. Cardiovascular disease is one main cause of T2DM mortality. Increased
prevalence of diabetes and associated heart failure (HF) is common in older populations, so accurately
evaluating heart-related injury and T2DM risk factors and conducting early intervention
are important. Quantitative cardiovascular system imaging assessments, including functional imaging
during cardiovascular disease treatment, are also important. The left-ventricular ejection
fraction (LVEF) has been traditionally used to monitor cardiac function; it is often preserved or
increased in early T2DM, but subclinical heart deformation and dysfunction can occur. Myocardial
strains are sensitive to global and regional heart dysfunction in subclinical T2DM. Cardiac
magnetic resonance feature-tracking technology (CMR-FT) can visualize and quantify strain and
identify subclinical myocardial injury for early management, especially with preserved LVEF.
Meanwhile, CMR-FT can be used to evaluate the multiple cardiac chambers involvement mediated
by T2DM and the coexistence of complications. This review discusses CMR-FT principles,
clinical applications, and research progress in the evaluation of myocardial strain in T2DM.