bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract:
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.