bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unspecified Pain, Chronic Pain and High-Impact Chronic Pain in Lesotho, Southern Africa: a Population-based Cross-sectional study
Authors: Firima Emmanuel , Gonzalez Lucia , Manthabiseng Molulela , Sematle Mamoronts’ane P. , Bane Matumaole , Khomolishoele Makhebe , Lee Tristan , Chammartin Frédérique , Gupta Ravi , McCrosky Stephen , Weisser Maja , Amstutz Alain , Labhardt Niklaus Daniel 
Published: January 2025

Abstract

Background. Pain and its associated disorders are among the most common causes of disability and contributors to healthcare costs globally. Pain is understudied in Africa and there are no data on high-impact chronic pain from this region. In a population-based survey in Lesotho, Southern Africa, we assessed the prevalence of unspecified pain, chronic pain and high-impact chronic pain, and their determinants.
Method. We conducted a household-based, cross-sectional survey among adults ≥18 years old in 120 randomly sampled villages across Butha Buthe and Mokhotlong districts in Lesotho. Unspecified pain, chronic pain, and high-impact chronic pain were defined as current or recurrent pain regardless of duration; pain on most days of the week lasting for 3 or more months; and chronic pain with restriction of routine activities, respectively.
Result. Among the 6039 adults included, the median age was 39 years (interquartile range: 27-58), 3153/6039 (52.2%) were female. Overall, 1194 (19.8%) had unspecified pain (95% confidence interval [CI]: 18.8 – 20.8); 909 (15.1%) had chronic pain (95% CI: 14.2 – 16.0); and 428 (7.1%) had high-impact chronic pain (95% CI: 6.5 – 7.8) corresponding to 47.1% among the participants with chronic pain. Higher age groups were associated with increasing odds of unspecified pain, chronic pain and high-impact chronic pain. Male participants were less likely to have unspecified pain (adjusted odds ratio [aOR], 0.68; 95% CI: 0.56 – 0.82; p < 0.001). There was no association between sex and chronic pain or high-impact chronic pain. Participants living in less wealthy households had higher odds of high-impact chronic pain. Furthermore, high-impact chronic pain was associated with hypertension (aOR, 1.47; 95% CI: 1.14 – 1.90; p = 0.003), diabetes mellitus (aOR, 1.86; 95% CI: 1.27 – 2.74; p = 0.002), moderate to high risk of depression (aOR, 4.93; 95% CI: 2.75 – 8.86; p < 0.001), and moderate to high risk of generalized anxiety disorder (aOR, 2.85; 95% CI: 1.18 – 6.92; p = 0.023).
Conclusion. Prevalence of chronic pain, including high impact chronic pain was high in this population-based survey in Lesotho. Its association with further non-communicable chronic conditions, such as hypertension and diabetes, supports the need for health systems to provide integrated chronic care, including the management of chronic pain.
Performance Enhancement of Trimetallic Nanoparticles in Photocatalysis through Chemical Etching
Authors: Cheng Yu-Chun , Dou Yun-Qi , Deng Tian-Song 
Published: January 2025

Abstract

Trimetallic nanoparticles have shown significant potential as multifunctional nanomaterials due to their superior photocatalytic performance, making them highly promising in materials science and nanotechnology. In this study, we designed and synthesized a trimetallic nanostructure consisting of a gold nanorod (Au NR) core, a silver (Ag) intermediate shell, and a silver-platinum (AgPt) alloy outer layer. The Au@Ag core-shell structure was first prepared by depositing silver onto the Au NR surface through a reduction reaction. Subsequently, an AgPt alloy was deposited via a reduction and replacement process, followed by oxidative etching to remove excess silver, resulting in the etched trimetallic nanostructure (Au@AgPt-E). Using methylene blue (MB) as the model system, the photocatalytic activity of Au@AgPt-E under visible and near-infrared light irradiation was significantly enhanced, achieving a rate 4.19 times higher than Au@Ag@AgPt and 7.67 times higher than single-metal Au NRs. The performance enhancement is primarily attributed to the surface plasmon resonance (SPR) effect of the Au NR core, which efficiently absorbs light energy and converts it into heat, facilitating the generation and separation of charge carriers. Additionally, the etching process increases the catalytic active sites on the AgPt surface. This study provides a novel approach for developing efficient plasmon-mediated photocatalysts and demonstrates broad application prospects in photocatalytic reduction processes.
Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer
Authors: Kim Jin Su , Park Chan Hee , Lee Jinyoung , Kim Jeehoon , Kam Eun Hee , Nam Sanghee , Lee Hee Seung , Park Jeong Youp , Leem Galam , Bang Seungmin 
Published: January 2025

Abstract

Background
Pancreatic cancer is a highly lethal malignancy with limited treatment response. Despite advancements in treatment, systemic chemotherapy remains the primary therapeutic approach for over 80% of patients, with no established biomarkers to guide drug selection. Traditional two-dimensional (2D) culture models fail to replicate the tumor microenvironment, necessitating the development of more advanced models, such as three-dimensional (3D) organoid models.
Methods
We established 3D organoid cultures using patient-derived conditionally reprogrammed cell (CRC) lines, originally cultured under 2D conditions. These CRC organoids were developed using a Matrigel-based platform without organoid-specific medium components to preserve the intrinsic molecular subtypes of the cells. Morphological, molecular, and drug sensitivity analyses were performed to compare the clinical responses of 3D CRC organoids with those of their 2D counterparts and clinical responses.
Results
The 3D CRC organoids retained the molecular characteristics and mutational profiles of the original CRCs and displayed distinct morphologies corresponding to cancer stages and differentiation. Drug response profiling of gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX demonstrated that the 3D organoids more accurately mirrored patient clinical responses than the 2D cultures. Notably, the IC50 values for the 3D organoids were higher, reflecting the structural complexity and drug penetration barriers observed in vivo.
Conclusion
Matrigel-based 3D organoid culture models provide a robust platform for pre-clinical drug evaluation, overcoming the limitations of 2D models. Although time- and resource-intensive, integrating both 2D and 3D platforms enables efficient initial screening and validation. This approach holds promise for identifying predictive biomarkers and advancing precision medicine in pancreatic cancer treatment.
Plane based optimization method: A method for better global minimum cost function localization.
Authors: Bermudez Dalton H 
Published: January 2025

Abstract

Background As a popular optimization algorithm, gradient descent is more prone to converge at a local minimum rather than a global one since it is highly dependent on how initial values are instantiated and an iterative process of updates, reducing its efficiency for non-convex cost functions. This limitation is of utmost importance in domains such as medical physics, where there exist many treatment parameters that need to be optimized.Purpose We introduce the flat plane with maximum perpendicular distance method, a new optimization algorithm which identifies global minima robustly and efficiently in convex cost functions. This facilitates an initialization-free, non-iterative update method that serves as a complementary approach to classic methods.Methods 1D and 2D convex cost functions, with both global and relative minima, were tested using the flat plane method. Further, the approach was employed to determine optimal locations for radiation beams in a medical physics problem. Results were compared to existing gradient descent methods for effectiveness assessment.Results The flat plane algorithm found the global minimum in all the scenarios considered while the use of gradient descent would have failed to do so in many cases due to initialization issues. However, due to a less direct but highly parallelizable strategy (i.e. flat plane method), these techniques are certainly scalable for high-dimensional problems with potentially higher expense (e.g. dimensionality reduction, sampling, parallel computing).Conclusion In low-dimensional problems, the flat plane method provides a strong alternative to gradient descent for the global optimization problem. We are yet to adapt the method for high-dimensional applications but will work in that direction to increase its applicability over more complex optimization problems.
Novel mutations in the RECQL4 gene affect its helicase functions, interactions with the BLM helicase and chemotherapeutics-induced cell death
Authors: Kaminska Bozena , Kaczmarczyk Agnieszka , Sokolowski Mikolaj , Wojnicki Kamil , Pabiś Marta , Wojtas Bartosz , Poleszak Katarzyna , Gielniewski Bartlomiej , Król Sylwia , Guille Matthew , Glatt Sebastian 
Published: January 2025

Abstract

RecQ family of DNA helicases play pivotal roles in DNA replication, repair and responses to DNA damage or replication stress. Several human RecQ helicases are defective in diseases associated with chromosomal instability, premature aging and cancer. We recently discovered novel mutations in the RECQL4 gene in glioblastoma (GBM), the most malignant brain tumour in adults. Transcriptomic profiles of GBMs with REQCL4 mutations resembled those in REQCL4 KO glioma cells. We employ structural modelling and biochemical approaches to elucidate impacts of novel mutations on RECQL4 helicase activities. We modelled the impact of mutations on the DNA helicase domain. Using recombinant RECQL4P532S and RECQL4R766Q proteins we demonstrate that P532S substitution reduces the RECQL4 ability to unwind DNA and disrupts DNA-coupled ATP-hydrolysis activity. WT and mutated RECQL4 were overexpressed in RECQL4 KO glioma cells to study interactions with BLM helicases, cell viability and specific responses to UVC- and chemotherapy-induced DNA damage/repair. Overexpression of RECQL4P532S or RECQL4R766Q variants affected DNA repair and responses to chemotherapeutics in glioma cells, and RECQL4R766Q disturbed interactions with the BLM helicase. Our results reveal deleterious consequences of novel RECQL4 mutations in GBMs. The newly identified RECQL4 mutations affect RECQL4 helicases and their interactions with BLM contributing to glioma progression.
Mitochondrial DNA Mutations as a Factor in the Heritability of Atherosclerosis and Other Diseases
Authors: Orekhov Alexander N. , Orekhov Nikolay A. , Sukhorukov Vasily N. , Khotina Victoria A. , Kovianova Tatiana I. , Sobenin Igor A. 
Published: January 2025

Abstract:
This review discusses the possibility of inheritance of some diseases through
mutations in mitochondrial DNA. These are examples of many mitochondrial diseases
that can be caused by mutations in mitochondrial DNA. Symptoms and severity can
vary widely depending on the specific mutation and affected tissues. An association between
certain mutations in the mitochondrial genome and cancer was reported. In other
studies of 2-4 generations in each family, we found that mitochondrial mutations associated
with atherosclerosis are inherited. This may at least partially explain the inheritance
of predisposition to atherosclerotic disease by maternal line. Furthermore, to prove the
important role of mitochondrial mutations in the development of atherosclerotic manifestations
at the cellular level, we developed a technique for editing the mitochondrial
genome. A recent article described how one of the pro-atherogenic mutations, namely
m.15059G>A, was eliminated from such monocyte-derived cells using the technique we
developed. Elimination of this mutation resulted in the restoration to normal levels of initially
defective mitophagy and impaired inflammatory response. These data strongly
suggest that mitochondrial mutations are closely associated with the development of
atherosclerotic lesions. Considering that they are inherited, it can be assumed that, at
least partly, the genetic predisposition to atherosclerotic diseases is transmitted from
mother to offspring. Thus, despite the small size of mitochondrial DNA, its mutations
may play a role in the pathogenesis of diseases. Further study of their role will make it
possible to consider mitochondrial mutations as promising diagnostic markers and disorders
caused by mutations as pharmacological targets.
Experimental Research Progress of mPGES-1 Inhibitor 2,5-Dimethylcelecoxib in Various Diseases
Authors: Chen Zhanfei , Chen Rong , Wang Laiping , Yu Zihao , Chen Weitong , Lin Hua , Yu Liumin , Li Jinqiu , Chen Zhonghui , Shen Jianlin , Tang Nanhong 
Published: January 2025

Abstract:
Prostaglandin E2 (PGE2) plays a crucial role in inflammation. Non-steroidal
anti-inflammatory medications are commonly utilized to alleviate pain and address inflammation
by blocking the production of PGE2 and cyclooxygenase (COX). However,
selective inhibition of COX can easily lead to a series of risks for cardiovascular diseases.
Hence, it is imperative to discover safer and more efficient targets for reducing inflammation.
Research has demonstrated that mPGES-1 serves as the final enzyme that
controls the rate of prostaglandin E2 synthesis. Moreover, it is only triggered by inflammation
and could serve as a possible treatment target instead of COX in cases of inflammation.
2,5-dimethylcelecoxib (DMC) can effectively inhibit mPGES-1 expression,
maintain the overall balance of prostaglandins, reduce the secretion of PGE2, and, most
importantly, avoid the side effects of COX inhibitors. DMC has the ability to address illnesses
through the stimulation of autophagy and apoptosis, as well as the regulation of
the immune microenvironment and intestinal flora. This study provides a comprehensive
overview of the advancements in DMC within experimental research and offers suggestions
for potential avenues of future investigation.
Cordycepin and Its Structural Derivatives Effectively Suppress the High Expression of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase in Breast Carcinomas: A Computational Drug Development Approach
Authors: Bibi Shabana , Biswas Partha , Tareq Md. Mohaimenul Islam , Imtiaz Md. , Shovon Md. Hasan Jafre , Hossain Md Ridoy , Ahmed Nasim , Albekairi Norah A. , Alshammari Abdulrahman , Hasan Md. Nazmul 
Published: January 2025

Background:
Breast cancer is a frequently diagnosed malignant disease and the primary
cause of mortality among women with cancer worldwide. The therapy options are influenced by the
molecular subtype due to the intricate nature of the condition, which consists of various subtypes.
By focusing on the activation of receptors, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase
can be utilized as an effective drug target for therapeutic purposes of breast cancer.

Objectives:
The objective of this study is to compare the underlying pharmacological properties of
several modified agents to the parental Cordycepin to target and inhibit the EGFR tyrosine kinase
high expression, and to discover the inhibitor with the highest affinity for this drug target to treat the
breast cancer patients.

Methods:
The Maestro Application of Schrödinger Suite Paid Software was initially employed for
conducting extra precision (XP) structure-based virtual screening to evaluate the binding affinity of
the Cordycepin and its 500 structural derivatives with the EGFR tyrosine kinase protein structure. In
addition, the anti-breast cancer activity of the chosen compounds was assessed by looking at their
drug-likeness and ADMET characteristics using Lipinski's rule of five along with Quantitative structure-
activity relationship (QSAR) validation, the prediction of cell line anti-cancer, as well as anti-
breast cancer activity of top docked scored compounds. Subsequently, the Desmond paid software-
based molecular dynamics simulations (MDS) were conducted for a duration of 100 nanoseconds
on the promising candidates followed by the binding free energy estimation was performed
utilizing MM-GBSA analysis. To determine the stability of the protein-ligand complex, root-meansquare
deviation (RMSD), root-mean-square fluctuation (RMSF), protein-ligand interactions, and
other necessary parameters were evaluated from the 100 ns MDS Trajectory.

Results:
Based on the overall analysis of our study, N (6)-octylamine adenosine (CID-194932) reported
the optimum inhibitory potential against the EGFR tyrosine kinase protein, followed by
Adenosine 5-monophosphate (CID-83862) and Cordycepin (CID-6303), which compared favorably
to the control drug Vandetanib (CID-3081361).

Conclusion:
Consequently, these derivative compounds Cordycepin have the potential
to be utilized as lead molecules in the development of highly effective and potent EGFR
tyrosine kinase inhibitors for the treatment of breast cancer patients.
Theoretical Modeling of the Interactions of CoFe2O4-BaTiO3 Magnetoelectric Nanoparticles with Cancer and Healthy Cells
Authors: Sevim Gençay , Değer Gizem , Büyükköroğlu Gülay 
Published: January 2025

Introduction:
The effectiveness of pharmaceutical treatment methods is vital
in cancer treatment. In this context, various targeted drug delivery systems are being developed
to minimize or eliminate existing deficiencies and harms. This study aimed to
model the interaction of MEN-based drug-targeting systems with cancer cells and determine
the properties of interacting MENs.

Methods:
Magnetoelectric Nanostructures (MENs) have both targeting and nano-electroporation
effects due to their ferroic properties. Among these structures, the most used
nanoparticles as targeting mechanisms are CoFe2O4-BaTiO3 structures. For this purpose,
the electrical field produced by MENs was modeled using MATLAB R2023b, and a theoretical
data pool of appropriate physical properties was created. Testing and applying
other magnetoelectric materials defined in the literature may be costly and time-consuming.

Results:
The problems with MENs can be eliminated by performing theoretical simulations
of each material before proceeding with laboratory tests.

Conclusion:
By simulating the interaction of CoFe2O4-BaTiO3 MENs with cancer cells,
physical properties affecting drug targeting were theoretically identified and a data pool
of MENs with these properties was created.
Cinacalcet Improves Erythropoietin Resistance in Patients with Secondary Hyperparathyroidism Receiving Dialysis Treatment
Authors: Weng Wenjuan , Li Yingjuan , Lin Yongda , Wang Jiali , Chen Xiutian , Zhou Tianbiao 
Published: January 2025

Introduction:
Chronic Kidney Disease (CKD) is recognized as a major global public health problem.
Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in
patients with CKD. As patient survival increases, the treatment of complications becomes more important.
CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients
with CKD. Cinacalcet is a calcimimetic for the treatment of Secondary Hyperparathyroidism (SHPT) in adult
dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity
of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis
patients.

Method:
Forty-seven patients on dialysis with elevated parathyroid hormone were included. The selected patients
have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6
months.

Result:
During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid
hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly
erythropoietin dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).

Conclusion:
While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved
renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P
but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also
reduced ERI and improved renal anemia.
Betanin Mitigates Inflammation and Ankle Joint Damage by Subduing the MAPK/NF-κB Pathway in Arthritis Triggered by Type II Collagen in Rats
Authors: He Yongxiang , Hussain Shaik Althaf , Dai Wenjie 
Published: January 2025

Background:
Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune illness,
is characterized by synovitis, progressive joint damage, and bone erosion. Even though the
potent drugs available contain biologics, several patients fail to react to them or cause hostile effects.

Objectives:
Betanin (BTN), the betacyanin present in the red beetroot, has antioxidant, antiinflammatory,
and apoptotic properties. In this study, we assessed the anti-inflammatory and
apoptotic effect of BTN on collagen-induced arthritis (CIA).

Materials and Methods:
The rats were arbitrarily separated into four sets: Normal, CIA,
CIA+BTN (25 mg/kg bw), and CIA+BTN (50 mg/kg bw). The hematological, biochemical
markers, cytokines, inflammatory enzymes, histopathology of the ankle joint, and protein expression
of inflammatory and apoptotic proteins were studied.

Results:
Inflammatory enzymes, histopathological variations, cytokines generation, and joint inflammation
were strongly alleviated, and apoptosis was augmented by BTN in a concentrationdependent
manner. Bcl-2 and MAPK/NF-κB proteins were reduced, while the caspase-3, caspase-
9, and Bax were intensified. The anti-rheumatic action of BTN was correlated to the attenuation
of the MAPK/NF-κB pathway, which suppresses cytokine production, inflammation, and
reduced cartilage impairments.

Conclusion:
These outcomes recommend that BTN can be employed as a strong healing alternative
for RA management.
Effects of Inulin and Fructooligosaccharide on the Survival of Microencapsulated Probiotic Pediococcus pentosaceus GS4 in Alginate Beads Coated
with Chitosan in Simulated Gastrointestinal Fluid and at Different Storage Conditions
Authors: George Jeneesha , Ghosh Asit Ranjan 
Published: January 2025

Background:
Microencapsulated Pediococcus pentosaceus GS4 (MTCC 12683) with
prebiotics and chitosan coating can be used in food functional products, enhancing shelf life and
restoring probiotic properties.

Objective:
This study aimed to analyze the effects of inulin (I) fructooligosaccharide (FOS) and
chitosan coating in microencapsulation of probiotic strain P. pentosaceus GS4 survivability in simulated
gastrointestinal (GI) conditions and at different storage conditions.

objective:
To analyse the effects of inulin (I) and fructooligosaccharide (FOS) and chitosan coating in microencapsulation of probiotic strain P. pentosaceus GS4 survivability in simulated gastrointestinal (GI) conditions and at different storage conditions.

Methods:
To enhance the stable viability of probiotic P. pentosaceus, GS4, inulin, and FOS were
separately combined into alginate (Alg) following chitosan (C) coating during the process of microencapsulation.
Encapsulation efficiency, morphological characterization, and cell survival of
different microbeads were evaluated before and after exposure to simulated GI conditions at different
storage conditions.

Results:
Alginate-inulin-FOS combined chitosan coated (Alg/I/FOS/C) microbeads showed higher
viability than other groups. Chitosan-coated beads had increased diameter (2.52- 2.71 mm) in
comparison to uncoated beads (1.98- 2.42 mm). On successive challenges through simulated GI
conditions, microencapsulated probiotics demonstrated higher viable cells than control cells
(P<0.05). At different storage conditions, stable cell viability occurred at -20°C> 4°C> room temperature.

Conclusion:
In conclusion, Alg/I/FOS/C beads stored at -20°C maintained stable probiotic viability
and are found to be suitable for food technological applications.