bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity
Authors: Liu Binbin , Xie Yumo , Zhang Yu , Tang Guannan , Lin Jinxin , Yuan Ze , Liu Xiaoxia , Wang Xiaolin , Huang Meijin , Luo Yanxin , Yu Huichuan 
Published: January 2025

Abstract

Background
Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors.

Methods
Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity.

Results
In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs.

Conclusion
By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.
TC2N maintains stem cell-like characteristics to accelerate lung carcinogenesis by blockade of dual specificity protein phosphatase 3
Authors: Gu Jing , Lv Yang-fan , Xia Ji-ying , Bai Fu-hai , Gong Ji , Pan Guang-qiang , Liu Bo , Huang Lu , Guo Qiao-nan , Hao Xiang-lin 
Published: January 2025

Abstract

Background
Tandem C2 domains, nuclear (TC2N) is a protein that has been characterized to contain C2A domain, C2B domain, and a short C-terminus with a WHXL motif. In previous studies, we have uncovered the oncogenic role and mechanisms of TC2N in lung cancer: TC2N achieves this by inhibiting the p53 signaling pathway and activating the NF-kappaB signaling pathway. Beyond that, its precise function in tumorigenesis is not fully understood.

Methods
TC2N-engineered mice model was used to assess the effect of TC2N knockout on normal lung and urethane-induced carcinogenesis. Tumor tissues of 395 lung cancer patients were subjected to tissue microarray and further assessed the associations of TC2N expression with tumor differentiation degree. The protein levels of TC2N and stem cell markers in cell lines and tissue specimens were monitored by WB and immunohistochemistry. In vitro cell assays were performed to assess the effect of TC2N ectopic expression on the stem cell-like characteristics of lung cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics and proteomics, and the underlying mechanism was explored by WB and co-IP assays.

Results
Herein, TC2N appeared to have a strong effect in promoting lung tumorigenesis caused by urethane, whereas it seemed to lose its function in the normal lung. Meanwhile, we found that the functional differences of TC2N between lung tumor and normal lung were linked to its potential role in cancer cell stemness. Function-wise, TC2N overexpression maintained stem-like properties of lung cancer cell. Mechanism-wise, TC2N upregulated the phosphorylation of EGFR, ERK, STAT3 and FAK1 to activate these signaling pathways by the inhibition of DUSP3 phosphatase via a dual mechanism. Firstly, TC2N competes with EGFR, ERK, STAT3 and FAK1 for binding to DUSP3. This competition prevents these signaling molecules from being dephosphorylated by DUSP3, resulting in their sustained activation. Secondly, TC2N bind to DUSP3 and restrict the enzyme’s ability to dephosphorylate the signaling molecules.

Conclusions
Overall, this study revealed a previously unknown role and mechanism of TC2N in the regulation of tumorigenesis and stemness in lung cancer cells.
The resilience of parents and carers who administer medicines to children at home: a qualitative systematic review protocol
Authors: Morris Stephen , Pini Simon , Fylan Beth , Wilson Franki , Faulkner Helen , Alldred David P. 
Published: January 2025

Abstract

Background
Parents and carers are increasingly expected to administer prescribed medicines to their children at home. However, parents and carers are not always able to administer medicines as directed by the prescriber and ultimately must rely on their own judgment to administer medicines safely. This process is often unseen but may contain important learning for professionals, academics, and wider society. Studying safety in everyday healthcare work presents researchers with many challenges. However, recent developments in our understanding of resilience and how it manifests within healthcare can provide an effective framework for enquiry. The aim of this review is to use resilience theory to explore parents’ and carers’ experiences when administering medicines to children at home.

Methods
This systematic review will follow the framework synthesis method. An iterative search strategy, using a scoping search of the major databases (Embase, PyscINFO, CINAHL, Cochrane and PubMed) will be used. The three main search terms are parents and carers, administration of medicines, and the home environment. Included studies will contain qualitative data and investigate the experiences of parents or carers who administer prescribed medicines to children at home. Relevant studies will be quality assessed using the Joanna Briggs Institute critical appraisal checklist for qualitative research.
Framework synthesis will be completed by following five stages: familiarisation, thematic framework identification, indexing, charting, mapping, and interpretation. The findings identified in the data extraction phase will be indexed and charted according to the three elements of Moments of Resilience theory.

Discussion
This protocol describes a novel method to address an important patient safety issue. A strength of this review will be not only to identify, describe and collate existing studies, but also to learn about the application of resilience theory to a medication safety topic. The knowledge generated from this will inform intervention development to improve the support for families to administer medicines safely at home.

Systematic review registration
This review has been registered on the International Prospective Register of Systematic Reviews database (PROSPERO) #487154.
The Effect of Strength Training Targeting Medial Thigh Muscles on Neuromuscular and Biomechanical Risk Factors for Anterior Cruciate Ligament Injury: A Randomized Controlled Trial
Authors: Jeong Jiyoung , Choi Dai-Hyuk , Shin Choongsoo S. 
Published: January 2025

Abstract

Background
Knee valgus loading is thought to be an important contributor to noncontact anterior cruciate ligament (ACL) injuries, but the effects of training programs focusing on decreasing knee valgus loading on lower extremity biomechanics with respect to ACL injury risk remain unclear. Thus, this study aimed to examine the effect of strength training designed to strengthen the medial thigh muscles on lower extremity joint kinematics, kinetics and muscle activity during single-leg landing.

Methods
A total of 35 healthy participants randomly conducted either exercises targeting medial thigh muscles (intervention group) or exercises that did not target specific lower extremity muscles (control group). Three-dimensional hip, knee, and ankle kinematic/kinetic data and muscle activity for lower extremity muscles were obtained during single-leg landing. Two-way analyses of variance were conducted for each dependent variable to determine the effect of 8-week of strength training targeting medial thigh muscles.

Results
The intervention group showed decreased knee varus-valgus excursion (P = 0.009), peak valgus moment (P = 0.032), and peak hip internal rotation moment (P = 0.009) but increased gluteus medius activity in the precontact phase (P = 0.012) and vastus medialis-to-vastus lateralis (VM: VL) coactivation ratio in the postcontact phase (P = 0.043). The change in coronal plane knee excursion was negatively correlated with both the change in gluteus medius activity (R2 = 0.321, P = 0.014) and the change in VM: VL coactivation ratio (R2 = 0.276, P = 0.025).

Conclusions
Strength training targeting medial thigh muscles can modify the biomechanics associated with ACL injuries; thus, this intervention might be considered when designing ACL injury prevention programs to reduce dynamic knee valgus during sports-related tasks.
Cultural foundations of global health: a critical examination of universal child feeding recommendations
Authors: Scheidecker Gabriel , Funk Leberecht , Chaudhary Nandita , Chapin Bambi L. , Schmidt Wiebke J. , El Ouardani Christine 
Published: January 2025

Abstract
There has been a rising call to decolonize global health so that it more fully includes the concerns, knowledge, and research from people all over the world. This endeavor can only succeed, we argue, if we also recognize that much of established global health doctrine is rooted in Euro-American beliefs, values, and practice rather than being culturally neutral. This paper examines the cultural biases of child feeding recommendations as a case in point. We argue that the global promotion of Responsive Feeding—a set of allegedly best practices for child feeding promulgated by the WHO and others—is based on a tacit conviction that certain Western middle-class feeding practices are universally best, along with a promise that future evidence will demonstrate their superiority. These recommendations denounce feeding practices that diverge from this style as Non-Responsive Feeding, thereby pathologizing the many valued ways of feeding children in communities all over the world without sound scientific evidence. Drawing on ethnographic research, we show that there is a wide variety in feeding practices around the world and these are closely interlinked with the understandings and priorities of caregivers, as well as with favored forms of relationships and ways of maintaining them. For global health nutrition interventions to be justified and effective, they would need to be based on more pertinent, culturally responsive research than they currently are. We suggest the use of ethnographic research as an important tool in building empirically grounded, epistemically inclusive, and locally meaningful approaches to improving nutritional support for children in communities around the world and to global health efforts more broadly.
Updates on CAD risk assessment: using the coronary artery calcium score in combination with traditional risk factors
Authors: Rezaie-Kalamtari Kiara , Norouzi Zeinab , Salmanipour Alireza , Mehrali Hossein 
Published: January 2025

Abstract

Background
Coronary artery disease (CAD) is the third leading cause of death worldwide, so prevention and early diagnosis play important roles to reduce mortality and morbidity. Traditional risk-score assessments were used to find the at-risk patients in order to prevent or early treatment of CAD. Adding imaging data to traditional risk-score systems will able us to find these patients more confidently and reduce the probable mismanagements.

Main text
Measuring the vascular calcification by coronary artery calcium (CAC) score can prepare valuable data for this purpose. Using CAC became more popular in recent years. The most applicable method to evaluate CAC is Agatston scoring using computed tomography (CT) scanning. Patients are classified into several subgroups: no evidence of CAD (score 0), mild CAD (score 1–10), minimal CAD (score 11–100), moderate CAD (score 101–400), and severe CAD (score > 400) and higher than1000 as the extreme risk of CVD events.

Conclusions
CAC assessment was recommended in the patients older than 40 years old with CAD risk factors, the ones with stable angina, borderline-to-intermediate-risk group, etc. According to the results of the CAC the patients may be candidate for further evaluation for needing revascularization, medical treatment, or routine follow-up. Adding artificial intelligence (AI) to CAC will prepare more data and can increase the reliability of our approach to the patients promising a bright future to improve this technology.
High-Throughput Chemotherapeutic Drug Screening System for Gastric Cancer (Cure-GA)
Authors: Lee Jieun , Kim In Hee , Seol Donghyeok , Lee Sangjun , Yoo Mira , Lee Tae-Kyeong , Yoon So Hee , Lee Eunju , Hwang Duyeong , Kang So Hyun , Park Young Suk , Ku Bosung , Jeon Sang Youl , Choi Yongmun , Jung Keehoon , Kim Ji-Won , Kim Jin Won , Ahn Sang-Hoon , Lee Keun-Wook , Kim Hyung-Ho , Oh Hyeon Jeong , Lee Dong Woo , Suh Yun-Suhk 
Published: January 2025

Abstract

Background
Three dimensional (3D) cell cultures can be effectively used for drug discovery and development but there are still challenges in their general application to high-throughput screening. In this study, we developed a novel high-throughput chemotherapeutic 3D drug screening system for gastric cancer, named 'Cure-GA', to discover clinically applicable anticancer drugs and predict therapeutic responses.

Methods
Primary cancer cells were isolated from 143 fresh surgical specimens by enzymatic treatment. Cell-Matrigel mixtures were automatically printed onto the micropillar surface then stabilized in an optimal culture medium for 3 days to form tumoroids. These tumoroids were exposed in the drug-containing media for 7 days. Cell viability was measured by fluorescence imaging and adenosine triphosphate assays. On average, 0.31 ± 0.23 g of fresh tumor tissue yielded 4.05×106 ± 4.38×106 viable cells per sample.

Results
Drug response results were successfully acquired from 103 gastric cancer tissues (success rate = 72%) within 13 ± 2 days, averaging 6.4 ± 2.7 results per sample. Pearson correlation analysis showed viable cell numbers significantly impacted drug data acquisition (p < 0.00001). Tumoroids retained immunohistochemical characteristics, mutation signatures, and gene expression consistent with primary tumors. Drug reactivity data enabled prediction of synergistic drug correlations. Additionally, a multiparameter index-based prognosis model for patients undergoing gastrectomy followed by adjuvant XELOX was developed, showing significant differences in 1-year recurrence-free survival rates between drug responders and non-responders (p < 0.0001).

Conclusions
The Cure-GA platform enables rapid evaluation of chemotherapeutic responses using patient-derived tumoroids, providing clinicians with crucial insights for personalized treatment strategies and improving therapeutic outcomes.
Helicobacter pylori infection, clarithromycin-resistant genes and CYP2C19 gene polymorphisms in asymptomatic school-age children in Baigou New Town, Baoding City, Hebei Province
Authors: Zhang Jie , Yuan Weicheng , Xing Yutong , Ma Xinyu , Xuan Fan 
Published: January 2025

Objective: To investigate the prevalence of Helicobacter pylori (Hp) infection, clarithromycin (CAM)-resistant genes and CYP2C19 gene polymorphisms in asymptomatic school-age children in Baigou New Town, Baoding City, Hebei Province, China.
Methods: This retrospective study recruited 1,068 primary school students from Baigou New Town, Baoding City, Hebei Province, China, in November 2023 to screen for Hp infection and detect clarithromycin-resistant genes using stool samples. Additionally, blood samples were collected for CYP2C19 gene polymorphism analysis.
Results: The stool antigen test for Hp yielded a positive rate of 18.4% (197/1,068). Among the 197 Hp-positive patients, 36.5% were resistant to CAM. The polymorphism analysis revealed that, in the 23S rRNA V region, the overall mutation rate was 62.5% for the A2143G site, 77.7% for T2182C, 50% for A2143G and T2182C, 2.7% for A2142C and 1.3% for A2142G. Moreover, the analysis classified the study participants into three CYP2C19 phenotypes (i.e., extensive, intermediate and poor metabolisers; extensive metabolisers (EM), intermediate metabolisers (IM) and poor metabolisers (PM), respectively), and the prevalence was 45.6%, 44.6% and 9.6% for EM, IM and PM, respectively.
Conclusion: The local area showed a high CAM resistance, indicating that CAM is not preferred for Hp eradication. CYP2C19 gene polymorphism analysis revealed that the EM phenotype was highly prevalent. Therefore, a comprehensive analysis of CYP2C19 gene polymorphisms is recommended to identify ideal proton-pump inhibitors for Hp eradication.
doi: https://doi.org/10.12669/pjms.41.2.9838
How to cite this: Zhang J, Yuan W, Xing Y, Ma X, Xuan F. Helicobacter pylori infection, clarithromycin-resistant genes and CYP2C19 gene polymorphisms in asymptomatic school-age children in Baigou New Town, Baoding City, Hebei Province. Pak J Med Sci. 2025;41(2):484-487. doi: https://doi.org/10.12669/pjms.41.2.9838
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Water Birth – Benefits, Risks, and Controversies
Authors: Górny Julia , Kapciak Alicja , Naja Katarzyna , Zwardoń Jakub , Hawajski Artur , Jankowska Natalia , Kamieniecka Oliwia , Świerzyńska Adrianna , Mazur Weronika , Pawelec Natalia 
Published: January 2025

Introduction:
Water birth, involving immersion in water during childbirth, has gained popularity for its potential benefits, such as pain relief and comfort. While widely practiced in some countries, concerns regarding its safety, particularly for neonates, remain. This paper explores the maternal and fetal benefits and risks associated with water birth, as well as the epidemiological trends, medical protocols, and legal considerations.
Aim of Study:
The aim of this study is to evaluate the maternal and neonatal outcomes of water immersion and water birth, focusing on the safety, efficacy, and factors influencing its adoption in different populations.
Material and methods:
A comprehensive review of the literature on water birth including its benefits, risks and controversies was performed using the PubMed database.
Results and Conclusions:
Water immersion during labor is associated with significant maternal benefits, including reduced pain and anxiety, shorter labor, and fewer pharmacological interventions. Water birth, however, carries potential risks, such as neonatal respiratory complications and infections, although studies generally report no significant differences in neonatal outcomes compared to land birth. Epidemiological trends show higher water birth rates among women aged 30–39, while socioeconomic factors, such as deprivation, are linked to lower rates. Water birth has been shown to reduce the incidence of severe perineal tears and postpartum hemorrhage. While promising, the practice requires careful adherence to medical protocols to ensure safety, with further research needed to fully establish its long-term benefits and risks.
Multimodal Transportation Pricing Alliance Design: Large-Scale Optimization for Rapid Gains
Authors: Cummings Kayla , Vaze Vikrant , Ergun Özlem , Barnhart Cynthia 
Published: January 2025

Transit agencies have the opportunity to outsource certain services to established mobility-on-demand (MOD) providers. Such alliances can improve service quality, coverage, and ridership; reduce public sector costs and vehicular emissions; and integrate the passenger experience. To amplify the effectiveness of such alliances, we develop a fare-setting model that jointly optimizes fares and discounts across a multimodal network. We capture commuters’ travel decisions with a discrete choice model, resulting in a large-scale, mixed-integer, nonconvex optimization problem. To solve this challenging problem, we develop a two-stage decomposition with the pricing decisions in the first stage and a mixed-integer linear optimization of fare discounts and passengers’ travel decisions in the second stage. To solve the decomposition, we develop a new solution approach that combines customized coordinate descent, parsimonious second-stage evaluations, and interpolations using special ordered sets. This approach, enhanced by acceleration techniques based on slanted traversal, randomization, and warm-start, significantly outperforms algorithmic benchmarks. Different alliance priorities result in qualitatively different fare designs: flat fares decrease the total vehicle-miles traveled, whereas geographically informed discounts improve passenger happiness. The model responds appropriately to equity-oriented and passenger-centric priorities, improving system utilization and lowering prices for low-income and long-distance commuters. Our profit allocation mechanism improves the outcomes for both types of operators, thus incentivizing profit-oriented MOD operators to adopt transit priorities. Funding: This material is based on work supported by the National Science Foundation [Grants 1122374 and 1750587]. Supplemental Material: The online appendices are available at https://doi.org/10.1287/trsc.2023.0009 .
Determination of CO2 Sequestration into Bio-Concrete Bricks Pores using Fungi
Authors: Nikita Verma  , J. Satya Eswari  , Chinmaya Mahapatra  
Published: January 2025

The large amount of CO2 in the atmosphere cannot be sequestered by the technology now in use to reduce CO2 emissions. The progress of carbon dioxide (CO2) sequestration by its conversion into calcite was covered in the study, along with contemporary viewpoints on the subject. The process occurs in either geological or biological systems. Nevertheless, compared to bio-sequestration, geological sequestration is a more costly and slower process. Recently, research has investigated the use of microorganisms like bacteria and algae for the bio-sequestration of atmospheric CO2 into the soil. One potential future technique to lower high CO2 pollution is the inclusion of fungal species in the bio-concrete bricks and their ability to bio-sequester CO2. Fungal cells can capture CO2 by accelerating the carbonation processes, which convert carbon-dioxide into calcium carbonate (CaCO3) via carbon anhydrase and urease enzymes. It produces carbon anhydrases (CA) and urease enzymes to accelerate the sequestration process of CO2. The present paper aimed to highlight and discuss the applicability of fungi in the Bio-concrete for capturing and storing CO2. It is evident from the literature that the new trends to use bio-concrete might contribute to the reduction of CO2 by accelerating the carbonation process and strengthening the concrete.