bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melittin - the main component of bee venom: a promising therapeutic agent for neuroprotection through keap1/Nrf2/HO-1 pathway activation
Authors: Nguyen Cong Duc , Yoo Jaehee , Jeong Sang Jun , Ha Hai-Anh , Yang Ji Hye , Lee Gihyun , Shin Jeong Cheol , Kim Jae-Hong 
Published: November 2024

AbstractThe Nuclear factor erythroid 2–related factor (Nrf2)/ Heme oxygenase-1 (HO-1) pathway, known for its significant role in regulating innate antioxidant defense mechanisms, is increasingly being recognized for its potential in neuroprotection studies. Derived from bee venom, melittin's neuroprotective effects have raised interest. This study confirmed that melittin specificity upregulated the weakened Nrf2/HO-1 signaling in mice brain. Interestingly, we also revealed melittin’s efficient tactic, as it was suggested to first restore redox balance and then gradually stabilized other regulations of the mouse hippocampus. Using a neuro-stress-induced scopolamine model, chromatography and mass spectrometry analysis revealed that melittin crossed the compromised blood–brain barrier and accumulated in the hippocampus, which provided the chance to interact directly to weakened neurons. A wide range of improvements of melittin action were observed from various tests from behavior Morris water maze, Y maze test to immune florescent staining, western blots. As we need to find out what is the focus of melittin action, we conducted a careful observation in mice which showed that: the first signs of changes, in the hippocampus, within 5 h after melittin administration were the restoration of the Nrf2/HO-1 system and suppression of oxidative stress. After this event, from 7 to 12.5 h after administration, a diversity of conditions was all ameliorated: inflammation, apoptosis, neurotrophic factors, cholinergic function, and tissue ATP level. This chain reaction underscores that melittin focus was on redox balance's role, which revived multiple neuronal functions. Evidence of enhancement in the mouse hippocampus led to further exploration with hippocampal cell line HT22 model. Immunofluorescence analysis showed melittin-induced Nrf2 translocation to the nucleus, which would initiating the translation of antioxidant genes like HO-1. Pathway inhibitors pinpointed melittin's direct influence on the Nrf2/HO-1 pathway. 3D docking models and pull-down assays suggested melittin's direct interaction with Keap1, the regulator of the Nrf2/HO-1 pathway. Overall, this study not only highlighted melittin specifically effect on Nrf2/HO-1, thus rebalancing cellular redox, and also showed that this is an effective multi-faceted therapeutic strategy against neurodegeneration.
The epidemic of human papillomavirus virus-related oropharyngeal cancer: current controversies and future questions
Authors: Chen Allen M. 
Published: November 2024

AbstractThe incidence of human papillomavirus (HPV) associated oropharyngeal cancer has increased to epidemic-like proportions in the United States and other industrialized nations. While significant progress has been made in the understanding of this disease with respect to its underlying biology and clinical behavior, numerous questions persist regarding treatment. It is now firmly established that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, the selection criteria and specific means for de-escalation remain uncertain, and paradigms continue to evolve. Given that HPV-positive oropharyngeal cancer is increasingly recognized as a public health problem, the search for answers to many of these provocative questions has important societal implications and is the subject of this review.
Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer
Authors: Mussa Ali , Ismail Nor Hayati , Hamid Mahasin , Al-Hatamleh Mohammad A. I. , Bragoli Anthony , Hajissa Khalid , Mokhtar Noor Fatmawati , Mohamud Rohimah , Uskoković Vuk , Hassan Rosline 
Published: November 2024

AbstractBreast cancer (BC) is the most frequently diagnosed malignancy among women. It is characterized by a high level of heterogeneity that emerges from the interaction of several cellular and soluble components in the tumor microenvironment (TME), such as cytokines, tumor cells and tumor-associated immune cells. Tumor necrosis factor (TNF) receptor 2 (TNFR2) appears to play a significant role in microenvironmental regulation, tumor progression, immune evasion, drug resistance, and metastasis of many types of cancer, including BC. However, the significance of TNFR2 in BC biology is not fully understood. This review provides an overview of TNFR2 biology, detailing its activation and its interactions with important signaling pathways in the TME (e.g., NF-κB, MAPK, and PI3K/Akt pathways). We discuss potential therapeutic strategies targeting TNFR2, with the aim of enhancing the antitumor immune response to BC. This review provides insights into role of TNFR2 as a major immune checkpoint for the future treatment of patients with BC.
IRF4 regulates myeloid-derived suppressor cells expansion and function in Schistosoma japonicum-infected mice
Authors: Zhou Lu , Lin Peibin , Deng Guorong , Mo Lengshan , Hong Cansheng , Jiang Zhihan , Zhu Yiqiang , Zhao Yi , Qi Yanwei , Hu Tengfei , Wu Qianlian , Zhang Jian , Li Qingqing , Yang Quan 
Published: November 2024

Abstract
Background
Interferon regulatory factor 4 (IRF4) is a crucial member of the IRF family of transcription factors and is pivotal in orchestrating the body’s defense against tumors and infections by modulating the differentiation and functionality of immune cells. The role of IRF4 in mice during Schistosoma japonicum infection, as well as the effects of IRF4 deficiency on myeloid-derived suppressor cells (MDSCs), remains inadequately understood.

Methods
Hematoxylin and eosin staining was used to evaluate the pathological damage in different organs of mice following infection with S. japonicum. Flow cytometry was employed to study the effect of IRF4 on the proliferation and function of myeloid-derived suppressor cells (MDSCs) in S. japonicum-infected mice.

Results
Knockout of IRF4 in myeloid cells significantly mitigated pathological damage to the liver and lungs in mice infected with S. japonicum. Knockout of IRF4 in myeloid cells also inhibited the expansion and functionality of MDSCs by downregulating programmed death ligand 2 (PD-L2) expression and interleukin-1 alpha (IL-1α) secretion in mice infected with S. japonicum. Mechanistic studies revealed that IRF4 deficiency inhibited the expansion and function of MDSCs and that this inhibition was mediated by the STAT3 and AKT signaling pathways. Also, IRF4 myeloid knockout promoted the expansion of T cells in S. japonicum-infected mice, but had no significant effect on B cell aggregation.

Conclusions
Overall, these findings highlight the importance of IRF4 in regulating MDSCs and their impact on tissue damage during S. japonicum infection, providing valuable insights into potential therapeutic targets for managing the pathological consequences of this parasitic infection.

Graphical Abstract
Heterogeneity in the formation of primary and secondary visual fields during human prenatal development
Authors: Godovalova Olga , Proshchina Alexandra , Kharlamova Anastasia , Barabanov Valeriy , Krivova Yuliya , Junemann Olga , Shahina Marina , Saveliev Sergey 
Published: November 2024

AbstractThe human neocortex has a huge surface area with unique cytoarchitectonics, most of which is concealed in sulci. Some cytoarchitectonic fields are associated with macroscopic landmarks. In particular, the primary visual field 17 is associated with the calcarine sulcus. During the prenatal development of the human brain, neocortical gyri and sulci undergo changes and modifications after primary formation. To explore the morphogenetic processes in visual fields during the formation of the primary (provisional) and secondary (permanent) sulci, the occipital lobe of the human fetal brain was studied using immunohistochemical methods. The distribution of various glial and neuronal markers (S-100, β-III-tubulin, NeuN, reelin) in the calcarine sulcus and parietooccipital sulcus was compared. The heterogeneity in the formation of primary and secondary visual fields was demonstrated. The study revealed that the development of the primary visual field 17, linked with the calcarine sulcus, preceded the development of a shared anlage of fields 18 and 19 linked with the parietooccipital sulcus. The functional differentiation of the primary visual field begins during the period of thalamic afferent ingrowth. This process coincides with the temporal smoothing of the calcarine sulcus, indicating a simultaneous progression of functional specialization and structural modifications. At the late fetal period, cortical plate of gyri and sulci banks showed higher NeuN-labeling than inside the sulcus in the same cytoarchitectonic field.
Which dietary patterns fend off nonalcoholic fatty liver disease? A systematic review of observational and interventional studies
Authors: Bakhshimoghaddam Farnush , Baez Daniel , Dolatkhah Neda , Sheikh Mahdi , Poustchi Hossein , Hekmatdoost Azita , Dawsey Stanford , Kamangar Farin , Abnet Christian , Malekzadeh Reza , Etemadi Arash , Hashemian Maryam 
Published: November 2024

Abstract
Background
The global burden of non-alcoholic fatty liver disease (NAFLD) has significantly risen over the past decade. Dietary intake strongly influences its development and should be a component of any prevention and treatment plan strategy. Dietary pattern analysis enables the investigation of the overall diet and permits the consideration of interactions and cumulative effects of dietary components. The current study aimed to systematically review observational studies and intervention trials to determine the associations between various dietary patterns and NAFLD.

Methods
The protocol was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, and the Cochrane Library. We included studies that reported a priori dietary pattern (i.e., diet quality scores) or a posteriori method, which identified existing eating patterns (i.e., principal component analysis) in adult participants. Two investigators conducted independent screening, extraction, and quality assessment using the Newcastle‒Ottawa or Jadad scale. A third reviewer resolved conflicts.

Results
We identified 27 relevant observational and 16 interventional studies from 16 countries. A Mediterranean or DASH diet might prevent and improve NAFLD, whereas dietary patterns such as Western dietary patterns characterized by high consumption of sweets and animal foods such as red meat and fast food are positively associated with NAFLD. A low-carbohydrate diet effectively prevents and treats NAFLD; however, we need more research on the effects of a low-fat diet and the type of fats.

Conclusion
Healthy dietary patterns, mainly plant-based or adjusted macronutrient distributions, such as the adoption of a low-carbohydrate diet, are linked to a reduced risk of NAFLD and could halt its progression. We proposed recommendations for future studies to fill the gap in knowledge regarding the management of NAFLD via dietary modifications.
Ground ants as indicators of biodiversity in cashew agroecosystems in Tanzania
Authors: Olotu Moses I. 
Published: November 2024

Abstract
Background
Ants are a diverse and ecologically important group of insects that play vital roles in terrestrial ecosystems globally. In agricultural settings, they act as effective biocontrol agents against insect pests. Ants also serve as bioindicators of environmental health, reflecting changes in habitat and pollution. However, research on their diversity and population dynamics in cashew agroecosystems remains limited.

Results
The sampling was conducted using a pitfall trap that targeted three sampling zones viz., under African weaver ants colonised (AWAC) cashew trees, AWA-uncolonised (AWAUC) ones, and buffer zones (BZ). A total of 14,004 ants from six subfamilies, 18 genera, and 32 species were sampled, with 7,686 sampled during season one and 630 sampled during season two. The study found significant differences in ant populations across sampled zones, which were significantly different in season one (F(2.107) = 5.4; P = 0.01) and season two (F(2.107) = 3.32; P = 0.04). However, more ants were sampled under AWAUC cashew trees compared to AWAC cashew trees and the BZ (F(2.74) = 4.46; P = 0.02) at Nyamato during season one. The Shannon–Wiener diversity index yielded comparable results to Margalef’s species richness index for all three zones, which differed significantly in both seasons at Nyamato and season one at Chambezi. A SIMPER analysis showed an overall dissimilarity of 94.5% at Soga due to the presence of invasive species (Pheidole megacephala and Anoplolepis custodiens) and AWA, which was consistently observed across all the experimental sites.

Conclusion
The variety and number of ant species in cashew agroecosystems are influenced by several factors, including the presence of dominant ant species and weeding practices. Promoting biodiversity in agricultural ecosystems is crucial for supporting beneficial insect populations and mitigating the risks posed by invasive ant species. Currently, there is no effective bait available for controlling these invasive ant species, indicating a need for further research to develop such bait. This would facilitate the foraging activities of other ant species, including beneficial ones.
Primary pleural small-cell carcinoma with paraneoplastic syndrome: a case series
Authors: Gupta Rahul Kumar , Pundir Sammi , Agrawal Vaibhav 
Published: November 2024

Abstract Small-cell lung carcinoma (SCLC) is a highly aggressive neuroendocrine tumour that usually presents as a centrally located mass or mediastinal lesion. It clinically manifests as a feature of airway obstruction or haemoptysis with paraneoplastic syndrome being common entity. Extrapulmonary origin and metastatic pleural involvement are rare. Primary pleural involvement without lung lesion is extremely rare in small-cell cancer. In this case series, we are describing clinical features with radiological findings and thoracoscopic appearance and histopathology of three cases diagnosed as small-cell lung cancer with primary pleural involvement and different paraneoplastic syndrome with their response to chemotherapy.
Targeting Metabolomics in Primary Hypertrophic Osteoarthropathy: Uncovering Novel Insights into Disease Pathogenesis
Authors: Pang Qianqian , Qi Xuan , Chi Yue , Jiajue Ruizhi , Zhang Li , Cui Lijia , Wang Ou , Li Mei , Xing Xiaoping , Jiang Yan , Gong Yiyi , Xia Weibo 
Published: November 2024

Abstract

Context
Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder characterized by skeletal and skin abnormalities. Genetic defects in prostaglandin E2 (PGE2) metabolism are known to cause PHO. However, the global impact and clinical significance of eicosanoids and oxylipins beyond PGE2 remain to be elucidated.

Objective
This study aimed to investigate oxylipin networks in PHO, including the 2 subtypes, PHOAR1 and PHOAR2, and examine their associations with clinical characteristics.

Methods
We conducted a targeted metabolomic study involving 16 patients with PHO and 16 age- and sex-matched healthy controls. Serum samples were collected at the time of diagnosis. Metabolites were quantified using ultra-high–performance liquid chromatography-tandem mass spectrometry.

Results
Laboratory analyses confirmed elevated levels of PGE2 in patients with PHO, consistent with the established pathogenesis. About 60 oxidized lipid metabolites were identified, with 19 differentially expressed in PHO. Besides the COX/PGE2 pathway, the lipoxygenase-mediated pathway was also involved in PHO. The metabolites 5-OxoETE, 15-OxoETE, 8S,15S-DiHETE, PGE2, 11β-PGE2, PGB2, LTB4, and LTE4 were significantly altered. Correlation analyses revealed associations between oxylipin metabolites and clinical features, including bone microarchitecture. Notably, the study highlighted differences in the oxylipin metabolite profiles between patients with PHOAR1 and patients with PHOAR2, suggesting distinct metabolic signatures for each subtype.

Conclusion
Our study indicated a significant perturbation in oxylipin metabolism among patients with PHO, with distinct metabolic signatures observed between PHOAR1 and PHOAR2. The disruption extended beyond the metabolism of PGE2. It encompassed a broader alteration across the polyunsaturated fatty acid metabolism spectrum, including various eicosanoids and oxylipins. Our work provided a comprehensive understanding of the pathogenesis of PHO, and underscored the potential for subtype-specific therapeutic interventions.
Torque–angle relationships of human toe flexor muscles highlight their capacity for propulsion in gait
Authors: Wisdish Samuel J. , Rice Hannah M. , Farris Dominic J. 
Published: November 2024

ABSTRACT
Human proficiency for bipedal locomotion relies on the structure and function of our feet, including the interplay between active muscles and passive structures acting on the toes during the propulsive phase of gait. However, our understanding of the relative contributions of these different structures remains incomplete. We aimed to determine the distinct toe-flexion torque–angle relationships of the plantar intrinsic muscles (PIMs), extrinsic muscles and passive structures, therefore offering insight into their force-generating capabilities and importance for walking and running. Torque–angle data were twice collected from nine healthy individuals (6 males, 3 females; 28±5 years) using supramaximal transcutaneous electrical stimuli applied at two tibial nerve sites to distinguish between muscle-driven and passive toe-flexion torque about the metatarsophalangeal (MTP) joint. Innervating extrinsic muscles and PIMs concurrently produced peak torques (hallux=3.05±0.70 N m, MTP angle=48.0±13.6 deg; lesser digits=3.19±0.98 N m, MTP angle=42.6±13.4 deg) exceeding by 208% (hallux) and 150% (lesser digits), respectively, those from PIM stimulation alone. Notably, MTP joint angles pertinent to gait corresponded to the ascending limb of the active torque–angle relationship, with active muscle joint torques being the dominant contributor over passive torques. The latter finding suggests that human toe flexors are well adapted to generate the MTP joint torques that are necessary for walking and running. This further supports the notion that muscles acting within the foot play an important role in the foot's mechanical function and our ability to walk and run in an upright posture.
Diastolic dysfunction evaluation by cardiovascular magnetic resonance derived E, a, e’: Comparison to echocardiography
Authors: Lamy Jérôme , Xiang Jie , Shah Nimish , Kwan Jennifer M. , Kim Yekaterina , Upadhyaya Krishna , Reinhardt Samuel W. , Meadows Judith , McNamara Robert L. , Baldassarre Lauren A. , Peters Dana C. 
Published: November 2024

AbstractTransthoracic echocardiography (TTE) is the first‐line and most useful imaging modality for evaluating diastolic dysfunction (DD). Cardiovascular magnetic resonance (CMR) has not been fully evaluated for this task. We investigated the utility of CMR for DD evaluation.Thirty‐one patients with a recent TTE (within 4 months) were prospectively enrolled, along with 12 healthy age‐matched subjects. CMR imaging was performed at 1.5 T to assess diastolic function by quantifying mitral inflow velocities (E and A), mitral annular velocities (e’), and left atrial volume (LAVi). Measurements by TTE and CMR were compared using regression. The diagnostic accuracy of CMR for DD was determined.CMR derived E, A, E/A, e’ and E/e’ all correlated moderately to strongly with TTE, and more strongly when comparing studies performed closer in time (E: r = 0.68, E deceleration time: r = 0.82, A: r = 0.78, e’ r = 0.75, E/e’: r = 0.80, p = 0.001; LAVi: r = 0.79, p < 0.001; E/A: r = 0.82, p < 0.001, n = 14 within 45 days). Using CMR criteria analogous to TTE, there was 82% (23/28) agreement regarding the presence of DD (95% CI [63 to 93%]), with 100% sensitivity and 75% specificity, and 71% (20/28) agreement in the absolute DD grade.CMR can evaluate diastolic function, with overall strong agreement to TTE.
Translingual practices for critical language awareness in English as an additional language writing education
Authors: Feng Huan , Sun Yachao 
Published: November 2024

Abstract
This study explores the impact of translingual practices on Critical Language Awareness (CLA) in English as an Additional Language (EAL) writing education within a non-English Medium Instruction (non-EMI) Chinese higher education context. A case study approach was employed to investigate five students’ EAL writing practices and language ideologies. Data collection included screen recordings of students’ writing processes, semi-structured interviews, and their written products. The findings revealed that translingual practices facilitated CLA development. Students adeptly meshed their home language and English, which reflected a complex interplay of linguistic identity and power dynamics in academic settings. The study found that translingual practices enabled students to challenge monolingual ideologies and develop a critical understanding of the socio-political implications of language use. The findings indicate that translingual practices can not only facilitate content learning but also promote a deeper engagement with social justice issues within EAL writing education. Hence, this study emphasizes the necessity for EAL writing education to embrace translingual practices, thereby enriching students’ CLA.
Study on hydrophobicity and aging characteristics of epoxy resin modified with nano-MgO
Authors: Zhou Lijun , Min Xiyao , Fu Anzhi , Chen Jihui , Chen Sixiang , Xia Yingyi , Zhao Chen , Wang Dongyang 
Published: November 2024

Abstract
The 10 kV switchgear is widely utilized in power systems due to its convenience and reliability. However, in high-humidity environments, switchgear is susceptible to condensation, which can severely damage its internal insulation components. To address this issue, this study modifies epoxy resin (EP) by incorporating nano-MgO to improve its hydrophobic properties. Initially, molecular dynamics simulations were conducted to determine the optimal doping ratio of nano-MgO by evaluating modified materials with varying concentrations. MgO/EP composites were then synthesized with nano-MgO doping levels of 1, 5, 10, and 15 wt%, and their hydrophobic and electrothermal properties were assessed. Following this, a thermal aging test was performed to evaluate the long-term performance of the composites. The findings demonstrate that the addition of nano-MgO enhances the hydrophobicity, thermal conductivity, and insulating properties of the EP. Specifically, as the concentration of nano-MgO increases, both the contact angle and thermal conductivity of the composites improve, while the volume resistivity first increases and then decreases with higher nano-MgO content. Nonetheless, all composites consistently outperform pure EP. Throughout each aging stage, the contact angle, thermal conductivity, and volume resistivity of the nano-MgO-modified EP remain superior to those of the unmodified EP.