bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of kynurenines in migraine-related neuroimmune pathways
Authors: Körtési Tamás , Nagy-Grócz Gábor , Vécsei László 
Published: August 2024

AbstractMigraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of the trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by the immune system may play a role in migraine pathophysiology. Neuroinflammation is often associated with migraine attacks, with cytokines serving as crucial mediators in the process. Elevated levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed in the blood and cerebrospinal fluid of individuals experiencing migraine attacks. These cytokines have the capacity to sensitize pain pathways in the brain, thereby increasing sensitivity to pain stimuli. This phenomenon, known as central sensitization, is believed to contribute to the intensity and persistence of migraine pain. Kynurenines, endogenous mediators of glutamatergic mechanisms, can significantly influence the pathophysiology of primary headache disorders. The kynurenine system is collectively known as the kynurenine pathway (KP), which can act on multiple receptors, such as glutamate receptors, aryl hydrocarbon receptors (AhRs), G protein-coupled receptors 35 (GPR35), and α-7 nicotinic acetylcholine (α7 nACh) receptors. These receptors are also found on various cells of the immune system, so the role of the KP in the pathomechanism of primary headaches may also be mediated through them. In this review, our goal is to show a possible link between the receptors of the KP and immune system in the context of inflammation and migraine. Migraine research in recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as potential pathogenic factors and possible therapeutic approaches. These peptides share many similarities in their characteristics and roles. For instance, they exhibit potent vasodilation, occur in both the peripheral and central nervous systems, and play a role in transmitting nociception and neurogenic inflammation. The investigation of potential connections between the aforementioned neuropeptides and the kynurenine pathway could play a significant role in uncovering the pathomechanism of migraine and identifying new drug candidates.
Nanomaterial-based sensors for microbe detection: a review
Authors: Khan Muhammad Qamar , Khan Jahangir , Alvi Muhammad Abbas Haider , Nawaz Hifza , Fahad Muhammad , Umar Muhammad 
Published: August 2024

AbstractAirborne microorganisms pose a significant health threat, causing various illnesses. Traditional detection methods are often slow and complex. This review highlights the potential of nanomaterial-based biosensors, particularly colorimetric sensors, for rapid and on-site detection of airborne microbes. Colorimetric sensors offer real-time visual detection without complex instrumentation. We explore the integration of these sensors with Lab-on-a-Chip technology using PDMS microfluidics. This review also proposes a novel PDMS-based colorimetric biosensor for real-time detection of airborne microbes. The sensor utilizes a color change phenomenon easily observable with the naked eye, simplifying analysis and potentially enabling point-of-care applications.
Graphical Abstract
Rectus abdominis muscle flap in complex vesico-vaginal fistula repair: unique situation, uncommon option
Authors: Aravind T. K. , Yadav Siddharth , Singh Harshdeep 
Published: August 2024

Abstract
Background
Complex vesico-vaginal fistulae (VVF) pose unique surgical challenges and necessitate the use of interposition tissue to ensure surgical success. Herein, we describe a case of complex VVF with right uretero-vaginal fistula post radical surgery for locally advanced ovarian cancer and chemotherapy in which the rectus abdominis muscle flap was used as the interposition tissue, as the more routine used options such as omentum and peritoneum were removed in the prior radical surgery.

Case presentation
We describe a case report of a vesico-vaginal and right uretero-vaginal fistula in a 34-year-old female post ovarian cancer radical surgery managed surgically with the traditional transvesical technique of repair and ureteric reimplantation with a unique interposition with rectus abdominis muscle considering the absence of the more routine options.

Conclusion
Complex VVFs pose unique surgical challenges and necessitate the use of interposition tissue to ensure surgical success. The inferior pedicle based rectus abdominis muscle flap is an excellent interposition tissue for repairs via the transabdominal approach especially in scenarios where the more routine options are unavailable.
Few chemoreceptor genes in the ambrosia beetle Trypodendron lineatum may reflect its specialized ecology
Authors: Biswas Twinkle , Vogel Heiko , Biedermann Peter H. W. , Lehenberger Maximilian , Yuvaraj Jothi Kumar , Andersson Martin N. 
Published: August 2024

AbstractBackgroundChemoreception is crucial for insect fitness, underlying for instance food-, host-, and mate finding. Chemicals in the environment are detected by receptors from three divergent gene families: odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs). However, how the chemoreceptor gene families evolve in parallel with ecological specializations remains poorly understood, especially in the order Coleoptera. Hence, we sequenced the genome and annotated the chemoreceptor genes of the specialised ambrosia beetleTrypodendron lineatum(Coleoptera, Curculionidae, Scolytinae) and compared its chemoreceptor gene repertoires with those of other scolytines with different ecological adaptations, as well as a polyphagous cerambycid species.ResultsWe identified 67 ORs, 38 GRs, and 44 IRs inT. lineatum(‘Tlin’). Across gene families,T. lineatumhas fewer chemoreceptors compared to related scolytines, the coffee berry borerHypothenemus hampeiand the mountain pine beetleDendroctonus ponderosae, and clearly fewer receptors than the polyphagous cerambycidAnoplophora glabripennis. The comparatively low number of chemoreceptors is largely explained by the scarcity of large receptor lineage radiations, especially among the bitter taste GRs and the ‘divergent’ IRs, and the absence of alternatively spliced GR genes. Only one non-fructose sugar receptor was found, suggesting several sugar receptors have been lost. Also, we found no orthologue in the ‘GR215 clade’, which is widely conserved across Coleoptera. Two TlinORs are orthologous to ORs that are functionally conserved across curculionids, responding to 2-phenylethanol (2-PE) and green leaf volatiles (GLVs), respectively.ConclusionsTrypodendron lineatumreproduces inside the xylem of decaying conifers where it feeds on its obligate fungal mutualistPhialophoropsis ferruginea.Like previous studies, our results suggest that stenophagy correlates with small chemoreceptor numbers in wood-boring beetles; indeed, the few GRs may be due to its restricted fungal diet. The presence of TlinORs orthologous to those detecting 2-PE and GLVs in other species suggests these compounds are important forT. lineatum. Future functional studies should test this prediction, and chemoreceptor annotations should be conducted on additional ambrosia beetle species to investigate whether few chemoreceptors is a general trait in this specialized group of beetles.
Predicting incident radiographic knee osteoarthritis through quantitative meniscal lesion parameters: data from the osteoarthritis initiative
Authors: Bo Kaida , Xie Xiangpeng , Liu Xin , Ou Jianliang , Zhang Yuanyi , Wang Xu , Yang Shuo , Zhang Wei , Zhang Lelei , Chang Jun 
Published: August 2024

Abstract
Background
This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study.

Objectives
Quantitative measurements of meniscal parameters alteration could serve as predictors of OA’s occurrence and progression.

Methods and materials
A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis.

Results
Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56–49.73) mean ± (7.70–9.52) mm SD vs. (38.14–40.78) mean ± (5.51–7.05)mm SD; (58.61–68.95) mean ± (8.52–11.40) mm SD vs. (52.52–56.35) mean ± (6.53–7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA.

Conclusions
The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.
The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma
Authors: Zhou Liang , Le Kehao , Chen Qianming , Wang Huiming 
Published: August 2024

Abstract
Background
Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined.

Methods
57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR.

Results
This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK.

Conclusions
This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.
Effect of the use of remineralization agents before resin infiltration on the treatment of initial enamel lesions: an in-vitro study
Authors: Doğu Kaya Bengü , Manav Özen Aybike , Yılmaz Atalı Pınar , Sarıalioğlu Güngör Ayça , Dalkılıç Evrim , Alkan Elif , Tağtekin Dilek , Türkmen Cafer 
Published: August 2024

Abstract
Aim
This study aimed to evaluate the effect of the use of remineralization agents before the application of resin infiltration on the treatment of initial enamel lesions.

Materials and methods
Eighty buccal enamel samples were prepared from human molars, and artificial initial lesions were formed after 96 h of incubation with a demineralizing solution. The samples were randomly divided into 8 groups (n = 10) including a remineralizing agent (Tooth Mousse, Medical Mineral Gel, Remin Pro), resin infiltration (ICON), and a combined treatment of both. Remineralizing agents were applied in pH cycle for 7 days. Baseline, demineralization, and after-treatment fluorescence (FluoreCam and DIAGNOdent Pen), surface microhardness (HMV-2T), surface roughness (M300C), OCT (Maestro-2) and ultrasonic system (Novascope 4500) data were obtained for all groups. The sample surfaces were examined under SEM/EDX (SU3500) at x1000. Data were statistically analyzed using the Two-Way Robust ANOVA and Bonferroni tests (p < 0.05).

Results
There was no statistically significant difference between the groups for microhardness, roughness, OCT, DIAGNOdent Pen, ultrasound, and FluoreCam size/intensity values (p = 0.582; p = 0.963; p = 0.884; p = 0.923; p = 0.051; p = 0.268; p = 0.793 respectively). The effect of the treatment procedure showed a significant difference (p < 0.001), except for the roughness values (p = 0.984). The lowest Calcium (Ca) ratio (%atomic) was observed in the RI group in the EDX analysis.

Conclusion
Remineralizing agents and resin infiltration methods may be used in combination or alone in the treatment of initial enamel lesions. Combining remineralizing agents with resin infiltration does not alter the efficacy of the treatment.
Competencies required to make use of Information Science and Technology among Japanese medical students: a cross-sectional study
Authors: Ota Yuma , Asada Yoshikazu , Mieno Makiko , Matsuyama Yasushi 
Published: August 2024

Abstract
Background
Competency in the use of information science and technology (IST) is essential for medical students. This study identified learning objectives and competencies that correspond with low self-assessment related to use of IST and factors that improve such self-assessment among medical students.

Methods
A questionnaire was administered to sixth-year medical students across 82 medical schools in Japan between November 2022 and February 2023.

Results
Three learning objectives were identified as difficult for the students to achieve: (1) provide an overview of the regulations, laws, and guidelines related to IST in medicine; (2) discuss ethical issues, such as social disparities caused by the digital divide that may arise in the use of IST in medicine; and (3) understand IST related to medical care. Further, problem-based learning, engaging with IST beyond class, and learning approach impacted the students’ acquisition of competencies related to IST. Furthermore, it was recognized that the competencies required by medical students may change over the course of an updated medical school curriculum.

Conclusions
It is important for medical students to recognize the significance of learning, establishing active learning methods, and gaining experience in practically applying these competencies.
Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy
Authors: Sheikh Khadija , Daniel Bruce L. , Roumeliotis Michael , Lee Junghoon , Hrinivich William T. , Benkert Thomas , Bhat Himanshu , Seethamraju Ravi T. , Viswanathan Akila N. , Schmidt Ehud J. 
Published: August 2024

Abstract
Purpose
To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).

Methods
Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction.

Results
FDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.

Conclusions
Results suggest that FDense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.
Network proteomics of the Lewy body dementia brain reveals presynaptic signatures distinct from Alzheimer’s disease
Authors: Shantaraman Anantharaman , Dammer Eric B. , Ugochukwu Obiadada , Duong Duc M. , Yin Luming , Carter E. Kathleen , Gearing Marla , Chen-Plotkin Alice , Lee Edward B. , Trojanowski John Q. , Bennett David A. , Lah James J. , Levey Allan I. , Seyfried Nicholas T. , Higginbotham Lenora 
Published: August 2024

AbstractLewy body dementia (LBD), a class of disorders comprising Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), features substantial clinical and pathological overlap with Alzheimer’s disease (AD). The identification of biomarkers unique to LBD pathophysiology could meaningfully advance its diagnosis, monitoring, and treatment. Using quantitative mass spectrometry (MS), we measured over 9,000 proteins across 138 dorsolateral prefrontal cortex (DLPFC) tissues from a University of Pennsylvania autopsy collection comprising control, Parkinson’s disease (PD), PDD, and DLB diagnoses. We then analyzed co-expression network protein alterations in those with LBD, validated these disease signatures in two independent LBD datasets, and compared these findings to those observed in network analyses of AD cases. The LBD network revealed numerous groups or “modules” of co-expressed proteins significantly altered in PDD and DLB, representing synaptic, metabolic, and inflammatory pathophysiology. A comparison of validated LBD signatures to those of AD identified distinct differences between the two diseases. Notably, synuclein-associated presynaptic modules were elevated in LBD but decreased in AD relative to controls. We also found that glial-associated matrisome signatures consistently elevated in AD were more variably altered in LBD, ultimately stratifying those LBD cases with low versus high burdens of concurrent beta-amyloid deposition. In conclusion, unbiased network proteomic analysis revealed diverse pathophysiological changes in the LBD frontal cortex distinct from alterations in AD. These results highlight the LBD brain network proteome as a promising source of biomarkers that could enhance clinical recognition and management.
Research progress of brain organoids in the field of diabetes
Authors: Su Ying , Liu Aimei , Chen Hongguang , Chen Qingjie , Zhao Bo , Gao Runze , Zhang Kangwei , Peng Tie , Zhang Zhenwang , Ouyang Changhan , Zhu Dan 
Published: August 2024

AbstractHuman embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.
Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma
Authors: Chen Hsien-Chung , Lin Hong-Yi , Chiang Yung-Hsiao , Yang Wen-Bin , Wang Chung-Han , Yang Pei-Yu , Hu Siou-Lian , Hsu Tsung-I 
Published: August 2024

Abstract
Introduction
Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity.

Methods
We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration.

Results
Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3−/CD19−/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells.

Conclusion
The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.