bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exopeptidase combination enhances the degradation of isotopically labelled gluten immunogenic peptides in humans
Authors: Mourabit Sulayman , Römer Sarah , Bonner Erin R. , Winter Fabian , Tschollar Julian , Tzvetkov Mladen V. , Weitschies Werner , Engeli Stefan , Tschollar Werner 
Published: October 2024

IntroductionCeliac disease is a common autoimmune-like enteropathy caused by an aberrant response to incompletely digested dietary gluten. Gluten immunogenic peptides including the immunodominant 33-mer are thought to be resistant to proteolytic digestion by human gastrointestinal peptidases. We developed a novel enzyme therapy approach to support gluten peptide digestion using a combination of two tandem-acting exopeptidases, AMYNOPEP, that complement the intrinsic enzymatic activity of intestinal brush border enterocytes.MethodsWe evaluated the effects of AMYNOPEP supplementation on 33-mer degradation in vitro and in vivo. In a cross-over clinical study, healthy volunteers with no gastrointestinal disorders were given stable isotope (SI) labelled 33-mer peptides in the presence of varying peptide substrates and caloric loads, with and without AMYNOPEP. 33-mer degradation products (SI-labelled single amino acids) were measured in the blood plasma using LC-MS/MS.ResultsAMYNOPEP achieved rapid, complete amino-to-carboxyl terminal degradation of the 33-mer in vitro, generating single amino acids and dipeptides. In healthy volunteers, AMYNOPEP supplementation significantly increased 33-mer degradation and absorption of SI-labelled amino acids even in the presence of competing substrates. Specifically, we observed a 2.8-fold increase in the Cmax of stable isotope-labelled amino acids in the presence of wheat gluten. The absorption kinetics of labelled amino acids derived from 33-mer digestion with AMYNOPEP closely resembled that of SI-labelled X-Proline dipeptides administered without enzyme supplementation, highlighting the rapid hydrolytic activity of AMYNOPEP on polypeptides.ConclusionsAMYNOPEP achieved complete degradation of the 33-mer into single amino acids and dipeptides in vitro and significantly improved 33-mer degradation kinetics in healthy volunteers, as measured by labelled amino acid detection, warranting further investigation into the potential therapeutic benefits of exopeptidase combinations for patients with gluten-related health disorders including celiac disease.
Efficacy and safety of natural killer cell therapy in patients with solid tumors: a systematic review and meta-analysis
Authors: Park Heesook , Kim Gyurin , Kim Najin , Ha Sungyoen , Yim Hyeonwoo 
Published: October 2024

IntroductionIn 2020, global cancer statistics reported 19.3 million new cases and 10 million deaths annually, highlighting the urgent need for effective treatments. Current therapies, such as surgery, radiation, and chemotherapy, have limitations in comprehensively addressing solid tumor. Recent advances in cancer biology and immuno-oncology, including CAR-T cell therapy, show promise but face efficacy challenges against solid tumors.MethodsThis meta-analysis systematically reviewed studies from PubMed, Embase, Cochrane, and ClinicalTrials.gov databases up to May 2024 to evaluate the clinical efficacy and safety of unmodified NK cell therapies in solid tumors. The included trials focused on reporting objective response rates (ORR).ResultsThirty-one trials involving 600 patients across various cancers (e.g., NSCLC, HCC, breast, ovarian) were analyzed. NK cell therapies demonstrated promising ORRs, particularly 72.3% in hepatocellular carcinoma, often in combination with local therapies. Safety profiles were favorable, with fatigue being the most common adverse event.DiscussionNK cell therapies represent a promising treatment option for solid tumors, offering a viable alternative to genetically modified cell therapies like CAR-T. Further research is needed to optimize the clinical utility of NK cell therapy and integrate it effectively into standard cancer treatment regimens.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023438410, identifier CRD42023438410.
Fatty acid metabolism prognostic signature predicts tumor immune microenvironment and immunotherapy, and identifies tumorigenic role of MOGAT2 in lung adenocarcinoma
Authors: Fu Denggang , Zhang Biyu , Fan Wenyan , Zeng Fanfan , Feng Jueping , Wang Xin 
Published: October 2024

BackgroundAberrant fatty acid metabolism (FAM) plays a critical role in the tumorigenesis of human malignancies. However, studies on its impact in lung adenocarcinoma (LUAD) are limited.MethodsWe developed a prognostic signature comprising 10 FAM-related genes (GPR115, SOAT2, CDH17, MOGAT2, COL11A1, TCN1, LGR5, SLC34A2, RHOV, and DKK1) using data from LUAD patients in The Cancer Genome Atlas (TCGA). This signature was validated using six independent LUAD datasets from the Gene Expression Omnibus (GEO). Patients were classified into high- and low-risk groups, and overall survival (OS) was compared by Kaplan-Meier analysis. The signature’s independence as a prognostic indicator was assessed after adjusting for clinicopathological features. Receiver operating characteristic (ROC) analysis validated the signature. Tumor immune microenvironment (TIME) was analyzed using ESTIMATE and multiple deconvolution algorithms. Functional assays, including CCK8, cell cycle, apoptosis, transwell, and wound healing assays, were performed on MOGAT2-silenced H1299 cells using CRISPR/Cas9 technology.ResultsLow-risk group patients exhibited decreased OS. The signature was an independent prognostic indicator and demonstrated strong risk-stratification utility for disease relapse/progression. ROC analysis confirmed the signature’s validity across validation sets. TIME analysis revealed higher infiltration of CD8+ T cells, natural killers, and B cells, and lower tumor purity, stemness index, and tumor mutation burden (TMB) in low-risk patients. These patients also showed elevated T cell receptor richness and diversity, along with reduced immune cell senescence. High-risk patients exhibited enrichment in pathways related to resistance to immune checkpoint blockades, such as DNA repair, hypoxia, epithelial-mesenchymal transition, and the G2M checkpoint. LUAD patients receiving anti-PD-1 treatment had lower risk scores among responders compared to non-responders. MOGAT2 was expressed at higher levels in low-risk LUAD patients. Functional assays revealed that MOGAT2 knockdown in H1299 cells promoted proliferation and migration, induced G2 cell cycle arrest, and decreased apoptosis.ConclusionsThis FAM-related gene signature provides a valuable tool for prognostic stratification and monitoring of TIME and immunotherapy responses in LUAD. MOGAT2 is identified as a potential anti-tumor regulator, offering new insights into its role in LUAD pathogenesis.
The immunological and prognostic significance of the diabetes mellitus-related gene WFS1 in endometrial cancer
Authors: Li Wenzhe , Ke Da , Xu Yi , Wang Ya , Wang Qian , Tan Jie , Wu Hongyan , Cheng Xianglin 
Published: October 2024

BackgroundDiabetes is associated with the incidence and prognosis of various malignancies, most notably endometrial cancer (EC). This study investigated the connection between diabetes and EC, with a specific focus on elucidating the biological implications of the diabetes mellitus (DM)-related gene WFS1.MethodsUsing the CTD, GeneCards, and GSEA databases, we identified WFS1 as a diabetes-related gene and then conducted an extensive investigation focusing on WFS1 in the context of EC. First, we identified WFS1 as the target gene and obtained EC data from the TCGA database. Then, comprehensive analyses and verification experiments, including differential expression analysis, prognostic modeling, functional enrichment analysis, gene mutation profiling, assessment of immune cell infiltration, immunophenoscore (IPS), tumor stemness index scoring, drug sensitivity analysis, single-cell transcriptomic analysis, glycolytic pathway analysis, and clinical verification, were performed to comprehensively evaluate the clinical value of WFS1 in EC.ResultsThe EC group had significantly lower WFS1 expression, with an AUC of 0.857 for the ROC diagnostic curve. Overall survival analysis revealed that WFS1 was an independent risk factor for EC; low WFS1 expression was correlated with a poor prognosis. Stemness index analysis revealed that decreased WFS1 expression was associated with increased tumor grade and enhanced tumor stemness, suggesting increased malignancy of EC. In addition, WFS1 expression was correlated with tumor microenvironment features such as immune cell infiltration. WFS1 was also associated with tumor drug resistance.ConclusionEC patients with low WFS1 expression have a worse prognosis. WFS1 can be used as diagnostic and prognostic marker for EC.
Effects of varied inundation characteristics on early life stages of a salt marsh plant
Authors: Wang Qing , Luo Meng , Cui Baoshan , Chen Cong , Xie Tian , Li Xia , Lu Feng 
Published: October 2024

Tidal inundation is a major stress in salt marshes that regulates the patterns of plant distribution and the associated functions provided by vegetation communities. Usually, frequency is used to represent inundation intensity and can be estimated using elevation. However, frequency is only a statistical indicator of tidal inundation conditions during a given period, which ignores many details of tidal inundation characteristics based on a single tidal event. On the scale of a single tidal event, duration and water depth are important characteristics for describing inundation conditions, which vary along the elevation gradient. The frequency of tidal events of a specific duration and water depth also varied. To unravel the impact of varied inundation characteristics on the key life stages of a foundation plant, we designed an experiment with varied inundation treatments of different frequencies, durations, and depths. Our results showed that the frequency, duration, and depth of inundation events significantly influenced seed emergence, seedling survival, and growth. Stress can be strengthened by a higher frequency with a longer duration and larger depth. Among these factors, frequency had a dominant impact, followed by duration and water depth. Specifically, there is a trade-off between frequency, duration, and depth, suggesting that an inundation event with shallower depth and/or shorter duration would reduce the stress from higher frequency. The findings fill a gap in the loss of details of varied inundation characteristics on plant establishment on a fine scale. Further, it will help explicit inundation stress more accurately and clearly and provide important implications for stress relief solutions in coastal ecological restoration.
Analysis of factors affecting the accuracy of colposcopic diagnosis of cervical lesions: a retrospective cohort study
Authors: Chu Yuqing , Chen Qi , Liu Ruixue , Zhou Xu , Bao Meijing , Wang Hong , Lin Yang 
Published: October 2024

BackgroundCervical cancer is a leading cause of cancer-related deaths among women. However, in developing countries, the primary focus for cervical cancer prevention and control remains on the timely detection and treatment of precancerous lesions. This study aims to evaluate the accuracy of colposcopic diagnosis of cervical intraepithelial lesions and analyze the factors influencing its accuracy.MethodsThis study collected data from 512 eligible patients who visited the gynecology outpatient clinic of the Second Hospital of Jilin University from January 2022 to August 2023. The final diagnosis was based on the highest grade observed in both biopsy pathology and postoperative pathology. A self-controlled, retrospective analysis was conducted to evaluate the accuracy of colposcopic diagnosis. Univariate analysis was used to assess the impact of factors such as menopausal status, duration of menopause, high-risk human papillomavirus (HR-HPV) genotypes, and transformation zone (TZ) types on the accuracy of colposcopic diagnosis of cervical lesions.ResultThe overall colposcopy diagnostic concordance rate was 78.71%. The concordance rates between the premenopausal and postmenopausal groups differed significantly (χ2 = 75.450, p &lt; 0.05). The HPV16/18 positive group and the non 16/18 HR-HPV positive group also showed a significant difference in concordance rates (χ2 = 5.890, p &lt; 0.05). There were significant differences in concordance rates between TZ2 and TZ3 (χ2 = 10.585, p &lt; 0.05), as well as between TZ1 and TZ3 (χ2 = 14.607, p &lt; 0.05).ConclusionFactors such as menopausal status, duration of menopause, HR-HPV genotypes, and TZ types influence the accuracy of colposcopic diagnosis. Therefore, a comprehensive evaluation incorporating these factors should be performed in clinical practice to enhance diagnostic accuracy.
Deep brain stimulation for Parkinson’s disease: bibliometric analysis of the top 100 cited literature
Authors: Zhao Weijie , Shao Xinxin , Wang Ziyue , Mi Chuanhao , Wang Yu , Qi Xianghua , Ding Xiao 
Published: October 2024

BackgroundDeep Brain Stimulation (DBS) has been widely applied and accepted in the treatment of neurological and psychiatric disorders. Despite numerous studies exploring the effects of DBS on the progression of neurodegenerative diseases and the treatment of advanced Parkinson’s disease (PD), there is a limited number of articles summarizing this research. The purpose of this study is to investigate the current trends, hot topics, and potential in research surrounding DBS therapy for PD, as well as to anticipate the challenges of such research.MethodsWe searched the Web of Science Core Collection database (WoSCC) for DBS research literature related to PD published from January 2014 to January 2024, utilized CiteSpace, VOS viewer, the bibliometric online analysis platform, Scimago Graphica, Microsoft Excel 2021, and R software version 4.2.3 for data analysis. And we conducted quantitative research on publications, citations, journals, authors, countries, institutions, keywords, and references, visualized the results in network graphs.ResultsFrom 2014 to 2024, papers from 39 journals from 11 countries were among the top 100 cited. Most papers were published in Neurology, with the highest average citations per paper in Nature Neuroscience. The United States (US) contributed the most publications, followed by the United Kingdom (UK) and Germany. In terms of total publications, University College London (UCL) contributed the most papers. The primary classifications of articles were Clinical Neurology, Neurosciences, and Surgery. The top five keywords were subthalamic nucleus, DBS, PD, medical therapy, and basal ganglia. Cluster analysis indicates that DBS research focus on improving quality of life and applying computational models.ConclusionThrough bibliometric analysis, researchers could quickly and clearly understand the hotspots and boundaries of their research field, thus guiding their research direction and scope to improve research efficiency and the quality of outcomes. Although studies indicate that DBS is currently a crucial method for treating advanced PD, in the long run, creating a personalized, low-cost treatment regimen with precise targeting and long-term efficacy poses a challenge.
Bipolar and Laplacian montages are suitable for high-gamma modulation language mapping with stereoelectroencephalography
Authors: Mitsuhashi Takumi , Iimura Yasushi , Suzuki Hiroharu , Ueda Tetsuya , Nishioka Kazuki , Nomura Kazuki , Nakajima Madoka , Sugano Hidenori , Kondo Akihide 
Published: October 2024

ObjectiveTo determine the optimal montage and vocalization conditions for high-gamma language mapping using stereoelectroencephalography.MethodsWe studied 12 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of auditory-naming related high-gamma modulations. We determined the effects of electrode montage and vocalization conditions of the response on the high-gamma (60–140 Hz) amplitudes.ResultsCompared to common average reference montage, bipolar and Laplacian montages effectively reduced the degree of auditory naming-related signal deflections in the white matter during the stimulus and response phases (mixed model estimate: −21.2 to −85.4%; p &lt; 0.001), while maintaining those at the cortical level (−4.4 to +7.8%; p = 0.614 to 0.085). They also reduced signal deflections outside the brain parenchyma during the response phase (−90.6 to −91.2%; p &lt; 0.001). Covert responses reduced signal deflections outside the brain parenchyma during the response phase (−17.0%; p = 0.010).ConclusionOn depth electrode recording, bipolar and Laplacian montages are suitable for measuring auditory naming-related high-gamma modulations in gray matter. The covert response may highlight the gray matter activity.SignificanceThis study helps establish the practical guidelines for high-gamma language mapping using stereoelectroencephalography.
Amplification of vibration induced nystagmus in patients with peripheral vestibular loss by head tilt
Authors: Shemesh Ari Aharon , Kattah Jorge C. , Zee David S. , Zuma E Maia Francisco , Otero-Millan Jorge 
Published: October 2024

IntroductionIn patients with unilateral loss of vestibular function (UVL) vibration of the skull leads to a response of the vestibulo-ocular reflex (VOR) called vibration-induced nystagmus (VIN), with slow phases usually directed toward the paretic ear. This response is thought to result from the difference between the neural discharge in semicircular canal afferents from the healthy and the affected labyrinth. The brain interprets this difference as a sustained imbalance in angular (rotational) vestibular tone, which in natural circumstances would only occur when the head was rotating at a constant acceleration.MethodsTo study this effect, we used a contemporary model of the neural network that combines sensory information about head rotation, translation, and tilt relative to gravity to estimate head orientation and motion. Based on the model we hypothesize that in patients with UVL, the brain may estimate not only a “virtual” rotation from the induced canal imbalance but also a subsequent “virtual” translation from the incorrect computation of the orientation of the head relative to gravity. If this is the case, the pattern of vibration-induced nystagmus will depend on the orientation of the head relative to gravity during the stimulation. This model predicts that this “virtual” translation will alter the baseline VIN elicited with the head upright; augmenting it when the affected ear is down and diminishing it when the affected ear is up.ResultsConfirming this hypothesis, we recorded VIN in 3 patients with UVL (due to vestibular neuritis) in upright, right ear-down, and left ear-down positions and each showed the expected pattern.DiscussionFrom a practical, clinical view, our results and modeling suggest that positional VIN might reveal a hidden imbalance in angular vestibular tone in patients with UVL, when patients have equivocal signs of a vestibular imbalance, such as a minute amount of spontaneous or vibration-induced nystagmus with the head upright. This research provides insights into the underlying mechanisms of vestibular processing, the analysis of nystagmus in patients with UVL, and guides the design of a new bedside diagnostic test to assess vestibular function in patients with dizziness and imbalance.
Case report: Diagnostic trap: a extremely rare metastatic myoepithelial carcinoma of breast
Authors: Luo Shuai , Tian Xiaoxue , Xu Ting , Wang Jinjing 
Published: October 2024

BackgroundMyoepithelial carcinoma (MECA) is a malignant tumor primarily affecting the salivary gland, most frequently in the parotid gland. It can manifest as primary or secondary to pleomorphic adenoma or benign myoepithelioma. MECA exhibits aggressive behaviors. In particular, primary MECA is more aggressive, frequently recurring or metastasizing distantly. Its morphological and immunohistochemical characteristics overlap with various tumors, posing challenges in its recognization as a distinct entity. Consequently, MECA may be frequently misdiagnosed, mainly when occurred in the mammary gland. This chance for misdiagnosis poses significant challenges in clinical diagnosis and treatment.Case demonstrationA 77-year-old woman with a history of pleomorphic adenoma presented with a palpable lump in the right breast for 3 months. Subsequent core needle biopsy (CNB) and modified radical mastectomy were performed, with samples subjected to histopathological examination. Based on the patient’s history, histomorphologic features, immunohistochemistry (IHC) results and results of FISH, the pathological diagnosis confirmed MECA in the mammary gland. Postoperative chemotherapy was administered, and the patient exhibited a favorable prognosis during a 40-month follow-up period.ConclusionsPrimary MECA in the mammary gland is exceedingly rare, metastasis from the salivary gland MECA to the mammary gland is even rarer and has not been previously reported. This study presents the first documented case of MECA originating from the parotid gland metastasizing to the mammary gland (also known as breast). Highlighting this case aims to raise awareness among clinical pathologists to prevent underdiagnosis and misdiagnosis of this tumor entity.
Apoptotic and proliferative processes in the small intestine of rats with type 2 diabetes mellitus after metformin and propionic acid treatment
Authors: Natrus Larysa , Lisakovska Olha , Smirnov Anton , Osadchuk Yuliia , Klys Yuliia 
Published: October 2024

BackgroundPropionic acid (PA) is an intermediate product of metabolism of intestinal bacteria and may protect the intestinal barrier from disruption. The aim of the study was to investigate the apoptotic and proliferative processes in the small intestine (SI) of rats with type 2 diabetes mellitus (T2DM) on the background of metformin monotherapy and its combination with PA.MethodsMale Wistar rats were divided: 1) control; 2) T2DM (3-month high-fat diet followed by streptozotocin injection of 25 mg/kg of body weight); 3) T2DM + metformin (60 mg/kg, 14 days, orally); 4) T2DM + PA (60 mg/kg, 14 days, orally); 5) T2DM + PA + metformin. Western blotting, RT-PCR, and scanning electron microscopy were performed.ResultsWe observed profound changes in the SI of diabetic rats suggesting the disturbed intestinal homeostasis: impaired mitochondrial ultrastructure, increased cristae volume, and decreased content of proliferative marker Ki67 with almost unchanged proapoptotic caspase-3 and its p17 subunit levels. Metformin and PA monotherapies also led to an increased cristae volume, however, after their combination, a tendency to normalization of ultrastructure of mitochondria was observed. While there was a significant inhibition of proliferation in T2DM and, in greater extent, after metformin and PA monotherapies, differential influence on apoptosis in the SI was observed. While metformin inhibited apoptosis via Bax declining, PA mainly acted via caspase-3-dependent mechanism elevating its active p17 subunit.ConclusionPA supplementation for the improvement of diabetes-induced gastrointestinal complications concurrently with metformin may be consider as a perspective supportive therapy. Data related to PA action on SI may be valuable during the development of new treatment strategies for diabetes-induced intestinal disturbances raised after metformin treatment.