bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of APOBEC3C in modulating the tumor microenvironment and stemness properties of glioma: evidence from pancancer analysis
Authors: Zhang Shoudu , Guo Yugang , Hu Yuanzheng , Gao Xiaofang , Bai Fanghui , Ding Qian , Hou Kaiqi , Wang Zongqing , Sun Xing , Zhao Hui , Qu Zhongyu , Xu Qian 
Published: September 2023

BackgroundIt is now understood that APOBEC3 family proteins (A3s) are essential in tumor progression, yet their involvement in tumor immunity and stemness across diverse cancer types remains poorly understood.MethodsIn the present study, comprehensive genome-wide statistical and bioinformatic analyses were conducted to elucidate A3 family expression patterns, establishing clinically relevant correlations with prognosis, the tumor microenvironment(TME), immune infiltration, checkpoint blockade, and stemness across cancers. Different experimental techniques were applied, including RT–qPCR, immunohistochemistry, sphere formation assays, Transwell migration assays, and wound-healing assays, to investigate the impact of A3C on low-grade glioma (LGG) and glioblastoma multiforme (GBM), as well as its function in glioma stem cells(GSCs).ResultsDysregulated expression of A3s was observed in various human cancer tissues. The prognostic value of A3 expression differed across cancer types, with a link to particularly unfavorable outcomes in gliomas. A3s are associated with the the TME and stemness in multiple cancers. Additionally, we developed an independent prognostic model based on A3s expression, which may be an independent prognostic factor for OS in patients with glioma. Subsequent validation underscored a strong association between elevated A3C expression and adverse prognostic outcomes, higher tumor grades, and unfavorable histology in glioma. A potential connection between A3C and glioma progression was established. Notably, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses implicated A3C in immune system-related diseases, with heightened A3C levels contributing to an immunosuppressive tumor microenvironment (TME) in glioma. Furthermore, in vitro experiments substantiated the role of A3C in sustaining and renewing glioma stem cells, as A3C deletion led to diminished proliferation, invasion, and migration of glioma cells.ConclusionThe A3 family exhibits heterogeneous expression across various cancer types, with its expression profile serving as a predictive marker for overall survival in glioma patients. A3C emerges as a regulator of glioma progression, exerting its influence through modulation of the tumor microenvironment and regulation of stemness.
Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT
Authors: Zeven Katty , De Groof Timo W.M. , Ceuppens Hannelore , Awad Robin Maximilian , Ertveldt Thomas , de Mey Wout , Meeus Fien , Raes Geert , Breckpot Karine , Devoogdt Nick 
Published: September 2023

IntroductionT cell Ig and ITIM domain receptor (TIGIT) is a next-generation immune checkpoint predominantly expressed on activated T cells and NK cells, exhibiting an unfavorable prognostic association with various malignancies. Despite the emergence of multiple TIGIT-blocking agents entering clinical trials, only a fraction of patients responded positively to anti-TIGIT therapy. Consequently, an urgent demand arises for noninvasive techniques to quantify and monitor TIGIT expression, facilitating patient stratification and enhancing therapeutic outcomes. Small antigen binding moieties such as nanobodies, are promising candidates for such tracer development.MethodsWe generated a panel of anti-human or anti-mouse TIGIT nanobodies from immunized llamas. In addition, we designed a single-chain variable fragment derived from the clinically tested monoclonal antibody Vibostolimab targeting TIGIT, and assessed its performance alongside the nanobodies. In vitro characterization studies were performed, including binding ability and affinity to cell expressed or recombinant TIGIT. After Technetium-99m labeling, the nanobodies and the single-chain variable fragment were evaluated in vivo for their ability to detect TIGIT expression using SPECT/CT imaging, followed by ex vivo biodistribution analysis.ResultsNine nanobodies were selected for binding to recombinant and cell expressed TIGIT with low sub-nanomolar affinities and are thermostable. A six-fold higher uptake in TIGIT-overexpressing tumor was demonstrated one hour post- injection with Technetium-99m labeled nanobodies compared to an irrelevant control nanobody. Though the single-chain variable fragment exhibited superior binding to TIGIT-expressing peripheral blood mononuclear cells in vitro, its in vivo behavior yielded lower tumor-to-background ratios at one hour post- injection, indicating that nanobodies are better suited for in vivo imaging than the single-chain variable fragment. Despite the good affinity, high specificity and on-target uptake in mice in this setting, imaging of TIGIT expression on tumor- infiltrating lymphocytes within MC38 tumors remained elusive. This is likely due to the low expression levels of TIGIT in this model.DiscussionThe excellent affinity, high specificity and rapid on-target uptake in mice bearing TIGIT- overexpressing tumors showed the promising diagnostic potential of nanobodies to noninvasively image high TIGIT expression within the tumor. These findings hold promise for clinical translation to aid patient selection and improve therapy response.
Combined network analysis and interpretable machine learning reveals the environmental adaptations of more than 10,000 ruminant microbial genomes
Authors: Yan Yueyang , Shi Tao , Bao Xin , Gai Yunpeng , Liang Xingxing , Jiang Yu , Li Qiushi 
Published: September 2023

BackgroundThe ruminant gastrointestinal contains numerous microbiomes that serve a crucial role in sustaining the host’s productivity and health. In recent times, numerous studies have revealed that variations in influencing factors, including the environment, diet, and host, contribute to the shaping of gastrointestinal microbial adaptation to specific states. Therefore, understanding how host and environmental factors affect gastrointestinal microbes will help to improve the sustainability of ruminant production systems.ResultsBased on a graphical analysis perspective, this study elucidates the microbial topology and robustness of the gastrointestinal of different ruminant species, showing that the microbial network is more resistant to random attacks. The risk of transmission of high-risk metagenome-assembled genome (MAG) was also demonstrated based on a large-scale survey of the distribution of antibiotic resistance genes (ARG) in the microbiota of most types of ecosystems. In addition, an interpretable machine learning framework was developed to study the complex, high-dimensional data of the gastrointestinal microbial genome. The evolution of gastrointestinal microbial adaptations to the environment in ruminants were analyzed and the adaptability changes of microorganisms to different altitudes were identified, including microbial transcriptional repair.ConclusionOur findings indicate that the environment has an impact on the functional features of microbiomes in ruminant. The findings provide a new insight for the future development of microbial resources for the sustainable development in agriculture.
Peppermint extract improves egg production and quality, increases antioxidant capacity, and alters cecal microbiota in late-phase laying hens
Authors: Bai Miaomiao , Liu Hongnan , Zhang Yihui , Wang Shanshan , Shao Yirui , Xiong Xia , Hu Xin , Yu Rongyao , Lan Wei , Cui Yadong , Kong Xiangfeng 
Published: September 2023

IntroductionPeppermint contains substantial bioactive ingredients belonging to the phytoestrogens, and its effects on the production of late-laying hens deserve more attention. This study evaluated the effects of dietary peppermint extract (PE) supplementation on egg production and quality, yolk fatty acid composition, antioxidant capacity, and cecal microbiota in late-phase laying hens.MethodPE powder was identified by UPLC-MS/MS analysis. Two hundred and sixteen laying hens (60 weeks old) were randomly assigned to four treatments, each for 28 days: (i) basal diet (control group, CON); (ii) basal diet + 0.1% PE; (iii) basal diet + 0.2% PE; and (iv) basal diet + 0.4% PE. Egg, serum, and cecal samples were collected for analysis.ResultsDietary PE supplementation increased the laying rate, serum triglyceride, immunoglobulin G, and total antioxidant capacity, while 0.2 and 0.4% PE supplementation increased eggshell thickness, serum total protein level, and superoxide dismutase activity of laying hens compared with the CON group (P &lt; 0.05). PE addition in diets increased the C14:0, C18:3n3, C18:3n6, C23:0, C24:0, and C24:1n9 contents in the yolk. In addition, the egg yolk saturated fatty acid content was higher (P &lt; 0.05) in the 0.2 and 0.4% PE groups compared with the CON and 0.1% PE groups. The microbiota analysis revealed that the cecal phylum Proteobacteria was decreased (P &lt; 0.05) in the PE-supplemented groups. A total of 0.4% PE supplementation increased the cecal richness of gram-positive bacteria and decreased the richness of gram-negative and potentially pathogenic bacteria compared with the 0.1% PE group (P &lt; 0.05). Microbial function prediction analysis showed that the cecal microbiota of the PE group was mainly enriched by fatty acid degradation, fatty acid metabolism, amino sugar metabolism, nucleotide sugar metabolism, and other pathways. Regression analysis suggested that 0.28–0.36% PE supplementation was the optimal level for improving egg production and quality, antioxidant capacity, and yolk fatty acid in late-phase laying hens.DiscussionDietary PE supplementation improved egg production and quality (including yolk fatty acid composition) by increasing serum IgG and antioxidant capacity and modulating the intestinal microbiota in late-phase laying hens.
Altered intrinsic functional brain architecture in patients with functional constipation: a surface-based network study
Authors: Yu Xiang , Yu Jingjie , Li Yuwei , Cong Jiying , Wang Chao , Fan Ran , Wang Wanbing , Zhou Lige , Xu Chen , Li Yiming , Liu Yawu 
Published: September 2023

BackgroundFunctional constipation (FCon) is a common functional gastrointestinal disorder (FGID). Studies have indicated a higher likelihood of psychiatric disorders, such as anxiety, depression, sleep disturbances, and impaired concentration, among patients with FCon. However, the underlying pathophysiological mechanisms responsible for these symptoms in FCon patients remain to be fully elucidated. The human brain is a complex network architecture with several fundamental organizational properties. Neurological interactions between gut symptoms and psychiatric issues may be closely associated with these complex networks.MethodsIn the present study, a total of 35 patients with FCon and 40 healthy controls (HC) were recruited for a series of clinical examinations and resting-state functional magnetic imaging (RS-fMRI). We employed the surface-based analysis (SBA) approach, utilizing the Schaefer cortical parcellation template and Tikhonov regularization. Graph theoretical analysis (GTA) and functional connectivity (FC) analysis of RS-fMRI were conducted to investigate the aberrant network alterations between the two groups. Additionally, correlation analyses were performed between the network indices and clinical variables in patients with FCon.ResultsAt the global level, we found altered topological properties and networks in patients with FCon, mainly including the significantly increased clustering coefficient (CP), local efficiency (Eloc), and shortest path length (LP), whereas the decreased global efficiency (Eglob) compared to HC. At the regional level, patients with FCon exhibited increased nodal efficiency in the frontoparietal network (FPN). Furthermore, FC analysis demonstrated several functional alterations within and between the Yeo 7 networks, particularly including visual network (VN), limbic network (LN), default mode network (DMN), and somatosensory-motor network (SMN) in sub-network and large-scale network analysis. Correlation analysis revealed that there were no significant associations between the network metrics and clinical variables in the present study.ConclusionThese results highlight the altered topological architecture of functional brain networks associated with visual perception abilities, emotion regulation, sensorimotor processing, and attentional control, which may contribute to effectively targeted treatment modalities for patients with FCon.
Low geriatric nutritional risk index predicts poor prognosis in patients with cirrhosis: a retrospective study
Authors: Kamioka Hiroshi , Saeki Chisato , Kinoshita Akiyoshi , Nakagawa Chika , Kanai Tomoya , Ueda Kaoru , Nakano Masanori , Oikawa Tsunekazu , Torisu Yuichi , Saruta Masayuki , Tsubota Akihito 
Published: September 2023

AimMalnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis.MethodsWe retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (&gt;98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality.ResultsThe median observation period was 54.9 (33.6–61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = −0.579), model for end-stage liver disease score (r = −0.286), and Mac-2 binding protein glycosylation isomer (r = −0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p &lt; 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p &lt; 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p &lt; 0.001, &lt;0.001, and = 0.013, respectively).ConclusionLow GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis.
IMRT in the treatment of locally advanced or inoperable NSCLC in the pre-durvalumab era: clinical outcomes and pattern of relapses, experience from the Oscar Lambret Center
Authors: Le Roy Thomas , Wallet Jennifer , Barthoulot Maël , Leguillette Clémence , Lacornerie Thomas , Pasquier David , Lartigau Eric , Le Tinier Florence 
Published: September 2023

BackgroundIntensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation.ObjectiveThe objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses.MethodsPatients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan–Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test.ResultsSeventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity.ConclusionThe use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.
Frailty and long-term survival of patients with gastric cancer: a meta-analysis
Authors: Liang Hongliang , Hu Aiping 
Published: September 2023

BackgroundThe relationship between frailty and the long-term clinical outcome of gastric cancer (GC) patients has not yet been established, although frailty is associated with a poor short-term outcome. The impact of frailty on long-term survival of GC patients was investigated through a systematic review and meta-analysis.MethodsObservational studies with longitudinal follow-ups for a minimum of one year were identified through a search of the PubMed, Embase, Cochrane Library, and Web of Science databases, in accordance with the objective of the meta-analysis. Combining the findings was achieved using a random-effects model, which accounted for inter-study heterogeneity.ResultsTen datasets from nine cohort studies were included, which involved 7613 patients with GC. A total of 2074 patients (27.2%) were with frailty at baseline, and the mean follow-up duration was 48.1 months. A pooled analysis of the results showed that frailty was linked to a poor long-term overall survival in GC patients (risk ratio [RR]: 1.65, 95% confidence interval [CI]: 1.27 to 2.13, p &lt; 0.001; I2 = 80%). Sensitivity analysis showed consistent results in older patients (≥ 65 years, RR: 1.51, p = 0.002) and the oldest old (≥ 80 years, RR: 1.41, p = 0.01). In addition, frailty was also associated with poor long-term progression-free survival (RR: 1.65, 95% CI: 1.39 to 1.96, p &lt; 0.001; I2 = 0%) and disease-specific survival (RR: 1.71, 95% CI: 1.23 to 2.37, p = 0.001; I2 = 4%).ConclusionFrailty is associated with poor long-term survival of patients with GC.
Baseline heart rate variability predicts placebo hypoalgesia in men, but not women
Authors: Krecké Joy , Dierolf Angelika M. , Rischer Katharina M. , Anton Fernand , van der Meulen Marian 
Published: September 2023

IntroductionPlacebo hypoalgesic effects vary greatly across individuals, making them challenging to control for in clinical trials and difficult to use in treatment. We investigated the potential of resting vagally-mediated heart rate variability (vmHRV) to help predict the magnitude of placebo responsiveness.MethodsIn two independent studies (total N = 77), we administered a placebo paradigm after measuring baseline HRV. In Study I, we delivered heat pain to the forearm, on skin patches treated with “real” and “control” cream (identical inactive creams). In Study II, electrical pulses to the forearm were modulated by sham transcutaneous electrical nerve stimulation. We combined data from both studies to evaluate the relationship between vagally-mediated HRV (vmHRV) parameters and the placebo response size, while also assessing sex differences in this relationship.Results and DiscussionThis revealed a positive association between vmHRV and the degree of pain relief, and this effect was driven by men. These results not only reveal new insights into the (sex-specific) mechanisms of placebo hypoalgesia, but also suggest that measuring vmHRV may be helpful in predicting placebo responsiveness. Given that placebo hypoalgesic effects contribute substantially to treatment outcomes, such a non-invasive and easily obtained predictor would be valuable in the context of personalized medicine.
Progressive tauopathy disrupts breathing stability and chemoreflexes during presumptive sleep in mice
Authors: Marciante Alexandria B. , Lurk Carter , Mata Luz , Lewis Jada , Reznikov Leah R. , Mitchell Gordon S. 
Published: September 2023

Rationale: Although sleep apnea occurs in over 50% of individuals with Alzheimer’s Disease (AD) or related tauopathies, little is known concerning the potential role of tauopathy in the pathogenesis of sleep apnea. Here, we tested the hypotheses that, during presumptive sleep, a murine model of tauopathy (rTg4510) exhibits: 1) increased breathing instability; 2) impaired chemoreflex function; and 3) exacerbation of these effects with tauopathy progression.Methods: rTg4510 mice initially develop robust tauopathy in the hippocampus and cortex, and eventually progresses to the brainstem. Type I and II post-sigh apnea, Type III (spontaneous) apnea, sigh, and hypopnea incidence were measured in young adult (5–6 months; n = 10–14/group) and aged (13–15 months; n = 22–24/group) non-transgenic (nTg), monogenic control tetracycline transactivator, and bigenic rTg4510 mice using whole-body plethysmography during presumptive sleep (i.e., eyes closed, curled/laying posture, stable breathing for &gt;200 breaths) while breathing room air (21% O2). Peripheral and central chemoreceptor sensitivity were assessed with transient exposures (5 min) to hyperoxia (100% O2) or hypercapnia (3% and 5% CO2 in 21% O2), respectively.Results: We report significant increases in Type I, II, and III apneas (all p &lt; 0.001), sighs (p = 0.002) and hypopneas (p &lt; 0.001) in aged rTg4510 mice, but only Type III apneas in young adult rTg4510 mice (p &lt; 0.001) versus age-matched nTg controls. Aged rTg4510 mice exhibited profound chemoreflex impairment versus age matched nTg and tTA mice. In rTg4510 mice, breathing frequency, tidal volume and minute ventilation were not affected by hyperoxic or hypercapnic challenges, in striking contrast to controls. Histological examination revealed hyperphosphorylated tau in brainstem regions involved in the control of breathing (e.g., pons, medullary respiratory column, retrotrapezoid nucleus) in aged rTg4510 mice. Neither breathing instability nor hyperphosphorylated tau in brainstem tissues were observed in young adult rTg4510 mice.Conclusion: Older rTg4510 mice exhibit profound impairment in the neural control of breathing, with greater breathing instability and near absence of oxygen and carbon-dioxide chemoreflexes. Breathing impairments paralleled tauopathy progression into brainstem regions that control breathing. These findings are consistent with the idea that tauopathy per se undermines chemoreflexes and promotes breathing instability during sleep.