bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer
Authors: Xu Yan , Xia Zhixiu , Sun Xiaoyu , Wei Baojun , Fu Yang , Shi Du , Zhu Yuyan 
Published: February 2023

BackgroundBladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes.MethodsWe used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis.ResultsThe GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins.ConclusionsThe GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel “Glutamine Metabolism-related Gene”-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer.
An arginase1- and PD-L1-derived peptide-based vaccine for myeloproliferative neoplasms: A first-in-man clinical trial
Authors: Grauslund Jacob Handlos , Holmström Morten Orebo , Martinenaite Evelina , Lisle Thomas Landkildehus , Glöckner Hannah Jorinde , El Fassi Daniel , Klausen Uffe , Mortensen Rasmus E. J. , Jørgensen Nicolai , Kjær Lasse , Skov Vibe , Svane Inge Marie , Hasselbalch Hans Carl , Andersen Mads Hald 
Published: February 2023

IntroductionArginase-1 (ARG1) and Programed death ligand-1 (PD-L1) play a vital role in immunosuppression in myeloproliferative neoplasms (MPNs) and directly inhibit T-cell activation and proliferation. We previously identified spontaneous T-cell responses towards PD-L1 and ARG1 derived peptide epitopes in patients with MPNs. In the present First-in-Man study we tested dual vaccinations of ARG1- derived and PD-L1-derived peptides, combined with Montanide ISA-51 as adjuvant, in patients with Janus Kinase 2 (JAK2) V617F-mutated MPN.MethodsSafety and efficacy of vaccination with ARG1- derived and PD-L1-derived peptides with montanide as an adjuvant was tested in 9 patients with MPN The primary end point was safety and toxicity evaluation. The secondary end point was assessment of the immune response to the vaccination epitope (www.clinicaltrials.gov identifier NCT04051307).ResultsThe study included 9 patients with JAK2-mutant MPN of which 8 received all 24 planned vaccines within a 9-month treatment period. Patients reported only grade 1 and 2 vaccine related adverse events. No alterations in peripheral blood counts were identified, and serial measurements of the JAK2V617F allelic burden showed that none of the patients achieved a molecular response during the treatment period. The vaccines induced strong immune responses against both ARG1 and PD-L1- derived epitopes in the peripheral blood of all patients, and vaccine-specific skin-infiltrating lymphocytes from 5/6 patients could be expanded in vitro after a delayed-type hypersensitivity test. In two patients we also detected both ARG1- and PD-L1-specific T cells in bone marrow samples at the end of trial. Intracellular cytokine staining revealed IFNγ and TNFγ producing CD4+- and CD8+- T cells specific against both vaccine epitopes. Throughout the study, the peripheral CD8/CD4 ratio increased significantly, and the CD8+ TEMRA subpopulation was enlarged. We also identified a significant decrease in PD-L1 mRNA expression in CD14+ myeloid cells in the peripheral blood in all treated patients and a decrease in ARG1 mRNA expression in bone marrow of 6 out of 7 evaluated patients.ConclusionOverall, the ARG1- and PD-L1-derived vaccines were safe and tolerable and induced strong T-cell responses in all patients. These results warrant further studies of the vaccine in other settings or in combination with additional immune-activating treatments.
Orally administered Lactiplantibacillus plantarum OLL2712 decreased intestinal permeability, especially in the ileum: Ingested lactic acid bacteria alleviated obesity-induced inflammation by collaborating with gut microbiota
Authors: Wang Yimei , Takano Tomohiro , Zhou Yingyu , Wang Rong , Toshimitsu Takayuki , Sashihara Toshihiro , Tanokura Masaru , Miyakawa Takuya , Nakajima-Adachi Haruyo , Hachimura Satoshi 
Published: February 2023

IntroductionChronic inflammation caused by dietary obesity has been considered to induce lifestyle-related diseases and functional ingredients with anti-inflammatory effects are attracting attention. Although multiple studies on obesity had proved the anti-inflammatory effects of ingestion of lactic acid bacteria (LAB) and other functional ingredients on adipose tissue, the precise effects on the intestine, especially on the individual intestinal segments have not been made clear. In this study, we elucidated the mechanisms of Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) OLL2712 in suppressing obesity-induced inflammation using high fat diet (HFD)-fed mice obesity model.MethodsWe orally administered heat-treated LAB to HFD-fed mice model, and investigated the inflammatory changes in adipose tissue and intestinal immune cells. We also analyzed gut microbiota, and evaluated the inflammation and permeability of the duodenum, jejunum, ileum and colon; four intestinal segments differing in gut bacteria composition and immune response.ResultsAfter 3-week LAB administration, the gene expression levels of proinflammatory cytokines were downregulated in adipose tissue, colon, and Peyer’s patches (PP)-derived F4/80+ cells. The LAB treatment alleviated obesity-related gut microbiota imbalance. L. plantarum OLL2712 treatment helps maintain intestinal barrier function, especially in the ileum, possibly by preventing ZO-1 and Occludin downregulation.DiscussionOur results suggest that the oral administration of the LAB strain regulated the gut microbiota, suppressed intestinal inflammation, and improved the gut barrier, which could inhibit the products of obesity-induced gut dysbiosis from translocating into the bloodstream and the adipose tissue, through which the LAB finally alleviated the inflammation caused by dietary obesity. Barrier improvement was observed, especially in the ileum, suggesting collaborative modulation of the intestinal immune responses by ingested LAB and microbiota.
Prognostic model for predicting outcome and guiding treatment decision for unresectable hepatocellular carcinoma treated with lenvatinib monotherapy or lenvatinib plus immunotherapy
Authors: Guo De-Zhen , Zhang Shi-Yu , Dong San-Yuan , Yan Jia-Yan , Wang Yu-Peng , Cao Ya , Rao Sheng-Xiang , Fan Jia , Yang Xin-Rong , Huang Ao , Zhou Jian 
Published: February 2023

BackgroundLenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions.Methods304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency.ResultsMultivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P&lt;0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II&lt;600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II&gt;600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II&gt;600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low.ConclusionThe PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.
The long-term observation of the rotation of implantable collamer lens as the management of high postoperative vault
Authors: Jiang Yang , Luo Yan , Li Ying , Lu Thomas 
Published: February 2023

PurposeThis study aimed to describe the effectiveness and stability of implantable collamer lens (ICL) rotation in reducing high postoperative vault.SettingThis study was conducted in the Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.DesignThis is a retrospective case series.MethodsTwenty-two eyes from 22 patients who had ICL (V4c EVO) implantation with high postoperative vault (&gt;=750 μm) were recruited for our study. All the lenses were rotated from a horizontal to an oblique position. The vault, SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° were measured pre-rotation, 1-week post-rotation, and in the at-least 1-year-follow-up.ResultsTwenty female patients and two male patients were recruited, with a mean age of 28.68 ± 6.08 years. The mean vault had declined significantly from 951.81 ± 154.26 μm pre-rotation to 772.27 ± 119.40 μm 1 week post-rotation (p &lt; 0.001). The SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° pre-rotation and 1-week post-rotation were 30.40 ± 7.91° and 45.14 ± 6.75°, 32.37 ± 7.48° and 46.23 ± 6.39°, 303.27 ± 87.99 and 522.45 ± 122.16 μm, 323.81 ± 89.15 and 536.13 ± 121.66 μm, 387.95 ± 99.43 and 630.81 ± 133.59 μm, 435.68 ± 106.72 and 643.36 ± 132.82 μm, 0.109 ± 0.034 and 0.202 ± 0.053 mm2, 0.123 ± 0.034 and 0.212 ± 0.051 mm2, 0.194 ± 0.056 and 0.345 ± 0.083 mm2, and 0.216 ± 0.055 and 0.358 ± 0.079 mm2 (all p &lt; 0.001). The mean vault value had changed from 747.50 ± 116.07 μm 1-week post-rotation to 586.87 ± 132.65 μm in the 1-year follow-up. However, the SSA, AOD500, AOD750, TISA500, and TISA750 at 180° and 0° had remained stable (p &gt; 0.05).ConclusionNon-toric ICL rotation is a novel and effective technique in the treatment of high postoperative vault. Our results are more robust given the extended period of follow-up.
Effectiveness and safety of cataract surgery in laminar air flow device versus traditional scrubs: A 1-year non-inferiority pilot study
Authors: Artus Arnaud , Fabro Filippo , Cochereau Isabelle , Caputo Georges , Tadayoni Ramin , Vignal Catherine , Galatoire Olivier , Salviat Flore , Gatinel Damien , Panthier Christophe 
Published: February 2023

PurposeThe study aimed to assess the safety and the non-inferiority of cataract surgery outside an operating room using the Surgicube®, a mobile laminar airflow (LAF) device.SettingsThis single-center study was conducted at the Rothschild Foundation, Paris, France.DesignThis is a retrospective cross-sectional study.MethodsAll patients operated on for cataracts using the Surgicube® between February 2020 and February 2021 were included and controlled by a cohort of patients operated on for cataracts in the traditional theater during the same period. Patients with a postoperative follow-up of less than 1 month were excluded. Data collection was carried out using the patient’s medical record. The primary endpoint was the evaluation of the number of endophthalmitis in the two groups. The secondary judgment criteria were the analysis of the various complications and the Logmar visual acuity at 1 month in the two groups. All the patients underwent an OCT retinal examination.ResultsA total of 923 randomized patients who underwent cataract surgery between 2020 and 2021 have been included in the study. Among them, 448 patients were operated on using the Surgicube, and 475 patients underwent surgery in the traditional operating room using the same lens phacoemulsification technique. There are no significant differences between the two groups (p &gt; 0.05).ConclusionCataract surgery using the Surgicube® outside a conventional operating room seems non-inferior to conventional scrub.
A rapid, accurate, and low-cost method for detecting Mycobacterium tuberculosis and its drug-resistant genes in pulmonary tuberculosis: Applications of MassARRAY DNA mass spectrometry
Authors: Yang Han , Li Aifang , Dang Liyun , Kang Tao , Ren Fei , Ma Jinbao , Zhou Yong , Yang Yuanli , Lei Jing , Zhang Tao 
Published: February 2023

IntroductionMycobacterium tuberculosis (MTB) identification and drug resistance diagnosis are very important for treatment of drug-resistant tuberculosis (DR-TB). Therefore, high throughput, accurate and low-cost molecular detection techniques are urgently needed. This study aimed to evaluate the clinical application value of MassARRAY in tuberculosis diagnosis and drug resistance screening.MethodsThe limit of detection (LOD) and clinical application value of MassARRAY were evaluated using reference strains and clinical isolates. MTB in bronchoalveolar lavage fluid (BALF) and sputum samples were detected using MassARRAY, quantitative real-time polymerase chain reaction (qPCR) and MGIT960 liquid culture (culture). Using culture as the standard, the efficacy of MassARRAY and qPCR for the detection of TB was analyzed. Mutation of drug resistance genes in MTB clinical isolates was tested using MassARRAY, high-resolution melting curve (HRM), and Sanger sequencing. Using sequencing as the standard, the efficacy of MassARRAY, and HRM for the detection of each drug resistance site of MTB was analyzed. Simultaneously, the mutation of drug resistance genes by the MassARRAY method was compared with the results of drug susceptibility testing (DST), and the genotype–phenotype relationship was analyzed. The ability of MassARRAY to discriminate mixed infections was detected using mixtures of standard strains (M. tuberculosis H37Rv) and drug-resistant clinical isolates and mixtures of wild-type and mutant plasmids.ResultsIn MassARRAY, 20 related gene mutations could be detected by two PCR systems. All genes could be accurately detected when the bacterial load was 104 CFU/mL. When the load of wild-type and drug-resistant MTB mixture was 105 CFU/mL (respectively reached 104 CFU/mL), variants and wild-type genes could be detected simultaneously. The sensitivity of MassARRAY (96.9%) for identification was higher than that of qPCR (87.5%) (p &lt; 0.001). The sensitivity and specificity of MassARRAY for all drug resistance gene mutations were 100.0%, with higher accuracy and consistency than HRM (sensitivity = 89.3% and specificity = 96.9%, p = 0.001). Analyzing the relationship between MassARRAY genotype and DST phenotype, the accuracy of katG_315, rpoB_531, rpsL_43, rpsL_88, and rrs_513 sites was 100.0%, and embB_306 and rpoB_526 were inconsistent with the DST results when the base changes were different.DiscussionMassARRAY can obtain base mutation information and identify heteroresistance infections simultaneously when the mutant proportion was at least 5–25%. It has good application prospects in the diagnosis of DR-TB with high throughput, accurate and low-cost.
Environment or genetic isolation? An atypical intestinal microbiota in the Maltese honey bee Apis mellifera spp. ruttneri
Authors: Gaggìa Francesca , Jakobsen Rasmus Riemer , Alberoni Daniele , Baffoni Loredana , Cutajar Simone , Mifsud David , Nielsen Dennis Sandris , Di Gioia Diana 
Published: February 2023

IntroductionApis mellifera evolved mainly in African, Asian, and European continents over thousands of years, leading to the selection of a considerable number of honey bees subspecies that have adapted to various environments such as hot semi-desert zones and cold temperate zones. With the evolution of honey bee subspecies, it is possible that environmental conditions, food sources, and microbial communities typical of the colonized areas have shaped the honey bee gut microbiota.MethodsIn this study the microbiota of two distinct lineages (mitochondrial haplotypes) of bees Apis mellifera ruttneri (lineage A) and Apis mellifera ligustica and carnica (both lineage C) were compared. Honey bee guts were collected in a dry period in the respective breeding areas (the island of Malta and the regions of Emilia-Romagna and South Tyrol in Italy). Microbial DNA from the honey bee gut was extracted and amplified for the V3-V4 regions of the 16S rRNA gene for bacteria and for ITS2 for fungi.ResultsThe analyses carried out show that the Maltese lineage A honey bees have a distinctive microbiota when compared to Italian lineage C honey bees, with the most abundant genera being Bartonellaceae and Lactobacillaceae, respectively. Lactobacillaceae in Maltese Lineage A honey bees consist mainly of Apilactobacillus instead of Lactobacillus and Bombilactobacillus in the lineage C. Lineage A honey bee gut microbiota also harbors higher proportions of Arsenophonus, Bombella, Commensalibacter, and Pseudomonas when compared to lineage C.DiscussionThe environment seems to be the main driver in the acquisition of these marked differences in the gut microbiota. However, the influence of other factors such as host genetics, seasonality or geography may still play a significant role in the microbiome shaping, in synergy with the environmental aspects.
Neuroprotective effect of Dl-3-n-butylphthalide against ischemia–reperfusion injury is mediated by ferroptosis regulation via the SLC7A11/GSH/GPX4 pathway and the attenuation of blood–brain barrier disruption
Authors: Xu Shuangli , Li Xuewei , Li Yutian , Li Xiangling , Lv E. , Zhang Xiaojun , Shi Youkui , Wang Yanqiang 
Published: February 2023

BackgroundStroke is one of the most severe diseases worldwide, resulting in physical and mental problems. Dl-3-n-butylphthalide, a compound derived from celery seed, has been approved for treating ischemic stroke in China. No study has evaluated how Dl-3-n-butylphthalide affects the ferroptosis SLC7A11/GSH/GPX4 signal pathway and blood–brain barrier (BBB) PDGFRβ/PI3K/Akt signal pathways in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model of ischemic stroke.MethodsSprague–Dawley rats were used to develop the MCAO/R model. Our study used three incremental doses (10, 20, and 30) of Dl-3-n-butylphthalide injected intraperitoneally 24 h after MCAO/R surgery. The neuroprotective effect and success of the model were evaluated using the neurofunction score, brain water content determination, and triphenyl-tetrazolium chloride-determined infarction area changes. Pathological changes in the brain tissue and the degree of apoptosis were examined by hematoxylin and eosin, Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, pathway proteins and RNA expression levels were studied to verify the effects of Dl-3-n-butyphthalide on both pathways. At the same time, commercial kits were used to detect glutathione, reactive oxygen species, and malondialdehyde, to detect oxidative stress in brain tissues.ResultsThe middle dose of Dl-3-n-butylphthalide not only improved MCAO-induced brain dysfunction and alleviated pathological damage, brain inflammatory response, oxidative stress, and apoptosis but also protected against ferroptosis and reduced BBB damage. These changes resulted in improved neurological function in the cerebral cortex.ConclusionWe speculate that Dl-3-n-butylphthalide has a neuroprotective effect on focal cerebral ischemia/reperfusion, which may be mediated through ferroptosis-dependent SLC7A11/GSH/GPX4 signal pathway and PDGFRβ/PI3/Akt signal pathway.
A simultaneous EEG-fMRI study of thalamic load-dependent working memory delay period activity
Authors: Gomes Bernard A. , Plaska Chelsea Reichert , Ortega Jefferson , Ellmore Timothy M. 
Published: February 2023

IntroductionWorking memory (WM) is an essential component of executive functions which depend on maintaining task-related information online for brief periods in both the presence and absence of interfering stimuli. Active maintenance occurs during the WM delay period, the time between stimulus encoding and subsequent retrieval. Previous studies have extensively documented prefrontal and posterior parietal cortex activity during the WM delay period, but the role of subcortical structures including the thalamus remains to be fully elucidated, especially in humans.MethodsUsing a simultaneous electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) approach, we investigated the role of the thalamus during the WM delay period in a modified Sternberg paradigm following low and high memory load encoding of naturalistic scenes. During the delay, participants passively viewed scrambled scenes containing similar color and spatial frequency to serve as a perceptual baseline. Individual source estimation was weighted by the location of the thalamic fMRI signal relative to the WM delay period onset.ResultsThe effects memory load on maintenance were observed bilaterally in thalamus with higher EEG source amplitudes in the low compared to high load condition occurring 160–390 ms after the onset of the delay period.ConclusionThe main finding that thalamic activation was elevated during the low compared to high condition despite similar duration of perceptual input and upcoming motor requirements suggests a capacity-limited role for sensory filtering of the thalamus during consolidation of stimuli into WM, where the highest activity occurs when fewer stimuli need to be maintained in the presence of interfering perceptual stimuli during the delay. The results are discussed in the context of theories regarding the role of the thalamus in sensory gating during working memory.