bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological role and prognostic value of the SKA family in pan-cancer analysis
Authors: Li Zhengtian , Huang Lanying , Li Jiachen , Yang Wenkang , Li Weichao , Long Qiuzhong , Dai Xinyu , Wang Hongtao , Du Gang 
Published: April 2023

BackgroundThe spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated.MethodsUsing data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes.ResultsOur results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group.ConclusionThe SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.
Study protocol: a prospective single-center study for non-invasive biomonitoring of renal complications in cancer patients treated with immune checkpoint inhibitors
Authors: Baier Eva , Korsten Peter , Strauß Arne , Thoms Kai-Martin , Overbeck Tobias , Ströbel Philipp , Tampe Björn 
Published: April 2023

BackgroundThe advent of immune checkpoint inhibitors (ICIs) has powerfully broadened the scope of treatment options for malignancies with an ongoing increase of indications, but immune-related adverse events (irAEs) represent a serious threat to treatment success. Agents directed against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) are known to cause renal complications with an incidence of 3%. In contrast, subclinical renal involvement is estimated to be much higher, up to 29%. We recently reported about urinary flow cytometry-based detection of urinary PD-L1-positive (PD-L1+) kidney cells correlating with tubular PD-L1-positivity that reflected susceptibility to develop ICI-related nephrotoxicity as an irAE attending ICI treatment. Therefore, we designed a study protocol to evaluate urinary detection of PD-L1+ kidney cells as a tool for non-invasive biomonitoring of renal complications in cancer patients treated with ICIs.MethodsA prospective, controlled, non-interventional, longitudinal, single-center observational study will be conducted at the Department of Nephrology and Rheumatology of the University Medical Center Göttingen, Germany. We intend to enroll approximately 200 patients treated with immunotherapy from the Departments of Urology, Dermatology, and Hematology and Medical Oncology of the University Medical Center Göttingen, Germany. First, we will assess clinical, laboratory, histopathological, and urinary parameters in addition to urinary cell collection. Then, we will perform a correlative analysis between urinary flow cytometry of different PD-L1+ cell of renal origin with the onset of ICI-related nephrotoxicity.DiscussionBecause of growing ICI-treatment applicability with an expectable incidence of renal complications, providing cost-efficient and easily performable diagnostic tools for treatment-attendant and non-invasive biomonitoring becomes vital to improve both renal and overall survival rates in cancer patients receiving immunotherapy.Trial registrationhttps://www.drks.de, DRKS-ID DRKS00030999.
Memory SARS-CoV-2 T-cell response in convalescent COVID-19 patients with undetectable specific IgG antibodies: a comparative study
Authors: Fernández-Moreno Raquel , Valle-Arroyo Jorge , Páez-Vega Aurora , Salinas Ana , Cano Angela , Pérez Ana B. , Torre-Cisneros Julián , Cantisán Sara 
Published: April 2023

BackgroundDuring the COVID-19 pandemic, a variable percentage of patients with SARS-CoV-2 infection failed to elicit humoral response. This study investigates whether patients with undetectable SARS-CoV-2 IgG are able to generate SARS-CoV-2 memory T cells with proliferative capacity upon stimulation.MethodsThis cross-sectional study was conducted with convalescent COVID-19 patients, diagnosed with a positive real-time PCR (RT-PCR) from nasal and pharyngeal swab specimens. COVID-19 patients were enrolled ≥3 months after the last PCR positive. Proliferative T-cell response after whole blood stimulation was assessed using the FASCIA assay.ResultsA total of 119 participants (86 PCR-confirmed COVID-19 patients and 33 healthy controls) were randomly filtered from an initial cohort. Of these 86 patients, 59 had detectable (seropositive) and 27 had undetectable (seronegative) SARS-CoV-2 IgG. Seropositive patients were subclassified as asymptomatic/mild or severe according to the oxygen supplementation requirement. SARS-CoV-2 CD3+ and CD4+ T cells showed significantly lower proliferative response in seronegative than in seropositive patients. The ROC curve analysis indicated that ≥ 5 CD4+ blasts/μL of blood defined a “positive SARS-CoV-2 T cell response”. According to this cut-off, 93.2% of seropositive patients had a positive T-cell response compared to 50% of seronegative patients and 20% of negative controls (chi-square; p &lt; 0.001).ConclusionsThis proliferative assay is useful not only to discriminate convalescent patients from negative controls, but also to distinguish seropositive patients from those with undetectable SARS-CoV-2 IgG antibodies. Memory T cells in seronegative patients are able to respond to SARSCoV-2 peptides, although at a lower magnitude than seropositive patients.
Antibiotic resistance associated lactic acid cross tolerance in Shiga-toxin producing E. coli
Authors: Oguadinma Ikechukwu , Mishra Abhinav , Dev Kumar Govindaraj 
Published: April 2023

IntroductionThe occurrence of antibiotic resistant (ABR) bacteria in foods is a growing public health challenge. We evaluated sanitizer cross-tolerance among ABR Escherichia coli (E. coli) O157:H7 and non-O157:H7 Shiga-toxin producing E. coli (STEC) serogroups. Sanitizer tolerance in STEC could be a public health concern as mitigation strategies against the pathogen might be compromised.MethodsResistance to ampicillin and streptomycin were evolved in E. coli serogroups: O157:H7 (H1730, and ATCC 43895), O121:H19 and O26:H11. Resistance to antibiotics was evolved chromosomally through incremental exposure to ampicillin (amp C) and streptomycin (strep C). Transformation using a plasmid was performed to confer resistance to ampicillin to generate amp P strep C.ResultsThe minimum inhibitory concentration (MIC) of lactic acid for all strains evaluated was 0.375% v/v. Analysis of bacterial growth parameters in tryptic soy broth amended with 0.0625% v/v, 0.125% v/v, and 0.25% v/v (subMIC) lactic acid indicated that growth correlated positively with the lag phase duration, and negatively with both the maximum growth rate and change in population density for all strains evaluated except for the highly tolerant variant- O157:H7 amp P strep C. Strains O121 NR (non-ABR), O121 amp C, O121 amp P strep C, O157:H7 H1730 amp C and O157:H7 H1730 amp P strep C were not inactivated after exposure to 1% and 2.5% v/v lactic acid for 300 s. No recovery of cells was observed after the strains were exposed to 5% v/v lactic acid for 300 s. ABR strains O157:H7 H1730 amp C and O157: H7 H1730 amp P strep C demonstrated a high tolerance to lactic acid (P ≤ 0.05).ConclusionABR in isolate E. coli O157: H7 H1730 may improve tolerance to lactic acid. Increased tolerance may be discerned by evaluating growth parameters of bacteria in presence of sub-MIC levels of lactic acid.
Alterations in the intestinal microbiome and metabolic profile of patients with cirrhosis supplemented with lactulose, Clostridium butyricum, and Bifidobacterium longum infantis: a randomized placebo-controlled trial
Authors: Lu Haifeng , Zhu Xiaofei , Wu Lingyun , Lou Xiaobin , Pan Xiaxia , Liu Bowen , Zhang Hua , Zhu Lingxiao , Li Lanjuan , Wu Zhongwen 
Published: April 2023

BackgroundLiver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent promising interventions for managing cirrhosis and its complications. However, the influences of the intestinal metagenomes and metabolic profiles of patients have not been fully elucidated.MethodsWe administered lactulose, Clostridium butyricum, and Bifidobacterium longum infantis as a synbiotic and used shotgun metagenomics and non-targeted metabolomics to characterize the results.ResultsPatients treated with the synbiotic for 12 weeks had lower dysbiosis index (DI) scores than placebo-treated patients and patients at baseline (NIP group). We identified 48 bacterial taxa enriched in the various groups, 66 differentially expressed genes, 18 differentially expressed virulence factor genes, 10 differentially expressed carbohydrate-active enzyme genes, and 173 metabolites present at differing concentrations in the Synbiotic versus Placebo group, and the Synbiotic versus NIP group. And Bifidobacteria species, especially B. longum, showed positive associations with many differentially expressed genes in synbiotic-treated patients. Metabolites pathway enrichment analysis showed that synbiotic significantly affected purine metabolism and aminoacyl-tRNA biosynthesis. And the purine metabolism and aminoacyl-tRNA biosynthesis were no longer significant differences in the Synbiotic group versus the healthy controls group. In conclusion, although littles influence on clinical parameters in the early intervention, the synbiotic showed a potential benefit to patients by ameliorating intestinal dysbiosis and metabolic defects; and the DI of intestinal microbiota is useful for the evaluation of the effect of clinical microbiota-targeting strategies on cirrhotic patients.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifiers NCT05687409.
Aging effect of cross-modal interactions during audiovisual detection and discrimination by behavior and ERPs
Authors: Ren Yanna , Li Yan , Xu Zhihan , Luo Rui , Qian Runqi , Duan Jieping , Yang Jiajia , Yang Weiping 
Published: April 2023

IntroductionNumerous studies have shown that aging greatly affects audiovisual integration; however, it is still unclear when the aging effect occurs, and its neural mechanism has yet to be fully elucidated.MethodsWe assessed the audiovisual integration (AVI) of older (n = 40) and younger (n = 45) adults using simple meaningless stimulus detection and discrimination tasks. The results showed that the response was significantly faster and more accurate for younger adults than for older adults in both the detection and discrimination tasks. The AVI was comparable for older and younger adults during stimulus detection (9.37% vs. 9.43%); however, the AVI was lower for older than for younger adults during stimulus discrimination (9.48% vs. 13.08%) behaviorally. The electroencephalography (EEG) analysis showed that comparable AVI amplitude was found at 220–240 ms for both groups during stimulus detection and discrimination, but there was no significant difference between brain regions for older adults but a higher AVI amplitude in the right posterior for younger adults. Additionally, a significant AVI was found for younger adults in 290–310 ms but was absent for older adults during stimulus discrimination. Furthermore, significant AVI was found in the left anterior and right anterior at 290–310 ms for older adults but in the central, right posterior and left posterior for younger adults.DiscussionThese results suggested that the aging effect of AVI occurred in multiple stages, but the attenuated AVI mainly occurred in the later discriminating stage attributed to attention deficit.
Dilation of the superior sagittal sinus detected in rat model of mild traumatic brain injury using 1 T magnetic resonance imaging
Authors: Burns Jennie M. , Kalinosky Benjamin T. , Sloan Mark A. , Cerna Cesario Z. , Fines David A. , Valdez Christopher M. , Voorhees William B. 
Published: April 2023

IntroductionMild traumatic brain injury (mTBI) is a common injury that can lead to temporary and, in some cases, life-long disability. Magnetic resonance imaging (MRI) is widely used to diagnose and study brain injuries and diseases, yet mTBI remains notoriously difficult to detect in structural MRI. mTBI is thought to be caused by microstructural or physiological changes in the function of the brain that cannot be adequately captured in structural imaging of the gray and white matter. However, structural MRIs may be useful in detecting significant changes in the cerebral vascular system (e.g., the blood-brain barrier (BBB), major blood vessels, and sinuses) and the ventricular system, and these changes may even be detectable in images taken by low magnetic field strength MRI scanners (&lt;1.5T).MethodsIn this study, we induced a model of mTBI in the anesthetized rat animal model using a commonly used linear acceleration drop-weight technique. Using a 1T MRI scanner, the brain of the rat was imaged, without and with contrast, before and after mTBI on post-injury days 1, 2, 7, and 14 (i.e., P1, P2, P7, and P14).ResultsVoxel-based analyses of MRIs showed time-dependent, statistically significant T2-weighted signal hypointensities in the superior sagittal sinus (SSS) and hyperintensities of the gadolinium-enhanced T1-weighted signal in the superior subarachnoid space (SA) and blood vessels near the dorsal third ventricle. These results showed a widening, or vasodilation, of the SSS on P1 and of the SA on P1–2 on the dorsal surface of the cortex near the site of the drop-weight impact. The results also showed vasodilation of vasculature near the dorsal third ventricle and basal forebrain on P1–7.DiscussionVasodilation of the SSS and SA near the site of impact could be explained by the direct mechanical injury resulting in local changes in tissue function, oxygenation, inflammation, and blood flow dynamics. Our results agreed with literature and show that the 1T MRI scanner performs at a level comparable to higher field strength scanners for this type of research.
Anti-LGI1 encephalitis with initiating symptom of seizures in children
Authors: Wang Yang , Zhang Dongqing , Tong Lili , Yang Lu , Yin Ping , Li Jun , Lei Gefei , Yang Xiaofan , Li Baomin 
Published: April 2023

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis.MethodsThree anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail.ResultsCase 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy.ConclusionChildhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.
The underpinning of meaningful activities by brain correlates: a systematic review
Authors: Cruyt Ellen , De Vriendt Patricia , De Geyter Nele , Van Leirsberghe Janne , Santens Patrick , De Baets Stijn , De Letter Miet , Vlerick Peter , Calders Patrick , De Pauw Robby , Oostra Kristine , Van de Velde Dominique 
Published: April 2023

IntroductionEngaging in meaningful activities contributes to health and wellbeing. Research identifies meaningfulness by analysing retrospective and subjective data such as personal experiences in activities. Objectively measuring meaningful activities by registering the brain (fNIRS, EEG, PET, fMRI) remains poorly investigated.MethodsA systematic review using PubMed, Web of Science, CINAHL, and Cochrane Library.FindingsThirty-one studies investigating the correlations between daily activities in adults, their degree of meaningfulness for the participant, and the brain areas involved, were identified. The activities could be classified according to the degree of meaningfulness, using the attributes of meaningfulness described in the literature. Eleven study activities contained all attributes, which means that these can be assumed to be meaningful for the participant. Brain areas involved in these activities were generally related to emotional and affective processing, motivation, and reward.ConclusionAlthough it is demonstrated that neural correlates of meaningful activities can be measured objectively by neurophysiological registration techniques, “meaning” as such has not yet been investigated explicitly. Further neurophysiological research for objective monitoring of meaningful activities is recommended.
Systematic reviews and meta-analyses on major depressive disorder: a bibliometric perspective
Authors: Chen Pan , Feng Yuan , Li Xiao-Hong , Li Jia-Xin , Wang Yue-Ying , Zheng Wan-Ying , Su Zhaohui , Cheung Teris , Ungvari Gabor S. , Ng Chee H. , Sha Sha , Xiang Yu-Tao 
Published: April 2023

BackgroundThere is a vast amount of evidence-based medicine research on the major depressive disorder (MDD) available in the literature, however, no studies on the overall performance, productivity and impact of such research have been published to date. This study explored and mapped the research outputs of MDD-related systematic reviews and meta-analyses (SR/MA) from a bibliometric perspective.MethodsRelevant data were retrieved with search terms on MDD, systematic review and meta-analysis.ResultsA total of 4,870 papers with 365,402 citations published from 1983 to 2022 were included in the analysis. The publication output has grown steadily over time with the most publications originating from the USA (1,020; 20.94%), the UK (516; 10.60%) and China (448; 9.20%). The research collaborations between countries were most frequent between the USA and UK (266; 5.46%). Journal of Affective Disorders (379; 7.78%) was the most productive journal, while Cuijpers P was the most productive author (121; 2.48%), and University of Toronto (569; 11.78%) was the most productive institution. The top 10 most cited articles on MDD-related SR/MA had citations ranging from 1,806 to 3,448. The high-frequency keywords were mainly clustered into four themes, including psychiatric comorbidities, clinical trials, treatment, and brain stimulation in MDD.ConclusionThe rapid increase in the number of SR/MA of MDD in recent years highlights the importance of this research field. Psychiatric comorbidities, clinical interventions, and treatment of MDD have been identified as hot topics, while biological mechanisms in MDD are likely to be an emerging research priority.