bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virulence capacity of different Aspergillus species from invasive pulmonary aspergillosis
Authors: Chen Biao , Qian Guocheng , Yang Zhiya , Zhang Ning , Jiang Yufeng , Li Dongmei , Li Renzhe , Shi Dongmei 
Published: March 2023

IntroductionThe opportunistic filamentous fungus Aspergillus causes invasive pulmonary aspergillosis (IPA) that often turns into a fatal infection in immunocompromised hosts. However, the virulence capacity of different Aspergillus species and host inflammation induced by different species in IPA are not well understood.MethodsIn the present study, host inflammation, antimicrobial susceptibilities and virulence were compared among clinical Aspergillus strains isolated from IPA patients.ResultsA total of 46 strains were isolated from 45 patients with the invasive infection, of which 35 patients were diagnosed as IPA. Aspergillus flavus was the dominant etiological agent appearing in 25 cases (54.3%). We found that the CRP level and leukocyte counts (elevated neutrophilic granulocytes and monocytes, and reduced lymphocytes) were significantly different in IPA patients when compared with healthy individuals (P &lt; 0.05). Antifungal susceptibilities of these Aspergillus isolates from IPA showed that 91%, 31%, 14%, and 14% were resistant to Fluconazole, Micafungin, Amphotericin B and Terbinafine, respectively. The survival rate of larvae infected by A. flavus was lower than larvae infected by A. niger or A. fumigatus (P &lt; 0.05).DiscussionAspergillus flavus was the dominant clinical etiological agent. Given the prevalence of A. flavus in our local clinical settings, we may face greater challenges when treating IPA patients.
Deciphering the role of QPCTL in glioma progression and cancer immunotherapy
Authors: Liu Yu’e , Lu Shaojuan , Sun Yihong , Wang Fei , Yu Shibo , Chen Xi , Wu Lei-lei , Yang Hui , Shi Yufeng , Zhao Kaijun 
Published: March 2023

BackgroundGlioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy.MethodsQPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors.ResultsIn contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p &lt; 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p &lt; 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness.ConclusionHigh QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.
Association between salivary microbiota and renal function in renal transplant patients during the perioperative period
Authors: Xiang Xuyu , Peng Bo , Liu Kai , Wang Tianyin , Ding Peng , Li Hao , Zhu Yi , Ming Yingzi 
Published: March 2023

IntroductionRenal transplantation is an effective treatment for the end stage renal disease (ESRD). However, how salivary microbiota changes during perioperative period of renal transplant recipients (RTRs) has not been elucidated.MethodsFive healthy controls and 11 RTRs who had good recovery were enrolled. Saliva samples were collected before surgery and at 1, 3, 7, and 14 days after surgery. 16S rRNA gene sequencing was performed.ResultsThere was no significant difference in the composition of salivary microbiota between ESRD patients and healthy controls. The salivary microbiota of RTRs showed higher operational taxonomic units (OTUs) amount and greater alpha and beta diversity than those of ESRD patients and healthy controls, but gradually stabilized over time. At the phylum level, the relative abundance of Actinobacteria, Tenericutes and Spirochaetes was about ten times different from ESRD patients or healthy controls for RTRs overall in time. The relative abundance of Bacteroidetes, Fusobacteria, Patescibacteria, Leptotrichiaceae and Streptococcaceae was correlated with serum creatinine (Scr) after renal transplantation.DiscussionIn short, salivary microbiota community altered in the perioperative period of renal transplantation and certain species of salivary microbiota had the potential to be a biomarker of postoperative recovery.
Test-re-test reliability and dynamics of the Fukuda–Unterberger stepping test
Authors: Hemm Simone , Baumann Denise , Duarte da Costa Vasco , Tarnutzer Alexander Andrea 
Published: March 2023

BackgroundThe Fukuda-stepping-test (FST), i.e., repetitive walking on the spot while blindfolded, has been proposed as a means to assess the integrity of the vestibular pathways. While its sensitivity to detect abnormalities in patients is limited, it may be useful in studying the physiology of the subjective-straight-ahead (SSA). Considering reported systematic shifts in SSA in humans, we hypothesize that such asymmetries arise from individual differences in the orientation/configuration of the macular organs and in central processing of vestibular input. We hypothesize that such asymmetries are stable over time in individual subjects. Alternatively, such asymmetries may arise from random noise in the sensory/motor systems involved, demonstrating low reproducibility over time.Materials and methodsTwenty-four subjects walked on the spot over 60 s while blindfolded (n = 6 trials per subject). Using an inertial measurement unit (IMU) placed at the chest, angular deviations were recorded and compared to manually-measured final positions. Both static (direction, magnitude) and dynamic (time-to-onset of deviation, pattern of deviations) parameters were retrieved from the yaw slopes.ResultsSignificant deviations were found in 15/24 participants for the manual measurements (leftwards = 8; rightwards = 7), whereas when using the IMU-sensor 13/24 participants showed significant shifts (leftwards = 9; rightwards = 4). There was a high correlation (0.98) between manually measured rotation angles (average absolute deviations = 58.0 deg ± 48.6 deg; intra-individual variability = 39 deg ± 24 deg) and sensor-based yaw slopes (1.00 deg/s ± 0.88 deg/s; 0.67 deg/s ± 0.41 deg/s). Relevant yaw deviation was detected 22.1 s ± 12.3 s (range = 5.6 s-59.2 s) after the onset of marching (no relevant yaw-deviation in 15/139 measurements), showing a mostly linear behavior over time.ConclusionWe observed significant inter-individual variability in task performance in the FST, reproducing findings from previous studies. With test-re-test reliability being moderate only, but at the same time observing a preference in the side of shifts in most trials and subjects, we conclude that likely both individually varying estimates of straight-ahead and random noise contribute to the pattern of angular deviations observed. Using an IMU-sensory based approach, additional dynamic parameters could be retrieved, emphasizing the value of such a quantitative approach over manual measurements. Such an approach may provide useful additional information to distinguish patients from healthy controls.
INPH and parkinsonism: A positive shunt response with a negative tap test
Authors: Giannini Giulia , Jusue-Torres Ignacio , Mantovani Paolo , Mazza Liliana , Pirina Alessandro , Valsecchi Nicola , Milletti David , Albini-Riccioli Luca , Cevoli Sabina , Yasar Sevil , Palandri Giorgio 
Published: March 2023

IntroductionThe aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery.Materials and methodsThis is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P−). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery.ResultsA total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P−. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p &lt; 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P− on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P− for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P− significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299).ConclusionPatients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.
Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis
Authors: Yang Zhe-Lun , Liang Ze-Yan , Lin Yi-Ke , Lin Fa-Bin , Rao Jian , Xu Xiong-Jie , Wang Chun-Hua , Chen Chun-Mei 
Published: March 2023

BackgroundThere was still no effective treatment for traumatic brain injury (TBI). Recently, many preclinical studies had shown promising efficacy of extracellular vesicles (EVs) from various cell sources. Our aim was to compare which cell-derived EVs were most effective in treating TBI through a network meta-analysis.MethodsWe searched four databases and screened various cell-derived EVs for use in preclinical studies of TBI treatment. A systematic review and network meta-analysis were conducted for two outcome indicators, modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), and they were ranked by the surface under the cumulative ranking curves (SUCRA). Bias risk assessment was performed with SYRCLE. R software (version 4.1.3, Boston, MA, USA) was used for data analysis.ResultsA total of 20 studies were included in this study, involving 383 animals. Astrocyte-derived extracellular vesicles (AEVs) ranked first in response to mNSS at day 1 (SUCRA: 0.26%), day 3 (SUCRA: 16.32%), and day 7 (SUCRA: 9.64%) post-TBI. Extracellular vesicles derived from mesenchymal stem cells (MSCEVs) were most effective in mNSS assessment on day 14 (SUCRA: 21.94%) and day 28 (SUCRA: 6.26%), as well as MWM’s escape latency (SUCRA: 6.16%) and time spent in the target quadrant (SUCRA: 86.52%). The result of mNSS analysis on day 21 showed that neural stem cell-derived extracellular vesicles (NSCEVs) had the best curative effect (SUCRA: 6.76%).ConclusionAEVs may be the best choice to improve early mNSS recovery after TBI. The efficacy of MSCEVs may be the best in the late mNSS and MWM after TBI.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023377350.
Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis
Authors: Ndjana Lessomo Fabrice Yves , Wang Zhiquan , Mukuka Chishimba 
Published: March 2023

ObjectiveRecently, several researchers have reported the incidence of cardiac-related toxicities occurring with nivolumab (Opdivo) and pembrolizumab (Keytruda). There is still a need for balance between oncology treatment efficacy and reduction of cardiotoxicity burden in immune checkpoint inhibitor (ICI)-treated patients. Thus, the primary aim was to determine whether pembrolizumab or nivolumab would present with a greater risk for cardiotoxicity reports.Materials and methodsThis meta-analysis was performed with respect to the MOOSE reporting guidelines. Studies were retrieved by searching PubMed, Embase, and Google Scholar; the search terms were Keytruda or Pembrolizumab, PD1 inhibitors, anti-PD1 drugs, Nivolumab or Opdivo, and cardiotoxicities or cardiac toxicity. The study was restricted to original articles investigating ICI-induced cardiac immune-related adverse events (irAEs). The targeted population was cancer patients treated with either pembrolizumab or nivolumab monotherapy, of which those with records of any cardiac events following the therapy were labeled as events. The measures used to achieve the comparison were descriptive proportions, probabilities, and meta-analysis pooled odds ratios (ORs).ResultsFifteen studies were included in this meta-analysis. Nivolumab accounted for 55.7% cardiotoxicity and pembrolizumab, for 27.31% (P = 0.027). The meta-analysis was based on the Mantel–Haenszel method, and the random-effect model yielded a pooled OR = 0.73 (95% CI [0.43–1.23] P = 0.24), with considerable heterogeneity (I2 = 99% P = 0). Hence, the difference in cardiotoxicity odds risk between pembrolizumab and nivolumab was not statistically significant. On subgroup analysis based on cardiotoxicity type, the “myocarditis” subgroup in which there was no statistical heterogeneity was associated with a significant cardiotoxicity risk increase with pembrolizumab (OR = 1.30 [1.07;1.59], P&lt; 0.05; I2 = 0%, Ph = 0.4).ConclusionTo our knowledge, this is the first meta-analysis to compare the cardiotoxicity potentials of nivolumab and pembrolizumab. In contrast to previous reports, the overall findings here demonstrated that nivolumab-induced cardiotoxicity was more commonly reported in the literature than pembrolizumab; however, myocarditis seemed more likely to occur with pembrolizumab therapy.
Case report: Complete pathological admission in N3 unresectable locally advanced lung adenocarcinoma with a novel INTS10-ALK and EML4-ALK fusion after neoadjuvant crizotinib
Authors: Zhai Xiaoqian , Wang Ting , Lin Yiyun , Zhang Jiabi , Wang Yuqing , Wang Weiya , Zhou Qinghua , Zhu Daxing 
Published: March 2023

BackgroundAlthough anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have impressive response in advanced lung adenocarcinoma with anaplastic lymphoma kinase (ALK) fusion, no guidelines point to the potential benefits of neoadjuvant ALK-TKIs for N3 unresectable locally advanced lung cancer. Current ongoing clinical trials mainly focus on the efficacy of neoadjuvant ALK-TKIs in resectable locally advanced lung cancer and ignore the role of neoadjuvant ALK-TKIs in N3 unresectable locally advanced lung cancer.Materials and methodsWe report a lung cancer case with a novel INTS10-ALK and EML4-ALK rearrangement that achieved complete pathologic response to neoadjuvant crizotinib. We conducted molecular pathologic analysis by using next-generation sequencing (NGS). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples and profiled using a capture-based targeted sequencing panel consisting of 56 lung cancer-related genes.ResultsOur study reported a patient with stage IIIB-N3 lung adenocarcinoma with an unreported dual ALK rearrangement (INTS10-ALK and EML4-ALK) who received 5 months of crizotinib, followed by R0 right upper lobectomy, achieving complete pathological response (ypT0 ypN0). No recurrence of the tumor was found for 3 years postoperatively.ConclusionThe case supports the strategy of neoadjuvant ALK inhibitors for N3 unresectable locally advanced lung cancer, expanding the spectrum of treatment of stage IIIB-N3 lung cancer.
Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab
Authors: Duminuco Andrea , Romano Alessandra , Leotta Dario , La Spina Enrico , Cambria Daniela , Bulla Anna , Del Fabro Vittorio , Tibullo Daniele , Giallongo Cesarina , Palumbo Giuseppe A. , Conticello Concetta , Di Raimondo Francesco 
Published: March 2023

IntroductionPatients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment.MethodsWe enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses.ResultsAt 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection.ConclusionMonitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.
Genomic landscape and survival analysis of ctDNA “neo-RAS wild-type” patients with originally RAS mutant metastatic colorectal cancer
Authors: Nicolazzo Chiara , Magri Valentina , Marino Luca , Belardinilli Francesca , Di Nicolantonio Federica , De Renzi Gianluigi , Caponnetto Salvatore , De Meo Michela , Giannini Giuseppe , Santini Daniele , Cortesi Enrico , Gazzaniga Paola 
Published: March 2023

BackgroundThe term “neo-RAS wild-type” refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of “neo-RAS wild-type” is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of “true neo-RAS wild- type”.Patients and methods70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test.ResultsThe most commonly detected actionable mutations in “neo-RAS wild-type” were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with “neo-RAS wild-type” compared to those who remained RAS mutant (p&lt;0.001 for both).ConclusionsDe-novo-targetable mutations occured in a large percentage of “neo-RAS wild-type”, being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival.