bluuebunny/crossref_metadata_2025_split huggingface dataset:
18F-FDG-Uptake in Mediastinal Lymph Nodes in Suspected Prosthetic Valve Endocarditis: Predictor or Confounder?
Authors: Hove Derk ten , Sinha Bhanu , Glaudemans Andor W. J. M. , Gomes Anna , Swart Laurens E. , Tanis Wilco , Budde Ricardo P. J. , Slart Riemer H. J. A. 
Published: August 2021

Introduction: Prosthetic valve endocarditis (PVE) is a serious disease affecting ~0.4% of prosthetic valve recipients per year. 18F-FDG-PET/CT has high sensitivity and specificity for PVE and is included as major criterion for the diagnosis in recent guidelines of the European Society of Cardiology. We addressed the question whether increased FDG-uptake in mediastinal lymph nodes could help to support the visual diagnostic assessment of PVE.Methods: In this sub-analysis of a previously published retrospective multicentre study, 160 unique patients were identified who underwent 18F-FDG-PET/CT for evaluation of suspected PVE. 18F-FDG-PET/CT was performed in adherence to the European Association of Nuclear Medicine guidelines of 2015 and scans were assessed for signs of mediastinal lymph node activity by 2 experienced nuclear medicine physicians who were blinded to clinical context. Clinical diagnosis of PVE had been established based on surgical findings or multidisciplinary consensus after a 1-year follow-up in 80 of 160 patients (50%).Results: In total, 52 patients showed increased mediastinal lymph node activity. Mediastinal lymph node activity on 18F-FDG-PET/CT did not increase diagnostic accuracy when added to the visual analysis of scans for signs of PVE: X2: 0.118, p = 0.731). After excluding patients with known confounders for 18F-FDG-PET/CT, namely use of Bioglue® during prosthetic valve implantation and C-reactive protein levels below 40 mg/L, mediastinal lymph node activity was still not of additional diagnostic value compared to visual analysis alone (X2:0.129, p = 0.723).Discussion: Assessment of mediastinal lymph node activity did not improve 18F-FDG-PET/CT diagnostic accuracy for suspected PVE compared to visual assessment of the valve alone, as it seems to be a rather a specific finding, that might be caused by sternal wound or mediastinal infections or even by subclinical respiratory infections. Future studies might elucidate whether increased FDG active lymph nodes indicate a high-risk patient group and whether more detailed assessment of mediastinal lymph nodes could improve their additional diagnostic benefit.
Early-Phase Urine Output and Severe-Stage Progression of Oliguric Acute Kidney Injury in Critical Care
Authors: Huang Haoquan , Bai Xiaohui , Ji Fengtao , Xu Hui , Fu Yanni , Cao Minghui 
Published: August 2021

Background: The relationship between urine output (UO) and severe-stage progression in the early phase of acute kidney injury (AKI) remains unclear. This study aimed to investigate the relationship between early-phase UO6−12h [UO within 6 h after diagnosis of stage 1 AKI by Kidney Disease: Improving Global Outcomes (KDIGO) UO criteria] and severe-stage progression of AKI and to identify a reference value of early-phase UO6−12h for guiding initial therapy in critical care.Methods: Adult patients with UO &lt; 0.5 ml/kg/h for the first 6 h after intensive care unit (ICU) admission (meeting stage 1 AKI by UO) and UO6−12h ≥ 0.5 ml/kg/h were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. The primary outcome was progression to stage 2/3 AKI by UO. After other variables were adjusted through multivariate analysis, generalized additive model (GAM) was used to visualize the relationship between early-phase UO6−12h and progression to stage 2/3 AKI by UO. A two-piecewise linear regression model was employed to identify the inflection point of early-phase UO6−12h above which progression risk significantly leveled off. Sensitivity and subgroup analyses were performed to assess the robustness of our findings.Results: Of 2,984 individuals, 1,870 (62.7%) with KDIGO stage 1 UO criteria progressed to stage 2/3 AKI. In the multivariate analysis, early-phase UO6−12h showed a significant association with progression to stage 2/3 AKI by UO (odds ratio, 0.40; 95% confidence interval, 0.34–0.46; p &lt; 0.001). There was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was identified as the inflection point, above which progression risk significantly leveled off (p = 0.780). Patients with early-phase UO6−12h ≥ 1.1 ml/kg/h had significantly shorter length of ICU stay (3.82 vs. 4.17 days, p &lt; 0.001) and hospital stay (9.28 vs. 10.43 days, p &lt; 0.001) and lower 30-day mortality (11.05 vs. 18.42%, p &lt; 0.001). The robustness of our findings was confirmed by sensitivity and subgroup analyses.Conclusions: Among early-stage AKI patients in critical care, there was a non-linear relationship between early-phase UO6−12h and progression of AKI. Early-phase UO6−12h of 1.1 ml/kg/h was the inflection point above which progression risk significantly leveled off.
Risk Factors, Clinical Outcomes, and Prognostic Factors of Bacterial Keratitis: The Nottingham Infectious Keratitis Study
Authors: Ting Darren Shu Jeng , Cairns Jessica , Gopal Bhavesh P. , Ho Charlotte Shan , Krstic Lazar , Elsahn Ahmad , Lister Michelle , Said Dalia G. , Dua Harminder S. 
Published: August 2021

Background/Aim: To examine the risk factors, clinical characteristics, outcomes, and prognostic factors of bacterial keratitis (BK) in Nottingham, UK.Methods: This was a retrospective study of patients who presented to the Queen's Medical Centre, Nottingham, with suspected BK during 2015–2019. Relevant data, including the demographic factors, risk factors, clinical outcomes, and potential prognostic factors, were analysed.Results: A total of 283 patients (n = 283 eyes) were included; mean age was 54.4 ± 21.0 years and 50.9% were male. Of 283 cases, 128 (45.2%) cases were culture-positive. Relevant risk factors were identified in 96.5% patients, with ocular surface diseases (47.3%), contact lens wear (35.3%) and systemic immunosuppression (18.4%) being the most common factors. Contact lens wear was most commonly associated with P. aeruginosa whereas Staphylococci spp. were most commonly implicated in non-contact lens-related BK cases (p = 0.017). At presentation, culture-positive cases were associated with older age, worse presenting corrected-distance-visual-acuity (CDVA), use of topical corticosteroids, larger epithelial defect and infiltrate, central location and hypopyon (all p &lt; 0.01), when compared to culture-negative cases. Hospitalisation was required in 57.2% patients, with a mean length of stay of 8.0 ± 8.3 days. Surgical intervention was required in 16.3% patients. Significant complications such as threatened/actual corneal perforation (8.8%), loss of perception of light vision (3.9%), and evisceration/enucleation (1.4%) were noted. Poor visual outcome (final corrected-distance-visual-acuity of &lt;0.6 logMAR) and delayed corneal healing (&gt;30 days from initial presentation) were significantly affected by age &gt;50 years, infiltrate size &gt;3 mm, and reduced presenting vision (all p &lt; 0.05).Conclusion: BK represents a significant ocular morbidity in the UK, with ocular surface diseases, contact lens wear, and systemic immunosuppression being the main risk factors. Older age, large infiltrate, and poor presenting vision were predictive of poor visual outcome and delayed corneal healing, highlighting the importance of prevention and early intervention for BK.
Neuroradiologic Evaluation of MRI in High-Contact Sports
Authors: McAllister Derek , Akers Carolyn , Boldt Brian , Mitchell Lex A. , Tranvinh Eric , Douglas David , Goubran Maged , Rosenberg Jarrett , Georgiadis Marios , Karimpoor Mahta , DiGiacomo Phillip , Mouchawar Nicole , Grant Gerald , Camarillo David , Wintermark Max , Zeineh Michael M. 
Published: August 2021

Background and Purpose: Athletes participating in high-contact sports experience repeated head trauma. Anatomical findings, such as a cavum septum pellucidum, prominent CSF spaces, and hippocampal volume reductions, have been observed in cases of mild traumatic brain injury. The extent to which these neuroanatomical findings are associated with high-contact sports is unknown. The purpose of this study was to determine whether there are subtle neuroanatomic differences between athletes participating in high-contact sports compared to low-contact athletic controls.Materials and Methods: We performed longitudinal structural brain MRI scans in 63 football (high-contact) and 34 volleyball (low-contact control) male collegiate athletes with up to 4 years of follow-up, evaluating a total of 315 MRI scans. Board-certified neuroradiologists performed semi-quantitative visual analysis of neuroanatomic findings, including: cavum septum pellucidum type and size, extent of perivascular spaces, prominence of CSF spaces, white matter hyperintensities, arterial spin labeling perfusion asymmetries, fractional anisotropy holes, and hippocampal size.Results: At baseline, cavum septum pellucidum length was greater in football compared to volleyball controls (p = 0.02). All other comparisons were statistically equivalent after multiple comparison correction. Within football at baseline, the following trends that did not survive multiple comparison correction were observed: more years of prior football exposure exhibited a trend toward more perivascular spaces (p = 0.03 uncorrected), and lower baseline Standardized Concussion Assessment Tool scores toward more perivascular spaces (p = 0.02 uncorrected) and a smaller right hippocampal size (p = 0.02 uncorrected).Conclusion: Head impacts in high-contact sport (football) athletes may be associated with increased cavum septum pellucidum length compared to low-contact sport (volleyball) athletic controls. Other investigated neuroradiology metrics were generally equivalent between sports.
Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway
Authors: Zhang Yu , Xiang Jingjing , Zhu Ni , Ge Hangping , Sheng Xianfu , Deng Shu , Chen Junfa , Yu Lihong , Zhou Yan , Shen Jianping 
Published: August 2021

BackgroundBoth omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.MethodsCell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs).ResultsIn this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P &lt; 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P &lt; 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P &lt; 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P &lt; 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P &lt; 0.01).ConclusionOur findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.
m6A Methyltransferase METTL14-Mediated Upregulation of Cytidine Deaminase Promoting Gemcitabine Resistance in Pancreatic Cancer
Authors: Zhang Congjun , Ou Shuangyan , Zhou Yuan , Liu Pei , Zhang Peiying , Li Ziqian , Xu Ruocai , Li Yuqiang 
Published: August 2021

ObjectivePancreatic cancer is one of the most lethal human malignancies. Gemcitabine is widely used to treat pancreatic cancer, and the resistance to chemotherapy is the major difficulty in treating the disease. N6-methyladenosine (m6A) modification, which regulates RNA splicing, stability, translocation, and translation, plays critical roles in cancer physiological and pathological processes. METTL14, an m6A Lmethyltransferase, was found deregulated in multiple cancer types. However, its role in gemcitabine resistance in pancreatic cancer remains elusive.MethodsThe mRNA and protein level of m6A modification associated genes were assessed by QRT-PCR and western blotting. Then, gemcitabine‐resistant pancreatic cancer cells were established. The growth of pancreatic cancer cells were analyzed using CCK8 assay and colony formation assay. METTL14 was depleted by using shRNA. The binding of p65 on METTL14 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Protein level of deoxycytidine kinase (DCK) and cytidine deaminase (CDA) was evaluated by western blotting. In vivo experiments were conducted to further confirm the critical role of METTL14 in gemcitabine resistance.ResultsWe found that gemcitabine treatment significantly increased the expression of m6A methyltransferase METTL14, and METTL14 was up-regulated in gemcitabine-resistance human pancreatic cancer cells. Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. Moreover, we identified that transcriptional factor p65 targeted the promoter region of METTL14 and up-regulated its expression, which then increased the expression of cytidine deaminase (CDA), an enzyme inactivates gemcitabine. Furthermore, in vivo experiment showed that depletion of METTL14 rescue the response of resistance cell to gemcitabine in a xenograft model.ConclusionOur study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.
Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition – Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 Immunohistochemistry
Authors: Placke Jan-Malte , Rawitzer Josefine , Reis Henning , Rashidi-Alavijeh Jassin , Livingstone Elisabeth , Ugurel Selma , Hadaschik Eva , Griewank Klaus , Schmid Kurt Werner , Schadendorf Dirk , Roesch Alexander , Zimmer Lisa 
Published: August 2021

BackgroundGastritis induced by checkpoint inhibitors (CPI) is a rare but severe drug-related side effect. The reference standard for confirming CPI-associated gastritis (CPI-assGastritis) is histopathological assessment; however, the histopathological features of CPI-assGastritis are not yet adequately defined.Materials and MethodsGastric biopsies of melanoma patients with histopathologically suspected CPI-assGastritis were compared with gastric biopsies of patients with inflammation free gastric mucosa (IFGM), type A, B, and C gastritis with respect to apoptosis count and predominant histopathological features. Immunohistochemical anti-caspase-3 staining was performed to identify apoptosis. Quantification was performed by manually counting the number of apoptotic events per 10 high-power fields (HPF). Clinical symptoms, treatment, and follow-up data of patients with CPI-assGastritis were examined. The nonparametric Mann–Whitney U test was used for statistical testing.ResultsFive melanoma patients (three women, two men; median age: 45 years) were treated with PD-1-based CPI. The patients reported epigastric pain, weight loss, nausea, and vomiting. Histologically, the patients with CPI-assGastritis showed a partly lymphocytic, partly granulocytic inflammatory infiltrate. Manual counting of apoptotic cells in biopsy tissue slides stained against caspase 3 revealed a median of 6 apoptotic events/10 HPF (95% CI, 2.75-17.30) in the patients with CPI-assGastritis. Results for the comparison cohort (patients n = 21) were a median of 1 apoptotic event/10 HPF (95% CI, 0.5–4.5) for type-A gastritis (six patients), a median of 2 apoptotic events/10 HPF (95% CI, 0–4.5) for type-B gastritis (five patients), and no apoptosis for IFGM and type-C gastritis (five patients). Patients with CPI-assGastritis had a significantly higher apoptosis count than patients with IFGM (p&lt;0.01), type A (p&lt;0.05), B (p&lt;0.05), and C gastritis (p&lt;0.01). None of the CPI-assGastritis biopsies showed evidence of Helicobacter pylori. All CPI-assGastritis patients responded to systemic treatment with corticosteroids.ConclusionCPI-assGastritis manifests with nonspecific symptoms but histologically shows a high number of apoptotic events, which can best be visualized by anti-caspase-3 immunohistochemistry. This histopathological feature may help to histologically differentiate CPI-assGastritis from other forms of gastritis and inform decision-making regarding its optimal management.
Variation in Pediatric Anesthesiologist Sedation Practices for Pediatric Gastrointestinal Endoscopy
Authors: Hartjes Kayla T. , Dafonte Tracey M. , Lee Austin F. , Lightdale Jenifer R. 
Published: August 2021

Background: Despite a worldwide shift toward anesthesiologist-administered sedation for gastrointestinal endoscopy in children, ideal sedation regimens remain unclear and best practices undefined.Aim: The aim of our study was to document variation in anesthesiologist-administered sedation for pediatric endoscopy. Outcomes of interest included coefficients of variation, procedural efficiency, as well as adverse events.Methods: IRB approval was obtained to review electronic health records of children undergoing routine endoscopy at our medical center during a recent calendar year. Descriptive and multivariate analyses were used to examine predictors of sedation practices.Results: 258 healthy children [2–21 years (median 15, (Q1–Q3 = 10–17)] underwent either upper and/or lower endoscopies with sedation administered by anesthesiologists (n = 21), using different sedation regimens (29) that ranged from a single drug administered to 6 sedatives in combination. Most patients did not undergo endotracheal tube intubation for the procedure (208, 81%), and received propofol (255, 89%) either alone or in combination with other sedatives. A total of 10 (3.8%) adverse events (9 sedation related) were documented to occur. The coefficient of variation (CV) for sedation times was high at 64.2%, with regression analysis suggesting 8% was unexplained by procedure time. Multivariable model suggested that longer procedure time (p &lt; 0.0001), younger age (p &lt; 0.0001), and use of endotracheal tube intubation (p = 0.02) were associated with longer sedation time.Discussion: We found great variation in anesthesiologist administered regimens for pediatric endoscopy at our institution that may be unwarranted, presenting may opportunities for minimizing patient risk, as well as for optimizing procedural efficiency.
No Evidence of Unexpected Transgenic Insertions in T1190 – A Transgenic Apple Used in Rapid Cycle Breeding – Following Whole Genome Sequencing
Authors: Patocchi Andrea , Keilwagen Jens , Berner Thomas , Wenzel Stefanie , Broggini Giovanni A. L. , Altschmied Lothar , Hanke Magda-Viola , Flachowsky Henryk 
Published: August 2021

Rapid cycle breeding uses transgenic early flowering plants as crossbreed parents to facilitate the shortening of breeding programs for perennial crops with long-lasting juvenility. Rapid cycle breeding in apple was established using the transgenic genotype T1190 expressing the BpMADS4 gene of silver birch. In this study, the genomes of T1190 and its non-transgenic wild-type PinS (F1-offspring of ‘Pinova’ and ‘Idared’) were sequenced by Illumina short-read sequencing in two separate experiments resulting in a mean sequencing depth of 182× for T1190 and 167× for PinS. The sequencing revealed 8,450 reads, which contain sequences of ≥20 bp identical to the plant transformation vector. These reads were assembled into 125 contigs, which were examined to see whether they contained transgenic insertions or if they are not using a five-step procedure. The sequence of one contig represents the known T-DNA insertion on chromosome 4 of T1190. The sequences of the remaining contigs were either equally present in T1190 and PinS, their part with sequence identity to the vector was equally present in apple reference genomes, or they seem to result from endophytic contaminations rather than from additional transgenic insertions. Therefore, we conclude that the transgenic apple plant T1190 contains only one transgenic insertion, located on chromosome 4, and shows no further partial insertions of the transformation vector.Accession Numbers: JQ974028.1.
The Relationship Between Inflammation and Post-traumatic Stress Disorder
Authors: Sun Yajing , Qu Yuanyuan , Zhu Jianwei 
Published: August 2021

Background: Stress disorders, such as post-traumatic stress disorder (PTSD), are attracting much attention. However, the relationship between traumatic stress and inflammation is rarely discussed.Subjects and Methods: As studies have linked PTSD to altered susceptibility to various diseases, such a psychiatric condition may lead to long-term systematic changes in physiological functions. We searched PubMed with the keywords “traumatic stress,” “stress disorders,” “post-traumatic stress disorder,” and “inflammation.”Results: Based on 65 previously published studies, we reviewed the long-term effects of PTSD, as well as traumatic events, on inflammatory function from both epidemiological and biological perspectives. Post-traumatic stress disorder is related to the immune response, including an increase in inflammatory factors and a reduction in anti-inflammatory factors. Additionally, it has been demonstrated that traumatic stress disorder and immune disease share a common genetic basis at the gene expression level.Conclusions: Understanding this relationship is of great significance for optimizing treatment plans for patients with PTSD.