bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study
Authors: Loft Josefine Amalie , Møller Dina Leth , Thudium Rebekka Faber , Knudsen Jenny Dahl , Ostrowski Sisse Rye , Andersen Åse Bengård , Nielsen Susanne Dam 
Published: March 2022

IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.
E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter pylori: Importance of the Prevalence of Metronidazole Resistance
Authors: Chen Jinnan , Huang Yu , Ding Zhaohui , Liang Xiao , Lu Hong 
Published: March 2022

BackgroundA number of studies have shown that E-test overestimated the presence of Helicobacter pylori resistance compared to agar dilution.ObjectiveThe purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori.MethodE-test and agar dilution were used to assess the susceptibility of H. pylori to metronidazole, clarithromycin, and levofloxacin in 281 clinical isolates obtained from China where the resistance was high. Cohen’s kappa analysis, McNemar’s test, and essential and categorical agreement analysis were performed for these two methods.ResultsOverall, the result of the E-test showed a similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement of the E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin was moderate at 89.0 and 79.7%, respectively, but only 45.9% for metronidazole. The results shown by a categorical agreement (CA) between the E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and the rate of a very major error was 1.8%.ConclusionE-test can be an alternative method to detect the metronidazole susceptibility of H. pylori.
Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders
Authors: Sato Akemi , Tominaga Koji , Iwatani Yoshiko , Kato Yoko , Wataya-Kaneda Mari , Makita Kai , Nemoto Kiyotaka , Taniike Masako , Kagitani-Shimono Kuriko 
Published: March 2022

ObjectiveTuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).MethodsA total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.ResultsThe TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.ConclusionThe disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.
Abnormal Brain MRI Findings in Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Correlation With Outcomes
Authors: Lei Chunyan , Chang Xiaolong , Li Haijiang , Zhong Lianmei 
Published: March 2022

PurposeThe reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we investigated the prevalence of abnormal MRI findings in Chinese patients and explored whether such findings are correlated with clinical outcomes.MethodsThis retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the “MRI-normal” or the “MRI-abnormal” group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission.ResultsThirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months.ConclusionsWe found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term.
Efficacy and Safety of Diet Therapies in Children With Autism Spectrum Disorder: A Systematic Literature Review and Meta-Analysis
Authors: Yu Yuping , Huang Jinyue , Chen Xiaofang , Fu Jia , Wang Xinhui , Pu Linjie , Gu Chunyu , Cai Chunquan 
Published: March 2022

ObjectiveAutism Spectrum Disorder is a neurodevelopmental disorder, with a rapid increase in recognition over the past decade. Interest in alternative therapies is growing annually, such as dietary therapies including gluten-free and/or casein-free diet, and the ketogenic diet. However, there is no consensus on the efficacy and safety of dietary therapy in children with ASD up to now. This study aimed to assess the efficacy and safety of these diet interventions for children with ASD based on a meta-analysis of global data.MethodsSeven databases (Cochrane Library, PubMed, EMBASE, Web of Science, VIP, CNKI, and Wanfang) were searched according to the established inclusion criteria, from the inception of the databases to August 18, 2021. The Cochrane Bias risk assessment tool was intended to assess the quality of the included studies. Review Manager 5.4 software was used as an efficacy analysis tool of the included studies, taking the core autistic symptoms and scales of ASD as therapeutic efficacy evaluations.ResultsIn total, 7 RCTs with 338 participants were finally obtained. All studies assessed the association between core autistic symptoms and therapeutic diet, showing a statistically significant effect (standard mean difference (SMD) of −0.51, 95% confidence interval (Cl): −0.81 to −0.21), in which two studies which followed the GFD diet reported significant reductions in social behaviors (SMD of−0.41, 95% Cl: −0.75 to −0.06), showing no correlation with the length of the interventions (P &lt; 0.05). Two studies were performed in KD diet suggested a significant effect in core symptoms (SMD of −0.67, 95% Cl: −1.04 to −0.31). No statistically significant changes were observed in the GFCF diet, GFD diet, cognition, communication, and stereotypical behaviors subgroups (all P &gt; 0.05).ConclusionThe results of a meta-analysis suggest that diet therapies can significantly ameliorate core symptoms of ASD, and GFD diets are conducive to improving social behaviors. Although the results suggest the effectiveness of dietary therapy for ASD, limited by the small sample size of RCTs, more well-designed, and high-quality clinical trials are needed to validate the above conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021277565.
Aneurysm Location Affects Clinical Course and Mortality in Patients With Subarachnoid Hemorrhage
Authors: Göttsche Jennifer , Piffko Andras , Pantel Tobias F. , Westphal Manfred , Dührsen Lasse , Czorlich Patrick , Sauvigny Thomas 
Published: March 2022

ObjectiveThe influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality.MethodsThe data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale.ResultsA total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms (p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms (p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex (p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 −0.893)].ConclusionsThe aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH.
Case Report: Dysfunction of the Paraventricular Hypothalamic Nucleus Area Induces Hypersomnia in Patients
Authors: Wang Zan , Zhong Yu-Heng , Jiang Shan , Qu Wei-Min , Huang Zhi-Li , Chen Chang-Rui 
Published: March 2022

BackgroundHypersomnia is a common and highly impairing symptom marked by pathological excessive sleepiness, which induces suboptimal functioning and poor quality of life. Hypersomnia can be both a primary (e.g., hypersomnolence disorder) and secondary (e.g., tumors, and head trauma) symptom of disorders. However, its underlying mechanisms remain largely unknown.Case PresentationWe report that three clinical cases with lesions around the paraventricular nucleus of the hypothalamus (PVH) area showed excessive daytime sleepiness and a prolonged nocturnal sleep lasting more than 20 h per day. Sleep architecture and subjective daytime sleepiness were examined by polysomnography. These cases were presented with stroke, myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders and neuromyelitis optical spectrum disorder (NMOSD), respectively. Magnetic resonance imaging (MRI) showed lesions around the PVH area in all these three patients. After treatment of their primary disorders, their excessive sleep decreased as the PVH area recovered.ConclusionOur findings suggest that the PVH may play an essential role in the occurrence of hypersomnia.
Preoperative Collateral Perfusion Using Arterial Spin Labeling: A Predictor of Surgical Collaterals in Moyamoya Angiopathy
Authors: Wang Maoxue , Wang Yi , Zhang Wen , Zhao Xiance , Yang Yongbo , Zhang Bing 
Published: March 2022

ObjectivesVarious degrees of surgical collateral circulation are often found in moyamoya angiopathy (MMA) patients after revascularization. Little is known about arterial spin labeling (ASL) that affects surgical collateral circulation. This study aimed to investigate the effect of ASL on surgical collaterals in patients with MMA after combined bypass surgery.MethodsMMA patients with complete radiological and clinical information, who had undergone combined bypass, were enrolled in this study. Surgical collaterals were classified as good or poor based on the Matsushima standard. Cerebral perfusion on ASL was quantitatively analyzed as relative cerebral blood flow (rCBF). The qualitative collateral score was calculated using a four-grade scale. Univariable and multivariable logistic regressions were performed to identify the predictors for surgical collaterals after combined bypass.ResultsIn total, 66 hemispheres of 61 patients (47 years old ± 8.66) were prospectively included (29 and 37 hemispheres with good and poor surgical collaterals, respectively). The presurgical collateral score was significantly lower in patients with good surgical collaterals (13.72 scores ± 7.83) than in those with poor surgical collaterals (19.16 scores ± 6.65, P = 0.005). The presurgical rCBF and modified Rankin scale (mRS) scores were not significantly different between the two groups (PrCBF = 0.639, PmRS = 0.590). The collateral score was significantly elevated (good: 13.72 scores ± 7.83 vs. 20.79 scores ± 6.65, P &lt; 0.001; poor: 19.16 scores ± 6.65 vs. 22.84 scores ± 5.06, P &lt; 0.001), and the mRS was reduced (good: 1.66 scores ± 1.14 vs. 0.52 scores ± 0.83, P &lt; 0.001; poor: 1.49 scores ± 0.90 vs. 0.62 scores ± 0.76, P &lt; 0.001) in patients after revascularization. Multivariable logistic regression showed that preoperative collateral scores [odds ratio (OR): 0.791; 95% confidence interval (CI): 0.695, 0.900; P &lt; 0.001], age (OR: 0.181; 95% CI: 0.039, 0.854; P = 0.031), sex (OR: 0.154; 95% CI: 0.035, 0.676; P = 0.013), and hypertension (OR: 0.167; 95% CI: 0.038, 0.736; P = 0.018) were predictors of surgical collaterals after combined revascularization.ConclusionThe preoperative collateral score based on ASL could be a predictor for surgical collaterals in patients with MMA after combined bypass surgery. Combined with age, sex, and hypertension, it may have a better predictive effect.
An MRI-Based Radiomic Model for Individualized Prediction of Hepatocellular Carcinoma in Patients With Hepatitis B Virus-Related Cirrhosis
Authors: Wei Yichen , Gong Jie , He Xin , Liu Bo , Liu Tiejun , Yang Shuohui , Zhou Zhipeng , Liang Lingyan , Zhan Songhua , Xia Ziqiang , Duan Gaoxiong , Lin Bin , Han Qiuli , Li Shasha , Qin Wei , Pickhardt Perry J. , Deng Demao 
Published: March 2022

ObjectiveTo develop and validate a radiomic nomogram for individualized prediction of hepatocellular carcinoma (HCC) in HBV cirrhosis patients based on baseline magnetic resonance imaging examinations and clinical data.Methods364 patients with HBV cirrhosis from five hospitals were assigned to the training, internal validation, external validation-1 or external validation-2 cohort. All patients underwent baseline magnetic resonance image (MRI) scans and clinical follow-up within three-year time. Clinical risk factors and MRI-based features were extracted and analyzed. The radiomic signatures were built using the radiomics-score (Rad-score) that calculated for each patient as a linear weighted combination of selected MRI-based features. Prognostic performances of the clinical and radiomic nomograms were evaluated with Cox modeling in the training and validation cohorts.ResultsEighteen features were selected for inclusion in the Rad-score prognostic model. The radiomic signature from multi-sequence MRI yielded a concordance index (C-index) of 0.710, 0.681, 0.632 and 0.658 in the training, internal validation, external validation-1, external validation-2 cohorts, respectively. Sex and Child-Turcotte-Pugh (CTP) class were the most prognostic clinical risk factors in univariate Cox proportional hazards analyses. The radiomic combined nomogram that integrated the radiomic signature with the clinical factors yielded a C-index of 0.746, 0.710, and 0.641 in the training, internal validation, and external validation-1 cohorts, respectively, which was an improvement over either the clinical nomogram or radiomic signature alone.ConclusionWe developed an MRI-based radiomic combined nomogram with good discrimination ability for the individualized prediction of HCC in HBV cirrhosis patients within three-year time.
Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age
Authors: Lamot Mirta , Miler Marijana , Nikolac Gabaj Nora , Lamot Lovro , Milošević Milan , Harjaček Miroslav , Abdović Slaven 
Published: March 2022

BackgroundFebrile illnesses in young children can be a major diagnostic challenge, despite the routine use of various laboratory markers. Recent advancements in the understanding of inflammatory processes have highlighted the role of calprotectin, a heterodimer consisting of S100A8 and S100A9 proteins, with many studies suggesting its clinical value as a biomarker of inflammation. This research aimed to evaluate the usefulness of serum calprotectin (sCal) as a biomarker of urinary tract infection (UTI), which was due to its high pooled prevalence and feasibility of urine culture as a diagnostic reference standard selected for a model of bacterial infection in children.MethodsFebrile children aged 0–36 months with suspected UTI based on positive urinalysis or viral respiratory tract infection were included. Children with significant bacteriuria in urine culture were labeled as cases (n = 58), while those with confirmed viral infection (n = 51), as well as those with suspected UTI but sterile urine culture who went on to develop symptoms consistent with viral respiratory infection (n = 7), were labeled as controls. sCal levels were determined by a commercial immunoassay. Conventional inflammation markers (C-reactive protein, procalcitonin, white blood cell count, absolute neutrophil count, and neutrophil percentage) were measured on the day of the clinical examination. Differences in measured inflammatory markers between cases and controls were analyzed with Mann-Whitney U-test. ROC analysis reported cut-off values with the best sensitivity and specificity to distinguish bacterial UTI from viral respiratory infection.ResultsAll analyzed inflammatory biomarkers, including sCal, were significantly higher in cases than in controls. Median concentration of sCal was 4.97 μg/mL (IQR 3.43–6.42) and 2.45 μg/mL (IQR 1.63–3.85) for cases and controls, respectively (p &lt; 0.001). For identifying bacterial UTI, sensitivity and specificity of sCal were 77.6 and 69.0%, respectively, at an adjusted cut-off point of &gt;3.24 μg/mL (AUC 80.2%).ConclusionsCal could have substantial added value in the management of a child with fever and positive urinalysis and is a promising biomarker in distinction between bacterial UTI and viral respiratory causes of febrile illness in children under the age of 3 years.