bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of cerebrospinal inflammatory profile with radiological features in newly diagnosed treatment-naïve patients with multiple sclerosis
Authors: Ashida Shinji , Kondo Takayuki , Fujii Chihiro , Hamatani Mio , Mizuno Toshiki , Ochi Hirofumi 
Published: September 2022

ObjectiveMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Without reliable diagnostic biomarkers, the clinical and radiological heterogeneity of MS makes diagnosis difficult. Although magnetic resonance imaging (MRI) is a major diagnostic tool for MS, the association of MRI findings with the inflammatory profile in cerebrospinal fluid (CSF) has been insufficiently investigated. Therefore, we focused on CSF profile of MS patients and examined its association with MRI findings.MethodsConcentrations of 26 cytokines and chemokines were determined in CSF of 28 treatment-naïve MS patients and 12 disease-control patients with aquaporin-4 antibody-seropositive neuromyelitis optica spectrum disorder (NMOSD).ResultsHigh levels of interleukin (IL)-6, IL-17A, B-cell activating factor (BAFF), a proliferation inducing ligand (APRIL), and CD40 ligand were correlated with the absence of at least one of the following three MRI findings in MS: an ovoid lesion, three or more periventricular lesions, and a nodular and/or ring-shaped contrast-enhancing lesion. The multivariate analysis revealed that elevated IL-17A was an independent predictor of absence of ovoid lesion and periventricular lesions less than three. MS patients were classified into a group with all three MRI findings (MS-full) and a group with less than three (MS-partial). The discriminant analysis model distinguished three groups: MS-full, MS-partial, and NMOSD, with 98% accuracy.ConclusionThe CSF inflammatory profile was associated with radiological findings of treatment-naïve MS. This result indicates the possible utility of combined CSF and MRI profiling in identifying different MS phenotypes related to the heterogeneity of underlying immune processes.
Spinal dural arteriovenous fistula: A rare but treatable disease that should not be missed by orthopedic surgeons
Authors: Yang Baohui , Lu Teng , He Xijing , Li Haopeng 
Published: September 2022

ObjectiveSpinal dural arteriovenous fistula (SDAVF) is a rare disease that is often misdiagnosed by orthopedic surgeons. We analyzed the reasons for the misdiagnosis and proposed countermeasures.MethodsTwenty-two SDAVF patients who were initially treated in orthopedics were included. The patients were divided into a correct diagnosis group (A) and a misdiagnosis group (B). The clinical data and prognosis were evaluated.ResultsThere were 10 patients in group A and 12 patients in group B. The clinical manifestations included limb numbness, weakness, and bladder and bowel dysfunction. Among these patients without spinal degenerative diseases which had typical magnetic resonance imaging (MRI) features in Group A were more than Group B (P &lt; 0.05). More patients had spinal degenerative diseases in group B. In group A, seven patients were primarily diagnosed with a SDAVF after multidisciplinary teamwork (MDT). In group B, five patients were misdiagnosed with lumbar spinal stenosis, four with lumbar disc herniation, two with thoracic spinal stenosis, and one with cervical spinal stenosis and lumbar spinal stenosis and underwent cervical spinal canal and lumbar spinal canal decompression. The length of time for confirming the diagnosis was 7 months longer in group B than in group A. All patients underwent microsurgery treatment. The average follow-up duration was 11 months. The modified Aminoff-Logue Disability Scale scores showed a statistically significant difference in improvement between the two groups (P &lt; 0.05).Conclusionwhen patients with dysuria especially, have intermittent spinal nerve dysfunction, the possibility of SDAVF should be considered. Awareness of the specific clinical and spinal cord edema and flow voids on MRI of a SDAVF needs to be promoted for orthopedic surgeons. Timely MDT is an important measure for reducing misdiagnosis, and steroids or inappropriate surgery should be avoided until a SDAVF is completely excluded.
Dynamic connectivity patterns of resting-state brain functional networks in healthy individuals after acute alcohol intake
Authors: Zhang Gengbiao , Li Ni , Liu Hongkun , Zheng Hongyi , Zheng Wenbin 
Published: September 2022

AimsCurrently, there are only a few studies concerning brain functional alterations after acute alcohol exposure, and the majority of existing studies attach more importance to the spatial properties of brain function without considering the temporal properties. The current study adopted sliding window to investigate the resting-state brain networks in healthy volunteers after acute alcohol intake and to explore the dynamic changes in network connectivity.Materials and methodsTwenty healthy volunteers were enrolled in this study. Blood-oxygen-level-dependent (BOLD) data prior to drinking were obtained as control, while that 0.5 and 1 h after drinking were obtained as the experimental group. Reoccurring functional connectivity patterns (states) were determined following group independent component analysis (ICA), sliding window analysis and k-means clustering. Between-group comparisons were performed with respect to the functional connectivity states fractional windows, mean dwell time, and the number of transitions.ResultsThree optimal functional connectivity states were identified. The fractional windows and mean dwell time of 0.5 h group and 1 h group increased in state 3, while the fraction window and mean dwell time of 1 h group decreased in state 1. State 1 is characterized by strong inter-network connections between basal ganglia network (BGN) and sensorimotor network (SMN), BGN and cognitive executive network (CEN), and default mode network (DMN) and visual network (VN). However, state 3 is distinguished by relatively weak intra-network connections in SMN, VN, CEN, and DMN. State 3 was thought to be a characteristic connectivity pattern of the drunk brain. State 1 was believed to represent the brain’s main connection pattern when awake. Such dynamic changes in brain network connectivity were consistent with participants’ subjective feelings after drinking.ConclusionThe current study reveals the dynamic change in resting-state brain functional network connectivity before and after acute alcohol intake. It was discovered that there might be relatively independent characteristic functional network connection patterns under intoxication, and the corresponding patterns characterize the clinical manifestations of volunteers. As a valuable imaging biomarker, dynamic functional network connectivity (dFNC) offers a new approach and basis for further explorations on brain network alterations after alcohol consumption and the alcohol-related mechanisms for neurological damage.
The efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A Chinese multicenter real-world study
Authors: Zheng Hao-Ran , Jiang Ai-Min , Gao Huan , Liu Na , Zheng Xiao-Qiang , Fu Xiao , Ruan Zhi-Ping , Tian Tao , Liang Xuan , Yao Yu 
Published: September 2022

BackgroundPatients with extensive-stage small-cell lung cancer (ES-SCLC) have high recurrence rates and bleak prognosis. This multicenter real-world study aimed to explore the efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy as the first-line treatment of ES-SCLC.MethodsPathologically confirmed ES-SCLC patients receiving anlotinib plus platinum-etoposide chemotherapy as the first-line treatment were enrolled in this retrospective study. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse reactions. The Cox regression analyses were employed to investigate the independent prognostic factors for OS and PFS of these individuals.ResultsIn total, 58 patients were included in this study. The median PFS was 6.0 months [95% confidence interval (CI): 3.5-8.5], and the median OS was 10.5 months (95%CI 8.7-12.3). Thirty-four patients achieved partial response (PR), 18 patients achieved stable disease (SD), and 6 patients achieved progressive disease (PD). The ORR and DCR were 58.6% and 89.6%. The main treatment-related adverse reactions were generally tolerated. Myelosuppression (44.8%) was the most common adverse reaction, followed by hypertension (41.4%), fatigue (34.5%), gastrointestinal reaction (32.7%), and hand-foot syndrome (24.1%). Multivariate analysis showed that post-medication hand-foot syndrome [PFS 8.5 vs. 5.5 months, Hazards Ratio (HR)=0.23, 95%CI 0.07-0.72, P =0.012] was the independent predictor of PFS, and hypertension (OS 15.9 vs. 8.3 months, HR=0.18, 95%CI 0.05-0.58, P =0.005) was the independent predictor of OS.ConclusionAnlotinib combined with platinum-etoposide chemotherapy as the first-line treatment for ES-SCLC appears to be effective and well-tolerated in the real-world. Well-designed large-scale prospective studies are urgently needed in the future to verify our findings.
The impact of tumor metabolic activity assessed by 18F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
Authors: Waltenberger Maria , Furkel Jennifer , Röhrich Manuel , Salome Patrick , Debus Charlotte , Tawk Bouchra , Gahlawat Aoife Ward , Kudak Andreas , Dostal Matthias , Wirkner Ute , Schwager Christian , Herold-Mende Christel , Combs Stephanie E. , König Laila , Debus Jürgen , Haberkorn Uwe , Abdollahi Amir , Knoll Maximilian 
Published: September 2022

BackgroundSelective uptake of (18)F-fluoro-ethyl-tyrosine (18F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG).Methods18F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell).ResultsIn pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm3 in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm3 in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (&gt;3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (&gt;2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx.ConclusionThe benefits of 18F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.
Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting
Authors: Maluf Fernando Cotait , Zibetti Graziela Dal Molin , Paulino Eduardo , de Melo Andreia Cristina , Racy Douglas , Ferrigno Robson , Uson Junior Pedro Luiz Serrano , Ribeiro Reitan , Moretti Renato , Sadalla Jose Carlos , Nogueira Rodrigues Angelica , Carvalho Filomena Marino , Baiocchi Glauco , Callegaro-Filho Donato , Angioli Roberto 
Published: September 2022

IntroductionDue to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed.MethodsThe panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care.ResultsConsensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations.ConclusionThe development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.
Willingness to pay for and willingness to vaccinate with the COVID-19 vaccine booster dose in China
Authors: Zhou Hui Jun , Pan Lei , Shi Hui , Luo Ji Wei , Wang Pei , Porter Hannah K. , Bi Ye , Li Minghui 
Published: September 2022

Objective: The present study aims to assess the willingness to pay (WTP) for and willingness to vaccinate (WTV) with the Coronavirus (COVID-19) vaccine booster dose in China when the pandemic is under adequate control and the majority of the population is vaccinated. This study is also to identify significant factors associated with the WTP.Methods: This was a cross-sectional study on adults with no past or present COVID-19 infection. An online questionnaire was distributed to collect data on vaccination status, quarantine experience, and factors related to health beliefs on vaccination. The WTV was assessed through the vaccination preference. The WTP was examined by payment scale (PS) and iterative bidding game (IBG) administered in random order. Three IBG algorithms with different starting-price were presented randomly. The average WTP of PS and IBG were analyzed as primary outcomes using univariate and multivariate analyses. Multivariate ordered logistic regression was performed to identify significant factors for the WTP.Results: The survey recruited 543 participants with a mean age of 32 years and 57.80% being female. The WTV rate was 86.74%, while 94.66% of participants completed full-schedule or enhanced vaccination. The mean WTP was CNY 149 (±CNY 197) and the median WTP was CNY 80. Regarding significant factors for the WTP, urban residents were 57% more likely (95% CI: 1.11-2.22) to pay for a high-priced vaccine than rural residents. Respondents who completed full-schedule vaccination were 46% more likely (95% CI: 1.03–2.07) to pay for a high-priced vaccine than those who completed enhanced vaccination. Respondents with a low household income of CNY 40k or lower were 62% less likely (95% CI: 0.21–0.66) to pay for a high-priced vaccine than those with a middle household income of CNY 110k–210k. Other significant factors associated with the WTP included the perceived benefit of vaccination and peer environmental pressure in the health belief model.Conclusion: The WTV with the COVID-19 vaccine booster dose was high in China. The WTP was influenced by the place of residence, vaccination status, household income, perceived benefit of vaccination, and environmental peer pressure. Study findings can inform policymakers to better design vaccination programs and financial schemes involving out-of-pocket payments.
In vitro anti-gastrointestinal cancer activity of Toxocara canis-derived peptide: Analyzing the expression level of factors related to cell proliferation and tumor growth
Authors: Bahadory Saeed , Sadraei Javid , Zibaei Mohammad , Pirestani Majid , Dalimi Abdolhossein 
Published: September 2022

Background: Recently, a hypothesis about the negative relationship between cancers and parasites has been proposed and investigated; some parasitic worms and their products can affect the cancer cell proliferation. Due to the potential anti-cancer effect of helminthic parasites, in the present study, the excretory–secretory protein of Toxocara canis (T. canis) parasite was used to evaluate the possible anti-cancer properties and their effect on gastrointestinal and liver cancer cell proliferation-related genes in laboratory conditions.Methods and materials: The selected synthesized peptide fraction from the T. canis excretory–secretory Troponin protein peptide (ES TPP) was exposed at 32, 64, 128, and 256 μg/ml concentrations to three gastrointestinal cancer cell lines AGS, HT-29, and Caco 2, as well as HDF cells as normal cell lines. We used the MTT assay to evaluate cellular changes and cell viability (CV). Variations in gene (Bcl-2, APAF1, ZEB1, VEGF, cyclin-D1, and caspase-3) expression were analyzed by real-time RT-PCR.Results: After 24 h of exposure to pept1ides and cell lines, a decrease in CV was observed at a concentration of 64 μg/ml and compared to the control group. Then, after 48 h, a significant decrease in the CV of Caco 2 cells was observed at a concentration of 32 μg/ml; in the other cancer cell lines, concentrations above 32 μg/ml were effective. The peptide was able to significantly alter the expression of the studied genes at a concentration of 100 μg/ml.Conclusion: Although the studied peptide at high concentrations could have a statistically significant effect on cancer cells, it is still far from the standard drug and can be optimized and promising in future studies.
Cost-effectiveness of osimertinib versus standard EGFR-TKI as first-line treatment for EGFR-mutated advanced non-small-cell lung cancer in China
Authors: Shu Yamin , Ding Yufeng , He Xucheng , Liu Yanxin , Wu Pan , Zhang Qilin 
Published: September 2022

Objective: The purpose of this study was to estimate the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated advanced non-small-cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system.Methods: A Markov model was developed to simulate the outcomes and direct medical costs of osimertinib or standard EGFR-TKI in the first-line treatment of patients with previously untreated EGFR-mutated advanced NSCLC. Individual patient survival data were extracted from the FLAURA randomized clinical trial. Clinical costs and utilities’ input estimates were collected from the local hospital and available literature reports. The quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), incremental net monetary benefit (INMB), and incremental net health benefit (INHB) were calculated for the two treatment strategies over a 10-year lifetime horizon. In addition, one-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to test the robustness of the model.Results: On baseline analysis, osimertinib achieved additional 0.39 QALYs and $15,443.78 incremental costs compared with standard EGFR-TKI (gefitinib or erlotinib), which resulted in the ICER of $39,369.53/QALY. The INMB was -$755.11, and the INHB was -0.02 QALYs at a WTP threshold of $37,663.26/QALY in China. The one-way sensitivity analysis showed that the utility of PFS had the strongest association with the ICER. Osimertinib had approximately 46.4% probability of being cost-effective at the WTP threshold of $37,663.26/QALY.Conclusion: First-line osimertinib therapy might not be cost-effective in China for patients with EGFR-mutated advanced NSCLC compared with standard EGFR-TKI based on its current marketed price. A significantly more favorable cost-effectiveness could be achieved when the price of osimertinib was reduced by 5%.
Comparing the effects of olfactory-based sensory stimulation and board game training on cognition, emotion, and blood biomarkers among individuals with dementia: A pilot randomized controlled trial
Authors: Lin Li-jung , Li Kuan-yi 
Published: September 2022

Olfactory dysfunction can indicate early cognitive decline and is associated with dementia symptoms. We developed an olfactory-based sensory stimulation program and investigated its effects on cognition and emotion, and board game training were used as a comparison. In this parallel design pilot study, 30 participants with mild to moderate dementia were equal randomly assigned to the control (CONT), olfactory stimulation with cognitive training (OS), and board game (BG) groups. Two participants were withdrawn from CONT and OS groups, respectively. The intervention was a 12-week program with one 30-min session twice a week. We employed a blood-based biomarker technique and several cognitive and psychological tests to measure basal and after-intervention values. No significant differences were observed between the groups after intervention, as measured using the Mini-Mental State Examination, Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), Top International Biotech Smell Identification Test, and Geriatric Depression Scale (GDS). The results showed that the OS group had a lower plasma Tau level than the other groups following intervention, whereas the CONT group had a significantly increased plasma amyloid ß1-42 level. OS participants had a lower concentration ratio of plasma Tau and amyloid Aß1-42 and showed more stable or improved cognition, olfactory function, and mood state. Both the OS and BG groups had a higher percentage of participants with stable or improved cognition and emotion. Taken together, these results suggest that olfactory-based sensory stimulation can be a beneficial intervention for patients with dementia.Clinical trial registration[Clinicaltrials.gov], identifier [NCT05168098].