bluuebunny/crossref_metadata_2025_split huggingface dataset:
A zero-dose synthetic baseline for the personalized analysis of [18F]FDG-PET: Application in Alzheimer’s disease
Authors: Hinge Christian , Henriksen Otto Mølby , Lindberg Ulrich , Hasselbalch Steen Gregers , Højgaard Liselotte , Law Ian , Andersen Flemming Littrup , Ladefoged Claes Nøhr 
Published: November 2022

PurposeBrain 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG-PET) is widely used in the diagnostic workup of Alzheimer’s disease (AD). Current tools for uptake analysis rely on non-personalized templates, which poses a challenge as decreased glucose uptake could reflect neuronal dysfunction, or heterogeneous brain morphology associated with normal aging. Overcoming this, we propose a deep learning method for synthesizing a personalized [18F]FDG-PET baseline from the patient’s own MRI, and showcase its applicability in detecting AD pathology.MethodsWe included [18F]FDG-PET/MRI data from 123 patients of a local cohort and 600 patients from ADNI. A supervised, adversarial model with two connected Generative Adversarial Networks (GANs) was trained on cognitive normal (CN) patients with transfer-learning to generate full synthetic baseline volumes (sbPET) (192 × 192 × 192) which reflect healthy uptake conditioned on brain anatomy. Synthetic accuracy was measured by absolute relative %-difference (Abs%), relative %-difference (RD%), and peak signal-to-noise ratio (PSNR). Lastly, we deployed the sbPET images in a fully personalized method for localizing metabolic abnormalities.ResultsThe model achieved a spatially uniform Abs% of 9.4%, RD% of 0.5%, and a PSNR of 26.3 for CN subjects. The sbPET images conformed to the anatomical information dictated by the MRI and proved robust in presence of atrophy. The personalized abnormality method correctly mapped the pathology of AD subjects while showing little to no anomalies for CN subjects.ConclusionThis work demonstrated the feasibility of synthesizing fully personalized, healthy-appearing [18F]FDG-PET images. Using these, we showcased a promising application in diagnosing AD, and theorized the potential value of sbPET images in other neuroimaging routines.
User-centered design and development of TWIN-Acta: A novel control suite of the TWIN lower limb exoskeleton for the rehabilitation of persons post-stroke
Authors: Semprini Marianna , Lencioni Tiziana , Hinterlang Wiebke , Vassallo Christian , Scarpetta Silvia , Maludrottu Stefano , Iandolo Riccardo , Carè Marta , Laffranchi Matteo , Chiappalone Michela , Ferrarin Maurizio , De Michieli Lorenzo , Jonsdottir Johanna 
Published: November 2022

IntroductionDifficulties faced while walking are common symptoms after stroke, significantly reducing the quality of life. Walking recovery is therefore one of the main priorities of rehabilitation. Wearable powered exoskeletons have been developed to provide lower limb assistance and enable training for persons with gait impairments by using typical physiological movement patterns. Exoskeletons were originally designed for individuals without any walking capacities, such as subjects with complete spinal cord injuries. Recent systematic reviews suggested that lower limb exoskeletons could be valid tools to restore independent walking in subjects with residual motor function, such as persons post-stroke. To ensure that devices meet end-user needs, it is important to understand and incorporate their perspectives. However, only a limited number of studies have followed such an approach in the post-stroke population.MethodsThe aim of the study was to identify the end-users needs and to develop a user-centered-based control system for the TWIN lower limb exoskeleton to provide post-stroke rehabilitation. We thus describe the development and validation, by clinical experts, of TWIN-Acta: a novel control suite for TWIN, specifically designed for persons post-stroke. We detailed the conceived control strategy and developmental phases, and reported evaluation sessions performed on healthy clinical experts and people post-stroke to evaluate TWIN-Acta usability, acceptability, and barriers to usage. At each developmental stage, the clinical experts received a one-day training on the TWIN exoskeleton equipped with the TWIN-Acta control suite. Data on usability, acceptability, and limitations to system usage were collected through questionnaires and semi-structured interviews.ResultsThe system received overall good usability and acceptability ratings and resulted in a well-conceived and safe approach. All experts gave excellent ratings regarding the possibility of modulating the assistance provided by the exoskeleton during the movement execution and concluded that the TWIN-Acta would be useful in gait rehabilitation for persons post-stroke. The main limit was the low level of system learnability, attributable to the short-time of usage. This issue can be minimized with prolonged training and must be taken into consideration when planning rehabilitation.DiscussionThis study showed the potential of the novel control suite TWIN-Acta for gait rehabilitation and efficacy studies are the next step in its evaluation process.
Reduced serum cholinesterase is an independent risk factor for all-cause mortality in the pediatric intensive care unit
Authors: Yue Chaoyan , Zhang Chunyi , Ying Chunmei , Jiang Hua 
Published: November 2022

ObjectiveOur aim was to assess the relationship between serum cholinesterase levels at intensive care unit admission and all-cause mortality in the pediatric intensive care unit.MethodsWe used the pediatric intensive care unit database (a large pediatric intensive care database in China from 2010 to 2018) to conduct a retrospective analysis to evaluate the serum cholinesterase levels at intensive care unit admission of 11,751 critically ill children enrolled to the intensive care unit. We analyzed the association between serum cholinesterase and all-cause mortality. Adjusted smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between proportional risk between serum cholinesterase and death.ResultsOf the 11,751 children, 703 (5.98%) died in hospital. After adjusting for confounders, there was a negative association between serum cholinesterase and the risk of death in pediatric intensive care unit. For every 1,000 U/L increase in serum cholinesterase, the risk of death was reduced by 16% (adjusted OR = 0.84, 95% CI: 0.79, 0.89). The results of sensitivity analysis showed that in different stratified analyses (age, intensive care unit category, albumin, alanine aminotransferase, creatinine, neutrophils), the effect of serum cholinesterase on all-cause mortality remained stable.ConclusionAfter adjusting for inflammation, nutrition, and liver function factors, cholinesterase reduction is still an independent risk factor for pediatric intensive care unit all-cause mortality.
Establishment and validation of a prognostic nomogram for extrahepatic cholangiocarcinoma
Authors: Zhao Fangrui , Yang Dashuai , He Jiahui , Ju Xianli , Ding Youming , Li Xiangpan 
Published: November 2022

Simple summaryAccurately estimate the prognosis of patients with ECCA is important. However, the TNM system has some limitations, such as low accuracy, exclusion of other factors (e.g., age and sex), and poor performance in predicting individual survival risk. In contrast, a nomogram-based clinical model related to a comprehensive analysis of all risk factors is intuitive and straightforward, facilitating the probabilistic analysis of tumor-related risk factors. Simultaneously, a nomogram can also effectively drive personalized medicine and facilitate clinicians for prognosis prediction. Therefore, we construct a novel practical nomogram and risk stratification system to predict CSS in patients with ECCA.BackgroundAccurately estimate the prognosis of patients with extrahepatic cholangiocarcinoma (ECCA) was important, but the existing staging system has limitations. The present study aimed to construct a novel practical nomogram and risk stratification system to predict cancer-specific survival (CSS) in ECCA patients.Methods3415 patients diagnosed with ECCA between 2010 and 2015 were selected from the SEER database and randomized into a training cohort and a validation cohort at 7:3. The nomogram was identified and calibrated using the C-index, receiver operating characteristic curve (ROC), and calibration plots. Decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and the risk stratification were used to compare the nomogram with the AJCC staging system.ResultsNine variables were selected to establish the nomogram. The C-index (training cohort:0.785; validation cohort:0.776) and time-dependent AUC (&gt;0.7) showed satisfactory discrimination. The calibration plots also revealed that the nomogram was consistent with the actual observations. The NRI (training cohort: 1-, 2-, and 3-year CSS:0.27, 0.27,0.52; validation cohort:1-,2-,3-year CSS:0.48,0.13,0.34), IDI (training cohort: 1-, 2-, 3-year CSS:0.22,0.18,0.16; validation cohort: 1-,2-,3-year CSS:0.18,0.16,0.17), and DCA indicated that the established nomogram significantly outperformed the AJCC staging system (P&lt;0.05) and had better recognition compared to the AJCC staging system.ConclusionsWe developed a practical prognostic nomogram to help clinicians assess the prognosis of patients with ECCA.
A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer
Authors: Jin Ying , Li Jin , Shen Lin , Xu Jianming , Zhang Yanqiao , Zhang Jingdong , Pan Hongming , Qu Xiujuan , Chen Yamin , Zhang Qiang , Li Jinnan , Sun Miaomiao , Qin Shukui 
Published: November 2022

ObjectiveThe objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs.Materials and methodsThe arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan–Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively.ResultsOverall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 vs. 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, p = 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; p=0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; p=0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; p=0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; p=0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; p=0.042).ConclusionWith the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.
Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: A retrospective study
Authors: Yi Yong , Sun Bao-Ye , Weng Jia-Lei , Zhou Cheng , Zhou Chen-Hao , Cai Ming-Hao , Zhang Jing-Yun , Gao Hong , Sun Jian , Zhou Jian , Fan Jia , Ren Ning , Qiu Shuang-Jian 
Published: November 2022

PurposeWe aimed to investigate the feasibility of lenvatinib plus anti-PD-1 therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC).MethodsPatients with initially unresectable HCC who received combined lenvatinib and anti-PD-1 antibody between May 2020 and Jan 2022 in Zhongshan Hospital were retrospectively analyzed. Tumor response and resectability were assessed by imaging every two months according to RECIST version 1.1 and modified RECIST (mRECIST) criteria.ResultsA total of 107 patients were enrolled. 30 (28%) of them received conversion surgery within 90.5 (range: 53–456) days after the initiation of lenvatinib plus anti-PD-1 therapy. At baseline, the median largest tumor diameter of these 30 patients was 9.2 cm (range: 3.5-15.0 cm), 26 patients had Barcelona Clinic Liver Cancer stage B-C, and 4 had stage A. Prior to surgery, all cases displayed tumor regression and 15 patients achieved objective response. Pathological complete response (pCR) was observed in 10 patients. No severe drug-related adverse events or surgical complications were observed. After a median follow-up of 16.5 months, 28 patients survived and 11 developed tumor recurrence. Survival analysis showed patients achieving tumor response before surgery or pCR had a longer tumor-free survival. Notably, patients with microvascular invasion (MVI) had significantly higher recurrence rate and poorer overall survival than patients without.ConclusionsLenvatinib combined with anti-PD-1 therapy represents a feasible conversion strategy for patients with initially unresectable HCC. Patients achieving tumor responses are more likely to benefit from conversion resection to access a longer term of tumor-free survival.
Efficacy and safety of 177Lu-DOTATATE targeted therapy in advanced/metastatic pulmonary neuroendocrine tumors: A systematic review and meta-analysis
Authors: Ma Jiao , Hu Xin , Li Lanying , Rao Zijuan , Zhang Chunyin 
Published: November 2022

ObjectiveTo perform a meta-analysis of the efficacy and safety about 177Lu-DOTATATE therapy for advanced/metastatic pNETs based on the current clinical evidence.MethodsThis systematic review follows the PRISMA guideline. Search PubMed, Medline, EMBASE and CNKI, VIP, Wanfang databases, from establishment to June 2022, on the study of 177Lu-DOTATATE for advanced/metastatic pNETs, the primary endpoint was to evaluate the treatment effect through DRRs and DCRs. Secondary endpoint included assessment of OS, PFS, and treatment-related adverse events across all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using stata16.0 software, and the data were merged and displayed using forest graphs.ResultsA total of 5 studies, 174 patients, on 177Lu-DOTATATE for advanced/metastatic pNETs were included. The pools of DRRs and DCRs were 24% (95% CI: 15%~32%) and 77% (95% CI: 62%~92%), respectively. The pool of OS was 48.78 months (95% CI: 41~56.57 months) and the pool of PFS was 21.59 months (95% CI: 17.65~25.53 months). In all studies, the most common side effect of treatment was hematological toxicity. In 174 patients, hematological toxicity of grade III accounted for 4.0% (7/174), and only 4.0% (7/174) and 1.0% (2/174) of patients had mild nephrotoxicity and hepatotoxicity. Gastrointestinal adverse reactions in 3% (6/174), nausea in 2% (3/174), superior vena cava occlusion in 0.5% (1/174).Conclusion177Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients’ survival, and has low treatment-related toxicity and high safety. However, its efficacy and safety need to be further evaluated in high-quality, multicenter randomized controlled trials in the future.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022344436.
Success rate and duration of orotracheal intubation of premature infants by healthcare providers with different levels of experience using a video laryngoscope as compared to direct laryngoscopy in a simulation-based setting
Authors: V. Salis-Soglio Nicolaus , Hummler Helmut , Schwarz Stephan , Mendler Marc R. 
Published: November 2022

BackgroundEndotracheal intubation of very low birth weight infants (VLBWI) is an essential procedure in NICUs, but intubation experience is often limited. Video laryngoscopy (VL) has been described as a tool to improve intubation skills, but studies in high-risk neonatal populations are limited.ObjectiveThe aim of this study was to investigate whether VL is a useful tool to support airway management in high-risk premature infants with inexperienced operators.MethodsIn this crossover study predominantly inexperienced participants were exposed in random sequence to VL and conventional direct laryngoscopy (DL) for endotracheal intubation of a VLBWI simulation manikin to measure total time, number of attempts, success rate on first attempt, view of the vocal cords and perceived subjective safety until successful intubation.ResultsIn our study group of 94 participants there was no significant difference in the total time (mean VL: 34 s (±24 s); DL: 37 s (±28 s), p = 0.246), while the number of intubation attempts using VL was significantly lower (mean VL: 1.22 (±0.53); DL: 1.37 (±0.60), p = 0.023). Success rate of VL during the first attempt was significantly higher (VL: 84%; DL 69%, p = 0.016), view of the vocal cords was significantly better and perceived subjective safety was increased using VL.ConclusionsOur study results suggest that with rather inexperienced operators, VL can be a useful tool to increase rate of successful endotracheal intubation of VLBWI and to improve their perceived safety during the procedure, which may have an impact on mortality and/or morbidity.
Clinical efficacy of Bupleurum inula flower soup for immune damage intervention in Hashimoto’s thyroiditis: A placebo-controlled randomized trial
Authors: Meng Xiangfei , Liu Shiyi , Deng Xiumin , Li Xintong , Lei Jia , Jiang Hongye , Liu Mengyao , Zhang Ning , Liu Shiwei 
Published: November 2022

Background: Antibody-mediated humoral immune response is involved in the damage process in Hashimoto’s thyroiditis (HT). Although the traditional Chinese medicine (TCM) formula bupleurum inula flower soup (BIFS) is often used in HT treatment, it has not been evaluated through high-quality clinical research. Rigorously designed randomized, double-blind, prospective clinical studies are urgently needed to evaluate BIFS for intervening in the HT immune damage process, and to improve clinical prognosis and patient quality of life.Methods: A prospective randomized, double-blind, placebo-controlled trial was used to evaluate the efficacy of BIFS. Fifty participants diagnosed with HT with hypothyroidism were randomly assigned at a 1:1 ratio to the BIFS (levothyroxine with BIFS) or control (levothyroxine with placebo) group. Participants received 8 weeks of treatment and were followed for 24 weeks. They were monitored for: levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid stimulating hormone (TSH); scores for depression, anxiety, and health-related quality of life (HRQoL); thyroid volume; safety indicators including routine blood tests, liver and kidney functions, and electrocardiogram; and levothyroxine dose.Results: Forty-eight participants completed the study and were included in the final analysis. At baseline, there were no significant between-group differences in the observed indicators (p &gt; 0.05). Post-treatment, compared with the control group, the BIFS group had significantly lower levels of TPOAb (275.77 ± 132.98 vs. 441.78 ± 195.50, p = 0.001), TgAb (385.92 ± 281.91 vs. 596.17 ± 282.26, p = 0.013), and TSH (6.57 ± 3.73 vs. 9.63 ± 5.34, p = 0.001). Compared with the control group, the BIFS group’s scores improved significantly for depression (47.00 ± 5.12 vs. 51.04 ± 3.22, p = 0.002), anxiety (43.21 ± 4.22 vs. 48.08 ± 2.81, p = 0.005), and HRQoL physical (62.08 ± 5.97 vs. 57.96 ± 4.71, p = 0.011) and psychological (60.17 ± 5.94 vs. 55.75 ± 7.09, p = 0.024) subscores. At 24-week follow-up, levothyroxine combined with TCM allowed a significantly reduced levothyroxine dose (0.58 ± 0.43 vs. 1.02 ± 0.45, p = 0.001). The post-treatment clinical efficacy rates differed significantly (p = 0.03), with 75% (18/24) for the BIFS group and 46% (11/24) for the control group. There were no significant between-group differences in thyroid volume or safety indicators after eight treatment weeks or at the 24-week follow-up (p &gt; 0.05).Conclusion: The TCM BIFS can effectively reduce thyroid titer, relieve clinical and emotional symptoms, and improve HRQoL in patients with HT.Clinical Trial Registration:https://www.chictr.org.cn/, identifier ChiCTR1900020987
Is not workplace gossip bad? The effect of positive workplace gossip on employee innovative behavior
Authors: Dai Yuping , Zhuo Xiangzhi , Hou Jie , Lyu Bei 
Published: November 2022

PurposeThe purpose of this study is to examine the role of positive workplace gossip (PWG) in employee innovative behavior, whereby a mediating effect of employee loyalty is proposed in this relationship. The moderating effect of organizational trust (OT) is also examined on the indirect of PWG on employee innovative behavior through employee loyalty.Design/methodology/approachThis research used a survey data of 327 employees from the enterprises selected from the Pearl River and Yangtze River Delta region of China. Based on the literature review, five main hypotheses were formulated and explored. The SPSS-Process Macro Plugin was used to analyze the hypothesized model.FindingsResults show there is a positive and significant relationship between PWG and employee innovative behavior. This study also confirm that employee loyalty is an intervening variable and OT as a moderator.Practical implicationsOrganizations should pay more attention to workplace gossip phenomena, encourage employees to take appropriate part in positive workplace gossip and to communicate positive information about other colleagues, and build an inclusive, open, sincere, and interdependent platform in the organization.Originality/valueEmployee innovative behavior plays an essential role in organization’s survival and development. Few studies have investigated PWG may promote employee innovative behavior through employee loyalty. The data, model, and findings of this research address the gap and complement the current state of knowledge.